FAST FACTS AND CONCEPTS

Corticosteroids for Common Palliative Care Symptoms #395

- corticosteroids which are often prescribed to address symptoms common to patients with terminal illnesses (1). - Pharmacology: Dexamethasone is often selected in palliative care given its prolonged half-life, multiple routes of administration, and relatively low mineralocorticoid effect (thus less likelihood of fluid retention) (2). Prednisone, prednisolone, and methylprednisolone may be acceptable alternatives depending on the clinical circumstance. Prednisone is converted by liver enzymes to the active compound prednisolone. Therefore, prednisolone or methylprednisolone are preferred in liver impairment (3). - Adverse Effects: Although the risk of adverse effects increases with dose and duration of any corticosteroid, long-term treatment (e.g. longer than a month) with relatively low doses (defined as a prednisone 5 mg or less) is generally well tolerated. - Early adverse effects (seen in days): hyperglycemia, fluid retention, and mental disturbances (insomnia, agitation, euphoria, paranoia, see Fast Fact #323). -Late adverse effects (weeks to months): myopathy leading to proximal limb muscle weakness and reduced respiratory force; infection risk (especially fungal such as oral thrush); additive risk of GI bleed with NSAIDS (5). Proton pump inhibitors and/or H2 antagonists are likely only needed for daily doses of ≥ 140 mg of dexamethasone or those taking concomitant NSAIDs. Considerations when prescribing corticosteroids: Monitor regularly. Aim to discontinue corticosteroids within 5-7 days if there is an insufficient clinical response. Doing so can prevent the need to reduce the dose gradually (taper). Aim for the lowest therapeutic dose to prevent side effects. If taking ≤ 4 mg of dexamethasone (or its equivalent) for 3 weeks or less, it is likely safe to stop steroids abruptly without a taper (4). Unless an emergency, most corticosteroids can be administered once daily in the morning, or twice daily with the last dose before 2:00 pm. This dosage schedule reduces suppression of the hypo-pituitary-adrenal axis and the risk of insomnia (3). Consider prognosis. Side-effects become a cumulative problem when prognosis is months or more. Monitor for hyperglycemia, especially in patients with an anticipated prognosis of months or more. Consult the primary oncologist before starting corticosteroids, as they may impact the effectiveness of immune-based systemic cancer treatments.

The Anorexia-Cachexia Syndrome: Definitions, Evaluation, and Non-Pharmacologic Management.

-ACS is incorporated into numerous prognostication scales and is considered a common manifestation on the terminal illness pathway. -Refractory cachexia is associated with a prognosis < 3 months. -The clinical recognition of ACS can help clinicians assess where a patient may be at on an illness trajectory. -Hence, clinicians should utilize the presence of ACS to improve their prognostic disclosure and clinical recommendations regarding the role of pleasure feeding over artificial nutrition especially for refractory cachexia. -Additionally, the Glasgow Prognostic Index, which involves a simple 0,1,2 scoring system based on the presence of elevated c-reactive protein levels and/or low albumin levels, has been validated to assess the extent of disease-related inflammation and offer reliable prognostic information for cancer and non-cancer illnesses. Non-pharmacologic management: ACS can be very distressing given the lack of efficacious therapies. Patient-family strife may result as loved ones may not understand why previously cherished foods lovingly prepared are not being eaten. While a separate Fast Factwill review the utility of pharmacotherapies and supplements for ACS, patient counseling is the cornerstone to the clinical management of ACS. -Education that ACS is not a patient choice, but rather a manifestation of a hormonally-advanced, underlying illness may be the most crucial aspect of ACS care. In fact, experts suggest that the presence of refractory cachexia should prompt a goals of care discussion and nutritional refocusing away from weight gain and caloric intake and more towards alleviating hunger and thirst. -Most experts do not recommend enteral nor parenteral artificial nutrition for refractory cachexia, as neither meaningfully improve quality of life or survival. -Controlled studies in patients undergoing cancer treatment suggest that consultation with a licensed nutritionist may offer quality-of-life benefits in the pre-cachexia phase via improved dietary intake from fortified food, nutritional supplementation, and counseling. -The nutritional counseling often involves liberalizing diet restrictions and encouraging patients to eat frequent, small meals with preferably the bulk of calorie intake occurring the morning. Additionally, some patients may wish to limit exposure to strong aromas and spicy flavors. However, the evidence underlying this nutritional counseling and/or consultation, is not established in patients with more advanced illness.

Opioids withdrawal (# 95)

-Can occur to anyone with physical dependence on opiods who stops use suddenly, has a rapid reduction in opioid dose, or receives an opoiod antagonist such as naloxone or high dose of a partial agonist like buprenorphine. -Physical dependence is a normal and predictable neurophysiological response to regular treatment with opioids for more than 1-2 weeks. -Continouos or near continuous opioid blood levels are required for physical dependence Signs and Symptoms of withdrawal: -yawning, sweating, lacrimation, rhinorrhea, anxiety, restlessness, insomnia, dilated pupils, piloerection, chills, tachycardia, htn, n/v, cramping abd pains, diarrhea, myalgias. -Unlike withdrawal from EtOH or benzos, opoid withdrawal is not life threatening. -It takes 6-12 hours after the last dose of a short-acting drug or 72-96 hours following methadone. -Duration and intensity of withdrawal are related to clearance of the drug such that withdrawal is shorter (5-10 days) and more intense for opioids like morphine and less severe and more protracted with methadone and buprenorphine. -A validated tool to assess severity of withdrawal symptoms as well as aid in appropriate medication mgt is the (COWS) Clinical opioid withdrawal scale. Prevention: -The current CDC recommendations are to decrease the dose by 10% per month for pts on opioids greater than one year and a decrease of 10% per week for patients with weeks to months on opioid medications.

Choose the best answer regarding tramadol as an analgesic in cancer pain in comparison with morphine (Fast Fact #290 Tramadol)? Tramadol has an increased risk of respiratory depression compared with morphine Tramadol has an increased risk of hypoglycemia compared with morphine Tramadol is 1/6th the cost of an equivalent dose of morphine No guidelines support the use of tramadol as an analgesic in cancer pain.

A large population cohort study from the UK comparing tramadol with codeine found a significantly increased risk of hospitalization from hypoglycemia, especially in the first 30 days of initiation in non-diabetic patients. Other studies have found that tramadol may have less risk for respiratory depression, abuse and misuse than with other opioids. Morphine is about ½ the cost of an equivalent dose of immediate release tramadol and 1/6th the cost of sustained release tramadol. Tramadol is a Step II agent on the World Health Organization's (WHO) pain ladder (1) and has FDA approval for the treatment of moderate to severe pain in adults.

Tapering Opioids in Patients with Serious Illness: Who to Taper (# 413)

Background -In general, this discussion applies to patients with longer and indefinite prognoses; opioid tapering in patients in their final months of life is rarely indicated. -This Fast Fact does not discuss opioid tapering in patients with opioid use disorders (OUD). Important Caveat -Deciding who to taper is a complex, individualized assessment, which includes the patient's own preferences. Scenarios for chronic pain after treatment for serious illness -Ongoing pain is common after definitive treatment of a painful serious illness (such as a localized cancer or life-threatening trauma). For instance, approximately 5-10% of all cancer survivors have chronic pain that interferes with functioning (1). -Chronic pain after serious illness can be the result of surgery, radiation, chemotherapy, hormonal therapy, osteoporosis, bisphosphonates, and fractures. -Syndromes include surgical neuralgias, neuromas, phantom pain, cystitis, fibrosis of skin or myofascia, plexopathies, chemotherapy-induced peripheral neuropathy, osteonecrosis, fistulae, and pelvic insufficiency fractures (1). Clinician assessment of risks vs benefits of continuing COT -Typically clinicians have a lot of objective, individualized 'data' about the risks and benefits of opioids for a patient who has been on COT for some time: side effects, function, hospitalizations, motor vehicle crashes, refill history, and patient's mood, coping, and social well-being. -Ask yourself, do you, as the treating clinician, fundamentally think tapering is in the patient's best interests? This is likely to be a far more clinically useful question than "Does the patient continue to have severe pain?" Even in the setting of ongoing pain, tapering may be indicated. -Patients may have poor pain control and high pain interference despite being on COT. -Indeed, in the chronic noncancer pain literature, a significant number of patients report reduced pain and/or improved function after tapering high-dose COT (over 120 mg of oral morphine a day or its equivalent). -Patients may have severe side effects or high medical risk with ongoing COT that does not outweigh any analgesic benefit in the opinion of the prescribing clinician (e.g., patients with severe sleep apnea, CO2 retention, chronic benzodiazepine use, falls, active nonopioid substance use disorders). Patient motivation to taper -Despite ongoing pain some patients do not want to continue COT due to ongoing side effects or concerns about addiction. -Others are fearful about tapering, but are willing to try it with encouragement, education, and support. -Available evidence shows that patients who participate in the tapering plan using shared decision making have better outcomes than those who are forced to taper (3). Patient prognosis -The benefits of opioid tapering are greater for patients with longer prognoses, since they are more likely to experience long-term adverse effects of COT including tolerance, hyperalgesia, and OUD. -However, certain patients with shorter prognoses (e.g., less than a year), may benefit or want to taper opioids due to side effects, improvement of their underlying pain, or other reasons.

#222 The Family Meeting Part 1 - Preparing

Background A cornerstone procedure in Palliative Medicine is leadership of family meetings to establish goals of care, typically completed at a time of patient change in status, where the value of current treatments needs to be re-evaluated. As with any procedure, preparation is essential to ensure the best outcome. Data Review · Review the medical history relevant to the current medical situation (e.g. history of disease progression, symptom burden, past treatments, treatment-related toxicity, and prognosis). · Review all current treatments (e.g. renal dialysis, artificial nutrition, antibiotics) and any positive and/or negative treatment effects. · Review all treatment options being proposed. · Determine the prognosis with and without continued disease-directed treatments. Prognostic information includes data concerning future patient function (physical/cognitive), symptom burden, and time (longevity). · Solicit and coordinate medical opinions about the utility of current treatments among consultants and the primary physician. If possible, families need to hear a single medical consensus—all relevant clinicians should be contacted and consensus reached prior to the meeting. If the consultants do not agree, then prior to the family meeting they should meet to negotiate these differences and attempt to reach consensus regarding the plan. If there is no consensus, a plan should be developed for how to describe these differences to families. · If the patient lacks capacity, review any Advance Directive(s), with special attention to discover if the patient has named a surrogate decision maker, and if the patient has indicated any specific wishes (e.g. DNR status, 'no feeding tubes'). · Seek out patient/family psychosocial data. Focus on psychological issues and family dynamics (e.g. anger, guilt, fear) potentially impacting decision making. These issues may be long-standing, or due to the current illness. Note: talking to the patient's social worker, bedside nurses, and primary and consulting physicians can help you get a better sense of the family and how they make decisions. o Review what transpired in prior family meetings. o Learn about particular cultural/religious values and/or or social/financial issues that may impact decision making. Information Synthesis Based on your review of the medical and prognostic data, make an independent determination of which current and potential tests/treatments will improve, worsen, or have no impact on the patient's function/quality of life (physical/cognitive) and time (longevity). Meeting Leadership Leading a family meeting requires considerable flexibility to ensure that all relevant participants have the opportunity to have their points of view expressed. Though it is useful to have one person designated as the main orchestrator and coordinator of the meeting, the essential skills for making a family meeting successful can come from more than one participant. These skills include: · Group facilitation skills. · Counseling skills. · Knowledge of medical and prognostic information. · Willingness to provide leadership/guidance in decision making. Information Synthesis Based on your review of the medical and prognostic data, make an independent determination of which current and potential tests/treatments will improve, worsen, or have no impact on the patient's function/quality of life (physical/cognitive) and time (longevity). Meeting Leadership Leading a family meeting requires considerable flexibility to ensure that all relevant participants have the opportunity to have their points of view expressed. Though it is useful to have one person designated as the main orchestrator and coordinator of the meeting, the essential skills for making a family meeting successful can come from more than one participant. These skills include: · Group facilitation skills. · Counseling skills. · Knowledge of medical and prognostic information. · Willingness to provide leadership/guidance in decision making. Invitations A decisional patient can be asked who he/she wants to participate from his/her family/community, including faith leaders; in general it is wise not to set any arbitrary limits on the number of attendees. The medical care team should likewise decide who they want to participate. Note: it is important not to overwhelm a family with too many health professionals. On the other hand, a physician from the primary team as well as a nurse and social worker should attend when possible; these individuals can help ensure the consistency of information as well as help deal with complicated dynamics. If the patient has a long-time treating physician whom he/she trusts, this person should ideally be present. Setting The ideal setting is private and quiet, with chairs arranged in a circle or around a table. Everyone should be able to sit down if they wish. For non-decisional patients, the clinical team should negotiate with the surrogate whether or not to have the meeting in the presence of the patient. The Pre-Meeting Meeting The participating health care members should meet beforehand to confirm: a) the goals for the meeting (e.g. information sharing, specific decisions sought), b) who will be the meeting leader to start the meeting, and c) likely sources of conflict and initial management strategies.

The Family Meeting Part 1 - Preparing #222

Background A cornerstone procedure in Palliative Medicine is leadership of family meetings to establish goals of care, typically completed at a time of patient change in status, where the value of current treatments needs to be re-evaluated. As with any procedure, preparation is essential to ensure the best outcome. Data Review · Review the medical history relevant to the current medical situation (e.g. history of disease progression, symptom burden, past treatments, treatment-related toxicity, and prognosis). · Review all current treatments (e.g. renal dialysis, artificial nutrition, antibiotics) and any positive and/or negative treatment effects. · Review all treatment options being proposed. · Determine the prognosis with and without continued disease-directed treatments. Prognostic information includes data concerning future patient function (physical/cognitive), symptom burden, and time (longevity). · Solicit and coordinate medical opinions about the utility of current treatments among consultants and the primary physician. If possible, families need to hear a single medical consensus—all relevant clinicians should be contacted and consensus reached prior to the meeting. If the consultants do not agree, then prior to the family meeting they should meet to negotiate these differences and attempt to reach consensus regarding the plan. If there is no consensus, a plan should be developed for how to describe these differences to families. · If the patient lacks capacity, review any Advance Directive(s), with special attention to discover if the patient has named a surrogate decision maker, and if the patient has indicated any specific wishes (e.g. DNR status, 'no feeding tubes'). · Seek out patient/family psychosocial data. Focus on psychological issues and family dynamics (e.g. anger, guilt, fear) potentially impacting decision making. These issues may be long-standing, or due to the current illness. Note: talking to the patient's social worker, bedside nurses, and primary and consulting physicians can help you get a better sense of the family and how they make decisions. o Review what transpired in prior family meetings. o Learn about particular cultural/religious values and/or or social/financial issues that may impact decision making. Information Synthesis Based on your review of the medical and prognostic data, make an independent determination of which current and potential tests/treatments will improve, worsen, or have no impact on the patient's function/quality of life (physical/cognitive) and time (longevity). Meeting Leadership Leading a family meeting requires considerable flexibility to ensure that all relevant participants have the opportunity to have their points of view expressed. Though it is useful to have one person designated as the main orchestrator and coordinator of the meeting, the essential skills for making a family meeting successful can come from more than one participant. These skills include: · Group facilitation skills. · Counseling skills. · Knowledge of medical and prognostic information. · Willingness to provide leadership/guidance in decision making. Invitations A decisional patient can be asked who he/she wants to participate from his/her family/community, including faith leaders; in general it is wise not to set any arbitrary limits on the number of attendees. The medical care team should likewise decide who they want to participate. Note: it is important not to overwhelm a family with too many health professionals. On the other hand, a physician from the primary team as well as a nurse and social worker should attend when possible; these individuals can help ensure the consistency of information as well as help deal with complicated dynamics. If the patient has a long-time treating physician whom he/she trusts, this person should ideally be present. Setting The ideal setting is private and quiet, with chairs arranged in a circle or around a table. Everyone should be able to sit down if they wish. For non-decisional patients, the clinical team should negotiate with the surrogate whether or not to have the meeting in the presence of the patient. The Pre-Meeting Meeting The participating health care members should meet beforehand to confirm: a) the goals for the meeting (e.g. information sharing, specific decisions sought), b) who will be the meeting leader to start the meeting, and c) likely sources of conflict and initial management strategies.

#124 The Palliative Prognostic Score

Background Accurate prognostic information is vital for patients, families and clinicians. This Fast Fact reviews the Palliative Prognostic Score (PaP); see Fast Fact #125 for information on the Palliative Performance Scale (PPS). The PaP uses the Karnofsky Performance Score (KPS) and five other criteria to generate a numerical score from 0 to 17.5 with specific cutoff values to assign patients to three risk groups according to a 30-day survival probability. Unlike many other validated prognostic scales, a significant scoring weight is given to the treating clinician's "gestault" survival prediction. Also, the PaP requires a full blood count for calculation, something which may not always be performend in palliative settings (especially home and inpatient hospice settings). Validation and Use of the PaP The PaP has been validated in large prospective studies in adult and pediatric oncology settings, as well as patients in inpatient hospices, inpatient palliative care units, and patients seen by palliative care consult teams. It has been shown to be reliable in various non-cancer diagnoses but large-scale validation studies have not been published. Variant of the PaP Including Delirium (D-PaP) Since delirium has been shown to be a significant prognostic contributor, the D-PaP was developed to incorporate the clinical presence of delirium. Patients receive 2 extra points if a clinician determines that delirium is present utilizing the CAM algorithm. Therefore, the maximum score is 19.5 instead of 17.5. In a retrospective analysis of terminally ill cancer patients, the D-PaP performed slightly better than the PaP. Comparative Efficacy of the PaP There are a few retrospective and prospective studies comparing the PaP to other prognostic scoring systems (PPI, PPS, D-PaP). These studies suggest that the PPI, D-PaP, and PaP all identify classes of patients with different survival probabilities with good accuracy. The PaP and D-PaP may be slightly more accurate among cancer patients admitted to a hospice unit, but larger studies are needed to validate this finding.

Moderating an End-of-Life Family Conference #16

Background At some point during the course of a terminal illness, a meeting between health care professionals and the patient/family is usually necessary to review the disease course and develop end-of-life goals of care. Learning the process steps of a Family Conference is an important skill for physicians, nurses and others who are in a position to help patients and families reach consensus on end-of-life planning. See Fast Facts # 222 on Preparing for the Family Meeting and #223 on The Family Meeting: Starting the Conversation. Family Conference Process Steps 1) Why are you meeting: Clarify conference goals of what you hope to accomplish? 2) Where: A room with comfort, privacy and circular seating. 3) Who: Patient (if capable); legal decision maker/health care power of attorney; family members; social support; key health care professionals. 4) Introduction and Relationship Building - Introduce self/others; review meeting goals and which decisions need to be made. - Establish ground rules: each person will have a chance to ask questions and express views; no interruptions; identify legal decision maker; and describe importance of supportive decision making. - If you are new to the patient/family, spend time seeking to know the "person"—ask about hobbies, family, what is important in her or his life, etc. 5) Determine what the patient/family already knows. Tell me your understanding of the current medical condition? Ask everyone in the room to speak. Also ask about the past 1-6 months—what has changed in terms of functional decline, weight loss, etc. 6) Review medical status Review current status, prognosis and treatment options. Ask each family member in turn if they have any questions about current status, plan & prognosis. Defer discussion of decision making until the next step. Respond to emotional reactions (See Fast Facts #29, 59, 224). 7. Family Discussion with a Decisional Patient Ask the patient What decision(s) are you considering? Ask each family member Do you have questions or concerns about the treatment plan? How can you support the patient? 8. Family Discussion with a Non-Decisional Patient Ask each family member in turn What do you believe the patient would choose if the patient could speak for him or herself? Ask each family member What do you think should be done? Ask if the family would like you to leave room to let family discuss alone. If there is consensus, go to 10; if no consensus, go to 9 9. When there is no consensus: Re-state: What would the patient say if they could speak? -Ask: Have you ever discussed with the patient what he or she would want in a situation like this? If you, as a clinician, have a firm opinion about the best plan of care, recommend it simply and explicitly, and explain why. Use time as ally: schedule a follow-up conference the next day. Try further discussion: What values is your decision based upon? How will the decision affect you and other family members? Identify other resources: Minister/priest; other physicians; ethics committee. 10) Wrap-up: -Summarize consensus, disagreements, decisions, & plan. -Caution against unexpected outcomes. -Identify family spokesperson for ongoing communication. -Document in the chart who was present, what decisions were made, follow-up plan. -Don't turf discontinuation of treatment to nursing. -Continuity - Maintain contact with family and medical team. Schedule follow-up meetings as needed. See additional related Fast Facts: Delivering Bad News (#6, 11); Dealing with Anger (#59), Conflict Resolution (#183, 184, 225), Helping Surrogates Make Decisions (#226); End of Life Goal Setting (#227); .

Opioid Use in Renal Failure (#161)

Background Chronic pain is common in chronic kidney disease impacting 50% of hemodialysis patients, 82% of whom experience moderate to severe pain. The absorption, metabolism, and renal clearance of opioids are complex in renal failure. -This Fast Fact offers best practice suggestions for opioid use in the setting of renal failure. Not Recommended for Use: - Meperidine is not recommended in renal failure due to accumulation of normeperidine, which may cause seizures. - Codeine has been reported to cause profound toxicity which can be delayed and may occur after trivial doses. We recommend that codeine be avoided in patients with a Glomerular Filtration Rate (GFR) <30 mL/min. -Dextropropoxyphene is associated with central nervous system (CNS) and cardiac toxicity and is not recommended for use in patients with renal failure. -Morphine and hydromorphone both have 3-glucuronide metabolites that accumulate in renal failure and may case neurotoxicity, so these should be utilized with caution for chronic use in renal insufficiency (GFR <30 mL/min) due to the rapid accumulation of these metabolites. -For patients receiving hemodialysis, the metabolities associated with hydromorphone appear to be more effectively removed via dialysis. Therefore, with careful monitoring, low to moderate doses (oral morphine daily equivalent of <60 mg) may be used safely. Minimize the use of long-acting preparations of morphine if possible and monitor closely for toxicity. Use with Caution: Oxycodone is metabolized in the liver with 19% excreted unchanged in the urine. While oxycodone does have metabolites, they do not appear to be as associated with clinically-significant neurotoxicity. However, the parent compound does accumulate in renal failure, and there are reports of accumulation of oxycodone in patients with renal failure resulting in overdose. Less Associated Risk in Renal Insufficiency: -Fentanyl is considered relatively safe in renal failure as it has no active metabolites. However, very little pharmacokinetic data exist regarding fentanyl in end stage renal disease. -Fentanyl is not dialyzable due to high protein binding and a high volume of distribution. Caution with dosage and close monitoring for sedation is still recommended. -Methadone is considered relatively safe in renal failure. It has no active metabolites and limited plasma accumulation in renal failure due to enhanced elimination in the feces. -Burpenorphine is considered by many experts to be a good option in renal failure due to lack of active metabolites or accumulation of parent compound. However, there is less data on the safety and efficacy on buprenorphine in palliative or cancer pain than many other opoids. -Dosing: -Broadbent et al recommended decreasing the dose morphine, oxycodone, or hydromorphone by 25% if Cr Cl is 10-50ml/min and 50% if CrCl <10mL/min. Methadone and buprenorphine likely do not require dose adjustment in renal insufficiency. -While many opioids can be used when GFR is <50, they require closer monitoring and constant reassessment to ensure that accumulation of active metabolites does not result in toxicity or overdose. Multimodal Therapy: A multimodal approach to pain therapy is recommended if feasible for patients with renal impairment. While beyond the scope of this Fast Fact, other analgesic options including acetaminophen, nortriptyline, renally-dosed gabapentin or pregabalin, corticosteroids, tizanidine, interventional therapies, and physical therapy should be considered.

The Family Meeting Part 6 - Goal Setting and Future Planning #227

Background End-of-life goal setting is a key palliative care skill, typically occurring as part of a family meeting (see Fast Facts #16, 65, 222-226). This Fast Fact discusses an approach to goal setting when the expected length of life is short. Establishing patient-centered goals Here is an example of how to start the conversation (the patient should be given sufficient time to respond to each of these questions): I/we have discussed your current condition and that time may be short. With that in mind - What are you hoping for now? What is important to you? What do you need to accomplish? Who do you need to see in the time that is left? Common responses invoke family, home, and comfort; often surviving until a specific future family event/date or visit with a key family member is described as an important goal. Re-state your understanding: What I hear you saying is that you want to be home, comfortable, and survive until your daughter gives birth - you hope to meet your next grandchild. Note: if you believe the patient's goal of survival to a specific event/date is not practical, it is important to say so and discuss alternative plans. Future hospitalizations, ICU admissions, laboratory and radiology tests. Resuscitation orders/code status (see Fast Facts #23-24). Current/future use of blood products, antibiotics, artificial hydration/nutrition. If present, the potential continuation or stopping of dialysis or cardiac devices. Role of a second (or third) opinion. Exploration of experimental therapy. Exploration of treatment options the patient or family may bring into the conversation. Disposition options to best meet the goals (e.g. home hospice referral). Note: There is no need to ask about each option as a yes/no question (Do you want blood products?). Based on what you know about the patient's goals, make a recommendation about what should and should not be done in light of the patient's goals, condition and prognosis. If you are unsure, you can explore the issue with the patient/family (Given that your dad wanted to get home as soon as possible and yet he was also willing to do easy things that might help him live longer, I am unsure whether it makes sense to stay in the hospital an extra day or two to finish the antibiotics. What do you think he would say?). 'Long-shot' goals If patients are going to pursue 'long-shot' or experimental therapy, perhaps even against the recommendation of the treating team, it is useful to ensure the following: Reinforce the team's respect for the decision, and desire to make sure the treatment has the best possible chance of working. Simultaneously, try to maximize quality of life in the present, including the best possible pain and symptom management and support. Encourage the patient and family to prepare in case treatment is not successful and the patient dies sooner rather than later. Useful language is to say, I'd encourage us all to hope for the best, but prepare for the worst. Reinforce that the team will not abandon the patient and family even if the decision is not what is being recommended. Close the meeting Following this discussion, restate your understanding of the patient's goals and agreed-upon next steps to meet those goals, invite and answer questions, and close the meeting. Discussion & documentation Discuss the goals with key staff not in attendance (e.g. consulting physicians, patient's nurse, discharge planner, primary care provider). Document the goals, preferably using a templated family meeting note (see Reference 1): who was present, what was discussed (e.g. treatment options, prognosis), what was decided, next steps. Debriefing A useful step after every family meeting is to debrief the process - what went well, what could have been improved and, most importantly, addressing the emotional reaction and needs of the care team.

#227 The Family Meeting Part 6 - Goal Setting and Future Planning

Background End-of-life goal setting is a key palliative care skill, typically occurring as part of a family meeting (see Fast Facts #16, 65, 222-226). This Fast Fact discusses an approach to goal setting when the expected length of life is short. Establishing patient-centered goals Here is an example of how to start the conversation (the patient should be given sufficient time to respond to each of these questions): I/we have discussed your current condition and that time may be short. With that in mind - What are you hoping for now? What is important to you? What do you need to accomplish? Who do you need to see in the time that is left? Common responses invoke family, home, and comfort; often surviving until a specific future family event/date or visit with a key family member is described as an important goal. Re-state your understanding: What I hear you saying is that you want to be home, comfortable, and survive until your daughter gives birth - you hope to meet your next grandchild. Note: if you believe the patient's goal of survival to a specific event/date is not practical, it is important to say so and discuss alternative plans. Recommend a care plan based on the goals Once the goal(s) is/are established, you can then review the patient's current treatments (e.g. antibiotics, chemotherapy), monitoring (e.g. pulse oximetry), planned tests (e.g. colonoscopy), and medications (e.g. anti-hypertensives), and decide which will help meet, or not, the patient's goals. Anything that will not help meet the goals should be discussed for potential discontinuation. Depending on the specific disease/patient condition, other issues that are naturally discussed at this point include: -Future hospitalizations, ICU admissions, laboratory and radiology tests. -Resuscitation orders/code status (see Fast Facts #23-24). -Current/future use of blood products, antibiotics, artificial hydration/nutrition. -If present, the potential continuation or stopping of dialysis or cardiac devices. -Role of a second (or third) opinion. -Exploration of experimental therapy. -Exploration of treatment options the patient or family may bring into the conversation. -Disposition options to best meet the goals (e.g. home hospice referral). Note: There is no need to ask about each option as a yes/no question (Do you want blood products?). Based on what you know about the patient's goals, make a recommendation about what should and should not be done in light of the patient's goals, condition and prognosis. If you are unsure, you can explore the issue with the patient/family (Given that your dad wanted to get home as soon as possible and yet he was also willing to do easy things that might help him live longer, I am unsure whether it makes sense to stay in the hospital an extra day or two to finish the antibiotics. What do you think he would say?). 'Long-shot' goals If patients are going to pursue 'long-shot' or experimental therapy, perhaps even against the recommendation of the treating team, it is useful to ensure the following: Reinforce the team's respect for the decision, and desire to make sure the treatment has the best possible chance of working. Simultaneously try to maximize quality of life in the present, including the best possible pain and symptom management and support. Encourage the patient and family to prepare in case treatment is not successful and the patient dies sooner rather than later. Useful language is to say, I'd encourage us all to hope for the best, but prepare for the worst. Reinforce that the team will not abandon the patient and family even if the decision is not what is being recommended. Close the meeting Following this discussion, restate your understanding of the patient's goals and agreed-upon next steps to meet those goals, invite and answer questions, and close the meeting. Discussion & documentation Discuss the goals with key staff not in attendance (e.g. consulting physicians, patient's nurse, discharge planner, primary care provider). Document the goals, preferably using a templated family meeting note (see Reference 1): who was present, what was discussed (e.g. treatment options, prognosis), what was decided, next steps. Debriefing A useful step after every family meeting is to debrief the process - what went well, what could have been improved and, most importantly, addressing the emotional reaction and needs of the care team.

The Family Meeting Part 3 - Responding to Emotion #224

Background Family meetings are stressful events, often provoking strong emotional reactions. Fast Fact #29 presents a general outline on the topic of how clinicians can respond to emotions. Consider your role. It is important to reflect on the role of clinicians in responding to patient/family emotions at the time life-altering information is shared. The goal is not to prevent a patient/family from having those emotions. Sadness, fear, anger, and loss are normal responses to unwelcome news. Instead your role is: 1) to maintain a trusting therapeutic relationship and safe/supportive environment that allows emotions to be expressed in a way that meets the patient's/family's needs; and 2) not to worsen the experience for the patient/family by ignoring or delegitimizing their responses, or confusing them with medical information when they are not ready to hear it. Recognize that most families find clinicians' expressions of empathy tremendously supportive and these are associated with family satisfaction. Acknowledge that emotion is being expressed. If you have a good sense of what the emotion is, then it is useful to name it. If not, using more general language is preferable. I can see this is really affecting you. This information is very upsetting. Legitimize the appropriateness and normalcy of the reaction. Medical professionals are in a powerful position to help patients and families feel that strong emotions under these circumstances are normal and to be expected. Anyone receiving this news would feel devastated. It is completely expected to be very distressed by this kind of news. Explore more about what is underneath the emotion. It is tempting to try to limit the emotion, and be prematurely reassuring. But it is generally more helpful and ultimately more time-efficient to allow the patient and family to more deeply explore their feelings and reactions. Tell me what is the scariest (most difficult) part for you. Tell me more about that.... (Keep the exploration going until it is fully expressed and understood.) Empathize (if you genuinely feel it). Empathy means being able to emotionally imagine what the patient is going through. Clinicians can initiate the prior responses (acknowledge, legitimize, explore) without having a clear feeling for the patient's experience. These responses can be adequate in themselves. If the clinician cannot imagine the patient's experience, he or she can still sensitively explore the experience and provide caring and support. But if you have a strong sense of what the patient is experiencing, it can be very therapeutic to express it. This seems really unfair. I can imagine that you might feel very disappointed. Explore strengths/coping strategies. This may occur at this phase of the interview, or it may be postponed to a later phase when planning for next steps begins. In past circumstances, what has helped? How have you adapted to difficult circumstances in the past? What are you hoping for now?

The Family Meeting Part 2 - Starting the Conversation #223

Background Fast Fact #16 gives a concise overview of running a family meeting. Fast Fact #222 provides a list of preparatory steps in planning for a family meeting to discuss end-of-life goals; this Fast Fact reviews the early steps of the actual meeting. Introductions & setting goals for the meeting The meeting leader begins the meeting by introducing him or herself, and suggesting that each person present (medical team and family/community) introduce themselves including their relationship to the patient. The meeting leader should summarize the meeting goals (e.g. We are here to discuss next steps in the care of Mr. Jones) and ask the family to confirm these goals and/or add other agenda items. Note: if you do not know the patient or family well, take a moment to build relationship. Ask a non-medical question such as I am just getting to know you. I had a chance to look at your chart and learn about your medical condition but it does not say much about your life before you got sick. Can you tell us about the things you liked to do before you got sick? Similarly, if the patient is not able to participate in the meeting, ask family to describe the patient prior to his becoming ill: As we get started, can you describe what Mr. Jones was like before he became ill? 2. Determine what the patient/family already knows This step is essential as it guides you in providing a synthesis of the medical information (see below). Always invite the patient and all family members to provide their understanding of the medical information. Examples of opening lines: Tell me what the doctors have told you about your condition? Can you describe for me your sense of how things are going? For patients who have been declining from a chronic illness, you can ask: Tell me about the past 3-6 months: what types of changes have you noted? The patient or family will typically describe changes in terms of function (physical or cognitive) and quality of life. 3. The Medical Review Once you know what the patient/family understands, you are in a good position to confirm their understanding, or provide new information/correct misunderstandings. First, ask if you can bring them up-to-date about what is going on; asking shows politeness and also signals that they should attend to what you are trying to say. The clinician most closely aligned with the patient's ongoing treatment should begin this discussion, supplemented with information from consulting services if relevant. Do not provide information using medical jargon or in an organ system approach (e.g. The creatinine is improving, but there is a new pleural effusion and the heart rate has become irregular). A more patient-centered approach is to provide a succinct summary of the current condition, without any medical jargon, focusing on the issues of most importance, which are usually function/quality/time. Give a 'bottom-line' statement: 'getting worse,' 'not going to improve,' 'dying and time is likely very short.' The worsening weakness and pain you describe is from the cancer which is growing despite the chemotherapy. You are telling me that despite the recent hospitalization, you are not able to do as much around the house; unfortunately your lung disease is getting worse despite all our best treatments. Despite our best efforts, your wife's brain injury from the car crash is getting worse. She can no longer stay awake or move her arms/legs. Using the 'D word' if relevant: when a patient is clearly deteriorating and death is likely within the next days to weeks, or even a few months, it is appropriate to use the word dying in the conversation. Both patients and surrogates find that saying the word dying, if done compassionately, is helpful in clearing what is often a confusing and frightening situation. I'm afraid we have run out of options to shrink the cancer. Based on your declining function, I believe you are dying. 4. Silence Whether or not you use the word dying, when you have presented bad news (such as information about disease progression), the next step is for you to allow silence, and let the family/patient respond. In truth, no matter what you might imagine the response from the patient/family to be once the bad news is delivered, you really cannot predict their emotional reaction (e.g. relief, anxiety, anger, regret, fear). This silence can be uncomfortable; resist the urge to fill it with more facts as they will not be heard. Not all patients/families express emotions at this point and instead respond practically (Well, what happens next then?). This is fine, but you need to wait, silently, to see what response the patient/family demonstrates. In addition, even practical questions have underlying emotions (Are you sure? Or - There must be something you can do?). It is important to respond to both the factual aspect of the question (Yes I am sure. Or - There are no more effective treatments available.), as well as the emotional level (I wish I had better news for you. Or - I wish our treatments worked better than they do.). When the patient/surrogates openly acknowledge that current treatments are no longer effective, that death is coming, they will generally ask one or all of the following questions: How long? What will happen? Will there be suffering? What do we do now? Your response at this point should be to address prognosis in terms of time, function, and symptoms, as best you can (see Fast Facts #13,141,143,149,150). This will answer the first two questions; the last questions will require more discussion of patient-centered goals (see Fast Fact #227).

Neuroexcitatory Effects of Opioids: Treatment (#58)

Background Fast Fact #57 reviewed the pharmacology and patient assessment aspects of opioid induced neurotoxicity, notably myoclonus. This Fast Fact discusses treatment. -General Approach Decisions about the most appropriate treatment approach need to take into account features of the physical examination (the frequency and intensity of symptoms, hydration status, and estimated prognosis) and information from the medical record (temporal pattern of opioid use and dose escalation, other medications, the presence of electrolyte abnormalities and major organ dysfunction). Whenever medically appropriate, easily treatable causes or exacerbating factors should be corrected (e.g. correct hypomagnesemia). -Treatment Strategies The range of options for management of pain and direct opioid neurotoxic effects divides into strategies to treat the myoclonus and strategies to reduce the offending opioid. -Opioid dose reduction. Seeing that some observational studies suggest that neuroexcitatory symptoms from opioid may not develop until a certain neuroexcitatory threshold of 3-glucoronide metabolites is surpassed, myoclonus may resolve over a few days with a decrease in opioid dose. However, make sure you are not reducing the opioid dose solely to control myoclonus at the expense of good pain control. Rotate to a dissimilar opioid. Rotating to a lower dosage of a structurally dissimilar opioid will often reduce myoclonus and other neuroexcitatory effects within 24 hours, while achieving comparable pain control (Fast Fact #175 discusses opioid structural classes.) Rotation is especially important in patients with opioid-induced hyperalgesia. As a general rule, decrease the morphine equianalgesic dose by at least 50% when switching to a new medication (see Fast Fact # 36). For patients on very high doses, rotate to a new opioid at 20-25% of the morphine equianalgesic dose. Historically, methadone and fentanyl have been considered to be better opioids to rotate to as they have no active metabolites (which are implicated in the neuroexcitatory effects of other opioids). This observation is empiric, and has not been evaluated in clinical trials; clinicians should be cautious of using methadone without familiarity with its pharmacology (see Fast Facts #75, 86). Adjuvant and other analgesic therapy. Adjuvant analgesics (e.g. anticonvulsants, antidepressants, corticosteroids) or non-drug therapies (e.g. acupuncture, TENS, heat, cold) may allow for opioid reduction, with preservation of analgesia. Benzodiazepines and other drugs to reduce myoclonus. The addition of a benzodiazepine can reduce myoclonus without alteration of the opioid dose, although increasing sedation may be an unwanted side effect. Start with clonazepam 0.5-1 mg at night or 0.5 mg 2-3 times a day. Alternative agents include lorazepam orally or sublingually, starting at 1-2 mg q8 hours. A continuous infusion of midazolam (Versed) is an expensive but effective option. Alternatives to benzodiazepines include baclofen, gabapentin, and nifedipine. Start baclofen at 5 mg 3 times a day and increase as needed/tolerated to 20 mg 3 times a day. Start gabapentin at 100 mg 3 times a day and increase as needed to 900-3600 mg total a day. Nifedipine (10 mg 3 times a day) can also be used.

#175 Opioid Allergic Reactions

Background Fast Fact #57 reviewed the pharmacology and patient assessment aspects of opioid induced neurotoxicity, notably myoclonus. This Fast Fact discusses treatment. General Approach Decisions about the most appropriate treatment approach need to take into account features of the physical examination (the frequency and intensity of symptoms, hydration status, and estimated prognosis) and information from the medical record (temporal pattern of opioid use and dose escalation, other medications, the presence of electrolyte abnormalities and major organ dysfunction). Whenever medically appropriate, easily treatable causes or exacerbating factors should be corrected (e.g. correct hypomagnesemia). Treatment Strategies The range of options for management of pain and direct opioid neurotoxic effects divides into strategies to treat the myoclonus and strategies to reduce the offending opioid. Observation. Mild myoclonus may trouble family members more than the patient. If the patient is satisfied with current therapy, explaining the cause/progression of symptoms may be all that is necessary. Opioid dose reduction. Seeing that some observational studies suggest that neuroexcitatory symptoms from opioid may not develop until a certain neuroexcitatory threshold of 3-glucoronide metabolites is surpassed, myoclonus may resolve over a few days with a decrease in opioid dose. However, make sure you are not reducing the opioid dose solely to control myoclonus at the expense of good pain control. Rotate to a dissimilar opioid. Rotating to a lower dosage of a structurally dissimilar opioid will often reduce myoclonus and other neuroexcitatory effects within 24 hours, while achieving comparable pain control (Fast Fact #175 discusses opioid structural classes.) Rotation is especially important in patients with opioid-induced hyperalgesia. As a general rule, decrease the morphine equianalgesic dose by at least 50% when switching to a new medication (see Fast Fact # 36). For patients on very high doses, rotate to a new opioid at 20-25% of the morphine equianalgesic dose. Historically, methadone and fentanyl have been considered to be better opioids to rotate to as they have no active metabolites (which are implicated in the neuroexcitatory effects of other opioids). This observation is empiric, and has not been evaluated in clinical trials; clinicians should be cautious of using methadone without familiarity with its pharmacology (see Fast Facts #75, 86). Adjuvant and other analgesic therapy. Adjuvant analgesics (e.g. anticonvulsants, antidepressants, corticosteroids) or non-drug therapies (e.g. acupuncture, TENS, heat, cold) may allow for opioid reduction, with preservation of analgesia. Benzodiazepines and other drugs to reduce myoclonus. The addition of a benzodiazepine can reduce myoclonus without alteration of the opioid dose, although increasing sedation may be an unwanted side effect. Start with clonazepam 0.5-1 mg at night or 0.5 mg 2-3 times a day. Alternative agents include lorazepam orally or sublingually, starting at 1-2 mg q8 hours. A continuous infusion of midazolam is an expensive but effective option. Alternatives to benzodiazepines include baclofen, gabapentin, and nifedipine. Start baclofen at 5 mg 3 times a day and increase as needed/tolerated to 20 mg 3 times a day. Start gabapentin at 100 mg 3 times a day and increase as needed to 900-3600 mg total a day. Nifedipine (10 mg 3 times a day) can also be used.

#58 Neuroexcitatory Effects of Opioids: Treatment

Background Fast Fact #57 reviewed the pharmacology and patient assessment aspects of opioid induced neurotoxicity, notably myoclonus. This Fast Fact discusses treatment. General Approach Decisions about the most appropriate treatment approach need to take into account features of the physical examination (the frequency and intensity of symptoms, hydration status, and estimated prognosis) and information from the medical record (temporal pattern of opioid use and dose escalation, other medications, the presence of electrolyte abnormalities and major organ dysfunction). Whenever medically appropriate, easily treatable causes or exacerbating factors should be corrected (e.g. correct hypomagnesemia). Treatment Strategies The range of options for management of pain and direct opioid neurotoxic effects divides into strategies to treat the myoclonus and strategies to reduce the offending opioid. Observation. Mild myoclonus may trouble family members more than the patient. If the patient is satisfied with current therapy, explaining the cause/progression of symptoms may be all that is necessary. Opioid dose reduction. Seeing that some observational studies suggest that neuroexcitatory symptoms from opioid may not develop until a certain neuroexcitatory threshold of 3-glucoronide metabolites is surpassed, myoclonus may resolve over a few days with a decrease in opioid dose. However, make sure you are not reducing the opioid dose solely to control myoclonus at the expense of good pain control. Rotate to a dissimilar opioid. Rotating to a lower dosage of a structurally dissimilar opioid will often reduce myoclonus and other neuroexcitatory effects within 24 hours, while achieving comparable pain control (Fast Fact #175 discusses opioid structural classes.) Rotation is especially important in patients with opioid-induced hyperalgesia. As a general rule, decrease the morphine equianalgesic dose by at least 50% when switching to a new medication (see Fast Fact # 36). For patients on very high doses, rotate to a new opioid at 20-25% of the morphine equianalgesic dose. Historically, methadone and fentanyl have been considered to be better opioids to rotate to as they have no active metabolites (which are implicated in the neuroexcitatory effects of other opioids). This observation is empiric, and has not been evaluated in clinical trials; clinicians should be cautious of using methadone without familiarity with its pharmacology (see Fast Facts #75, 86). Adjuvant and other analgesic therapy. Adjuvant analgesics (e.g. anticonvulsants, antidepressants, corticosteroids) or non-drug therapies (e.g. acupuncture, TENS, heat, cold) may allow for opioid reduction, with preservation of analgesia. Benzodiazepines and other drugs to reduce myoclonus. The addition of a benzodiazepine can reduce myoclonus without alteration of the opioid dose, although increasing sedation may be an unwanted side effect. Start with clonazepam 0.5-1 mg at night or 0.5 mg 2-3 times a day. Alternative agents include lorazepam orally or sublingually, starting at 1-2 mg q8 hours. A continuous infusion of midazolam is an expensive but effective option. Alternatives to benzodiazepines include baclofen, gabapentin, and nifedipine. Start baclofen at 5 mg 3 times a day and increase as needed/tolerated to 20 mg 3 times a day. Start gabapentin at 100 mg 3 times a day and increase as needed to 900-3600 mg total a day. Nifedipine (10 mg 3 times a day) can also be used.

Withdrawal of Dialysis: Decision Making (#207)

Background Historically, stopping dialysis was considered by many to be a form of suicide. Now, it is a widely accepted practice in most countries, with broad ethical and legal consensus that dialysis can be stopped when it is no longer achieving a meaningful goal for the patient. Why dialysis is stopped The goal of dialysis is not only to prolong life by providing renal replacement therapy, but to maintain a patient's quality of life at an acceptable level (see Fast Fact #163). Discussions to stop dialysis usually occur when: -Dialysis is no longer serving to substantially prolong life or is only prolonging a patient's death (e.g., a patient dying from advanced cancer or sepsis with multiorgan system failure). -The burdens of dialysis and its complications outweigh its life-prolonging benefits to a patient (e.g., a patient with progressive frailty who is becoming bedbound; a patient with severe cognitive failure). In these scenarios dialysis is likely to prolong life but is not helping to restore a patient to an acceptable level of quality of life as assessed by the patient or her/his surrogate decision maker. -Demographics The demographics of dialysis withdrawal have been studied at length. Patient characteristics associated with withdrawal are older age, female, white race, longer duration of dialysis, higher educational level, living alone, severe pain, and comorbidity (with chronic or progressive diseases). -Ethnic differences have been observed, with African Americans and Hispanics being less likely to stop dialysis than European Americans. -Responding to a request to stop dialysis For patients who are otherwise dying, counsel about terminal care issues surrounding dialysis withdrawal (see Fast Fact #208). For patients not otherwise close to death, explore reasons for withdrawal, especially for treatable factors that might contribute to the desire to withdraw dialysis. -For patients whose desire to stop dialysis is being driven by factors that are potentially ameliorable, clinicians should make sure that the decision to stop dialysis is fully informed, including the possibility that some concerns could be addressed. These include: - Inadequately treated depression, anxiety, pain, and other physical or psychological symptoms (including spiritual and existential suffering) - Dissatisfaction or difficulties with dialysis itself (e.g., modality, time commitment, or treatment setting) - Inadequate social support, or concerns with being a burden to loved ones. - Offer to evaluate and treat these concerns; consider a time-limited trial to see if a patient's quality of life can be improved. However, once a clinician feels a patient or surrogate is making a fully informed choice that is consistent with a patient's values and goals, that decision should be honored. Proactively address any concerns patients may voice about the ethics of withdrawal. Broaching dialysis withdrawal: -Dialysis should be discussed as part of an overall medical plan and framed as how it can or cannot address the care goals. "Dialysis will likely make your mother live longer. However - given everything that has been happening - it is not going to improve her strength, memory, or ability to take care of herself. Based on what you've told me about your mother and what is important for her, I would recommend stopping the dialysis as it is only serving to maintain her in a state she would find unacceptable."

#13 Determining Prognosis in Advanced Cancer

Background How long do I have, Doc? is among the most common questions asked by cancer patients, especially when informed that there are no further effective anti-neoplastic treatment options. Although prognostication is not an exact science, there are data to help clinicians provide useful information to patients and families - information critical to making realistic end-of-life decisions and referrals for home hospice service (see Fast Fact #30). Performance Status The single most important predictive factor in cancer is Performance Status ('functional ability,' 'functional status'): a measure of how much a patient can do for themselves, their activity and energy level. Patients with solid tumors typically lose ~ 70% of their functional ability in the last 3 months of life. The most common scales used to measure functional ability are the Karnofsky Index (100 = normal; 0 = dead) and the ECOG scale (Eastern Cooperative Oncology Group), (0 = normal; 5 = dead). A median survival of 3 months roughly correlates with a Karnofsky score <40 or ECOG > 3. Newer prognostic scales have been developed to help provide prognostic information (See Fast Facts #124, 125). The simplest method to assess functional ability is to ask patients: How do you spend your time? How much time do you spend in a chair or lying down? If the response is >50% of the time, and is increasing, you can roughly estimate the prognosis at 3 months or less. Survival time tends to decrease further with increasing numbers of physical symptoms, especially dyspnea, if secondary to the cancer. Other Factors Several common cancer syndromes have well-documented short median survival times: Malignant hypercalcemia: 8 weeks, except newly diagnosed breast cancer or myeloma (see Fast Fact #151) Malignant pericardial effusion: 8 weeks (see Fast Fact #209) Carcinomatous meningitis: 8-12 weeks (see Fast Fact #135) Multiple brain metastases: 1-2 months without radiation; 3-6 months with radiation. Malignant ascites (see Fast Fact #176), malignant pleural effusion (#209), or malignant bowel obstruction: < 6 months. Modified Glasgow Prognostic Score (mGPS): multiple studies have shown that an increased mGPS — meaning an elevated serum c-reactive protein and a reduced serum albumin - is associated with a reduced cancer specific survival curve irrespective of cancer type. Other Comments In general, a patient with metastatic solid cancer, acute leukemia or high-grade lymphoma, who will not be receiving systemic chemotherapy (for whatever reason), has a prognosis of less than 6 months. Notable exceptions to this are patients with metastatic breast or prostate cancer with good performance status, as these cancers may have an indolent course. In these patients additional features suggesting short prognosis are needed (declining functional status, dyspnea, weight loss). Discussing Prognosis When discussing prognosis with patients/families, the following four step approach is recommended: Preparation; Content; Patient's Response; Close. Remember to: Confirm that the patient/family are ready to hear prognostic information. Present information using a range: a few days to weeks; 2-4 months, etc. Allow silence after you provide information; respond to emotion (see Fast Fact #29). Use prognostic information for eliciting end-of-life goals (see Fast Fact #65).

Prognosis in Decompensated Chronic Liver Failure

Background In 2009, chronic liver disease and cirrhosis resulted in approximately 30,000 deaths, making it the twelfth leading cause of death in the United States. Patients with compensated chronic liver failure (without ascites, variceal bleeding, encephalopathy, or jaundice) have a median survival of 12 years. After decompensation, median survival drops to ~ 2 years. This Fast Fact reviews prognosis in chronic liver failure, focusing on two validated prognostic indices. Of note, these indices predict prognosis for patients without liver transplantation. Patients are grouped into three classes based on the total CTP score, which is simply the sum of the scores for each of the 5 variables. Patients scoring 5-6 points are considered to have 'Class A' failure; their 1 and 2 year median survivals are 95% and 90%, respectively. A score of 7-9 is considered Class B with median survivals of 80% at 1 year and 70% at two years. Class C patients (10-15) have far greater mortality: 1-year median survival is 45% and 2-year is 38%. Variations in the timing and subjectivity inherent in the scoring of the CTP (e.g. in grading ascites or encephalopathy) are its major limitations. In addition, the scale does not include renal function, an important prognostic factor in liver failure. The Model for End-stage Liver Disease (MELD) score was developed in 2000 to overcome the above-mentioned limitations and determine survival benefit from transjugular intrahepatic portosystemic shunting. It is currently used to help determine organ allocation for liver transplantation, and there is increasing evidence that it can also be used generally to predict survival in patients with chronic liver failure. The MELD score relies on laboratory values alone (serum creatinine, total bilirubin, and INR). An additional benefit over CTP is that it can predict prognosis on the order of months with more precision - making it helpful for determining hospice eligibility in the US.

#86 Methadone: Starting Dosing Information

Background Methadone is an effective opioid analgesic for severe pain. Because of low cost (a month's supply may be US $5-10) and apparent efficacy in complex pain syndromes, it is increasingly used as a first-line opioid. Retrospective analyses of consecutive patients initiated on methadone in an outpatient palliative care clinic confirm its effectiveness and safety (1). It is, in effect, a combination drug - part opioid and part NMDA receptor antagonist - although there is yet to be any evidence from controlled trials that it is a superior first-line analgesic to other opioids. Methods of dose conversion to methadone from other opioid analgesics that account for its dual action were discussed in Fast Fact # 75. This Fast Fact will describe strategies for beginning methadone when the patient has not been taking a strong opioid. Note: due to its complex pharmacology, clinicians are advised to seek consultation prior to initiating therapy (see Fast Fact #171). Pharmacology Methadone is lipophilic, thus it takes time to develop tissue stores that maintain serum levels. There is enormous interindividual variation in how long this takes. After a single dose there is a short distribution phase (associated with acute pain relief) with a half-life of 2-3 hours and a slow elimination phase (half-life 15-60 hours). Dosing must account for the accumulation of drug over days. It is this accumulation that accounts for most therapeutic misadventures. Liver metabolites are inactive; therefore no dose reduction is required with renal failure. After steady-state is reached, about two-thirds of patients will get adequate pain relief with twice a day dosing. Note: a number of drugs will alter methadone metabolism, so there needs to be close follow-up to drug interactions. There are several approaches to starting methadone for the treatment of pain. All take into account the long-half life of the drug that leads to drug accumulation over days. I. Conservative Approach Begin fixed dose methadone 5 or 10 mg orally bid or tid for 4-7 days. If incomplete pain relief, increase the dose by 50% and continue for 4-7 days. Continue increasing dose every 4-7 days until stable pain relief achieved. Breakthrough pain: use an alternative short acting oral opioid with short half-life (e.g. morphine 10 mg) every 1 h PRN for breakthrough pain and to provide pain relief during titration phase. This dose too may need to be titrated based on efficacy. II. Loading Dose Approach Load: Start methadone at fixed oral dose (e.g. 5 or 10 mg) q 4h PRN only. Calculate Maintenance: On day 8, calculate the total methadone dosage taken over the last 24 hour period and give that in scheduled, divided doses bid or tid. Give 10% of total daily methadone as PRN drug q1h for breakthrough pain. Instruct the patient to call you if they need to use more than 5 breakthrough doses per day. Example: if someone took a total of 45 mg methadone on day 7 they would be converted to 15 mg tid scheduled with 5 mg as the prn dose. Cardiac Safety Due to methadone's potential to prolong the QTc interval, an independent expert panel developed five cardiac safety recommendations for clinicisns (4): 1. Clinicians should inform patients for the potential risk for arrhythmia before initiating methadone 2. Clinicians should ask about any history of structural heart disease, arrhythmia or syncope 3. Clinicians should obtain a pretreatment ECG to measure the QTc interval as well as a follow up ECG within 30 days, annually, and/or if the dosage exceeds 100 mg/day or an unexplained syncopal event occurs If the QTc > 500 ms, consider discontinuing methadone, reducing the dose, or eliminating cofactors which may raise the QTc unless prognosis is short (i.e. weeks to months). 4. If the QTc is between 450 ms to 500 ms, the clinician should discuss the risks and benefits with the patient 5. Clinicians should be aware of drug interactions with methadone which could slow its metabolism or prolong the QTc even more.

#135 Neoplastic Meningitis

Background Neoplastic meningitis (NM) - also known as leptomeningeal metastases, meningeal carcinomatosis, or leukemic meningitis, is a common oncologic complication representing spread of tumor cells to the subarachnoid space (SAS). It is a complication which often portends a very short prognosis. Epidemiology NM is found in 20% of cancer patients at autopsy. Among solid tumors, NM is common in breast cancer, small cell lung cancer, and melanoma while rare in gastrointestinal and gynecologic cancers. 90% of solid tumor patients with NM have widespread metastatic disease. NM is found in 40-50% of patients with hematological malignancies, mostly commonly the acute leukemias and high-grade lymphomas (such as large cell and Burkitt lymphomas). Signs/Symptoms Tumor reaches the SAS by hematogenous spread via arachnoid vessels or direct invasion along nerve roots. Cancer cells in the subarachnoid space have the potential to: a) settle in dependent portions of the neuraxis (base of brain/cranial nerves or lower spinal canal), b) grow into the surface of the brain and fill the sulci, and c) block normal paths of cerebral spinal fluid (CSF) flow. Thus, the hallmark of diagnosis is neurological signs/symptoms at more than one level of the neuraxis: Brain - headaches, nausea/vomiting, seizure, hydrocephalus. Cranial Nerves - diplopia, hearing loss, facial numbness, dysphagia, dysphonia. Spinal - radicular pain, weakness (usually legs), parenthesis, bladder and bowel dysfunction. Diagnosis Lumbar puncture typically reveals a CSF profile of high opening pressure, low glucose, high protein, and lymphocytic pleocytosis. Sensitivity for finding malignant cells is 50- 70% for one sample, increasing to 80-90% with three samples. MRI can identify nodular/bulky areas of disease, hydrocephalus, and/or enhancement of the cortex/tentorium if tumor growth along the sulci leads to neovascularization. NM commonly causes abnormal CSF flow; this can be demonstrated by a radionucleotide cisternogram. Prognosis and Treatment Patients with breast cancer or hematological malignancies that have not been extensively treated with chemotherapy, have a reasonable chance at remission of their CNS disease if their systemic cancer can also be controlled. In contrast, patients with other cancers (e.g. lung, melanoma) typically have a dismal prognosis (1-4 months) with or without treatment. In fact, the median survival of patients who underwent placement of an implanted intraventricular reservoir (Ommaya reservoir) for intrathecal chemotherapy administration was only 72 days in a multicenter retrospective analysis. Unlike spinal cord compression or brain metastases, there is no accepted role for corticosteroids except in lymphoid malignances. Treatment options include chemotherapy and/or radiation. Radiation: Either cranio-spinal irradiation (entire spinal column) or focused radiation therapy to sites of bulky or symptomatic areas (e.g. cauda equina for radicular leg pain). Chemotherapy: Options include systemic high-dose chemotherapy (Ara-C or Methotrexate) intrathecal chemotherapy (1-2 times per week) administered either by repeated lumbar puncture or via repeated puncture of an Ommaya reservoir. Commonly used intrathecal drugs include methotrexate or Ara-C. Summary For many patients, NM represents a pre-terminal diagnosis and no anti-neoplastic therapy is warranted. Establishing the diagnosis in such patients may be important to help prognosticate and to anticipate future neurological problems (e.g. seizures, headache, radicular pain). The decision whether or not to begin anti-neoplastic treatment should be made in consultation with a medical, radiation, or neurooncologist.

#216 Asking About Cultural Beliefs in Palliative Care

Background Patients' cultural backgrounds profoundly influence their preferences and needs regarding discussing bad news, decision-making, and the dying experience. This Fast Fact offers a framework for taking a 'cultural history' to better understand a patient's and family's needs. See also these related Fast Facts: #17 (illness experience), #19 (spiritual history), #26 (explanatory model), #183/184 (conflict resolution). C - Communication. Identify the patient's preferences regarding how and to whom medical information is shared. Some people want to know everything about their medical condition, and others do not. How much would you like to know? For those who request that the physician discuss their condition with family members: Would you like me to speak with them alone, or would you like to be present? Identify main contacts to give information to about the patient's condition. Carefully explore with families requests to hide information from a patient (see references #4 and #5; Fast Fact #219). U - Unique cultural values. Use respectful, curious, and open-ended questions about a patient's cultural heritage to identify their values. Is there anything that would be helpful for me to know about how you and your family view serious illness? Are there cultural beliefs, practices, or preferences that affect you during times of significant illness? If the patient is open to discussing death: What concerns do you have about dying? Are there things that are important to you or your family that I should know about? L - Locus of decision-making. For some patients medical decision-making is communally driven rather than individualistic. Multiple family members or a community elder or leader may need to be involved, often without prior official documentation because it is assumed or understood from the patient's perspective. Do you prefer to make medical decisions about tests and treatments yourself, or would you prefer that others in your family or community make them for you? T - Translators. Language barriers are extremely challenging, especially during times of severe illness. Utilize medical interpreters frequently and effectively. Refer to Fast Fact #154 for a detailed discussion on using interpreters in palliative care. U - Understanding the patient and learning as a provider. Reassess what is being heard, understood, and agreed upon frequently, from both the patient's and clinician's standpoint. Specifically confirm the patient's understanding or agreement (beyond nodding or "yes" responses). This is particularly important if a medical translator is involved as miscommunication is common even when using trained medical interpreters - see reference (6). Can you tell me - in your own words - what you have heard from me and what's most important to you about what I've said? R - Ritualized practices and restrictions. Determine if there are specific customs the patient desires to be followed. These must be communicated to other health care providers, especially in the hospital setting. It may be necessary to advocate for the patient and negotiate with healthcare facility administrators to find an agreeable way to honor a patient's wishes. Are there specific practices that you would like to have in the hospital or at home? Are there aspects of medical care that you wish to forgo or have withheld because of your cultural beliefs? Is anything discouraged or forbidden? If the patient is approaching death, and willing to discuss it: Are there specific practices that are important to you at the time of death or afterwards that we should know about? E - Environment at home. Given that a majority of hospice care happens in the patient's home environment, respectfully explore whether there are any needs that can be met by the health care system, and how open the patient, family or community is to receiving care at home. Recognize that patients may be hesitant to voice needs, or resistant to accepting help from outside the community. Even if a trusting, collaborative relationship has developed between a patient/family and clinicians in the hospital, this may not immediately translate into the home setting. With the patient's permission, expectations about cultural-specific aspects of a patient's care should be explicitly communicated to care providers outside the hospital.

Death Pronouncement in the Hospital #04

Background Physicians traditionally have little formal training in examining patients to determine death, notifying families, and in recording proper documentation. This Fast Fact reviews key steps in the death pronouncement and notification process. See also Fast Facts #76, 77 on telephone notification of death. The Phone Call "Please come and pronounce this patient" Find out the circumstances of the death from the nurse - expected or sudden? Is the family present? Preparation Before You Enter the Room 1) For residents, find out if the attending physician has been called. In general, see the patient before calling the attending, unless there are unusual family dynamics or details surrounding the death that you should discuss with the attending. 2) Determine if the family has requested or if you believe there is value in requesting an autopsy. Some institutions have specific policies about autopsy requests. 3) Determine if the patient/family has already been contacted by the Organ Donor Network (see Fast Fact #79 Discussing Organ Donation). 4) Review the chart for important medical (length of admission, cause of death) and family issues (Who is family? Faith? Is there a clergy contact?). In the Room You may want to ask the nurse or chaplain to accompany you; he/she can give you support and introduce you to the family. Introduce yourself (including your relationship to the patient) to the family. Ask each person their name and relationship to the patient. Empathetic statements are appropriate: "I'm sorry for your loss..." Or - "This must be very difficult for you...." Explain what you are there to do. Tell the family they are welcome to stay while you examine their loved one. Ask if family members have any questions or if they wish to speak with a chaplain. The Pronouncement Identify the patient by the hospital ID tag. Note the general appearance of the body. Ascertain that the patient does not rouse to verbal or tactile stimuli. Avoid overtly painful stimuli especially if family members are present. Nipple or testicle twisting, or deep sternal pressure are inappropriate. Listen for the absence of heart sounds; feel for the absence of carotid pulse. Look and listen for the absence of spontaneous respirations. Record the position of the pupils and the absence of pupillary light reflex. Record the time at which your assessment was completed. Documentation in the Medical Record Called to pronounce (name); Chart the findings of physical examination. Note date and time of death; Note if family and attending physician were notified. Document if family declines or accepts autopsy Document if the death was natural and if the coroner was notified. For the purposes of filling out the death certificate (see FF #155): document cause of death; length of time between onset of condition and death; and whether tobacco or alcohol may have contributed to the death.

#226 The Family Meeting Part 5 - Helping Surrogates Make Decisions

Background Surrogate decision makers are often placed in the difficult position of making what feels to them as life or death decisions. This Fast Fact reviews an approach to help surrogates through the decision process when patients cannot participate in decision-making themselves. Surrogate decision making The surrogate's role is clearly to exercise "substituted judgment" - that is, to make decisions as the patient would make them using the patient's values and preferences as previously expressed. The challenge was clearly expressed by the New Jersey Supreme Court in the Quinlan case: if (the patient) could wake up for 15 minutes, understand his current medical situation completely, and then had to go back into it, what would he tell us to do? In the case of children, surrogate decision makers (usually parents) are expected to make decisions that represent the child's 'best interests'; depending on the age and capacity of the child to participate in his/her own healthcare decision making, the applied 'best interest' judgment by the surrogate and healthcare providers may incorporate the patient's values and preferences to the extent possible, or may be solely based on the decision maker's interpretation of best interest. If there is conflict about what is in a child's best interest, or in cases of developmentally disabled adults who have never had capacity, consultation from ethics and law may be appropriate, as the rules governing decision-making vary considerably. Helping surrogates 1) Before making a recommendation, make sure there is a common understanding of the patient's condition and prognosis. Following this, the next step is to try to understand the patient's goals in light of these medical facts. 2) Bring the patient's "voice" into the decision process even if he/she cannot participate directly: If your father were sitting here with us, what would he say? If available, share a copy of any advance care planning document with the surrogate. Realize that it is common for the surrogate never to have seen the document. 3) Whenever possible, frame the decision around the treatment goals (e.g. life prolongation, allowing a peaceful death) in light of the patient's current condition, rather than focusing on very specific treatments (e.g. thoracentesis, antibiotics). The details of the medical plan should flow from the overall goals of care. 4) Do not make the surrogate feel that they are taking full responsibility for medical decisions, especially those which may result in the death of their loved one (We can do option a or b; what would like me to do?). Once you have a sense of the patient's goals in light of his/her medical condition, offer to make a recommendation that reflects those goals. Note: Many families are looking for support and guidance from medical professionals, especially the physician. Given what you have told me about your mother, and what we know about her medical condition, I would recommend.... Start with what you are going to do to achieve the patient's goals and then talk about what does not make sense given those goals. Remember, however, that some families may want information but not your recommendation. It is therefore important to offer your recommendation (Would it be helpful for me to say what medically makes the most sense, given what you've told me about your Dad?). 5) Remember that we are talking about the potential death of the surrogate's loved one. Emotions - sadness, frustration and guilt - are appropriate and to be expected. Use previously discussed emotion management skills to acknowledge, legitimize, empathize and support the family's emotional response (see Fast Facts #29 and #224). 6) Do not argue over the facts; repeating the facts over and over again is not likely to be effective. When the surrogate says He is a fighter, acknowledge that he is and has really fought hard. The surrogate saying I want you to do everything is as much a sign of emotional desperation as it is a factual request. Respond with empathy: It seems this is really hard for you. If hope for a miracle is expressed, it is appropriate to acknowledge that you hope for an unancticipated recovery as well, but that a miracle is truly what it would take at this point. 7) Rather than reiterating what medicine cannot do, consider using "I wish" statements to keep you in touch with the surrogate's feelings, while simultaneously expressing medicine's limitations (I wish our medicines were more effective; I wish we had more medical treatment to offer than we do...). 8) Recognize the importance of time and support for surrogates to do their necessary grief-work. Offer counseling services, either informal through the work of a palliative care team, or more formal resources available at your institution. Bring together your clinical care team and strategize potential resources for support such as chaplaincy, social services, psychology, palliative care or ethics consultation. Remember that time is your ally. The surrogate needs to process that their loved one is dying and conceptualize what life will be like without him or her. This grief work takes time and psychological support. Often, letting people think about what you have said and talking again over subsequent days provides them the space to do grief work. It also allows them to see for themselves that what you have advised is coming true (e.g. the patient is not getting better).

The Family Meeting Part 5 - Helping Surrogates Make Decisions #226

Background Surrogate decision makers are often placed in the difficult position of making what feels to them as life or death decisions. This Fast Fact reviews an approach to help surrogates through the decision process when patients cannot participate in decision-making themselves. Surrogate decision making The surrogate's role is clearly to exercise "substituted judgment" - that is, to make decisions as the patient would make them using the patient's values and preferences as previously expressed. The challenge was clearly expressed by the New Jersey Supreme Court in the Quinlan case: if (the patient) could wake up for 15 minutes, understand his current medical situation completely, and then had to go back into it, what would he tell us to do? In the case of children, surrogate decision makers (usually parents) are expected to make decisions that represent the child's 'best interests'; depending on the age and capacity of the child to participate in his/her own healthcare decision making, the applied 'best interest' judgment by the surrogate and healthcare providers may incorporate the patient's values and preferences to the extent possible, or may be solely based on the decision maker's interpretation of best interest. If there is conflict about what is in a child's best interest, or in cases of developmentally disabled adults who have never had capacity, consultation from ethics and law may be appropriate, as the rules governing decision-making vary considerably. Helping surrogates 1) Before making a recommendation, make sure there is a common understanding of the patient's condition and prognosis. Following this, the next step is to try to understand the patient's goals in light of these medical facts. 2) Bring the patient's "voice" into the decision process even if he/she cannot participate directly: If your father were sitting here with us, what would he say? If available, share a copy of any advance care planning document with the surrogate. Realize that it is common for the surrogate never to have seen the document. 3) Whenever possible, frame the decision around the treatment goals (e.g. life prolongation, allowing a peaceful death) in light of the patient's current condition, rather than focusing on very specific treatments (e.g. thoracentesis, antibiotics). The details of the medical plan should flow from the overall goals of care. 4) Do not make the surrogate feel that they are taking full responsibility for medical decisions, especially those which may result in the death of their loved one (We can do option a or b; what would like me to do?). Once you have a sense of the patient's goals in light of his/her medical condition, offer to make a recommendation that reflects those goals. Note: Many families are looking for support and guidance from medical professionals, especially the physician. Given what you have told me about your mother, and what we know about her medical condition, I would recommend.... Start with what you are going to do to achieve the patient's goals and then talk about what does not make sense given those goals. Remember, however, that some families may want information but not your recommendation. It is therefore important to offer your recommendation (Would it be helpful for me to say what medically makes the most sense, given what you've told me about your Dad?). 5) Remember that we are talking about the potential death of the surrogate's loved one. Emotions - sadness, frustration and guilt - are appropriate and to be expected. Use previously discussed emotion management skills to acknowledge, legitimize, empathize and support the family's emotional response (see Fast Facts #29 and #224). 6) Do not argue over the facts; repeating the facts over and over again is not likely to be effective. When the surrogate says He is a fighter, acknowledge that he is and has really fought hard. The surrogate saying I want you to do everything is as much a sign of emotional desperation as it is a factual request. Respond with empathy: It seems this is really hard for you. If hope for a miracle is expressed, it is appropriate to acknowledge that you hope for an unancticipated recovery as well, but that a miracle is truly what it would take at this point. 7) Rather than reiterating what medicine cannot do, consider using "I wish" statements to keep you in touch with the surrogate's feelings, while simultaneously expressing medicine's limitations (I wish our medicines were more effective; I wish we had more medical treatment to offer than we do...). 8) Recognize the importance of time and support for surrogates to do their necessary grief-work. Offer counseling services, either informal through the work of a palliative care team, or more formal resources available at your institution. Bring together your clinical care team and strategize potential resources for support such as chaplaincy, social services, psychology, palliative care or ethics consultation. Remember that time is your ally. The surrogate needs to process that their loved one is dying and conceptualize what life will be like without him or her. This grief work takes time and psychological support. Often, letting people think about what you have said and talking again over subsequent days provides them the space to do grief work. It also allows them to see for themselves that what you have advised is coming true (e.g. the patient is not getting better).

Which of the following is true regarding the concentrated oral morphine solution (20 mg/mL) (Fast Fact #53 Sublingual Morphine): The majority of the concentrated oral solution is absorbed gastrointestinally not sublingually The bioavailability of the concentrated oral morphine solution is significantly lower than soluble morphine tablets. The equi-analgesic ratio of soluble morphine tablets to the concentrated oral morphine solution is 3:1 Non-soluble morphine immediate release tablets administered have a greater percentage of sublingual absorption when crushed than the concentrated oral morphine solution.

Background The preferred route of administration of analgesics for most patients in pain is oral (PO) considering the longer duration of action and convenience of use in non-hospital settings compared with subcutaneous and intravenous formulations. Soluble tablets of morphine were once commonly used for off-label sublingual (SL) administration in patients who were unable to swallow pills or large quantities of solutions. Although some hospice pharmacies still may be able to compound soluble morphine for sublingual use, the manufacture of soluble tablets of morphine has not been available in the United States since 2007. Instead, most pharmacist experts recommend the use of concentrated oral solution (20 mg/mL) of morphine or oxycodone for this clinical application. Pharmacology of SL Morphine SL administration of morphine via soluble tablets was used to treat breakthrough pain to hasten analgesic onset and peak; however, available data do not support more rapid absorption of soluble morphine tablets when compared with more traditional oral formulations of morphine (1-3). Indeed, several clinical studies found no substantial advantage to the use of soluble morphine tablets over oral morphine (4-6). Mean time to maximum concentration has been shown to be shorter for PO morphine (0.8 + 0.35hr) compared with soluble morphine tablets (1.75 + 1.30 hr), indicating that soluble morphine tablets are likely swallowed and absorbed gastrointestinally rather than through the oral mucosa (3). The bioavailability (amount of drug eventually made available to the systemic circulation) of soluble morphine tablets are relatively low: only 9% Agents are most readily absorbed through the oral mucosa when they are potent, non-ionized at physiological pH, and lipid soluble (see Fast Fact #103). Morphine has a relatively low potency for an opioid, is 90% ionized at the pH of the mouth, and is one of the least lipid soluble opioids. These factors likely explain its poor performance as a SL or buccal medication. Pharmacology of Concentrated Oral Solutions of Morphine and Oxycodone In lieu of the poor evidence supporting the efficacy of soluble morphine tablets, they are not manufactured in the United States anymore. Instead, the use of concentrated (20 mg/mL) of oral morphine solution has been more commonly utilized for imminently dying patients who are unable to tolerate pills or significant volumes of an opioid solution. The bioavailability of the oral solution is 23.8%. Concentrated oral morphine solution is considered to be equianalgesic with soluble morphine tablets. The amount of SL absorption of the 20 mg/mL concentrated oral morphine solution is estimated to be only 18-20%. Its clinical effect is more likely due to the dose being swallowed with saliva and absorbed gastrointestinally. Oxycodone also comes available as a 20 mg/mL solution. The most concentrated oral solution available for methadone is a 10 mg/mL solution. Hydromorphone is not available in a concentrated oral solution. Formulation and Dosing There are several forms of short acting PO morphine available, however, only the soluble tablets or the concentrated oral solution are suitable for SL use. Nonsoluble morphine sulfate immediate release (MSIR) tablets will not be absorbed sublingually, even when crushed, because they will not liquefy under the tongue. A usual starting dose for an opioid naïve patient is 5-15 mg PO or every 3 hours. The equianalgesic ratio of IV to PO morphine is 1:3 (10mg of IV morphine is approximately equianalgesic to 30 mg PO/SL morphine).

Survival from a traumatic adult brain injury, with an initial Glasgow Coma Score of 3-5 can be expected in what percentage of patients (Fast Fact #239 Prognosis in Traumatic Brain Injury): 0-5% 15-20% 45-50% 70-85%

Background Traumatic brain injury (TBI) is defined as brain injury caused by an external force - most commonly falls, struck by/against events, motor vehicle collisions, and assaults. The vast majority of patients with mild to moderate TBIs have substantial recoveries; this is not true of severe TBIs. This Fast Fact discusses prognostication in severe TBI in adults. Initial TBI severity TBI severity is most commonly graded by the initial Glasgow Coma Scale (GCS) score. The GCS rates the patient's best verbal response, best motor response and the stimulus needed to elicit eye opening. Scores range from 3-15, with score ≤ 8 representing coma. 'Mild' TBI (accounting for ~80% of cases) is manifest by a 30 minute post-injury GCS of 13-15. 'Moderate' TBI consists of immediately altered or loss of consciousness for > 30 minutes and 6 hour post-injury GCS of 9-12. 'Severe TBI' involves immediate loss of consciousness for > 6 hours with residual GCS of 3-8. Predicting outcomes Overall 30-day mortality following TBI is estimated to be 20% with the highest mortality corresponding to the worst initial GCS scores. For patients with reliable initial GCS scores of 3-5, only 20% will survive and less half of those survivors will have what is often referred to in the research literature as a 'good outcome' (GOS 4-5). Older age, lower initial GCS score, abnormal initial pupil reactivity, longer length of coma and duration of post-traumatic amnesia, and certain computed tomography findings all indicate a smaller chance of recovery to GOS 4-5. Kothrari proposed the following prognostic guidelines, based on a comprehensive review of studies that looked at outcome in adults 6 months or later after severe TBI [8]: Helping families make decisions Families of patients with severe TBIs may be confronted with decisions about medical care (e.g. gastrostomy tube placement, chronic ventilatory support, dialysis). Such decisions often depend on a family's understanding of a patient's long-term functional outcome. The above-mentioned prognostic indicators can help clinicians provide objective information for families about the likelihood of recovery after a TBI. As with all prognostic tools, however, clinicians can only predict what would happen to a population of patients with a similar injury (e.g. 'only 10% of patients would recover such that they could live independently'); this is different from predicting any particular patient's course. It is important to communicate the uncertainty that accompanies most prognostic estimations. Counseling families about long-term functional prognosis, as well as the expected treatment course (what rehabilitation would involve) is important. Early and frequent family meetings can facilitate communication, built rapport, and are vital in expectation setting and establishing goals of care. If life sustaining treatments are initiated, framing the treatments in the context of time-limited trials is helpful. This empowers family members to discontinue certain cares after a specified period of time if the prognosis remains unchanged or if the treatment is not meeting the goals of care (e.g. helping to restore a patient to a functional status which is acceptable to the patient).

Tube Feed or Not Tube Feed #10

Background Tube feeding is frequently used in chronically ill and dying patients. The evidence for much of this use is weak at best. The Fast Fact reviews data on the use of tube feeding in advanced illness. For prevention of aspiration pneumonia -Numerous observational studies have demonstrated a high incidence of aspiration pneumonia in those who have been tube fed. Reduction in the chance of pneumonia has been suggested for non-bed-ridden post-stroke patients in one prospective, non-randomized study. For bedridden post-stroke patients, no reduction was observed. -Swallowing studies may be helpful in providing guidance regarding swallowing techniques and optimal food consistencies for populations amenable to instruction. See Fast Fact #128 for discussion of the role of swallowing studies. For life prolongation via caloric support -Data is strongest for patients with reversible illness in a catabolic state (such as acute sepsis). -Data is weakest in advanced cancer. No improvement in survival has been found (see exceptions noted below). -Individual patients may have weight stabilization or gain with tube feeding. However, when cohorts of patients have been studied in non-randomized retrospective or prospective studies, no survival advantage between tube fed and hand fed cohorts has been demonstrated. Tube feeding may be life-prolonging in select circumstances: Patients with good functional status and proximal GI obstruction due to cancer Patients receiving chemotherapy/XRT involving the proximal GI tract. Selected HIV patients Patients with Amyotrophic Lateral Sclerosis For enhancing quality of life - Where true hunger and thirst exist, quality of life may be enhanced (such as in very proximal GI obstruction). - Most actively dying patients (see Fast Fact #3) do not experience hunger or thirst. - Although dry mouth is a common problem, there is no relation to hydration status and the symptom of dry mouth - see Fast Fact #133. - A recent literature review using palliative care and enteral nutrition as search terms found no studies demonstrating improved quality of life through tube feeding. - Tube feeding may adversely affect quality of life if patients are denied the pleasure of eating. Summary - Although commonly used, current data does not provide much support for the use of artificial enteral nutrition in advanced dementia, or in patients on a dying trajectory from a chronic illness. - A recommendation to use, or not use, tube feeding should be made only after first establishing the overall Goals of Care (see Fast Fact #16). - Recommendations for how to discuss the issue tube feeding with patients/families can be found in Fast Fact #84.

#151 Hypercalcemia of Malignancy

Background Up to 30 percent of patients with cancer develop hypercalcemia. Approximately 50% of these patients will die within 30 days of a hypercalcemia diagnosis, even if the hypercalcemia is corrected, which suggests that hypercalcemia is a sign of hormonally advanced cancer. It is most commonly associated with squamous cell cancers of lung, head and neck, and esophagus, breast cancer, renal cell carcinoma, lymphomas and multiple myeloma. Pathophysiology Local osteolytic hypercalcemia due to direct effect of bone metastases. Humoral Hypercalcemia of Malignancy - secretion of parathyroid hormone related protein (PTHrP) by malignant tumors. 1,25(OH)2D (vitamin D) secreting lymphomas. Ectopic secretion of authentic PTH (very rare). Symptoms/Signs Symptoms roughly correlate with the degree of hypercalcemia (corrected) and the rapidity of rise: Mild (10.5-11.9 mg/dl); Moderate (12-13.9 mg/dl) Severe(>14 mg/dl). Cognitive: sedation, delirium, coma. Gastrointestinal: anorexia, nausea, vomiting. Renal: dehydration, polyuria, thirst/polydipsia. Diagnostics Total serum calcium, corrected for albumin (Formula: [(4 - albumin) x 0.8] + Ca++]). Ionized calcium. Renal function, phosphate, magnesium and potassium—monitor during treatment. Anti-Tumor Therapy Treatment of the underlying malignancy with systemic therapy (e.g. chemotherapy) is essential for long-term management. In cases where further anti-neoplastic therapy is not feasible, the decision to treat or not treat hypercalcemia should be made by careful exploration of the patient's goals of care. In advanced untreatable cancer, the decision to not treat hypercalcemia may be very appropriate. Supportive measures Saline hydration and loop diuretics: Normal saline 200-500 ml/hr increases GFR, increases filtered load of calcium, and is calciuretic. Loop diuretics (e.g. furosemide) blocks calcium resorption in the loop of Henle. Note: only use diuretics once dehydration has been corrected. Discontinue medications that can increase serum calcium (e.g. lithium, Vitamin D, supplements containing calcitriol, thiazides, calcium antacids); remove calcium from TPN. Increase mobility if possible. Bisphosphonates are the drug class of choice for most patients. They work via blocking osteoclastic bone resorption. Pamidronate and zoledronic acid are used in the US with full efficacy noted 2-4 days after administration; responses last 1-3 weeks. May lead to hypocalcemia or azotemia; use with caution in renal dysfunction. Pamidronate = 60-90 mg. Repeat only after 7 days have elapsed after 1st dose. Repeat infusions every 2-3 weeks or longer according to the degree and of severity of hypercalcemia. Zoledronic acid = 4 mg (maximum). Wait at least 7 days before considering retreatment. Denosumab is a human monoclonal antibody that is a potent inhibitor osteoclast mediated bone resorption. In repeated studies, it has led to durable responses in over 60% of patients with hypercalcemia refractory to bisphosphonates. Its cost may be prohibitive in hospice settings. Other Agents: Glucocorticoids are useful in lymphoid malignancies that secrete 1,25(OH)2 Vitamin D. Calcitonin may lead to transient and reductions in serum calcium (12-24 hours). It is administered intramuscularly or subcutaneously; initially 4 units/kg every 12 hours; may increase up to 8 units/kg every 12 hours to a maximum of every 6 hours. Mithramycin was the standard agent prior to bisphosphonates; now it is used only rarely due to a higher side effect profile. Gallium nitrate is usually impractical due to the need for a 5 day IV infusion. Renal Dialysis can be used in cases of acute/chronic renal failure. Summary Hypercalcemia is a common oncologic complication that often portends a very short prognosis. The decision to attempt reversal should be made after first exploring the goals of care and assessing the feasibility of future systemic anti-cancer treatments. Vigorous hydration and bisphosphonates are the cornerstones of short-term hypercalcemia therapy.

The Family Meeting Part 4 - Causes of Conflict #225

Background When family meetings are conducted with the goal of helping a patient/family cope with a shift in goals from life-sustaining treatments to a more comfort focused approach, communication can break down. This Fast Fact reviews the common causes of conflict. Recognizing Conflict When the patient/surrogates are not psychologically ready to accept the limits of medical interventions or the finality of the impending death, you will hear comments such as these: There must be some mistake; I know there are other treatments available; We want a second opinion; We believe in miracles; She is fighter, she will never give up; There must be something (medically) you can do. Health professionals may interpret these statements as 'denial.' But the term denial, by itself, is insufficient to help the clinician understand what is causing the impasse. Understanding the cause is essential in planning an effective strategy to move beyond the conflict to meet the needs of the patient and surrogates. Information Gaps -Inaccurate understanding of the patient's medical condition (e.g. overly optimistic/pessimistic prognosis). -Inconsistent information (One doctor tells us one thing and another something else.). -Confusing information (e.g. use of medical jargon, multiple treatment options presented without a clear recommendation). -Excessive information (well-meaning family/friends/clinicians providing information without full awareness of the problems). -Genuine uncertainty (e.g., predicting functional outcome from a brain injury in its immediate aftermath may be impossible). -Language/translation/cultural issues (We never tell someone they are dying in our culture.). Treatment Goal Confusion Inconsistent treatments and unclear goals, often due to physician/patient/surrogate emotional issues (see below): -Clinician initiated: We will keep your husband on blood pressure raising medicine but stop antibiotics. -Family initiated: We want you to do CPR, but not intubate her. Differing priorities about disease-directed treatment and comfort-oriented treatment between clinicians and patient/family. Lack of clarity about goals when several things are going on simultaneously (advanced cancer, severe infection, respiratory failure - Isn't the pneumonia potentially treatable?) Emotions Grief (I don't know how I will live without him.) Fear/anxiety (I don't want to be responsible for ending my father's life. My family will be angry at me for doing this.) Guilt (I haven't visited my sister in 20 years. I should have been here for her.) Anger (My mother was very abusive, I've never forgiven her; you are just giving up on her.) Hope (I'm still hoping and praying she can pull through this.) Family/Team dynamics Patient/family conflicted within themselves; may want different things at different times Dysfunctional family system (family members unable to put the patient's needs/values/priorities above their own). Surrogate lack of ability (cognitive deficit, psychological/psychiatric trait/illness). In pediatrics, this can be conflict between what is in the best interest of a child vs. a caregiver or family. Consulting teams disagree about the optimal approach, putting the patient/family in the middle of the dispute. Relationship between the Clinician and the Patient/Surrogate Lack of trust in the health care team/health care system. Past experiences where the patient has had a better outcome than predicted. Genuine value differences: -Cultural/religious values concerning life, dying, and death. -Clinician value to protect the patient from invasive, non-beneficial treatment while the family values wanting to prolong life no matter how much suffering it might entail. All of these issues represent a degree of conflict and will need to be addressed before proceeding to set end-of-life goals. See Fast Facts #183,184 for additional discussion on managing conflict. Debriefing Conflicts are stressful for all involved health professionals. It is helpful to debrief the process - what went well, what could have been improved, and - most importantly - addressing the emotional reaction and needs of the care team. See Fast Fact # 203 on managing clinician emotions.

#225 The Family Meeting Part 4 - Causes of Conflict

Background When family meetings are conducted with the goal of helping a patient/family cope with a shift in goals from life-sustaining treatments to a more comfort focused approach, communication can break down. This Fast Fact reviews the common causes of conflict. Recognizing Conflict When the patient/surrogates are not psychologically ready to accept the limits of medical interventions or the finality of the impending death, you will hear comments such as these: There must be some mistake; I know there are other treatments available; We want a second opinion; We believe in miracles; She is fighter, she will never give up; There must be something (medically) you can do. Health professionals may interpret these statements as 'denial.' But the term denial, by itself, is insufficient to help the clinician understand what is causing the impasse. Understanding the cause is essential in planning an effective strategy to move beyond the conflict to meet the needs of the patient and surrogates. Information Gaps - Inaccurate understanding of the patient's medical condition (e.g. overly optimistic/pessimistic prognosis). Inconsistent information (One doctor tells us one thing and another something else.). - Confusing information (e.g. use of medical jargon, multiple treatment options presented without a clear recommendation). - Excessive information (well-meaning family/friends/clinicians providing information without full awareness of the problems). - Genuine uncertainty (e.g., predicting functional outcome from a brain injury in its immediate aftermath may be impossible). - Language/translation/cultural issues (We never tell someone they are dying in our culture.). Treatment Goal Confusion Inconsistent treatments and unclear goals, often due to physician/patient/surrogate emotional issues (see below): Clinician initiated: We will keep your husband on blood pressure raising medicine but stop antibiotics. Family initiated: We want you to do CPR, but not intubate her. Differing priorities about disease-directed treatment and comfort-oriented treatment between clinicians and patient/family. Lack of clarity about goals when several things are going on simultaneously (advanced cancer, severe infection, respiratory failure - Isn't the pneumonia potentially treatable?) Emotions Grief (I don't know how I will live without him.) Fear/anxiety (I don't want to be responsible for ending my father's life. My family will be angry at me for doing this.) Guilt (I haven't visited my sister in 20 years. I should have been here for her.) Anger (My mother was very abusive, I've never forgiven her; you are just giving up on her.) Hope (I'm still hoping and praying she can pull through this.) Family/Team dynamics Patient/family conflicted within themselves; may want different things at different times. Dysfunctional family system (family members unable to put the patient's needs/values/priorities above their own). Surrogate lack of ability (cognitive deficit, psychological/psychiatric trait/illness). In pediatrics, this can be conflict between what is in the best interest of a child vs. a caregiver or family. Consulting teams disagree about the optimal approach, putting the patient/family in the middle of the dispute. Relationship between the Clinician and the Patient/Surrogate Lack of trust in the health care team/health care system. Past experiences where the patient has had a better outcome than predicted. Genuine value differences: Cultural/religious values concerning life, dying, and death. Clinician value to protect the patient from invasive, non-beneficial treatment while the family values wanting to prolong life no matter how much suffering it might entail. All of these issues represent a degree of conflict and will need to be addressed before proceeding to set end-of-life goals. See Fast Facts #183,184 for additional discussion on managing conflict. Debriefing Conflicts are stressful for all involved health professionals. It is helpful to debrief the process - what went well, what could have been improved, and - most importantly - addressing the emotional reaction and needs of the care team. See Fast Fact # 203 on managing clinician emotions.

Controlled Release Oxycodone (# 80)

Background: -Controlled release oxycodone (CRO) has received considerable attention in the lay press over the past several years. -Much of the coverage has been negative, related to the illicit use of CRO due to diversion outside of legitimate medical practice. -Within legitimate medical practice, CRO is an effective long-acting oral opioid product, very similar to controlled release morphine. Indication -CRO is indicated for moderate to severe pain requiring continuous, around-the-clock analgesia for an extended period of time in patients ≥ 18 years of age. Pharmacology -Oxycodone is a semi-synthetic opioid that interacts with both mu- and kappa-opioid receptors, but behaves in most respects identically to morphine. -CRO has greater oral bioavailability than morphine, and a bi-phasic absorption pattern, with peaks at 37 minutes and 6.2 hours. Peak pain relief occurs in one hour. -Unlike morphine, oxycodone has minimally active metabolites, demonstrating little to no analgesic or anti-analgesic properties. -Oxycodone should be used with caution in patients with renal and liver impairment and avoided in hemodialysis patients. -CRO can lead to all the traditional opioid side effects. -Anecdotal reports suggest less nausea, hallucinosis, and nausea compared to morphine, although these observations have not been substantiated in controlled trials. Equianalgesic Information: -The conversion factor between morphine and oxycodone has been controversial, but the most commonly accepted data suggests that 30 mg of morphine is equivalent to 20 mg of oxycodone. Since all equianalgesic values are rough guidelines, prescribers need to use their clinical judgment in determining the most appropriate starting dose. Dosage -The starting dose of CRO in an opioid naïve patient is 10 mg q12 hours; it can be dose escalated every 24-48 hours. -10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, 80 mg. -CRO must be taken intact; pills cannot be cut or crushed without risk of rapid absorption and subsequent overdose. Cost -CRO is more expensive than generic long-acting morphine; there is currently no generic CRO product on the market. Diversion -CRO has been associated with greater diversion to the illicit drug market than morphine. Illicit users will commonly crush the tablet and then chew, snort, or dissolve the product in water for intravenous injection. -CRO can bring $1-per-milligram or more on the illicit market. Summary -Due to cost and concerns about diversion, controlled release morphine is the drug of first choice for a long-acting oral opioid product.

Conservative Management of Patients With End Stage Renal Disease (#408; #207, #208)

Background: -ESRD describes advanced kidney failure (typically a glomerular filtration rate < 15 ml/min/m2) and is the point at which many patients start dialysis if they cannot receive a kidney transplant. -Significant symptom burden is common in patients with ESRD nearing the end-of life, including those receiving CM (1). Lack of energy: -Depression (see Fast Fact #404), volume imbalance, sleep disorders, poor nutrition, and anemia are common underlying causes of fatigue in patients with ESRD. -Blood transfusions have been shown to improve fatigue and self-reported well-being for palliative care patients who are anemic. -Erythropoietin-stimulating agents are transfusion-sparing interventions that can similarly mitigate fatigue and enhance quality of life for select ESRD patients on CM. -Psychostimulants do not have supporting evidence in the CKD population and may cause anorexigenic and cardiovascular effects. -Itchiness: Chronic kidney disease (CKD)-associated pruritus is a common and distressing symptom (5, 6) (See Fast Fact # 37). Except for gabapentin, which has been studied in variable doses from 100 mg daily to 400 mg twice weekly in a few trials (7), well-controlled evidence for other effective treatments is lacking. -Immunomodulating treatments such as topical tacrolimus (8), ultraviolet light B phototherapy (9), and opioid receptor antagonists have documented efficacy (10). -Dyspnea: See Fast Fact #27. Optimize volume status and anemia and address any underlying anxiety. -Pain Systemic NSAIDs are not recommended but topical NSAIDs have been shown to be effective in musculoskeletal syndromes. Opioids that are safer in renal insufficiency include (12): fentanyl, methadone, and buprenorphine. Hydromorphone is commonly used, but the neuroexcitatory effect of its metabolite is often overlooked. For patients with calciphylaxis (see Fast Fact #325), ketamine (13) and topical morphine (14) have been investigated. For the latter, a morphine 0.125% gel mixture (morphine sulfate 10 mg in 8 g of sterile gel) has been recommended up to three times daily (15); however, the systemic bioavailability of topical morphine seems to be low (16). See Fast Facts #161 and 325. -Volume derangements Hypervolemia is common in ESRD, depending on patients' residual renal function, diet, and use of diuretics. The management of volume overload which goes hand in hand with monitoring for renal function and metabolic abnormalities, is contingent on the patient's estimated prognosis. -The goal of preserving fluid balance is to manage symptoms such as dyspnea, cramping and debility while minimizing electrolyte derangements. -For patients expected to have a more protracted survival, aggressive diuresis with sequential nephron blockade using thiazide diuretics (like metolazone) and aldosterone antagonists (like spironolactone) can be offered (17) while obtaining occasional lab draws. -Subcutaneous (SQ) or intravenous (IV) furosemide can be used for urgent situations as its onset of action is within 30 minutes. If converting to a parenteral route, divide the oral dose by half; IV and SQ are dosed equally. -GI symptoms Renally-dosed haloperidol is a prudent initial step for nausea management, as it may improve other terminal symptoms in patients with ESRD such as agitation (19). Ondansetron and metoclopramide can be considered as well. The diet should be liberalized, despite metabolic concerns. Dysgeusia and anorexia should be assessed regularly. See Fast Facts # 100, 304, and 314. -Pharmacologic considerations Other interventions that can address electrolyte or acid-base derangements which can potentially cause distressing pain, cramping, or weakness should be discussed with the patient. These include therapies for hyperkalemia, acidemia, and mineral bone disease. Stopping blood pressure medications such as angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACE/ARB) is recommended as tight blood pressure control only conveys long-term benefits and elevated blood pressure is rarely symptomatic. -Hospice Prognosis is protracted for patients with ESRD on CM, with survival ranging from around 6 to 23 months (19). This is in sharp contrast to patients stopping dialysis, whose median life expectancy is around 7 days (20). As a result, hospice eligibility varies. In addition to an estimated GFR of <15 ml/min, hospice evaluation for CM patients is warranted for: 1) uncontrolled metabolic derangements such as hyperkalemia and acidemia, 2) uremic symptoms causing frailty or encephalopathy, 3) critical volume overload causing respiratory issues or nephrogenic ascites, and 4) calciphylaxis (21). Early referral to hospice has the potential to reduce healthcare dollar spending and to improve quality of life while effectively managing symptoms as patients approach their end of life (22).

#380 Cancer-Related Incident Bone Pain

Background: Cancer-related incident bone pain is a form of breakthrough pain caused by movement and is most commonly associated with bone metastases.It is often distinguished from other common forms of bone pain like arthritis or the pain associated from the administration of filgastrim-like products which are usually constant in nature and worse at night. Management of incident bone pain often requires a multimodal approach as the onset of oral immediate release (IR) opioidsmay be too slow to address a rapid-onset pain elicited by activity (1). Cancer-related incident bone pain is correlated with a decreased patient-reported quality of life, a reduced functional capacity, as well as increased psychological distress (2). Although there isn't a clear association with the size, location, or number of bone metastasis (2,3), approximately 70% of patients with bone metastases will develop pain (4). Pathophysiology: Bone metastases occur in up to 70% of those with prostate and breast cancer and up to 30% of those with cancers of the lung, bladder and thyroid (5). Osteolytic lesions (associated with multiple myeloma, lung, thyroid, kidney and breast cancer), osteoblastic lesions (usually associated with prostate cancer), and mixed lesions (associated with lymphoma, breast and lung cancer) all can cause pain via increased bone destruction, bone remodeling, and the loss of bone integrity (2). This process causes pain via the production of inflammatory by-products such as prostacyclins and cytokines which activate sensory nerves to transmit painful stimuli to the central nervous system (2,6). The pain is usually intense, easy to localize, and sudden in onset (1). Maximal pain usually occurs in 3 minutes and lasts 30 minutes after movement (1,7,8). Diagnostics: Depending on the oncologic situation, plain radiography, skeletal scintigraphy (aka bone scans for osteolytic lesions), computed tomography, magnetic resonance imaging, and positron emission tomography can identify if bone metastases match up with the site of pain (9). Oncologists can help in determining the appropriate radiologic study. Analgesic Options: For ambulatory patients, many experts recommend a multi-modal analgesic approach in which all the following analgesic options, including interventional ones, are considered simultaneously in the hopes of maximizing analgesia and functional capacity. As patients become moribund and less ambulatory from the dying process, cancer-related bone pain often diminishes. Opioids:There are several challenges in determining the best opioid dose, regimen, and timing for incident bone pain. First, many oral IR opioids have an onset of action around 20-40 minutes, which is often too delayed to manage bone pain brought on by activity. Furthermore, if scheduled opioids are dosed to manage pain at rest, they often are under-dosed for ambulation. Conversely, if scheduled opioids are based on ambulation pain requirements, patients may feel over-sedated at rest. The limited data available suggest that regularly scheduled long-acting opioids or basal opioid infusions provide better symptom relief, compared with only as needed fast acting opioids, even at initial doses and even for patients with little to no pain at rest (1). For activities that reliably incite pain (e.g. a physical therapy session), some experts suggest a trial dose of a prophylactic IR opioid given 20-30 minutes prior to the activity. A few industry-supported studies suggest that trans-mucosal fentanyl may have a quicker onset of analgesia (5-15 minutes) and superior analgesia compared with IR morphine for incident-bone pain (see Fast Facts#103 and #331) (7,8). Potential benefits of transmucosal fentanyl must be weighed against their considerable cost and regulatory and accessibility issues (7,8). External Beam Radiotherapy (EBR): Single fraction radiotherapy can offer analgesia in 24-48 hours for many patients with incident bone pain with similar efficacy as multi-fraction radiotherapy (see Fast Fact#335) (10). Despite its effectiveness, 20-30% of patients treated with EBR still experience refractory bone pain and may require additional analgesic modalities (11). Anti-inflammatories:Despite their widespread use, data supporting the use of NSAIDs and corticosteroids for bone metastases pain remain limited (12,13). Surveys of palliative medicine providers show that dexamethasone 4-8 mg by mouth daily is the most commonly used corticosteroid for metastatic bone pain (13). No NSAID is proven to be superior over any other, but some experts suggest a 3-day course of parenteral ketorolac 30 mg q8 in the inpatient setting for patients under 65 without a history of thrombocytopenia, renal failure, or gastrointestinal toxicities (14). Co-prescription of a H2 blocker (e.g. famotidine) or a proton pump inhibitor is often advised with NSAIDs (14). Bisphosphonatesare associated with bone stabilization and analgesia via bone resorption and increasing the pH of the tumor environment (see Fast Fact#113) (9). Analgesia typically begins within a week and lasts 12 weeks. Zoledronic acid and pamidronate have the best supporting evidence in this medication class and are usually prescribed by the treating oncologist (11,15). Radiopharmaceuticals:See Fast Fact#116. In patients with widespread painful bone metastases, the use of an injected intravenous radioactive isotopes like 89Sr (strontium), 153Sm (samarium), or 223R (radium, which is commonly utilized for prostate cancer) can target radiation to all metastatic skeletal sites and provide significant analgesia in up to 75% of selected patients (5). Onset of pain relief is usually 1-3 weeks and may last 6 months. Myelosuppression and renal insufficiency are relative contraindications.Cryoablation and Radiofrequency Ablation:These minimally invasive procedures are usually performed by interventional radiologists to direct either localized cold (cryoablation) or heat (radiofrequency ablation) to destroy metastatic lesions. They have been associated with improved analgesia of incident-bone pain (16,17). General anesthesia, conscious sedation or short post-procedure hospitalization may be required. Adjuvant Therapies:Animal model studies suggest that carbenoxolone may become a promising analgesic for cancer-induced bone pain (18). Although commonly prescribed, there is insufficient evidence to strongly recommend anti-depressants, scheduled acetaminophen, ketamine, topical lidocaine, acupuncture, or massage for the treatment of incident bone pain (12,19,20).

C. Changing drug and route (e.g. oral morphine to IV hydromorphone) Example: Change from 90 mg q12 Extended Release Morphine to IV Hydromorphone as a continuous infusion.

C. Changing drug and route (e.g. oral morphine to IV hydromorphone) Example: Change from 90 mg q12 Extended Release Morphine to IV Hydromorphone as a continuous infusion. 1. Calculate the 24 hour current dose: 90 Q12 x 2 = 180 mg PO Morphine/24 hrs 2. Use the equianalgesic ratio of PO to IV morphine: 30 mg po Morphine = 10 mg IV Morphine 3. Calculate new dose using ratios: 180/30 x 10 = 60 mg IV Morphine/24 hours 4. Use the equianalgesic ratio of IV Morphine to IV Hydromorphone: 10 mg Morphine = 1.5 mg Hydromorphone 5. Calculate new dose using ratios: 60/10 x 1.5 = 9 mg IV Hydromorphone/24 hours 6. Reduce dose 50% for cross-tolerance: 9 x 0.5 = 4.5 mg/24 hours = 0.2 mg IV continuous infusion 7. Note: one would also get the same amount of hydromorphone if you directly converted from oral morphine to IV hydromorphone using the 30 mg :1.5 mg ratio.

#17 Patient-Centered Interviewing

Clinical Case You admit Mary, a new patient, to the hospital. Mary has end-stage, metastatic pancreatic cancer. She has not seen a physician since she was given a terminal diagnosis 6 months ago at another institution. She is nutritionally depleted and has an apparent gastrointestinal obstruction causing significant bloating and discomfort. While you are admitting her she informs you that she is curing herself by drinking fresh fruit and vegetable juices. She refuses to discuss advanced directives because she "Does not trust you." Patient-centered Interviewing How might you begin to develop a working relationship with Mary? One strategy is to strive to understand both Mary's disease and her illness. Disease refers to a biological, pathophysiological process. Illness refers to the patient's experience. You can assess a patient's illness experience by asking about 4 dimensions—Feelings, Ideas, Function and Expectations. The acronym FIFE can be a helpful reminder. F = FEELINGS related to the illness, especially fears What are you most concerned about? Do you have any specific fears or worries right now? I imagine you have had many different feelings as you have coped with this illness. Sometimes people have fears that they keep to themselves and don't tell their doctor. I = IDEAS and explanations of the cause of a symptom or illness What do you think might be going on? What do you think this pain means? Do you have ideas about what might have caused this illness? F = FUNCTIONING - the illness' impact on daily life How has your illness affected you day to day? What have you had to give up because of your illness? What goals do you have now in your life? How has your illness affected your goals? How does this illness affect important people in your life? E = EXPECTATIONS of the doctor & the illness What do you expect or hope I can do for you today? Do you have expectations about how doctors can help? What do you hope this treatment will do for you? What are your expectations about what might happen with this illness?

Choose the single best answer regarding opioid-induced nausea (Fast Fact #25 Opioids and Nausea): The transdermal fentanyl patch is more nausea-inducing than long acting oral morphine Nausea is typically an early sign of an allergic response to opioids Patients typically do not develop tolerance to opioid-induced nausea The primary mechanism of opioid-induced nausea is stimulation of the chemoreceptor trigger zone

Common etiologies of N&V in patients with serious illness (4-8): Malignant bowel obstruction (MBO): See Fast Facts #45 and 119 for more specifics. Infections: generalized (sepsis, pneumonia, coronavirus) or more localized infectious processes (viral gastroenteritis, cholecystitis, bacterial peritonitis, clostridium difficile). Medications: Effects on the chemoreceptor trigger zone (CTZ) or sampling port near the blood brain barrier are thought to be the primary etiology. Collaborate with a pharmacist to examine medications and supplements for emetogenic agents. Common culprits: a) antibiotics; b) opioid-induced nausea (OIN); c) chemotherapy induced nausea and vomiting (CINV); d) antidepressants. Intracranial issues (e.g., brain metastases, increase in intracranial pressure, subarachnoid hemorrhage): address the underlying cause as feasible. Dexamethasone may be beneficial. Vestibular: when vertigo is present, patients typically describe an experience of the room spinning without much prompting from the clinician. Benign positional vertigo, vestibulitis, and Schwannomas are common vestibular etiologies for N&V. Other causes or factors: post-operative nausea and vomiting (PONV), dehydration, migraine, pregnancy, cannabis hyperemesis syndrome, food poisoning. Of note, constipation, anxiety, or emotional distress may compound N&V of any cause. If no obvious cause, or if symptoms ongoing, some experts recommend the following approach based on anecdotal experience (4-5): If predominantly nausea, consider a trial of an antidopaminergic medication. If predominantly vomiting, consider trial of 5HT3 antagonist such as ondansetron. If symptoms are refractory, consider a different medication class and/or additional workup. Anti-emetic Groups for N&V (4-9). Asterisk (*) indicates a risk for QTc prolongation. Group 1: Antidopaminergics (D2 antagonists): recommended for nausea related to medications (e.g., OIN) and other perceived toxins including PONV and CINV. Acute motor symptoms such as dystonic reactions are possible. Three categories of antidopaminergics have been described: 1A — more potent and longer acting: examples include haloperidol* (though IV formulations maybe less likely to prolong QTc than oral formulations), olanzapine (see Fast Fact #315), chlorpromazine (not a first-line agent per many experts due to risk of sedation). There is little evidence to titrate beyond the recommended dose of haloperidol (1-2 mg/day) and olanzapine (10 mg per day). Controlled data support the use of olanzapine both for CINV and cancer related nausea and vomiting. 1B -weaker/shorter acting: examples include prochlorperazine*, trimethobenzamide. 1C: Promotility: in addition to antidopaminergic effects, metoclopramide* is a promotility agent for gastroparesis. Use of metoclopramide for 3 months or more is associated with a risk for tardive dyskinesia, particularly in patients with renal/hepatic impairment, diabetes, or who are older than 70. Group 2: 5HT3 Antagonists: Ondansetron* is the most prescribed antiemetic in this group. Beyond their role for CINV, they are preferred anti-emetic options in patients with Parkinson's, Lewy Body Dementia, or restless leg syndrome, because of lack of effects on the dopamine receptor. Group 3: Antihistamines and Anticholinergics: Antihistamines with anti-emetic properties include promethazine*, meclizine, diphenhydramine*. Scopolamine is an anticholinergic with anti-emetic properties. Group 3 anti-emetics are most utilized for vertigo-related nausea. While they are commonly prescribed for other types of nausea (e.g., scopolamine to reduce GI secretions from an MBO), they should be used with caution in elderly populations due to their risk for delirium. Parenteral promethazine and diphenhydramine have been associated with misuse from temporary euphoric feelings caution. Of note, promethazine and prochlorperazine (an antidopaminergic) are very different drugs. Group 4: Miscellaneous: NK1 antagonists (e.g., arepiptant): primarily used for CINV due to cost and administration issues. Dexamethasone has been described as an anti-emetic for CINV, MBO, PONV, and increased intracranial pressure. Cannabinoids: prescription agents such as dronabinol (FDA approved for PONV and CINV) and nabilone (FDA approved for CINV) have shown effectiveness in some published trials. Cannabis might provide benefit but needs further research. See Fast Facts #93, 279, & 370. Inhaled isopropyl alcohol: controlled trials suggest effectiveness for PONV and gastroenteritis (9-12). Ginger: systematic reviews have shown anti-emetic effect over placebo for PONV and pregnancy (12,13). There are insufficient data regarding its role for CINV and other types of nausea (15). Lorazepam: antiemetic role is limited to anticipatory nausea and vomiting (anxiety) (16).

#224 The Family Meeting Part 3 - Responding to Emotion: Background Family meetings are stressful events, often provoking strong emotional reactions. Fast Fact #29 presents a general outline on the topic of how clinicians can respond to emotions.

Consider your role. It is important to reflect on the role of clinicians in responding to patient/family emotions at the time life-altering information is shared. The goal is not to prevent a patient/family from having those emotions. Sadness, fear, anger, and loss are normal responses to unwelcome news. Instead your role is: 1) to maintain a trusting therapeutic relationship and safe/supportive environment that allows emotions to be expressed in a way that meets the patient's/family's needs; and 2) not to worsen the experience for the patient/family by ignoring or delegitimizing their responses, or confusing them with medical information when they are not ready to hear it. Recognize that most families find clinicians' expressions of empathy tremendously supportive and these are associated with family satisfaction. Acknowledge that emotion is being expressed. If you have a good sense of what the emotion is, then it is useful to name it. If not, using more general language is preferable. I can see this is really affecting you. This information is very upsetting. Legitimize the appropriateness and normalcy of the reaction. Medical professionals are in a powerful position to help patients and families feel that strong emotions under these circumstances are normal and to be expected. Anyone receiving this news would feel devastated. It is completely expected to be very distressed by this kind of news. Explore more about what is underneath the emotion. It is tempting to try to limit the emotion, and be prematurely reassuring. But it is generally more helpful and ultimately more time-efficient to allow the patient and family to more deeply explore their feelings and reactions. Tell me what is the scariest (most difficult) part for you. Tell me more about that.... (Keep the exploration going until it is fully expressed and understood.) Empathize (if you genuinely feel it). Empathy means being able to emotionally imagine what the patient is going through. Clinicians can initiate the prior responses (acknowledge, legitimize, explore) without having a clear feeling for the patient's experience. These responses can be adequate in themselves. If the clinician cannot imagine the patient's experience, he or she can still sensitively explore the experience and provide caring and support. But if you have a strong sense of what the patient is experiencing, it can be very therapeutic to express it. This seems really unfair. I can imagine that you might feel very disappointed. Explore strengths/coping strategies. This may occur at this phase of the interview, or it may be postponed to a later phase when planning for next steps begins. In past circumstances, what has helped? How have you adapted to difficult circumstances in the past? What are you hoping for now?

Choose the best answer regarding tramadol as an analgesic in cancer pain in comparison with morphine (Fast Fact #290 Tramadol)? Two Tramadol has an increased risk of respiratory depression compared with morphine Tramadol has an increased risk of hypoglycemia compared with morphine Tramadol is 1/6th the cost of an equivalent dose of morphine No guidelines support the use of tramadol as an analgesic in cancer pain.

Correct! A large population cohort study from the UK comparing tramadol with codeine found a significantly increased risk of hospitalization from hypoglycemia, especially in the first 30 days of initiation in non-diabetic patients. Other studies have found that tramadol may have less risk for respiratory depression, abuse and misuse than with other opioids. Morphine is about ½ the cost of an equivalent dose of immediate release tramadol and 1/6th the cost of sustained release tramadol. Tramadol is a Step II agent on the World Health Organization's (WHO) pain ladder (1) and has FDA approval for the treatment of moderate to severe pain in adults. Cautions Tramadol carries four specific cautions: Seizures have been reported with higher than recommended dosage and with concomitant use of SSRI/SNRIs, MAOIs, triptans, and other drugs that reduce the seizure threshold (8). Serotonin-syndrome may occur only with the concomitant use of other serotonergic drugs and is characterized as a triad of clinical changes: cognitive (mental-status chances, agitation and hallucinations), neuromuscular (hyperreflexia, incoordination) and autonomic (tachycardia, labile blood pressure). Although the prevalence of serotonin-syndrome is unknown, the majority of cases present within 24 hours (and most within 6 hours), of a change in dose or initiation of a serotonergic medication (9). A large population cohort study from the UK comparing tramadol with codeine found a significantly increased risk of hospitalization from hypoglycemia, especially in the first 30 days of initiation and non-diabetic patients (10). Lastly in May of 2010, the FDA strengthened the warning for suicide risk for patients at high risk (defined as those who are addiction-prone, taking tranquilizers, or antidepressant drugs)(11).

A patient with painful spinal metastases is wondering if he might benefit from radiopharmaceutical therapy rather than radiation. How should you advise him (Fast Fact #116: Radiopharmaceuticals)? Patients with single bone lesions are better candidates for radiopharmaceutical therapy compared with those with multiple bone metastases There is less risk for marrow suppression with radiopharmaceuticals as compared to external beam radiation There is more established medical evidence supporting the use of radiopharmaceuticals for prostate and breast cancer as compared to other cancer types Administration of radiopharmaceutical therapy requires patient isolation for 4 hours after dose administration

Correct! Answer choice A is incorrect because patients with multiple painful bone metastases are the most appropriate candidates for radiopharmaceuticals. Answer choice B is incorrect because a predictable side effect of radiopharmaceuticals is a 30-70% drop in leukocyte and platelet counts, whereas this effect is less likely with XRT. Answer choice D is incorrect because radiopharmaceutical administration requires no special patient isolation. 116 Radiopharmaceuticals for Painful Osseous Metastases

You are caring for an elderly, non-decisional patient with end stage renal disease who is receiving chronic hemodialysis. His spouse notices a new, painful subcutaneous nodule with a surrounding lace-like purplish discoloration on both of his forearms. What would be the best diagnostic test to order to confirm the diagnosis of calciphylaxis (Fast Fact #325 Calciphylaxis)? Skin biopsy Doppler ultrasound Antineutrophilic antibody (ANA) No further testing is necessary

Correct! Calciphylaxis is a clinical diagnosis. Serum lab tests are usually non-specific. Although a skin biopsy is pursued in rare occasions, it is usually not necessary especially when cardinal clinical features such as livedo reticularis (lace-like purplish discoloration of the skin) are present in the upper extremities. Furthermore, skin biopsy has been associated with poor wound healing for this indication. Although X-rays and CT scans may show calcification, imaging is usually unnecessary.

What neurologic sign is an early indicator of opioid-induced neurotoxicity and should be routinely assessed on all patients receiving opioids (Fast Fact #57 Neuroexcitatory Effects of Opioids: Patient Assessment)? Hyperactive delirium Nystagmus Myoclonus Cheyne-stokes breathing pattern

Correct! Current research implicates the 3-glucuronide opioid metabolites as one likely cause of neuroexcitatory side effects with some suggestion that symptoms may not develop until a neurotoxic threshold is surpassed. Myoclonus is an early sign of opioid induced neurotoxicity. As myoclonus worsens, patients may develop other neuroexcitatory signs: hyperalgesia (increased sensitivity to noxious stimuli), delirium with hallucinations, and eventually grand mal seizures.

What neurologic sign is an early indicator of opioid-induced neurotoxicity and should be routinely assessed on all patients receiving opioids (Fast Fact #57 Neuroexcitatory Effects of Opioids: Patient Assessment)? Hyperactive delirium Nystagmus Myoclonus Cheyne-stokes breathing pattern

Correct! Current research implicates the 3-glucuronide opioid metabolites as one likely cause of neuroexcitatory side effects with some suggestion that symptoms may not develop until a neurotoxic threshold is surpassed. Myoclonus is an early sign of opioid induced neurotoxicity. As myoclonus worsens, patients may develop other neuroexcitatory signs: hyperalgesia (increased sensitivity to noxious stimuli), delirium with hallucinations, and eventually grand mal seizures. #57 Neuroexcitatory Effects of Opioids: Patient Assessment Background Everyone recognizes the common opioid side effects: constipation, nausea, pruritis, and urinary retention. Less well appreciated are the neuroexcitatory effects, commonly seen among patients on chronic opioids. Among these, myoclonus is typically the herald symptom. This Fast Fact will discuss risk factors and patient assessment of the neuroexcitatory opioid side effects, particularly myoclonus; Fast Fact #58 will discuss treatment options. Physiology and Risk Factors Myoclonus can occur in patients on chronic therapy with most opioids including morphine, hydromorphone, fentanyl, meperidine, and sufentanil. Higher doses more frequently result in myoclonus, but the dose relationship is variable. Myoclonus can occur with all routes of administration. Current research implicates the 3-glucuronide opioid metabolites as one likely cause of neuroexcitatory side effects with some suggestion that symptoms may not develop until a neurotoxic threshold is surpassed, although current understanding is limited. Co-morbid factors including renal failure, electrolyte disturbances, and dehydration can also contribute to myoclonus development. Clinical Scenarios Myoclonus - the uncontrollable twitching and jerking of muscles or muscle groups - usually occurs in the extremities, starting with only an occasional random jerking movement. A patient's spouse may be the first to recognize this symptom. With continued administration, the jerking may increase in frequency; at the extreme, there is constant jerking of random muscle groups in all extremities. As myoclonus worsens, patients may develop other neuroexcitatory signs: hyperalgesia (increased sensitivity to noxious stimuli), delirium with hallucinations, and eventually grand mal seizures. Well meaning clinicians may misinterpret the hyperalgesia as increasing pain, leading to a vicious cycle of increasing dose, increasing hyperalgesia, increasing dose, worsening delirium, and finally seizures. After identifying a patient with possible opioid toxicity, the clinician should complete a physical examination and chart review. Physical Examination Assess frequency of myoclonic jerks. Stand at the bedside and observe a patient for 30-60 seconds. Watch for and count the number of uncontrolled jerking movements. Determine if there is evidence of a new or worsening delirium. Complete a bedside mini-mental assessment. Assess hydration status. Estimate prognosis: hours, days, weeks, months or years? A longer prognosis demands a more definitive change in treatment. Chart review Review the recent opioid analgesic history. What is the current drug and dose? How has the dose changed over the past few days and weeks? Review the medication list for potentially exacerbating drugs. (e.g. haloperidol, phenothiazines) Review recent laboratory studies if available. Check renal and liver function, and for low magnesium, glucose or sodium.

You are called by the spouse of a patient for whom you have been prescribing immediate release oxycodone for bone pain related to multiple myeloma. He is currently on systemic cancer therapy, has life prolonging goals of care, and an estimated prognosis of several months to years. His spouse states he accidentally took three 15 mg oxycodone immediate release tablets instead of three 5 mg oxycodone immediate release tablets approximately 40 minutes ago. His spouse appropriately administered intranasal naloxone about 20 minutes later when the patient became unarousable and developed an agonal breathing pattern. He is now awake, alert, and back to his usual cognitive and respiratory baseline level of functioning. Which of the following statements would be correct to share with his wife (Fast Fact #328 Outpatient Use of Naloxone for Seriously Ill Patients): Call 911 immediately. If he becomes unarousable again it is ok to repeat the dose every 2-3 minutes in alternating nostrils No need to seek immediate medical attention because his mentation is back to baseline and the formulation of the ingested oxycodone was immediate release. The intranasal naloxone has a peak effect within 5-10 minutes The intranasal naloxone will begin to wear off in 6-8 hours

Correct! Family members should be advised to contact 911 after every administration of intranasal naloxone. The peak effect of intranasal naloxone is 20 to 30 minutes with a half-life of about 2 hours. Therefore, for his safety, answer a is the best response. Therefore, there is concern that many palliative care patients may be at risk for opioid overdose given their co-morbidities, relatively high doses of opioids needed to control symptoms, and, in some instances, a history of substance use disorders (see Fast Facts #127, 310 and 311) (5). There is also an emerging awareness of inappropriate or excessive use of opioids among patients with cancer-related pain. Co-prescribing of naloxone for patients on chronic opioids is currently being implemented through the US Veterans Affairs Medical System. Intranasal administration of naloxone begins to reverse opioid-induced respiratory depression and sedation in 8-13 minutes; peak effect is 20-30 min; and the half-life is about 2 hours. The nasal spray is supplied in a box containing two, 4 mg single-use nasal spray devices. A dose can be repeated every 2-3 minutes in alternating nostrils, if necessary. Establishing more rigorous evidence-based criteria for co-prescribing is needed, but the following patients may be at risk of an opioid-related fatality when death from their underlying illness is not imminently anticipated: Daily morphine equivalent doses of > 100 mg/day Methadone as a prescribed analgesic Benzodiazepines and/or antidepressants in combination with opioids History of unintentional or intentional overdose History of a substance use disorder including alcohol or tobacco History of chronic pulmonary, renal, or hepatic disease A recent history of incarceration The adverse effects of naloxone administration are primarily opioid-withdrawal related however precipitation of a pain crisis is of serious concern. Background Naloxone (Narcan®), a semisynthetic opioid antagonist, is indicated for the complete or partial reversal of life-threatening CNS/respiratory depression induced by opioids. Naloxone is often inappropriately used in the hospital setting, administered as a full ampule (0.4 mg) in response to physiologically normal opioid-induced decrease in respiratory rate or mild sedation. Mild bradypnea, which is not associated with physiologic consequences like hypoxemia, should be closely monitored. Depending on the dose administered, naloxone administration to a patient physically dependent on opioids will cause the abrupt return of pain and can precipitate an abstinence (withdrawal) syndrome, with symptoms ranging from mild anxiety, irritability and muscle aches to life-threatening tachycardia and hypertension. Once thought to be devoid of side effects, naloxone can cause cardiovascular collapse and pulmonary edema, probably through abrupt increase in sympathetic nervous system activity associated with opioid reversal.

Which one of the following statements is True about organ Donation after Cardiac Death (DCD) (Fast Fact #242 Organ Donation After Cardiac Death): A representative from the Organ Procurement Office (OPO) may meet with a family to discuss the option of DCD but not participate in any care decisions. DCD is considered unethical unless a patient also meets brain death criteria. Representatives from the organ transplant surgical team must meet with a family/POA and present the options of organ donation vs. no donation at least 24 hours before a planned terminal extubation. The Joint Commission requires involvement of a palliative care specialist in DCD decision making.

Correct! Organ donation is legally permissible after brain death or cardiac death criteria have been met (Fast Fact #115 for Brain Death Criteria). Aan OPO representative should be contacted prior to death to approach the family about organ donation, and consent the family/patient decision makers for organ donation. However, members of the OPO and organ recovery teams should not participate in patient care decisions or medical care prior to the declaration of death; this policy aims to prevent conflict of interest. There is no mandate to involve specialist palliative care providers in organ donation decisions. #242 Organ Donation After Cardiac Death Background Organ donation after cardiac death (DCD) refers to organ donation from a deceased donor who has been declared dead on the basis of cardio-pulmonary criteria (permanent cessation of circulatory and respiratory function) rather than on neurological "brain death" criteria (permanent cessation of brain function - see Fast Fact #115). This Fast Fact reviews key elements of the DCD process. Two Types of Organ Donation Donation after death by neurologic criteria occurs when a comatose patient meets brain death criteria. After obtaining consent from the family, the donor is brought to the operating room on the ventilator. Organ procurement occurs in the operating room while the patient remains intubated with a beating heart. Donation after cardiac death occurs when a decision is made to discontinue mechanical ventilation/other life-sustaining treatments in a comatose or gravely ill patient who is expected to die quickly after cessation of life-support. Depending on hospital policy, the patient may be extubated in the operating room (OR) to minimize the time between death and organ procurement and thereby optimize donor organ viability for transplantation. Most organ procurement organizations (OPO) have guidelines governing the amount of time between extubation and death during which the organs are considered viable for transplantation. This is generally 60 minutes. If the patient survives longer than that, excessive organ ischemia occurs rendering the patient an unsuitable donor. The patient is then returned to the ICU or other appropriate location for end-of-life care. Selecting Patients for DCD Appropriate patients are generally comatose patients for whom a decision has been made to discontinue life-sustaining treatments with the expectation of imminent death. The decision to discontinue life-sustaining treatments is made prior to any discussions of organ donation. Most institutions have policies and procedures which alert the OPO of potential donors. After discussion with their medical director and recipient transplant centers, the OPO determines donor suitability. Trained professionals - usually OPO representatives - approach the family about organ donation, and consent the family/patient decision makers for organ donation. Potential donors are generally between 0 and 60 years of age. Patients should not meet the criteria for death by neurologic criteria (they are candidates for organ donation via brain death protocols). The OPO staff prognosticate whether the patient is sufficiently likely to die within the 60 minute window after cessation of life-prolonging treatments. This estimate is based on physiologic parameters including spontaneous respiratory rate, negative inspiratory force, age, oxygen saturation, level of hemodynamic instability, and body mass index (BMI).

Which one of the following is the best answer regarding to the use of opioids for chronic pain in patients with a history of substance abuse (Fast Fact #311: Opioids for chronic pain in patients with a history of substance use disorders Part 1): Whether the patient's substance abuse is active or in recovery, should not play a major factor in the opioid-decision-making process for cancer patients. Prognosis of the underlying serious illness is an important patient selection factor. Federal statutes prohibit the continued prescription of opioids in the presence of marijuana on a urine drug screen. The initiation of long acting opioids has been shown to be safer than short acting opioids in this patient population.

Correct! The goal of analgesic therapy in chronic pain patients with a history of substance abuse is to ensure the therapy is safe, effective, and does not contribute to a worsening of substance use. As such, appropriate patient selection factors with regards to initiating opioids in this patient population involves a complex interplay of the patient's prognosis, status of the substance abuse (recovery vs active), pain severity, and risk of adverse opioid effects. Clinicians should differentiate active substance use from patients in recovery or enrolled in a treatment program. There are no federal laws prohibiting opioid use in chronic pain patients with + marijuana urine drug screens, rather the decision to use opioids in these patients should be done on a case-by-case basis. There is some emerging evidence that long-acting opioids may be more associated with unintentional overdoses than short-acting opioids in the first 2 weeks after initiation.

Tapering Opioids in Patients with Serious Illness: How to Taper (#414)

Decide a rate to taper: - The taper should be slow enough to minimize symptoms of withdrawal. - For patients on chronic opioid therapy (COT) for over a year, a ~10% reduction (of the original dose) per month taper is often appropriate (2). - The exact reduction amount will often depend on available pill/patch formulations, but typically is not more than 20%. - For example, a patient is on 90 mg of morphine extended release 3x daily; one could initiate the taper by reducing each dose by 15 mg (a ~15% reduction) each month. That is, reduce to 75 mg 3x daily for a month, then 60 mg 3x daily for a month, and so on. - For patients who have been on COT for less than a year, or when a more rapid taper is indicated, a faster taper can be used of approximately a 10% dose reduction (of the original dose) per week. If a patient demonstrates significant withdrawal symptoms along the way, you can switch to ~10% reductions of the remaining dose. Once the smallest available dose is reached, the interval between doses may be extended. - For a rapid taper example, consider a patient taking 30 mg of oxycodone 5 times a day, or 150 mg daily. Decrease the daily dose by 15 mg (10%) each week until the patient reaches 45 mg daily (approximately 30% of the original daily dose). Then decrease by 5 mg (approximately 10% of remaining daily dose) until the patient is taking 5 mg daily. -It is reasonable to stop opioid therapy completely when the patient is taking opioids less than once a day, meaning they are having occasional days without requiring opioids.

Responding to Patient Emotion #29

Introduction Listening to, recognizing, and responding to patient emotions is an essential skill for physicians who care for dying patients. We often think of this skill as innate—either we have the skill as an attribute of our personality, or we don't. In fact the skill of responding empathetically to patient emotions can be learned. Here are eight tasks that guide you in responding to patient emotion: 1. Listen to the patient. Listen - do not interrupt while the patient is talking. Patients and families facing end-of-life decisions want an opportunity to talk with their doctor about what they are thinking and feeling. 2. Listen to yourself. Be aware of your own emotions. Your feelings of sadness, anger, anxiety, fear or happiness are often the first clue that a patient is communicating an important emotional message. Avoid the trap of quickly acting on your emotions. 3.Reflect thoughts, feelings and behavior. Reflection means re-stating what a patient has said using their own words and phrases. Reflection 1) tells the patient that you are listening and care, giving permission to discuss sensitive topics; 2) allows the patient to listen to their own thoughts, heightening their self-awareness; and 3) allows the patient to confirm, correct or amplify upon your understanding. Example 1, Reflecting thoughts: Patient: This is a tough decision...I just can't decide whether I want to enter a hospice program or continue with chemotherapy. Physician: You're having a hard time deciding between hospice and chemotherapy. Example 2, Reflecting emotions: Patient: I've been feeling run down and discouraged. I'm a little overwhelmed. Physician: You have been feeling discouraged and overwhelmed ... Example 3, Reflecting behavior: Patient begins to cry. Physician: I see that you are crying.... 4. Affirmation & respect. Patients and families take a risk when they share their emotions; affirm and support the patient. Examples: Thank you for sharing your feelings and thoughts. Or, I'm glad that you are talking with me about your feeling. Or, I can do a better job as your doctor when I know how you are feeling. 5. Empathic curiosity. Be curious and request more information: I'd like to know more about this... Or, Please tell me more about the sadness you are feeling. 6.Summarize/paraphrase. Restate the patient's story in your own words. In contrast to reflection, paraphrase and summary involves interpretation and condensation of the patient's narrative. An effective comment is brief yet captures essential meaning and emotion. We have been talking for awhile about how things are going for you. Let me see if I can summarize what you have said, then you can let me know if I'm on track... 8. Offer Follow-up. I would like to check in with you next week and see how things are going. In the mean time, please let me know if you need to talk before then, OK? See Fast Facts: Delivering Bad News (#6, 11); Dealing with Anger (#59); Responding to Emotions in a Family Meeting (#224).

Integrating Spirituality in Palliative Care Goals of Care Conversations What do we mean when we say palliative care is care for the whole person? Our usual answer is palliative care attends to the body, mind, spirit, emotions, social setting, network of relationships, and other aspects of a patient's "whole person." Described this way, providing whole person care may sound like an overwhelming task for a solo palliative care clinician. Palliative care requires an interdisciplinary team or, in words attributed to Balfour Mount, "Whole person care requires a whole person. Until one comes along—use your team." The interdisciplinary team is absolutely central to the delivery of palliative care where each dimension of the patient is addressed discipline by discipline. The medical team members provide the diagnosis, prognosis, and interventions to ease pain and other symptoms. The social worker provides psychosocial care ranging from helping a patient find affordable in-home caregiving, to facilitating resolution of a long-standing family conflict, to "just" listening while the patient shares their fears, hopes, or sorrows. The chaplain provides spiritual care including everything from offering a prayer or religious ritual, to addressing a patient's sources of suffering, to connecting a patient with their own sources of meaning, comfort, and hope. All together, each discipline contributing their part provides care for the whole person.

It is often said as a scalpel is to a surgeon, so the goals of care conversation is to the palliative care clinician. As it has been well documented, an expertly facilitated patient or family meeting can reduce unwanted medical care and increase the chances that a person will receive care that aligns with their values, goals, and preferences, among many other benefits. Expertly crafted tools such as Ariadne Lab's Serious Illness Conversation Guide[3] and Weissman's et al. steps for conducting a family meeting,[4] outline the necessary elements of an effective goals of care conversation. These include opening introductions, exploration of the patient/family's understanding, sharing diagnostic and prognostic information, addressing patient emotions, discussing options for care, and then translating the entire discussion into an agreed upon plan of care. However, considering the patient statements above, it is not immediately apparent how a conversation guided by these steps might open the way for healing, or even more, how they might "prepare and hold the space where the miraculous may happen."[5] Seeking to address this gap and hold the tension between the dual obligations to cure when possible and heal always, the Supportive Care Coalition with palliative care physician Dr. Woodruff English created and piloted a goals of care conversation protocol. The protocol was designed to open the way for existential, spiritual, and psychosocial sources of patient and family suffering to emerge, be expressed, and addressed. For the sake of comparison, Weissman's 10-step and the 10-stage models are outlined below: At first glance, much of the two models appear to be the same. They both emphasize that first impressions matter. Careful planning of the initial patient/family meeting along with attention to important details such as introductions to establish rapport make a difference in the quality of what comes next. They both emphasize the importance of good communication. Sharing diagnostic and prognostic information in non-technical language is as essential as arriving at an agreed upon plan of care. Yet, in the midst of these and other similarities, there are several key differences: Stages instead of steps: The "10-stage" instead of "10-step" designation is intended to evoke the image of acts in a play, movements in a dance, or scenes in an improv routine. While steps tend to occur in a prescribed order, stages will occur as the team follows the lead of the patient and family. Some of the stages, such as the briefing/spiritual grounding, introductions, and debriefing/documenting, will happen at the opening and closing of the encounter, while the order of the remaining stages is determined by what arises as the team listens deeply to the spoken and unspoken communications of the patient and family. Briefing and intentional spiritual grounding: The 10-stage model assumes that multiple members of a palliative care team will not only be present at the family meeting but also that the team will gather for their own pre-meeting. During this time they will share relevant clinical information and engage in some form of centering or grounding practice. The model does not dictate what this grounding practice might look like, but instead suggests that the team find practices that assist them in setting aside their own non-relevant concerns or personal agendas so that they might be more fully present to the patient and family. Possible grounding practices can include pausing together for several moments of silence, reading a short poem aloud, or sharing a brief period of mindfulness meditation. Introductions/build relationships: In addition to sharing names and their relationship to the patient, at appropriate moments during the conversations, meeting participants are invited to enter into deeper conversation through questions such as:"What do we need to know about you/your loved one to give you the best care possible?"[6]"Can you tell me about (patient), what kind of person is he/she?""Where are you finding strength to get through this?""What are you hoping for?""Given all that is happening, what is most important right now?" Be present for lamentation and suffering: The discussion of the patient's diagnosis and prognosis can precipitate profound spiritual and emotional distress. Rather than attempt to dismiss, brush past, offer platitudes expressions of suffering, this conversation model encourages the palliative care team members to simply be compassionately present, grounded, attentive, and aware. Suffering, unlike physical pain, is often best honored with attuned silence, straightforward validation, and empathic acknowledgement. Pausing the conversation to recognize and name the suffering is much more important than trying to bypass or fix it. Express gratitude: While this may be the palliative care team's fourth or fifth family meeting of the day, this is likely the first time the patient/family have spoken to medical professionals in this way. Expressing genuine gratitude for the patient/family's willingness to participate, be open, and candid is an important way to acknowledge the courage and vulnerability shown during the conversation. Debrief and document: Each family meeting is an opportunity for the team to increase their skill level through a regular practice of giving and receiving feedback. Additionally, in this model, each family meeting is an opportunity to foster greater team member self-reflection and self-awareness by briefly exploring their thoughts, feelings, reactions, and behaviors in a post-family meeting debrief. During the debrief the team regularly asks and answers questions such as:What did we learn about the patient/family?How did we feel the meeting went?What did we learn about ourselves, as individuals, and as a team?How satisfied are we that as a team we listened intently for the patient/family's spiritual concerns, beliefs, and values and integrated these into the discussion? Over the span of three years, this 10-stage model was piloted with 20 palliative care teams from hospitals across the US. All of the teams were trained to use the model and record self-evaluation data on their effectiveness in integrating these new behaviors and principles into goals of care conversations. Participants consistently reported greater attunement to patient/family suffering, increased confidence in exploring patient and family existential and spiritual issues, and increased commitment to team self-care activities such as pre-meeting spiritual grounding and post-meeting debriefing. As providers of whole person care, palliative care team members are uniquely positioned to attend to the physical, mental, emotional, spiritual, and relational aspects of human persons, as well facilitate healing when a cure is not possible. This opportunity may be lost when the most important palliative care intervention, the family meeting, is approached from a "tick off the list" point of view. Pain and symptoms discussed? Check. Diagnosis and prognosis? Check. Psychosocial and Spiritual concerns? Check. Instead, this 10-stage model invites palliative care practitioners to approach the family meeting as an "I-Thou" encounter,[7] as a liminal or safe space where the "shy soul"[8] can appear. It is in this approach that the team becomes like an alchemist's vessel[9] - a vas bene clausum — a container for the patient/family's suffering, fears, and longings, and a place where healing can happen. If you are interested in learning more about the work of the Supportive Care Coalition and our spirituality toolkit, please visit our website: https://www.supportivecarecoalition.org

Corticosteroids for Common Palliative Care Symptoms

Symptom (Suggested dexamethasone dose) (2,6,9)Supporting clinical evidence in palliative care Cancer Related Fatigue (CRF):(2-4 mg a day) CRF and quality of life (QOL) benefits noted via improvements in Functional Assessment of Chronic Illness-Fatigue (FACIT-F) total QOL and subscale scores at day 15 of administration compared to placebo (10). Nausea and Vomiting (4-8 mg a day)Dexamethasone can prevent chemotherapy-induced nausea and vomiting, especially when combined with ondansetron or granisetron (11-13). There is only low-quality evidence supporting its effectiveness for nausea or vomiting unrelated to chemotherapy (14). Anorexia and Cachexia(2-4 mg a day) Dexamethasone may improve appetite in 68.5% of palliative care patients after a 7-day treatment course (15). Methylprednisolone may improve appetite in up to 77% of terminally ill patients after a 14-day course (16). Dyspnea(4-8 mg a day)There is mixed evidence for dexamethasone or prednisone to relieve dyspnea in patients with a terminal illness (17). There is no supporting evidence for methylprednisolone to prevent or relieve dyspnea in the terminally ill. Many clinicians target corticosteroid use to those with emphysema or asthma. Pain(8 mg a day) Dexamethasone is commonly prescribed for cancer-related bone pain, neuropathic pain, liver capsular pain, and radiation-induced pain (18,19). While dexamethasone and methylprednisolone have been shown to decrease patients' numeric pain score (most substantially for radiation-induced pain flares), the results have not always been significant (18-20). Malignant bowel obstruction (MBO)(8 mg a day) Literature on the effectiveness of dexamethasone to alleviate MBO or the symptoms associated has offered mixed results (21). There is no convincing evidence for the use of methylprednisolone to prevent or treat MBO. Metastatic Extradural Spinal Cord Compression (MESCC)(10 mg IV x1; then 16 mg/day) The evidence supporting dexamethasone to reduce pain and improve function from MESCC is promising but limited (22,23). See Fast Fact #238 for details on MESCC management. There is no supporting evidence for prednisone or methylprednisolone in those with a terminal illness and MESCC. Other Urgent Palliative Care Conditions(10 mg IV x 1; then 16 mg/day) Experts suggest similar dexamethasone dosing to palliate symptoms related to malignancy-induced intracranial pressure, superior vena cava syndrome, tracheal obstruction, and lymphangitis carcinomatosis; however, there is no controlled data for these indications.

B. Change drug, keep the same route (e.g. po morphine to po hydromorphone)

There is incomplete cross-tolerance between different opioids, but the exact amount will differ. Thus, equianalgesic tables are only approximations. Depending on age and prior side effects, most experts recommend starting a new opioid at 50% of the calculated equianalgesic dose, in the setting of well-controlled pain. Example: Change 90 mg q 12 Extended Release Morphine to oral Hydromorphone. 1. Calculate the 24 hour current dose: 90 Q12 x 2 = 180 mg PO Morphine/24 hrs 2. Use the equianalgesic ratio: 30 mg PO Morphine = 7.5 mg PO Hydromorphone 3. Calculate new dose using ratios: 180/30 X 7.5 = 45 mg oral Hydromorphone/24 hours. 4. Reduce dose 50% for cross-tolerance: 45 x 0.5 = 22 mg/24 hours = 4 mg q4

End of Life Care Considerations for the Pentecostal Patient Pentecostal beliefs & practices relevant to end-of-life care God intervenes directly and physically through the power of the Holy Spirit. Physical sickness can be a manifestation of spiritual illness or misdeeds, so physical healing may require spiritual healing (2-4). Spiritual practices for healing can include clapping, dancing, praying out loud, raising hands in prayer, anointing with oil, music, scripture reading, prophecy, and speaking in tongues (5). Patients/families may reference a "word(s) of knowledge" provided by a minister or prophet, or even themselves, which not only predict the patient's illness, but their eventual clinical recovery. "Spiritual warfare" may be a concern to the patient/family: the battle of good vs. evil and/or God vs. the Devil (6). As such it is important for most Pentecostals to "keep the faith" and maintain trust in a potential supernatural outcome. "Prayer warriors" may be mentioned as part of the patient's spiritual 'army' in the battle of good vs. evil (and health vs. death). The patient/family may believe that a miracle cannot occur if they allow in doubt or negativity. The miracle depends, at least in part, on their level of faith (7).

Tips for the medical clinician Ask for support from chaplains to conduct spiritual assessment and address spiritual concerns. When Pentecostal faith statements are made at the bedside or in a family meeting, VitalTalk's acronym NURSE (8) can be a useful tool to explore meaning, convey respect, and offer empathy. Offer to discuss a patient's condition with family away from the bedside if requested by the patient. Ask for permission to discuss prognosis or next steps. Phrases such as "we've reached the limits of what medicine/science can do" may be helpful. Enlist support from ethics if goals of care discussions reach an impasse. Tips for the chaplain Let the patient/family know that their minister is welcome at bedside (or via phone if visitation is not possible) to pray or anoint with oil, or to attend the next family meeting. Invite the patient/family to offer the prayer to allow you to better understand their theology and hopes. Bedside items such as a Bible lying open to a specific Scripture requested by the patient/family (9), anointing oil, or a blessed prayer cloth may be welcome signs of spiritual support. Scriptures that speak of God's protection from evil and God's healing are often requested, such as Psalm 91 ("Whoever dwells in the shelter of the Most High will rest in the shadow of the Almighty") or Isaiah 53:4-5 ("by his wounds we are healed"). Themes of divine protection, healing, trust, the power of the Holy Spirit, and imagery of the blood of Jesus providing atonement and healing may be welcome in theological discussion and prayer (10). If appropriate, explore with family if a miracle could occur without the use of artificial life support. For example, if extubation is being discussed, would the family find it acceptable with their faith to allow God to do a miracle if God wills after the breathing tube is removed? If appropriate, explore with family what may be a sign that God is "calling their loved one home." Reframe expressed feelings of guilt or 'lack of faith' if the hoped-for outcome does not occur and affirm the faith of the patient/family. For example, "Your trust in God has been incredible to witness and I want you to know that I do not see anything lacking in your faith in God. I will continue to pray along with you for God's presence and guidance during this hard time."

Which of the following is an appropriate conversion of 10 mg PO Oxycodone q4h to oral Hydromorphone (Fast Fact #36 Opioid Dose Conversions)? 0.5 mg PO q4h 2 mg PO q4h 4 mg PO q4h 8 mg PO q4h

Wrong! Calculate the 24 hour current dose: 10 x 6 doses in 24 hours = 60 mg PO Oxycodone/24 hrs Use the equianalgesic ratio of PO Oxycodone to PO Hydromorphone: 20-30 mg PO Oxycodone = 7.5 mg PO Hydromorphone Calculate new dose using ratios: 15-22.5 mg PO Hydromorphone in 24 hours Reduce dose 50% for cross-tolerance: 7.5-11.23 mg in 24 hours = 1.25-1.875 mg q4h

Which of the following medical conditions is a relative contraindication for the use of parenteral lidocaine for pain control (Fast Fact #180: Parenteral lidocaine for neuropathic pain)? Hyperthyroidism Paroxysmal Atrial fibrillation Hepatic dysfunction Chronic obstructive pulmonary disorder

Wrong! Lidocaine is extensively metabolized by the liver and metabolites are secreted by the kidney, therefore careful consideration of its use and dose adjustments should be made for patients with hepatic and renal insufficiency. Answer choice B is incorrect because cardiac monitoring during studies of normal volunteers has not demonstrated cardiac toxicity at clinically appropriate levels. Answer choices A and D are incorrect because the metabolism of lidocaine does not involve the thyroid or lungs and there are no known adverse effects relating to thyroid or pulmonary function.

A breast cancer patient has dull-achy midline back pain that is progressively more intense over several weeks. The patient has a normal neurological examination. The first diagnosis that should be ruled out is (Fast Fact #62 Epidural Metastases): Carcinomatous meningitis Epidural metastases Malignant pleural effusion Malignant hypercalcemia

Wrong! Progressive midline back pain in a cancer patient must be evaluated for epidural metastases, (spread of cancer into the epidural space). The time from onset of pain to onset of neurological deficits (spinal cord compression) is typically many weeks or longer. The incidence of epidural metastases is highest in those cancers that frequently spread to the axial skeleton: breast, lung, prostate, myeloma, melanoma and hypernephroma.

What is the principle mechanism of action for naloxone, methylnaltrexone, and naloxegel as treatments of opioid induced constipation (Fast Fact #295: Opioid Induced Constipation Part 2)? Stimulant laxative Peripheral opioid receptor antagonism Selective chloride channel activator Small intestine secretogue

Wrong! Since the majority of opioid induced constipation symptoms are felt to be secondary stimulation of mu-opioid receptors in the GI tract, naloxone, methylnaltrexone, and naloxegol are identified to be effective treatments for opioid induced constipation due to their peripheral opioid receptor antagonism in the GI tract. Hence b is the right answer. In general, these medications are reserved as second or third line treatments for opioid induced constipation due their cost, route of administration, and/or negative impact on opioid analgesia (as in the case of naloxone). Senna is an example of a stimulant laxative; lubiprostone is an example of a selective chloride channel-2 activator and liactolide is an example of a small intestine secretogogue. Route of delivery or increased opioid dosing does not appear to affect the risk of developing OIC (2). While patients usually develop tolerance to most other side effects from opioids, they do not develop tolerance to OIC (1).

Which one of the following is the best choice for emergency treatment of severe dyspnea in an opioid-naïve dying patient (Fast Fact #27 Dyspnea): hydromorphone 4 mg IV q 5-10 minutes morphine 1-3 mg IV q 1-2 hours prn transdermal Fentanyl 25 ug q72 Oxycontin 15 mg Q12

Wrong! Typically, dyspnea can be well managed with small doses in the opioid naïve patient thus small doses of a parenteral opioid is the best choice among these options. The key to treating severe dyspnea is a) picking a drug and dosage that can be administered and dose escalated quickly to achieve the desired effect, and b) safely so that respiratory depression can be avoided. Intravenous opioids have a rapid onset of effect allowing for rapid assessment and decisions about the need for changes. The oral route is too slow to provide needed relief although can be used if no parenteral drugs are available. The dose of hydromorphone in option a. is excessive, equivalent to ~ 20 mg of IV morphine. 27: Dyspnea at End-of-Life Etiology The causes of dyspnea include a wide spectrum of serious lung or heart conditions, anemia, anxiety, chest wall pathology, electrolyte disturbances or even urinary retention or constipation. Assessment Looking for simple problems is always warranted: is the Oxygen turned on? Is the tubing kinked? Is there fluid overload from IV fluids or TPN? Is dyspnea part of an acute anxiety episode, severe pain, constipation or urinary retention? Is there a new pneumothorax or worsening pleural effusion? Understanding 1) where patients are at in the dying trajectory, and 2) their identified goals of care, is essential to guide the extent of workup to discover reversible causes. If the patient is clearly dying (see Fast Fact #3), and the goals of care are comfort, then pulse oximetry, arterial blood gases, EKG, or imaging are not indicated. Treatment General measures Positioning (sitting up), increasing air movement via a fan or open window, and use of bedside relaxation techniques are all helpful. In the imminently dying patient, discontinuing parenteral fluids is appropriate. Treatment with opioids Opioids are the drugs of choice for dyspnea at the end-of-life as well as dyspnea refractory to the treatment of the underlying cause. In the opioid naïve patient, low doses of oral (5-10 mg) or parenteral morphine (2-4 mg) will provide relief for most patients; higher doses will be needed for patients on chronic opioids. When dyspnea is acute and severe, parenteral is the route of choice: 1-3 mg IV every 1-2 hours, or more aggressively if needed, until relief in the opioid naïve patient. In the inpatient setting, a continuous opioid infusion, with a PCA dose that patients, nurses or families can administer, will provide the timeliest relief (see Fast Facts #28, 54).

An 86 year old man with end-stage dementia is brought into the inpatient hospice unit for management of terminal delirium. On day three of admission he is noted to be unresponsive and patient's daughter who has held vigil at his bedside notes the onset of a "rattling" sound coming from the patient's mouth. Which of the following agents for retained oral secretions is the least associated with delirium (Fast Fact #109 Death rattle)? sublingual atropine sulfate subcutaneous atropine sulfate transdermal scopolamine subcutaneous glycopyrrolate

Wrong! "Death rattle" occurs in patients at the end of life as a result of the pooling of oral or bronchial secretions. While there is not clear evidence for their effectiveness, anticholinergic agents are routinely used in clinical practice to manage this symptom which is often very distressing for loved ones. While all of the agents listed above are reasonable choices to treat death rattle, atropine (answer a and b) and scopolamine (answer c) are tertiary amines which cross the blood brain barrier and can result in CNS toxicity. As such, these agents carry the risk of worsening the patient's delirium. Glycopyrrolate, a quaternary amine which does not cross the blood-brain barrier, carries less of a risk for delirium and thus is the most appropriate choice.

Choose the best description of a skin finding in an imminently dying hospitalized patient that would be consistent with a Kennedy Terminal Ulcer (Fast Fact #383 Kennedy Terminal Ulcer): Tiny non-blanching, flat red or purple spots seen on arms and legs in clusters Large purple net-like patterns of painful lumps seen on the thigh creating difficult to heal areas of black-brown crust An irregularly-shaped butterfly-appearing wound seen on the sacral region that was normal in appearance just 1 day ago, the wound is > 2 cm in diameter and has multicolored discoloration Swollen, boil-like red bumps that are painful and warm to touch; located on the lateral calf

Wrong! Answer choice (a) is a description of petechiae which commonly occur in patients with dangerously low platelet counts. Answer choice (b) is a description of calciphylaxis which is most commonly associated with end-stage renal disease. Answer choice (d) is a description of a MRSA skin infection. A Kennedy Terminal Ulcer is a term used to describe a skin wound that commonly occurs over the sacrum or other bony prominences despite best preventative measures and results from the skin failure associated with the dying process. The wound is usually irregularly-shaped, pear-shaped, or butterfly-shaped; > 2 inches in diameter; and may include red, yellow, black, and/or purple discoloration

Which one of the following is true regarding intrathecal drug delivery systems (also known as IT pumps) compared with epidural analgesia (Fast Fact #98: Intrathecal Analgesia)? IT pumps are preferred for patients with a prognosis < 3 months There are lower dose requirements associated IT pumps which may reduce side effects and drug costs There are fewer catheter problems associated with epidural analgesia such as catheter migration or tip occlusion Epidural analgesia is preferred in the presence of epidural pathology such as radiation fibrosis or metastatic disease.

Wrong! Answer choice A is incorrect as IT pumps are generally reserved for patients with a life expectancy > 3 months. Answer choice C is incorrect as IT pumps are associated with fewer catheter problems. Answer choice D is incorrect as IT pumps are preferred in the presence of epidural pathology.

Which one of the following is true regarding epidural analgesia via indwelling epidural catheters (Fast Fact #85: Epidural Analgesia)? Indwelling epidural catheters can remain in place for weeks to months There is a higher rate of systemic opioid side effects in comparison to intravenous administration Analgesia can only be delivered by a continuous infusion Epidural analgesia is most beneficial for difficult to localize or diffuse pain

Wrong! Answer choice B is incorrect because systemic side effects are minimized because the drug is delivered close to the site of action. Answer choice C is incorrect because analgesia can be administered by both a continuous infusion as well as patient controlled analgesia. Answer choice D is incorrect because epidural analgesia is most beneficial for well localized pain.

All of the following clinical features are suggestive of opioid induced hyperalgesia EXCEPT (Fast Fact #142: Opioid Induced Hyperalgesia): Inability to titrate the opioid dose to meet the patient's pain needs because of associated sedation Myoclonic jerks Worsening pain despite increasing dose of opioids Pain in the right upper quadrant of the abdomen that evolves into skin tenderness over the entire abdominal cavity

Wrong! Answers b-d are all recognized features of opioid hyperalgesia. Another common feature of hyperalgesia is allodynia; allodyina is pain that is elicited from an ordinarily non-painful stimuli, such as light touch of the distal extremity. Answer choice (a) is describing a known side effect of opioids (sedation) which is dose limiting for this patient and thereby prohibiting the patient from achieving optimal pain control. Sedation as a dose limiting opioid side effect is common, but it is not a sign of opioid-induced hyperalgesia.

Choose the best answer regarding prognosis in liver failure (Fast Fact #189 Prognosis in Cirrhosis). The Child's-Turcotte-Pugh (CTP) score utilizes renal function to calculate the probabilistic chances of survival in 3 and 6 months. The Model for End-stage Liver Disease (MELD) score utilizes the presence of ascites, hepatic encephalopathy, and serum albumin to calculate a 12-month mortality risk. The presence of hepatorenal syndrome is suggestive of a prognosis of 6 months or less. Patients with compensated cirrhosis, meaning no clinical evidence of past ascites, variceal bleeding, hepatic encephalopathy, or jaundice, have a median survival of 2 years.

Wrong! Both types of hepatorenal syndrome are associated with a 6 month or less survival. Hence the presence of hepatorenal syndrome should be a clinical sign that hospice care could be a viable care option for treating clinicians. Answer A is wrong because the CTP score neither utilizes renal function in its score nor is able to calculate a probabilistic chance of survival in 3 or 6 months, only probabilistic survival scores in 1 and 2 years. Answer B is wrong because the MELD score only utilizes three factors: serum creatinine, total bilirubin, and INR. Answer D is wrong because compensated cirrhosis is associated with a median survival of 12 years.

Choose the single best answer regarding opioid-induced nausea (Fast Fact #25 Opioids and Nausea): The transdermal fentanyl patch is more nausea-inducing than long acting oral morphine Nausea is typically an early sign of an allergic response to opioids Patients typically do not develop tolerance to opioid-induced nausea The primary mechanism of opioid-induced nausea is stimulation of the chemoreceptor trigger zone

Wrong! Commonly described as an allergy, opioid induced nausea is not an allergic reaction, but rather a side effect to which tolerance develops within 3-7 days in most patients. Hence b and c are wrong. There is little evidence in general comparing the emetogenic potential of various opioids, however there is some preclinical evidence that the transdermal fentanyl patch may be less nauseating and constipating compared with morphine. Background Why do patients get nauseated and vomit after receiving an opioid? Commonly described as an "allergy", opioid-induced nausea/vomiting is not an allergic reaction. In fact, rather than indicating a pathologic reaction, nausea indicates normal functioning of the brain. Opioid-induced nausea occurs through the following mechanisms: At the base of the 4th ventricle lies the chemoreceptor trigger zone (CTZ), a "sampling port", to detect substances that do not belong in the blood. Adjacent to the CTZ lies the medullary vomiting center which controls the complex muscular sequence of vomiting. When the CTZ detects a noxious chemical in the blood, a signal is sent to the VC and the vomiting reflex is initiated. Of note, this is the same mechanism when patients vomit after receiving chemotherapy. Opioids can directly stimulate the vestibular apparatus—patients note a spinning sensation with their nausea. Opioids cause constipation which can lead to nausea via stimulation of afferent cholinergic pathways. Do all opioids produce the same degree of nausea? There is little research data on this topic. In clinical practice, morphine and codeine are often mentioned as the worst offenders. Some clinical studies along with preclinical data in rats suggest that the transdermal fentanyl patch may have less nausea and constipation than morphine. What is the natural history of opioid-induced nausea? Most patients develop tolerance to the emetic effects, so that within 3-7 days, at a constant opioid dose, the emetic effect will abate. What are management approaches? Dose adjustment—if good pain relief is achieved but associated with nausea, it may be possible to lower the opioid dose, still retain good analgesia, but eliminate the nausea. Switching opioids—there is variability in emetic reaction to different opioids. Note: since tolerance to nausea develops, one never knows if a reduction in nausea is from the change of drug or tolerance. Anti-emetics— Whenever possible, choose a drug directed at the most likely cause of nausea (see Fast Fact # 5). There are little published data to guide physicians in specific choice of anti-emetic for opioid-induced nausea. Start with low-cost dopamine antagonists (e.g. prochlorperazine, haloperidol, or metoclopromide) or anti-cholinergics (e.g. scopolamine); Anti-histamines may be helpful for patients who note a spinning sensation. 5HT3 antagonists (e.g. ondansetron) can be used for more refractory cases. Two multi-center randomized trials have examined control of emesis associated with opioids not used for anesthesia. In one, 16 mg of ondansetron was more effective than 8 mg or placebo. In the other trial, stopped early due to lack of patient accrual, 24 mg ondansetron was no better than placebo or metoclopramide. Non-pharmacological approaches: there is little evidence to support non-pharmacological treatments for nausea outside of chemotherapy associated nausea; suggested approaches include acupressure and behavioral treatments.

Controlled trials have suggested that botulinum toxin injections (BoNTs) may have efficacy in palliating all of the following symptoms EXCEPT (Fast Fact #324 Palliative Uses of Botulinum Toxin): Spasticity of the upper or lower extremities Xerostomia (dry mouth) Neuropathic pain Depression

Wrong! Controlled studies have shown that serotype A BoNTs can help reduce spasmodic pain, hence it is FDA approved to treat spasticity of upper and lower extremities in adults. Smaller randomized trials have shown efficacy of BoNTs in reducing pain severity in post-herpetic neuralgia and trigeminal neuralgia. Although psychotherapy and anti-depressant medications remain the mainstay of depression treatment, BoNTs have been associated with anti-depressant effects lasting 2 weeks to 4 months in several small randomized controlled studies. While randomized studies have shown BoNTs to be useful for sialorrhea, nor controlled study has demonstrated a role for BoNTs to treat xerostomia.

"The Four A's" for the appropriate clinical monitoring chronic pain in patients with a history of substance use disorders include all of the following EXCEPT (Fast Fact #312 Opioids for chronic pain in patients with a history of substance use disorders Part 2): Analgesia or pain relief Adjuvant analgesics Adverse effects from analgesics Aberrant drug-taking behaviors

Wrong! It is recommended that the "Four A's of Pain" be utilized before and after every analgesic intervention in this patient population. The Four A's include: analgesia (pain relief); activities of daily living (functional status); adverse effects; aberrant drug-taking behaviors. Active Substance Abuse: If the patient needs addiction treatment: Taper and then discontinue opioid therapy. Provide resources for treatment with an addiction specialist. Continue to treat pain via non-opioid and non-pharmacologic means — "fire the opioid, not the patient". It is important to maintain a therapeutic relationship with the patient and assure non-abandonment.

Although anxiety related to the cancer diagnosis would seem an obvious cause of subsequent nightmares, which one of the following should be assessed as another common cause of nightmares (Fast Fact #88 Nightmares): CT or MRI to rule-out brain metastases current/recent alcohol intake history past history of depression requiring medication serum calcium level

Wrong! Nightmares can result from many causes including psychiatric illness, organic brain disease, hypoglycemia, alcohol/drug intoxication and withdrawal. Treatment of nightmares is usually multi-modal including assessment and intervention for psychiatric issues, assessment and intervention for drug/alcohol related problems and assessment/adjustment of prescribed medication. In some patients, specific medication can be added to help reduce nightmares such as benzodiazepines or atypical anti-psychotics. In this patient, brain metastases or hypercalcemia are extremely unlikely. While a past history of depression is always important, an immediate and very common cause of nightmares that can be quickly evaluated relates to alcohol use. Pharmacologic Management The pharmacologic treatment of nightmares has not been studied in controlled clinical trials. Case studies and anecdotal reports suggest the following drugs or drug classes may be effective: Atypical Antipsychotics: risperidone (0.5-2 mg qhs) and olanzapine (5 mg) have both been shown to reduce nightmares in small pilot studies of patients with acute stress and PTSD, including reduction in flashbacks, hyperarousal, and disturbed sleep. Alpha-1 Antagonists: prazosin (2-15 mg qhs) has been shown to reduce nightmares and other sleep-related symptoms in PTSD patients in multiple small studies and a single randomized controlled trial involving 13 patients. Benzodiazepines and Tricyclic Antidepressants may be of benefit in suppressing REM activity. Note: trazadone does not suppress REM activity. Other: Both cyproheptadine and topiramate have been reported to suppress nightmares in small case series.

Based on published medical evidence, match the agent with the best supported indication for use (): Cyclobenzaprine titrated over 6 weeks as an antispasmodic for mechanical back pain. Tizanidine as an antispasticity agent in the elderly with evidence of cognitive impairment. Baclofen as an antispasticity agent for involuntary jerks secondary to multiple sclerosis. Metaxalone for pain-induced insomnia from a chronic muscular strain

Wrong! Placebo-controlled trials have shown fairly convincing evidence that baclofen can safely reduce muscle hypertonicity, clonus and involuntary muscle movements associated with multiple sclerosis. Although a few skeletal muscle relaxants have shown some short term (approximately 2 weeks) analgesic efficacy for acute back pain, a systematic review showed no convincing evidence that skeletal muscle relaxants were effective analgesics for muscle pain or spasms from mechanical back pain beyond 2 weeks. Tizanidine is one of the more sedating skeletal muscle relaxants, therefore it should be avoided in the elderly with preexisting cognitive impairment due to its risk of eliciting delirium. Conversely, metaxalone is one of the least sedating skeletal muscle relaxants. So, for several reasons it would not be a prudent agent to prescribe for insomnia induced by chronic back pain.

You are caring for a patient with advanced cancer. The patient has had stable weights and states she has been eating normally with a retained appetite. On physical examination you notice diffuse muscle loss that is associated with an increase in fat mass and abdominal circumference. Which clinical term would best describe her condition (Fast Fact #386 The Anorexia-Cachexia Syndrome): Anorexia Cachexia Sarcopenia Orexigenic

Wrong! Sarcopenia describes diffuse muscle loss associated with an increase in fat mass and abdominal circumference. Anorexia describes appetite reduction and can be psychogenic (anorexia nervosa) or secondary to an underlying advanced illness. Cachexia is a >5% weight loss over 6 months in absence of starvation or a BMI 2% or appendicular skeletal muscle loss plus weight loss > 2%. An orexigenic is a term used to describe an appetite stimulant. Pre-cachexia: < 5% weight loss and presence of anorexia (4). Refractory cachexia: usually described in the published literature in the context of a progressive, incurable non-cancer illness at an advanced stage or an untreatable cancer (4,5). Introduction: Anorexia-cachexia encompasses a broad, multi-organ syndrome seen in several chronic diseases (1). The purpose of this Fast Fact is to review the anorexia-cachexia syndrome (ACS), its clinical evaluation, and its non-pharmacologic management. See other Fast Facts for related information: #10 (the role of enteral nutrition in serious illness), #100 (megestrol acetate); #190 (the role of parenteral nutrition for advanced cancer), #279 (cannabinoids), #314 (mirtazapine), and #315 (olanzapine). Prognostication: ACS is incorporated into numerous prognostication scales and is considered a common manifestation on the terminal illness pathway (16). Refractory cachexia is associated with a prognosis < 3 months (4,5,16). The clinical recognition of ACS can help clinicians assess where a patient may be at on an illness trajectory (see Fast Fact #326). Hence, clinicians should utilize the presence of ACS to improve their prognostic disclosure and clinical recommendations regarding the role of pleasure feeding over artificial nutrition especially for refractory cachexia. Non-pharmacologic management: ACS can be very distressing given the lack of efficacious therapies. Patient-family strife may result as loved ones may not understand why previously cherished foods lovingly prepared are not being eaten. While a separate Fast Factwill review the utility of pharmacotherapies and supplements for ACS, patient counseling is the cornerstone to the clinical management of ACS. Education that ACS is not a patient choice, but rather a manifestation of a hormonally-advanced, underlying illness may be the most crucial aspect of ACS care. In fact, experts suggest that the presence of refractory cachexia should prompt a goals of care discussion and nutritional refocusing away from weight gain and caloric intake and more towards alleviating hunger and thirst (5). Most experts do not recommend enteral nor parenteral artificial nutrition for refractory cachexia, as neither meaningfully improve quality of life or survival. The nutritional counseling often involves liberalizing diet restrictions and encouraging patients to eat frequent, small meals with preferably the bulk of calorie intake occurring the morning.

You are caring for a patient with advanced cancer. The patient has had stable weights and states she has been eating normally with a retained appetite. On physical examination you notice diffuse muscle loss that is associated with an increase in fat mass and abdominal circumference. Which clinical term would best describe her condition (Fast Fact #386 The Anorexia-Cachexia Syndrome): Anorexia Cachexia Sarcopenia Orexigenic

Wrong! Sarcopenia describes diffuse muscle loss associated with an increase in fat mass and abdominal circumference. Anorexia describes appetite reduction and can be psychogenic (anorexia nervosa) or secondary to an underlying advanced illness. Cachexia is a >5% weight loss over 6 months in absence of starvation or a BMI 2% or appendicular skeletal muscle loss plus weight loss > 2%. An orexigenic is a term used to describe an appetite stimulant.

You are admitting a patient into an inpatient hospice facility for severe bone pain from non-small cell lung cancer. The patient describes significant weight loss, anorexia, and functional decline. He has been on stable doses of buprenorphine/ naloxone (Suboxone) 8 mg per day sublingual tablets for two years which has helped him stay "clean" from heroin. He is still able to tolerate oral pills. Which of the following is the best management decision to address his cancer related bone pain (Fast Fact #221 Buprenorphine for Opioid Addiction): Double the buprenorphine/naloxone to 16 mg per day Rotate to buprenorphine sublingual tablets 8 mg per day without naloxone Rotate the buprenorphine/naloxone to methadone as a long acting opioid and utilize another opioid agonist for prn breakthrough agent Inform the patient that you must avoid opioids for prn use considering the history of addiction

Wrong! The challenge with the continued use of buprenorphine as this patient's principle analgesic, is that buprenorphine is a mixed opioid agonist/antagonist. Therefore, answers (a) and (b) are unlikely to meet the patient's analgesic needs. Answer d is wrong because the most concerning clinical issue is the patient's severe pain in the setting of cancer related bone pain and a prognosis of likely short weeks, not concern for potential addiction behaviors especially considering the closely supervised setting of an inpatient hospice. Answer c is recommended seeing that methadone is an effective analgesic for cancer pain and rotation from buprenorphine to methadone would allow other full mu-opioid receptor agonist medications to be added without issues related to use of a partial opioid agonist/antagonist.

You are caring for a terminally ill patient whose subcutaneous infusion of hydromorphone has been escalated from 0.4 mg/hr. to 1 mg/hr. in the last 24 hours. On physical examination, light touch to his distal upper extremities elicits moaning and discomfort. You also notice non-rhythmic jerking motions of her lower extremities. All of the following are potentially effective treatment strategies EXCEPT (Fast Fact #58 Neuroexcitatory Effects of Opioids: Treatment): Rotate to a subcutaneous infusion of fentanyl at half the equivalent dose Reduce the dose of the hydromorphone infusion Administer a dose of lorazepam Change the route of the hydromorphone to an intravenous infusion.

Wrong! The described symptoms are consistent with opioid-induced neuroexcitatory effects. Observation, opioid dose reduction, IV hydration, opioid rotation to a dissimilar opioid, benzodiazepine administration and administration of adjuvant analgesic therapy such as gabapentin or baclofen are all recognized strategies for approaching opioid induced neurotoxicity. However, changing the route of the subcutaneous infusion to intravenous is not a recommended strategy.

You are initiating opioid therapy for 68-year old patient with severe bone pain from metastatic cancer. He inquires about driving safety while on opioids. Choose the best answer (Fast Fact #248 Counseling Patients about Opioid Side Effects and Driving Restrictions). Randomized control studies show that driving is safe when being initiated on opioids as long as the morphine daily equivalent dose is < 50 mg. Federal law prohibits all patients receiving prescription opioids under the supervision of a medical licensed practitioner from driving a motor vehicle. Until he hears from you otherwise, he should avoid driving. Unfortunately, he will never be as safe of a driver as a patient not being prescribed opioids.

Wrong! There are no large, randomized studies directly examining the risk of driving while on opioids so (a) is not correct. (b and d) are wrong because there is no such US Federal law. Furthermore, one study of videotaped patients showed that those on chronic opioid therapies did not exhibit more driving errors nor attention errors as matched controls. (c) is correct because opioids can slow reaction time, cause drowsiness, or cloud judgment when they are first started or increased.

Corticosteroid-Induced Psychiatric Symptoms #323

-Background Corticosteroids are used for a wide spectrum of palliative care indications, including pain, nausea, anorexia, fatigue, and depression (1). These agents are known to induce psychiatric adverse drug reactions, ranging from subtle mood changes and memory deficits to frank psychosis. -Incidence and Risk Factors: In the published literature, the incidence of corticosteroid-induced psychosis has ranged from 1.8-62%. -Dose may be the most important risk factor for the development of steroid-induced psychosis, particularly when 80 mg of oral prednisone (dexamethasone dose equivalent of 12 mg po) or greater are prescribed. -Still, even at lower doses, idiosyncratic psychiatric effects are known to occur. -Clinical Manifestation: Early indicators of steroid-induced psychosis include confusion, perplexity, and agitation that typically occur within the first five days after initiation of treatment. - Patients may go on to develop hallucinations, delusions, and cognitive impairment. - Duration of psychiatric symptoms is dose and time-dependent; therefore, if clinicians encounter this reaction they should take prompt, appropriate clinical action. - Development of acute psychosis in a severely ill individual has many implications on the patient's survival and quality of life, including psychological distress and interference with the patient's ability to meaningful interact with friends and family members. -Management If patients are found to have severe symptoms of psychosis, the dose of the corticosteroid should first be tapered to <40 mg/day of prednisone (dexamethasone dose equivalent of 6 mg po), or the lowest dose possible (10,13). It has been reported that 92% of patients who undergo corticosteroid tapers can experience full symptom resolution (6). Caution is advised in aggressive tapering schedules due to the risk of corticosteroid withdrawal. -As evidenced in case reports, low-dose antipsychotics, such as haloperidol (0.5 to 1 mg/day), olanzapine (2.5-20 mg/day) and risperidone (1-4 mg/day), may lead to symptom resolution within days to weeks. Other Psychiatric-Induced Symptoms: In addition to psychosis, a multitude of psychiatric disorders can arise as adverse effects of corticosteroids. These include, but are not limited to, mood disorders with depressive or manic features and delirium.

Opioid Equianalgesic Conversion Ratios for use with the following examples: Morphine 10 mg parenteral = Morphine 30 mg oral = Hydromorphone 1.5 mg parenteral = Hydromorphone 7.5 mg oral = Hydrocodone 30 mg oral = Oxycodone 20-30 mg oral (see Reference 1).

A. Change route, keeping drug the same (e.g. oral to IV morphine) Example: Change 90 mg q12 Extended Release Morphine to Morphine by IV continuous infusion 1. Calculate the 24 hour current dose: 90mg q 12 = 180 mg Morphine/24 hours 2. Use the oral to parenteral equianalgesic ratio: 30 mg PO Morphine = 10 mg IV Morphine 3. Calculate new dose using ratios: 180/30 x 10 = 60 mg IV Morphine/24 hours or 2.5 mg/hour infusion 4. Some experts recommend starting the new opioid at 75% of the calculated dose to account for inter-individual variation in first pass clearance.

Neuroexcitatory Effects of Opioids: Patient Assessment

Background: Everyone recognizes the common opioid side effects: constipation, nausea, pruritis, and urinary retention. Less well appreciated are the neuroexcitatory effects, commonly seen among patients on chronic opioids. Among these, myoclonus is typically the herald symptom. Physiology and Risk Factors Myoclonus can occur in patients on chronic therapy with most opioids including morphine, hydromorphone, fentanyl, meperidine, and sufentanil. Higher doses more frequently result in myoclonus, but the dose relationship is variable. Myoclonus can occur with all routes of administration. Current research implicates the 3-glucuronide opioid metabolites as one likely cause of neuroexcitatory side effects with some suggestion that symptoms may not develop until a neurotoxic threshold is surpassed, although current understanding is limited. Co-morbid factors including renal failure, electrolyte disturbances, and dehydration can also contribute to myoclonus development. Clinical Scenarios Myoclonus - the uncontrollable twitching and jerking of muscles or muscle groups - usually occurs in the extremities, starting with only an occasional random jerking movement. -With continued administration, the jerking may increase in frequency; at the extreme, there is constant jerking of random muscle groups in all extremities. -As myoclonus worsens, patients may develop other neuroexcitatory signs: hyperalgesia (increased sensitivity to noxious stimuli), delirium with hallucinations, and eventually grand mal seizures. -Well meaning clinicians may misinterpret the hyperalgesia as increasing pain, leading to a vicious cycle of increasing dose, increasing hyperalgesia, increasing dose, worsening delirium, and finally seizures. Physical Examination -Assess frequency of myoclonic jerks. Stand at the bedside and observe a patient for 30-60 seconds. -Watch for and count the number of uncontrolled jerking movements. -Determine if there is evidence of a new or worsening delirium. Complete a bedside mini-mental assessment. Assess hydration status. Estimate prognosis: hours, days, weeks, months or years? A longer prognosis demands a more definitive change in treatment. Chart review -Review the recent opioid analgesic history. What is the current drug and dose? -How has the dose changed over the past few days and weeks? -Review the medication list for potentially exacerbating drugs. (e.g. haloperidol, phenothiazines) - Review recent laboratory studies if available. -Check renal and liver function, and for low magnesium, glucose or sodium.

Clinical Care Following Withdrawal of Dialysis (#208)

Background: Fast Fact #207 discussed decision-making around dialysis discontinuation; this Fast Fact addresses care of the patient around the time of discontinuation. Communication and care-planning at the time of dialysis cessation: -Counsel about what to expect: mean survival following dialysis withdrawal is 8-10 days (although rarely can be many weeks). Address the likelihood of progressive encephalopathy. -Reassure patients/families that symptoms can be adequately treated (see below), although drugs with sedating side effects may be necessary to ensure comfort. -Discuss diet: a liberal, pleasure-based diet is appropriate for many patients although they should be cautioned it could worsen symptoms from edema. -Address potential care sites for the final days of life. -Review other medical treatments the patient is receiving and discontinue those that will not improve their quality of life while dying; clarify treatment limitations including resuscitation (code) status. Provide emotional/psychological, spiritual, social work, and bereavement support services. Symptom Management: -In one cohort of hospitalized patients who stopped dialysis confusion/agitation was reported to affect 70% of patients, followed by pain (55%), dyspnea (48%), nausea (36%), twitching/seizures (27%), anxiety/psychological distress (27%), pruritis (24%), and peripheral edema (21%). -Pain management: Acetaminophen is the agent of choice for mild pain. Fast Fact #161 addresses opioid use in renal failure. Fentanyl and methadone are considered safest after dialysis discontinuation, although methadone should only be initiated by clinicians familiar with its use. Toxic hydromorphone metabolites, previously cleared by dialysis, can accumulate rapidly once dialysis is stopped and it should be used with caution and close monitoring of side effects. Gabapentin and pregabalin quickly accumulate once dialysis is stopped and should be discontinued or severely dose-reduced (see Fast Fact #49). -Shortness of breath: Oxygen, positioning, and opioids are the mainstays of therapy (see Fast Fact #27). Ultrafiltration is not recommended as it can be distressing for patients/family to see the patient back on a therapy which appears similar to hemodialysis. For the occasional patient who has a residual urine output of >100 ml/day, high dose diuretics can be used. -Anxiety/agitation/restlessness: Assure pain and psychosocial issues are addressed. Haloperidol or benzodiazepines are effective. Haloperidol may lower the seizure threshold and the metabolites are excreted in the urine and feces so it is recommended to dose at half the typical starting dose following dialysis withdrawal. While benzodiazepines do not accumulate in chronic kidney disease, clinical experience supports starting with low doses. -Restless legs: Clonazepam is particularly useful for the restless legs associated with uremia (0.5 - 2.0 mg bid). Clonidine (0.1-0.2 mg bid) can also be used. -Muscle cramps: Dialysis patients are often treated with quinine sulphate which accumulates rapidly once dialysis is stopped and should be discontinued. Clonazepam and other benzodiazepines are better in this setting. -Nausea: Reduced doses of metoclopromide (starting at 5 mg bid) are effective for gastroparesis. Uremia-induced nausea often responds well to dopamine antagonists such as haloperidol and prochloperazine which are often sedating in the context of uremia. Ondansetron has some advantages as it is less sedating and does not accumulate in kidney failure. -Pruritus: Emollients such as hydrourea cream, ondansetron, and antihistamines may be beneficial. Gabapentin, while effective, is too toxic in this population to initiate its use. -Myoclonus: See Fast Facts #114. Often it emerges from uremic encephalopathy and is mild in nature (e.g. 1-3 jerks per minute involving hands or feet). However, myoclonus can be distressful and wake patients from sleep. Empiric use of clonazepam or other benzodiazepines is the mainstay of treatment.

Syndrome of Imminent Death #03

Background: Virtually all dying patients go through a stereotypical pattern of symptoms and signs in the days prior to death. This trajectory is often referred to as "actively dying" or "imminent death". Prompt recognition of this trajectory is key for clinicians to provide the most appropriate interventions for both the patient and family. 1. Stages Early -Bed bound -Loss of interest and/or ability to drink/eat -Cognitive changes: increasing time spend sleeping and/or delirium. Middle - Further decline in mental status to obtundation (slow to arouse with stimulation; only brief periods of wakefulness) Late - Death rattle - pooled oral sections that are not cleared due to loss of swallowing reflex - Coma - Fever - usually from aspiration pneumonia - Altered respiratory pattern - periods of apnea, hyperpnea, or irregular breathing - Mottled extremities. 2. Time Course The time to traverse the various stages can be less than 24 hours or as long as ~14 days. Patients who enter the trajectory who are nutritionally intact, with no infection (e.g. acute stroke), are apt to live longer than cachectic cancer patients. 3. Common Family Concerns Family members present during the dying process often express the following concerns/questions. Clinicians can best help families by expecting these questions, providing education, reassurance, and responding to emotions (see also Fast Fact # 29; #149). 4. Treatment - Confirm treatment goals; recommend stopping treatments that are not contributing to comfort - pulse oximetry, IV hydration, antibiotics, finger sticks, etc. - Communicate clearly to others what is going on. - Write in progress notes: "patient is dying," not "prognosis is poor". - Treat symptoms/signs as they arise: common among these are: oral secretions (see Fast Fact #109, #158); delirium (#1, 60); dyspnea (# 27), fever (#256) and pain (# 53, 54). - Provide excellent mouth and skin care. - Provide daily counseling and support to families.

Delivering Bad News - Part 1 #06

Case Scenario: You are caring for a previously healthy 52 year old man with new abdominal pain. After conservative treatments fail, a diagnostic abdominal CT scan is done showing a focal mass with ulceration in the body of the stomach and numerous densities in the liver compatible with liver metastases. The radiologist feels that the findings are absolutely typical of metastatic stomach cancer. How do you prepare to discuss these test results with the patient? Preparing to Deliver Bad News 1.Create an appropriate physical setting: a quiet, comfortable room, turn off beeper, check personal appearance, have participants - including yourself - sitting down. 2.Determine who should be present. Ask the patient who they want to participate and clarify their relationships to the patient. Decide if you want others present (e.g. nurse, consultant, chaplain, social worker) and obtain patient/family permission. 3.Make sure you know basic information about the patient's disease: prognosis, treatment options, next steps. 4.Special circumstances: If the patient lacks decision-making capacity (e.g. developmentally delayed, demented, delirious, etc.), make sure the legal decision-maker is present. See Fast Fact # 226 Helping Surrogates Make Decisions. 5.Special circumstances: If the patient or family does not speak English, obtain a skilled medical interpreter. Use phone translation services if necessary. See Fast Fact #154 6.Special circumstances: If the patient or family is of anther cultural background, see Fast Fact # 216 Asking About Cultural Beliefs in Palliative Care. Precepting self-reflection Residents will invariably have strong emotions when they have to give bad news. This emotional response can be heightened by various factors—a young patient, an unexpected diagnosis, a patient with whom the physician has a long-standing relationship, etc. Preceptors need to support the resident. Key teaching points: 1. Residents may not spontaneously discuss their own emotional reaction with a preceptor, therefore preceptors need to introduce this topic. "This is a really hard case, how are you doing?" 2. Physicians often have strong emotional reactions when a patient encounters bad news. Normalize the experience for the resident. "It's normal to have strong feelings". 3 Three methods for coping with these feelings are: Identify your feelings (anger, sadness, fear, guilt); Talk with a colleague; Keep a personal journal. 4. Role play the discussion with the resident before you go into the room; ask them to reflect on how it "feels"...what is hard...what is easy. Encourage continued self-reflection. See related Fast Facts: Delivering Bad News Part 2 (#11); Death Pronouncement (#4); Moderating a Family Conference (#16, #222, 223, 224, 225, 227); Responding to Patient Emotion (#29); Dealing with Anger (#59).

Delivering Bad News - Part 2 #11

Case Scenario: You are caring for a previously healthy 52 year old man with a one-month of abdominal pain and weight loss. On exam he had a 2 cm hard left supraclavicular lymph node. A CT scan showed a focal mass with ulceration in the body of the stomach and numerous densities in the liver compatible with liver metastases. The radiologist feels that the findings are consistent with metastatic stomach cancer. How do you discuss these test results with the patient? Steps in Delivering Bad News 1.Determine what the patient & family knows; make no assumptions. Examples: What is your understanding of your present condition? What have the doctors told you? 2.Before presenting bad news, consider providing a brief overview of the patient's course so that every one has a common source of information. 3.Speak slowly, deliberately and clearly. Provide information in small chunks. Check reception frequently. 4.Give fair warning - I am afraid I have some bad news - then pause for a moment. 5.Present bad news in a succinct and direct manner. Be prepared to repeat information and present additional information in response to patient and family needs. 6.Sit quietly. Allow the news to sink in. Wait for the patient to respond. 7.Listen carefully and acknowledge patient's and family's emotions, for example by reflecting both the meaning and emotion of their response. 8.Normalize and validate emotional responses: feeling numb, angry, sad, and fearful. 9.Give an early opportunity for questions, comments. 10.Present information at the patient's or family's pace; do not overwhelm with detail. The discussion is like pealing an onion. Provide an initial overview. Assess understanding. Answer questions. Provide the next level of detail or repeat more general information depending upon the patient's and family's needs. 11.Assess thoughts of self-harm 12.Agree on a specific follow-up plan (I will return later today, write down any questions.). Make sure this plan meets the patient's needs. Involve other team members in follow-up. Family Conferences (#222, 223, 224, 225, 227)

#11 Delivering Bad News - Part 2

Case Scenario: You are caring for a previously healthy 52 year old man with a one-month of abdominal pain and weight loss. On exam he had a 2 cm hard left supraclavicular lymph node. A CT scan showed a focal mass with ulceration in the body of the stomach and numerous densities in the liver compatible with liver metastases. The radiologist feels that the findings are consistent with metastatic stomach cancer. How do you discuss these test results with the patient? Steps in Delivering Bad News 1.Determine what the patient & family knows; make no assumptions. Examples: What is your understanding of your present condition? What have the doctors told you? 2.Before presenting bad news, consider providing a brief overview of the patient's course so that every one has a common source of information. 3.Speak slowly, deliberately and clearly. Provide information in small chunks. Check reception frequently. 4.Give fair warning - I am afraid I have some bad news - then pause for a moment. 5.Present bad news in a succinct and direct manner. Be prepared to repeat information and present additional information in response to patient and family needs. 6.Sit quietly. Allow the news to sink in. Wait for the patient to respond. 7.Listen carefully and acknowledge patient's and family's emotions, for example by reflecting both the meaning and emotion of their response. 8.Normalize and validate emotional responses: feeling numb, angry, sad, and fearful. 9.Give an early opportunity for questions, comments. 10.Present information at the patient's or family's pace; do not overwhelm with detail. The discussion is like pealing an onion. Provide an initial overview. Assess understanding. Answer questions. Provide the next level of detail or repeat more general information depending upon the patient's and family's needs. 11.Assess thoughts of self-harm 12.Agree on a specific follow-up plan (I will return later today, write down any questions.). Make sure this plan meets the patient's needs. Involve other team members in follow-up. Precepting Points Residents often feel strong emotions when they have to give bad news to a patient. This emotional response can be heightened by various factors—a young patient, an unexpected diagnosis, a patient with whom the physician has a long-standing relationship, etc. As a preceptor, you will want to support the resident. Key teaching points: Residents may not spontaneously discuss their own emotional reaction with a preceptor, therefore you will want to introduce this topic. Physicians often have strong emotional reactions when a patient encounters bad news. This is normal and OK. Three methods for coping with these feelings: Identify your feelings (anger, sadness, fear, guilt); Talk with a colleague; Keep a personal journal.

Calculating Opioid Dose Conversions (#36)

Caution: See Fast Fact #2 about conversions involving transdermal fentanyl; #75 and #86 about methadone; and #181 about oxymorphone. The final prescribed dose needs to take into account a patients' age, renal, pulmonary and hepatic function; their current pain level and opioid side effects such as sedation; as well as prior and current opioid use. Opioid Equianalgesic Conversion Ratios for use with the following examples: Morphine 10 mg parenteral = Morphine 30 mg oral = Hydromorphone 1.5 mg parenteral = Hydromorphone 7.5 mg oral = Hydrocodone 30 mg oral = Oxycodone 20-30 mg oral (see Reference 1). A. Change route, keeping drug the same (e.g. oral to IV morphine) Example: Change 90 mg q12 Extended Release Morphine to Morphine by IV continuous infusion. 1) Calculate the 24 hour current dose: 90mg q 12 = 180 mg Morphine/24 hours 2) Use the oral to parenteral equianalgesic ratio: 30 mg PO Morphine = 10 mg IV Morphine 3) Calculate new dose using ratios: 180/30 x 10 = 60 mg IV Morphine/24 hours or 2.5 mg/hour infusion 4) Some experts recommend starting the new opioid at 75% of the calculated dose to account for inter-individual variation in first pass clearance. B. Change drug, keep the same route (e.g. po morphine to po hydromorphone). There is incomplete cross-tolerance between different opioids, but the exact amount will differ. Thus, equianalgesic tables are only approximations. Depending on age and prior side effects, most experts recommend starting a new opioid at 50% of the calculated equianalgesic dose, in the setting of well-controlled pain. Example: Change 90 mg q 12 Extended Release Morphine to oral Hydromorphone. 1) Calculate the 24 hour current dose: 90 Q12 x 2 = 180 mg PO Morphine/24 hrs. 2) Use the equianalgesic ratio: 30 mg PO Morphine = 7.5 mg PO Hydromorphone. 3) Calculate new dose using ratios: 180/30 X 7.5 = 45 mg oral Hydromorphone/24 hours. 4) Reduce dose 50% for cross-tolerance: 45 x 0.5 = 22 mg/24 hours = 4 mg q4h. C. Changing drug and route (e.g. oral morphine to IV hydromorphone). Example: Change from 90 mg q12 Extended Release Morphine to IV Hydromorphone as a continuous infusion. 1) Calculate the 24 hour current dose: 90 Q12 x 2 = 180 mg PO Morphine/24 hrs. 2) Use the equianalgesic ratio of PO to IV morphine: 30 mg po Morphine = 10 mg IV Morphine. 3) Calculate new dose using ratios: 180/30 x 10 = 60 mg IV Morphine/24 hours. 4) Use the equianalgesic ratio of IV Morphine to IV Hydromorphone: 10 mg Morphine = 1.5 mg Hydromorphone 5) Calculate new dose using ratios: 60/10 x 1.5 = 9 mg IV Hydromorphone/24 hours 6) Reduce dose 50% for cross-tolerance: 9 x 0.5 = 4.5 mg/24 hours = 0.2 mg IV continuous infusion 7) Note: one would also get the same amount of hydromorphone if you directly converted from oral morphine to IV hydromorphone using the 30 mg :1.5 mg ratio

Diarrhea in Palliative Care (#96)

Common Causes: -divided into different types and treatment will vary depending on cause: (a) secretory (b) osmotic (c) mechanical (d) disordered motility (e) In palliative care: overuse of laxatives, seen when the mgt of constipation is stepped up. (f) partial intestinal obstruction (g) pancreatic insufficiency (h) C-diff infection (i) radiation enteritis (j) chemotherapeutics are a common cause , incidence can be 60%, esp w/ 5 fluorouracil boluses. (k) Infectious diarrhea (Cryptosporidium, Giardia lamblia, E. histolytica, and Cytomegalovirus). (l) Severe constipation and fecal impaction can cause overflow diarrhea. -Evaluation: Review diet, meds, laxatives, timing of movements in relation to ingestion of food or liquids. Radiographs are necessary when suspecting partial bowel obstruction or overflow diarrhea. -Treatment: -General: * Ensure adequate hydration; encourage sips of clear liquids; parenteral hydration for severe dehydration. *Simple carbohydrates, toast or crackers, will add back small amounts of electrolytes and glucose *Milk and other lactose-containing products should be avoided -Medications: * Kaolin and Pectin (Kaopectate) -suspension of adsorbent and bulk-forming agent. Kaolin-pectin may take up to 48 hours to produce an effect and can interfere with the absorption of certain medications. *Abx: infectious diarrhea should be identified and treated appropriately, eg C. diff. *Bismuth: Has an additional antimicrobial effect, esp against enterotoxigenic E.coli. *Loperamide (Imodium): an opioid, reduces perstalsis in the gut, increases water reabsoprtion, and promotes fecal continence, making it a potnent anti-diarrheal agent. Dose is 4 -8 mg QD. Although the package insert recommends a maximum of 16 mg in a 24-hour period, up to 54 mg per day of loperamide has been used in palliative care settings with few adverse effects. Use w/ caution in infectious diarrhea. *Aspirin and Cholestyramine: can reduce diarrhea in radition-induced enteritis, as can addition og a stool bulking agent such as psyllium (metamucil). *Mesalamine: for IBD *Pancreatic enzymes: eg pancrealipase for pancreatic insufficiency. *Octreotide: is effective with profuse secretory diarrhea seen in HIV disease, chemotherapy induced diarrhea, and those with high effluent volume from a stoma. *Budesonide, probiotics, and activated charcoal: have been described in the literature for use in chemotherapy induced diarrhea, but there role in the clinical setting is not yet established.

Which of the following is true regarding the concentrated oral morphine solution (20 mg/mL) (Fast Fact #53 Sublingual Morphine): The majority of the concentrated oral solution is absorbed gastrointestinally not sublingually The bioavailability of the concentrated oral morphine solution is significantly lower than soluble morphine tablets. The equi-analgesic ratio of soluble morphine tablets to the concentrated oral morphine solution is 3:1 Non-soluble morphine immediate release tablets administered have a greater percentage of sublingual absorption when crushed than the concentrated oral morphine solution.

Correct! The bioavailability of the concentrated oral morphine solution is 23.8% which is greater than the bioavailability of SL morphine - just 9%. SL morphine and the concentrated oral morphine solution are equianalgesic. A crushed immediate release morphine tablet will not liquefy under the tongue and therefore are not believed to lead to any SL absorption. Only about 20% of the concentrated oral morphine solution is absorbed sublingually, the majority is felt to be absorbed through the gastro-intestinal tract. Hence (a) is the right answer.

The single most important feature in establishing a diagnosis of addiction (psychological dependence) to a medication is (Fast Fact #68 Pain vs Addiction): Evidence of continued substance use despite harm Pain complaints outside the norm Physical dependence Tolerance

Correct! There is much discussion and debate over definitions of physical and psychological dependence in the addiction literature. However, at its core, psychological dependence requires evidence of behavioral impact including use despite harm and loss of control. These features are distinct from drug withdrawal (physical dependence) or drug tolerance (the need to use increasing doses to achieve the same therapeutic effect).

#30 Prognostication

Doctors are poor prognosticators Physicians tend to be overly optimistic when dealing with prognosis. A study by Christakis illustrates this point (1). He asked 343 physicians to provide survival estimates for 468 terminally ill patients at the time of hospice referral. Only 20% of predictions were accurate (as defined as within 33% of actual survival). Overall, doctors overestimated by a factor of 5.3! Every type of doctor tended to overestimate, although the more experienced physicians had less error. Inaccurate predictions were given for all types of patients, including cancer patients and those with chronic non-malignant diseases. Interestingly, as the duration of the physician patient relationship increased, prognostic accuracy decreased. In other words, the longer a doctor knew his/her patient, the less likely he/she was to correctly predict prognosis. Why does it matter? Undue optimism may hurt patients in multiple ways. First of all, it may explain some of the findings of the SUPPORT trial (2). This study showed that a large number of do-not-resuscitate (DNR) orders are written in the last 2 days of life, and that physician knowledge about patient DNR preference is poor. Why review issues surrounding end-of-life (EOL) care when the prognosis is rosy? In the same vein, undue optimism may lead to late hospice referral. Hospice care, however, is most beneficial when utilized for months, not days, as commonly happens currently. Lastly, an overestimation of prognosis may cause patients to request futile care. Learning the true prognosis of a disease very late in the course is a difficult pill to swallow, and makes for an abrupt transition from curative/life-prolonging care to palliative care. Appropriate prognostic information is essential for informed advance planning decisions. This is often acutely true in the setting of the 'DNR discussion.' Murphy showed that people change EOL care decisions based on their perception of prognosis (3). He asked 371 adults age 65 or older if they wanted CPR in case of arrest during an acute illness. Before learning the true probability of survival 41% wanted CPR. After learning the true probability of CPR, only 22% wanted it. If asked about CPR wishes in the setting of a life-limiting illness, in which overall life expectancy was less than one year, only 5% wanted CPR after knowing accurate information about outcomes. What to do? Many reasons have been put forward for why we overestimate prognosis (see Christakis' book Death Foretold [4]). Probably the most important step in correcting the problem is recognizing that it exists. Ask yourself, "Would I be surprised if my patient died in the next year?" Answering "no" should trigger a re-assessment of the patient's current state and immediate future. There are many scientifically derived models of patient survival probability that can be used, and there are many well recognized clinical predictors. Metastatic cancer has the most predictable course (see Fast Fact #13); assessing where a patient is along the dying trajectory is relatively easy. Other diseases such as COPD or CHF are more difficult to predict (see Fast Facts #141, 143). Each exacerbation can lead to remission (and future exacerbation) or death, and knowing which will occur on any given admission can be extremely challenging. This uncertainty, however, can be an excellent starting place for discussion with the patient; communicating that one of the possible outcomes of an exacerbation is death allows you both to plan accordingly. Finally, you may want to consider a second opinion for patients you are particularly close to. Present the data objectively to a colleague and ask them to prognosticate using the information alone. Studies by Christakis and others suggest that impartial observers are more accurate than physicians well invested in the patient-physician relationship.

Establishing End-of-Life Goals: The Living Well Interview

Introduction "When a person faces a fatal disease that is likely incurable, he or she faces specific decisions not only about medical treatment but also about broader, existential issues concerning the best way in which to spend his or her remaining time." (Hammes 1998) Clinician-patient discussions about end-of-life treatment are often framed as a choice between "medical treatment vs. treatment withdrawal." When framed in this manner, treatment withdrawal is a negative choice that often implies giving up, abandonment, not giving the doctor a chance to do his or her job, and not caring; this option would seem to be no option at all. Bernard Hammes PhD suggests that clinicians reframe the clinician-patient dialogue about end-of-life treatment by starting a conversation with the patient focused on the question "How can we help you live well?" The goal of the living well interview is to elicit the patient's perspective regarding how they want to spend their remaining time. Treatment decisions are then discussed within this broader context of patient goals and hopes. Consequently, medical treatments become tools for achieving patient goals. The Living Well Discussion When: Begin soon after the diagnosis of a life-limiting condition. Who: Clinician (e.g. physician or advanced practice provider), members of the IDT (social worker, chaplain, nurse, psychologist, etc.) the patient, and family and/or other support persons. How: Begin by expressing a need and interest to understand the patient's views. The clinician's initial goal is to develop a broad understanding of the patient's hopes and goals, not to develop a specific medical plan. Utilize chaplains, social workers, psychologists and other members of the IDT in this discussion, as these professionals can draw upon their well-developed skills in empathy, compassion, and communication to attain a broader perspective of the patient's views, as well as foster clinician skill development in interviewing within the living-well framework. Specific treatment decisions are then made only after the patient and IDT have developed an understanding of the patient's broader goals. What to say: Given what we now know about your medical condition... How can we help you live well? What makes you happy? Maintaining or fulfilling what activities or experiences are most important for you to feel your life has quality, or for you to live well? What fears or worries do you have about your illness or medical care? If you had to choose, would you want us to focus on helping you live longer even if that made you feel worse or on feeling well even if that meant you may not live as long? What needs or services would you like to discuss? What do you hope for your family? Are there any special events or activities that you are looking forward to? What sustains you when you face serious challenges in your life? Do you have religious or spiritual beliefs that are important to you? In what way do you feel you could make this time especially meaningful to you? Most medical care is about making small sacrifices in the interest of improving your health for tomorrow. But considering your underlying illnesses, I am hoping you can guide me in helping you make today a better day for you.

Teaching the Family What to Expect When the Patient is Dying #149

Introduction Family members look to the physician and nurse to help them know what to expect when a loved one is dying. No matter the underlying causes, there is a common final pathway that most patients travel. Indicate your desire to be helpful. Say, Many families like to know what may happen so they will be prepared, is that true for you? If they say yes, describe the features on this list and answer their questions. 1. Social Withdrawal is normal for the dying patient as the person becomes less concerned about his or her surroundings. Separation begins first from the world - no more interest in newspaper or television, then from people - no more neighbors visiting, and finally from the children, grandchildren and perhaps even those persons most loved. With this withdrawal comes less of a need to communicate with others, even with close family. 2. Food: The patient will have a decreased need for food and drink as the body is preparing to die. This is one of the hardest things for some family to accept. There is a gradual decrease in interest in eating and appetite—even for their favorite foods. Interest may come and go. The patient is not starving to death—this reflects the underlying disease. Liquids are preferred to solids—follow the patient's lead and do not force feed. 3. Sleep: The patient will spend more and more time sleeping; it may be difficult for them to keep their eyes open. This is a result of a change in the body's metabolism as a result of the disease. Tell family to spend more time with the patient during those times when he/she is most alert; this might be the middle of the night. 4. Disorientation: The patient may become confused about time, place and the identity of people around him/her. He/she may see people who are not there, such as family members who have already died. Sometimes patients describe welcoming or beckoning. While the patient may not be distressed, it is frequently distressing to family or health care professionals. Gently orient the patient if he or she asks. There is no need to 'correct' the patient if he or she is not distressed. 5. Restlessness: The patient may become restless and pull at the bed linens. These symptoms are also a change in the body's metabolism. Talk calmly and assuredly with the patient so as not to startle or frighten them. If the patient is a danger to himself or others, you may prescribe sedating neuroleptics (e.g.chlorpromazine), or neuroleptics (e.g. haloperidol) in combination with benzodiazepines (e.g. lorazepam), to help the patient rest. 6. Decreased Senses: Clarity of hearing and vision may decrease. Soft lights in the room may prevent visual misinterpretations. Never assume that the patient cannot hear you, as hearing is the last of the five senses to be lost. 7. Incontinence of urine and bowel movements is often not a problem until death is very near. Invite family to participate in direct care; the nurse can help place absorbent pads under the patient for more comfort and cleanliness, or a urinary catheter may be used. The amount of urine will decrease and the urine become darker as death becomes near. 8. Physical Changes as death approaches: -The blood pressure decreases; the pulse may increase or decrease. -The body temperature can fluctuate; fever is common. -There is increased perspiration often with clamminess. -The skin color changes: flushed with fever, bluish with cold. A pale yellowish pallor (not to be confused with jaundice) often accompanies approaching death. -Breathing changes also occur. Respirations may increase, decrease or become irregular; periods of no breathing (apnea) are common. -Congestion will present as a rattling sound in the lungs and/or upper throat. This occurs because the patient is too weak to clear the throat or cough. The congestion can be affected by positioning, may be very loud, and sometimes just comes and goes. Anticholinergic medications (like scopolamine or glycopyrrolate) can help (see Fast Fact #109). Elevating the head of bed and swabbing the mouth with oral swabs give comfort and give the family something to do. -The arms and legs may become cool to the touch. The hands and feet become purplish. The knees, ankles and elbows are blotchy. These symptoms are a result of decreased circulation. -The patient will enter a coma before death and not respond to verbal or tactile stimuli. HOW TO KNOW THAT DEATH HAS OCCURRED -No breathing and heartbeat. -Loss of control of bowel or bladder. -No response to verbal commands or gentle shaking. -Eyelids slightly open; eyes fixed on a certain spot. -Jaw relaxed and mouth slightly open.

#36 Calculating Opioid Dose Conversions

Introduction A variety of published conversion tables exist to provide clinicians a rough guide for making calculations when switching between different opioid routes or preparations. Listed below are methods for common conversions using standard published conversion ratios. The examples assume a change in drug or route at a time of stable pain control using equianalgesic doses. See Fast Fact #2 about conversions involving transdermal fentanyl; #75 and #86 about methadone; and #181 about oxymorphone. Caution: Published values in equianalgesic tables should be considered a rough clinical guide when making dose conversions; substantial inter-individual variation exists. The final prescribed dose needs to take into account a patients' age, renal, pulmonary and hepatic function; their current pain level and opioid side effects such as sedation; as well as prior and current opioid use. Opioid Equianalgesic Conversion Ratios for use with the following examples: Morphine 10 mg parenteral = Morphine 30 mg oral = Hydromorphone 1.5 mg parenteral = Hydromorphone 7.5 mg oral = Hydrocodone 30 mg oral = Oxycodone 20-30 mg oral (see Reference 1). A. Change route, keeping drug the same (e.g. oral to IV morphine)

#209 Malignant Pericardial Effusions

Introduction Malignant pericardial effusions (MPEs) are a rare complication of advanced cancer, but are associated with high morbidity and mortality. This Fast Fact discusses the diagnosis and management of MPEs. Epidemiology and Prognosis Approximately 10% of patients with cancer develop cardiac metastases, with ~75% of these affecting the epicardium (1, 2). Only a third of these, however, will develop clinically significant MPEs (1). Lung and breast cancers are the most common causes. MPEs are associated with a poor prognosis. Studies suggest a median survival of 2-3 months after a MPE is diagnosed, with a mean survival of 5 months for solid tumors and 20 months for hematologic malignancies (3, 4). Physiology and Symptoms The pericardial space is normally filled with <50 ml of serous fluid. As this volume increases due to epicardial or pericardial metastases or lymphatic obstruction, both right and left ventricular failure can occur due to inadequate filling. Signs and symptoms include peripheral and pulmonary edema, chest discomfort, cough, shortness of breath, and orthopnea. Severity of symptoms depends on the volume of the MPE as well as the rapidity of its accumulation; severe cases can present with cardiac tamponade and shock. An echocardiogram is indicated whenever a MPE is suspected. Not only does it confirm the presence of an effusion, but its findings can dictate whether or not urgent treatment is indicated (e.g. if signs of tamponade are evident). A diagnostic pericardiocentesis or pericardial biopsy is sometimes needed to confirm the cause of the effusion. Treatment Options Systemic chemotherapy or radiotherapy are effective for chemo- or radio-sensitive tumors such as previously untreated breast cancer and many lymphomas. Reaccumulation rates for both modalities are about 1/3 overall, depending on the patient's overall course and response to therapy (5). Pericardiocentesis results in immediate symptom relief in most patients, however the effusion may re-accumulate, requiring repeat pericardiocentesis (within 1-2 weeks in some series) (6). Pericardial sclerosis involves instilling a sclerosing agent with the intention of scarring the pericardium to the epicardium, preventing reaccumulation of the MPE (similar to pleural effusions - see Fast Fact #157). Multiple agents have been studied including doxyclycline, minocycline, and bleomycin. Success rates (no reaccumulation at 30 days) are about 70-90% (7, 8). Longer term success rates are undefined due to the poor survival of study patients. The major side effect is chest pain (50-70%), cardiac arrhythmias, and fever (8, 9, 10). In head to head comparisons with doxycycline, bleomycin has been shown to have fewer side effects and to lead to shorter hospitalizations (10, 11, 12). Surgical decompression therapies range from less invasive (balloon pericardiotomy, subxiphoid or thorascopic pericardiostomy) to more extensive (open thoracotomy with pericardial stripping). A pericardial 'window' (which allows ongoing drainage of fluid externally or internally such as into the pleural cavity) is often created. Case series have suggested reaccumulation rates with surgical therapies are low (less than 15% up to 10 months out) (13, 14, 15). Decision-Making The treatment of MPEs depends on how urgently treatment is needed, the likelihood of the tumor responding to anti-neoplastic treatments, and the anticipated survival of the patient. A multidisciplinary approach to decision-making, involving input from medical and radiation oncology, cardiology, and thoracic surgery is recommended. Simple pericardiocentesis may be appropriate for patients with short prognoses (<1 month), particularly if their MPE is not expected to re-accumulate in their remaining life-span. A symptomatic patient with no signs of tamponade and a chemotherapy-sensitive tumor such as untreated breast cancer may receive a durable response from a pericardiocentesis for symptom relief, followed by chemotherapy. Patients with longer prognoses (>1 month) who are expected to re-accumulate their MPEs will likely benefit most from sclerosis or surgical decompression; there is no clear evidence currently suggesting one strategy is superior to the other. Symptom directed care without specific intervention for the MPE is an appropriate option for patients with very short prognoses and for those who decline more invasive treatments.

#75 Methadone for the Treatment of Pain

Introduction Methadone, a potent opioid agonist, has many characteristics that make it useful for the treatment of pain when continuous opioid analgesia is indicated. Although available for decades, its use has gained renewed interest due to its low cost, inactive metabolites, and many routes of administration. This Fast Fact will introduce methadone's pharmacology and clinical use as an analgesic. Pharmacology Unlike morphine, methadone is a racemic mix; one stereoisomer acts as a NMDA receptor antagonist, the other is a mu-opioid receptor agonist. The NMDA mechanism plays an important role in the prevention of opioid tolerance, potentiation of opioid effects. and is the theoretical basis for its use in neuropathic pain syndromes, although this latter impression is largely anecdotal. Methadone is highly lipophilic with rapid GI absorption and onset of action. It has a large initial volume of distribution with slow tissue release. Oral bioavailability is high, ~ 80%. Unlike morphine there are no active metabolites and biotransformation to an active drug is not required. The major route of metabolism is hepatic with significant fecal excretion; renal excretion can be enhanced by urine acidification (pH <6.0). Unlike morphine, no dose adjustment is needed in patients with renal failure since there are no active metabolites. Prescribing Methadone is available in tablet, liquid and injectable forms; oral preparations can be used rectally. Parenteral routes include IV bolus dosing or continuous infusion. Any clinician with a Schedule II DEA license can prescribe methadone for pain; a special license is only required to prescribe methadone for the treatment of addiction. In some jurisdictions, it is necessary to apply the words "for pain" on the prescription. Cautions Unlike morphine, hydromorphone, or oxycodone, methadone has an extended terminal half-life of up to 190 hours. This half-life does not match the observed duration of analgesia (6-12 hours) after steady state is reached. This long half-life can lead to increased risk for sedation and respiratory depression, especially in the elderly or with rapid dose adjustments. Rapid titration guidelines for other opioids do not apply to methadone. Given recent reports that high-dose methadone may be associated with development of QT interval prolongation and Torsades de Pointes, EKG monitoring may be appropriate when changes in dosage are made (depending upon life expectancy and goals of care). Pediatrics With close monitoring by an experienced prescriber, methadone has been used safely in children, although the safety, effectiveness, and the pharmacokinetics of methadone in patients below the age of 18 years have not been established by the Food and Drug Administration. Potency An important property of methadone is that its apparent potency, compared to other opioids, varies with the patient's current exposure to other opioids. See below for a suggested dosing guide for opioid tolerant patients (Reference 1). Key Points Compared to morphine, methadone is inexpensive, safe in renal failure, will provide a longer duration of action, and has a theoretic advantage in neuropathic pain, although the latter point has not been reliably demonstrated. Because of its long and variable elimination half-life methadone is not an ideal opioid when rapid dose adjustments are needed; do not increase oral methadone more frequently than every 4 days. Dose conversion to:from other opioids and methadone is complex and particularly more dangerous than other opioids; consultation with pain or palliative specialists familiar with methadone use is recommended. Patient and family education is essential as they may misinterpret prescription of methadone to mean that their physician believes that they are an addict.

The Anorexia-Cachexia Syndrome: Definitions, Evaluation, and Non-Pharmacologic Management #386

Introduction: Anorexia-cachexia encompasses a broad, multi-organ syndrome seen in several chronic diseases (1). The purpose of this Fast Fact is to review the anorexia-cachexia syndrome (ACS), its clinical evaluation, and its non-pharmacologic management. See other Fast Facts for related information: #10 (the role of enteral nutrition in serious illness), #100 (megestrol acetate); #190 (the role of parenteral nutrition for advanced cancer), #279 (cannabinoids), #314 (mirtazapine), and #315 (olanzapine). Definitions Sarcopenia: diffuse muscle loss often associated with an increase in fat mass and abdominal circumference. Anorexia: appetite reduction which can be psychogenic (anorexia nervosa) or secondary to an underlying advanced illness. Cachexia: >5% weight loss over 6 months in absence of starvation or BMI <20 and weight loss >2%; or appendicular skeletal muscle index consistent with sarcopenia and weight loss >2%. Pre-cachexia: < 5% weight loss and presence of anorexia. Refractory cachexia: usually described in the published literature in the context of a progressive, incurable non-cancer illness at an advanced stage or an untreatable cancer. Pathophysiology and associated disease processes: -Typically, ACS involves more than just a loss of appetite and is also associated with nausea, glucose intolerance, meat aversion, early satiety, and/or an unpleasant change in taste and smell. -Increases in cytokine release and other inflammatory mediators (e.g. IL-1, IL-6, IL-10, and TNF-alpha) brought upon by an underlying illness are thought to be the primary culprit across many chronic illnesses including cancer, chronic kidney disease, COPD, AIDS, rheumatoid arthritis, cirrhosis, and congestive heart failure. -These inflammatory mediators along with hormonal mediators like testosterone, insulin-like growth factor, and myostatin cause the ACS via: a) intracellular oxidative stress leading to catabolism and the breakdown of proteins (proteolysis); b) resistance of the hypothalamus to respond to orexigenic (appetite-stimulating) neurologic signals; and c) increases in total and resting energy expenditure -The Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire and the North Central Cancer Treatment Group (NCCTG) Anorexia/Cachexia questionnaire are validated tools to assess ACS. Clinical evaluation: ACS is a clinical diagnosis encountered in a patient with the appropriate degree of weight loss and in the context of an advanced illness. Typically, no additional testing is necessary to confirm the diagnosis, however, clinicians should be aware of potentially reversible ACS etiologies or cofactors and consider targeted testing and/or interventions as appropriate. -Uncontrolled disease-related symptoms: e.g. stomatitis, refractory dyspnea, odynophagia, pain. -Swallowing deficits: e.g. a localized tumor from head and neck. -GI symptoms: both diarrhea from chemotherapy-induced bowel ischemia and opioid-related constipation are common culprits. -Endocrine or metabolic disorders: e.g. hyperthyroidism, diabetes mellitus, uremia, hypercalcemia. -Infections: e.g. HIV, occult abscess, parasitic infections, osteomyelitis. -Dental issues: e.g. dental caries, thrush, poorly fitting dentures. - Social issues: food insecurity, poor nutritional literacy, and social isolation, especially in patients with functional impairments who require feeding assistance. Involve social workers as appropriate. -Mental health disorders: e.g. depression, bulimia, anorexia nervosa, untreated anxiety. - Medications: numerous drug classes (e.g. chemotherapeutics, antibiotics, anticonvulsants, cardiovascular medications, antidepressants) have been associated with altered taste, early satiety, dry mouth, dysphagia, and nausea. Involving a clinical pharmacist can help identify potential culprits.

#223 The Family Meeting Part 2 - Starting the Conversation: this Fast Fact reviews the early steps of the actual meeting.

Introductions & setting goals for the meeting The meeting leader begins the meeting by introducing him or herself, and suggesting that each person present (medical team and family/community) introduce themselves including their relationship to the patient. The meeting leader should summarize the meeting goals (e.g. We are here to discuss next steps in the care of Mr. Jones) and ask the family to confirm these goals and/or add other agenda items. Note: if you do not know the patient or family well, take a moment to build relationship. Ask a non-medical question such as I am just getting to know you. I had a chance to look at your chart and learn about your medical condition but it does not say much about your life before you got sick. Can you tell us about the things you liked to do before you got sick? Similarly, if the patient is not able to participate in the meeting, ask family to describe the patient prior to his becoming ill: As we get started, can you describe what Mr. Jones was like before he became ill? 2. Determine what the patient/family already knows This step is essential as it guides you in providing a synthesis of the medical information (see below). Always invite the patient and all family members to provide their understanding of the medical information. Examples of opening lines: Tell me what the doctors have told you about your condition? Can you describe for me your sense of how things are going? For patients who have been declining from a chronic illness, you can ask: Tell me about the past 3-6 months: what types of changes have you noted? The patient or family will typically describe changes in terms of function (physical or cognitive) and quality of life. 3. The Medical Review Once you know what the patient/family understands, you are in a good position to confirm their understanding, or provide new information/correct misunderstandings. First, ask if you can bring them up-to-date about what is going on; asking shows politeness and also signals that they should attend to what you are trying to say. The clinician most closely aligned with the patient's ongoing treatment should begin this discussion, supplemented with information from consulting services if relevant. Do not provide information using medical jargon or in an organ system approach (e.g. The creatinine is improving, but there is a new pleural effusion and the heart rate has become irregular). A more patient-centered approach is to provide a succinct summary of the current condition, without any medical jargon, focusing on the issues of most importance, which are usually function/quality/time. Give a 'bottom-line' statement: 'getting worse,' 'not going to improve,' 'dying and time is likely very short.' The worsening weakness and pain you describe is from the cancer which is growing despite the chemotherapy. You are telling me that despite the recent hospitalization, you are not able to do as much around the house; unfortunately your lung disease is getting worse despite all our best treatments. Despite our best efforts, your wife's brain injury from the car crash is getting worse. She can no longer stay awake or move her arms/legs. Using the 'D word' if relevant: when a patient is clearly deteriorating and death is likely within the next days to weeks, or even a few months, it is appropriate to use the word dying in the conversation. Both patients and surrogates find that saying the word dying, if done compassionately, is helpful in clearing what is often a confusing and frightening situation. I'm afraid we have run out of options to shrink the cancer. Based on your declining function, I believe you are dying. 4. Silence Whether or not you use the word dying, when you have presented bad news (such as information about disease progression), the next step is for you to allow silence, and let the family/patient respond. In truth, no matter what you might imagine the response from the patient/family to be once the bad news is delivered, you really cannot predict their emotional reaction (e.g. relief, anxiety, anger, regret, fear). This silence can be uncomfortable; resist the urge to fill it with more facts as they will not be heard. Not all patients/families express emotions at this point and instead respond practically (Well, what happens next then?). This is fine, but you need to wait, silently, to see what response the patient/family demonstrates. In addition, even practical questions have underlying emotions (Are you sure? Or - There must be something you can do?). It is important to respond to both the factual aspect of the question (Yes I am sure. Or - There are no more effective treatments available.), as well as the emotional level (I wish I had better news for you. Or - I wish our treatments worked better than they do.). When the patient/surrogates openly acknowledge that current treatments are no longer effective, that death is coming, they will generally ask one or all of the following questions: How long? What will happen? Will there be suffering? What do we do now? Your response at this point should be to address prognosis in terms of time, function, and symptoms, as best you can (see Fast Facts #13,141,143,149,150). This will answer the first two questions; the last questions will require more discussion of patient-centered goals (see Fast Fact #227).

Counseling Patients on Side Effects and Driving When Starting Opioids #248

Key Symptoms Patients should be reassured that most opioid side effects are short-lived or otherwise manageable, and they should seek help immediately for intolerable side effects. Constipation Background for clinicians: Very common, reported by 23-84% of patients in various studies. It does not diminish over time, even on a steady dose. Opioids delay gastric emptying, decrease peristalsis, decrease secretions, and slow small bowel transit time. Key counseling points: Most patients need an ongoing bowel regimen involving stimulant laxatives (stool softeners such as docusate or bulking agents like fiber are ineffective), which should be used as maintenance therapy to prevent constipation, not just rescue therapy to treat it after it has developed (1). Patients should aim for an unstrained bowel movement at least every other day. "If you have not had a bowel movement in 4 days, call me for advice." Nausea: Background for clinicians: Nausea occurs in ~25% of patients given opioids (2). There are many effective strategies to prevent and ameliorate opioid-induced nausea - see Fast Fact #25 for more details. Key counseling points: Nausea is usually transient and resolves in several days on a stable dose (3).Patients should use their prescribed anti-emetic if nausea develops, but should contact you immediately if ineffective and/or vomiting occurs so you can prescribe alternative agents. Sedation (See also the section on driving below.) Background for clinicians: Sedation occurs in 20-60% of patients (2), usually during opioid initiation or around the time of dose increases. Mild-to-moderate sedation usually resolves in a few days; if persistent, it may improve with drug therapy (4). Moderate-to-severe sedation responds to dose reduction, but may also necessitate opioid rotation. Key counseling points: Reassure patients that mild-to-moderate sedation usually resolves in a few days.Encourage patients to accept mild sedation (e.g. noticeable drowsiness, falling asleep unintentionally during relaxing activities such as watching TV or reading) for a few days as long as they are in a safe environment. Moderate (falling asleep during stimulating activities such as eating or having a conversation) or severe sedation should prompt a call to you immediately to discuss next steps. Less Common Symptoms Pruritus is rare and does not require extensive pre-emptive counseling. "If you feel itchy it might go away after a few days. If it's really bothering you or not going away, call me and we can make some changes." See Fast Fact #37. Urinary retention is rare but potentially an emergency. Counsel patients to seek medical care immediately if they lose the ability to urinate. See Fast Fact #287 for further information. Driving Safety There are no large, randomized studies directly examining the risk of driving while on opioids (6). Opioids can slow reaction time, cause drowsiness, or cloud judgment when they are first started or increased (7). Most experts agree that driving or operating heavy machinery is unsafe and should be avoided until a stable dose has been reached (8). Counseling bottom line: patients who have been on a stable dose for a week, who feel no cognitive changes (drowsiness, 'fuzziness,' difficulties in concentrating) can drive.

The Model for End-stage Liver Disease (MELD) score

Other important prognostic variables The hepatorenal syndrome (HRS) - renal failure from renal arterial under-filling due to decompensated liver failure - portends a particularly poor prognosis. Most patients with type-1 HRS (rapid and severe renal failure) die within 8-10 weeks even with therapy. Median survival with type-2 HRS (chronic, less severe renal failure with serum creatinine usually 1.5-2 mg/dL) is around 6 months. Both older age and hepatocellular carcinoma also adversely affect survival. While the CTP and MELD systems provide objective guidance to prognostication in liver failure, clinical judgment, patient comorbidities, the rate of decompensation, and the likelihood of transplantation all should additionally affect the assessment and communication of a patient's prognosis in liver disease.

#06 Delivering Bad News - Part 1

Preparing to Deliver Bad News 1.Create an appropriate physical setting: a quiet, comfortable room, turn off beeper, check personal appearance, have participants - including yourself - sitting down. 2.Determine who should be present. Ask the patient who they want to participate and clarify their relationships to the patient. Decide if you want others present (e.g. nurse, consultant, chaplain, social worker) and obtain patient/family permission. 3.Make sure you know basic information about the patient's disease: prognosis, treatment options, next steps. 4.Special circumstances: If the patient lacks decision-making capacity (e.g. developmentally delayed, demented, delirious, etc.), make sure the legal decision-maker is present. See Fast Fact # 226 Helping Surrogates Make Decisions. 5.Special circumstances: If the patient or family does not speak English, obtain a skilled medical interpreter. Use phone translation services if necessary. See Fast Fact #154 6.Special circumstances: If the patient or family is of anther cultural background, see Fast Fact # 216 Asking About Cultural Beliefs in Palliative Care. Precepting self-reflection Residents will invariably have strong emotions when they have to give bad news. This emotional response can be heightened by various factors—a young patient, an unexpected diagnosis, a patient with whom the physician has a long-standing relationship, etc. Preceptors need to support the resident. Key teaching points: Residents may not spontaneously discuss their own emotional reaction with a preceptor, therefore preceptors need to introduce this topic. "This is a really hard case, how are you doing?" Physicians often have strong emotional reactions when a patient encounters bad news. Normalize the experience for the resident. "It's normal to have strong feelings". Three methods for coping with these feelings are: Identify your feelings (anger, sadness, fear, guilt); Talk with a colleague; Keep a personal journal. 4. Role play the discussion with the resident before you go into the room; ask them to reflect on how it "feels"...what is hard...what is easy. Encourage continued self-reflection1

#02 Converting to Transdermal Fentanyl

Quick—what dose of the transdermal fentanyl patch (Duragesicâ) is equianalgesic to a 3 mg/hr morphine continuous infusion? Conversions to and from fentanyl transdermal are notoriously tricky, requiring knowledge of the published conversion data, general opioid pharmacology, and a generous dose of common sense. See also Fast Fact #36 on opioid dose conversions. Step 1:. Calculate the 24 hr morphine dose: 3 mg/hr x 24 hrs = 72 mg IV morphine/24 hrs. Step 2: Convert the IV dose to the equianalgesic oral morphine dose using a ratio of:1 mg IV = 3 mg oral. Thus, 72 mg IV = 216 mg po/24 hours. Step 3: Convert the oral morphine dose to transdermal fentanyl. There are two methods: Method 1 - Standard Table. Look up the FDA prescribing information for transdermal fentanyl (Reference 1, pp 29-30). It says that 135-224 mg of morphine per 24 hours = 50 mcg/hr patch. Note: this range of morphine is very broad which may result in significant under-dosing. Method 2 - Alternate Formula. In 2000, Brietbart, et al published an alternative method, based on the results of a multi-center trial by Donner, et al, that relied on a fixed dose conversion ratio to calculate the fentanyl transdermal dose. Brietbart recommended the ratio of:2 mg oral morphine/24 hr = 1 mcg/hr of transdermal fentanyl—rounded to the nearest patch size. In the case example above, 216 mg of oral morphine per day is approximately equianalgesic to the 100 mcg/hr fentanyl patch. Note: using this formula, 25 mcg/hr of transdermal fentanyl is roughly equivalent to 50 mg oral morphine/24 hours. This dose may be excessive when used in the opioid naïve or the elderly. Key Considerations 1. All equianalgesic ratios/formulas are approximations; clinical judgment is needed when making dose or drug conversions. 2. The FDA Prescribing Information indicates that their table should only be used when converting from another opioid to transdermal fentanyl. 3. The risk of sedation/respiratory depression with transdermal fentanyl is probably increased in the elderly or patients with liver and renal impairment due to its long half-life, thus, choose the lower end of the dosing spectrum. 4. When in doubt, go low and slow, using prn breakthrough doses generously while finding the optimal dosage of a long-acting drug. 5. The 'Alternate Formula' by Brietbart, et al is best used by experienced practitioners as it tends to give higher fentanyl patch doses than the FDA PI. Other teaching points about Duragesic: Start at the lowest dose, 12 mcg/hr, in an opioid naïve patient; there is no maximum dose. Therapeutic blood levels are not reached for 13-24 hours after patch application and drug will be continue to be released into the blood for at least 24 hours after patch removal. Opioid withdrawal symptoms can occur during dose conversions—care must be taken to avoid this by use of breakthrough opioids. Some patients will need to have their patches changed every 48 hours. The recommended upward dose titration interval is no more frequently than every 72 hours. Place patches on non-irradiated, hairless skin. Direct heat applied over the patch can increase drug absorption with increased toxic effects. There are no data that cachectic patients have reduced efficacy due to loss of subcutaneous fat; albeit cachectic patients may require higher dosing (6).

#390 Role of the Hospice and Palliative Care Social Worker Background Social workers provide unique knowledge and psychosocial skills for seriously ill patients and their family (1). Clinicians often collaborate with social workers when caring for seriously ill patients. In fact, the Medicare Hospice Benefit and the National Consensus Project for Quality Palliative Care state that social workers are a core member of a hospice or palliative care (PC) interdisciplinary team (IDT) (2). This Fast Fact will discuss the role of the hospice and palliative social worker.

Scope of Practice Major social work roles for the seriously ill include providing evidence-based interventions that empower the patient in the context of their health care and family situation and facilitating a dignified death as defined by the patient. - According to the NCP Guidelines, "social workers attend to family dynamics, assess and support coping mechanisms and social determinants of health, identify and facilitate access to resources, and mediate conflicts." Like other members of the PC IDT, social workers develop expertise relative to the patient situation. PC social workers are often engaged with adjustment to illness, decision making, and family coping along the illness trajectory. Hospice social workers are focused more specifically on end of life, though the job descriptions and tasks carried out are much the same as those in PC social work. Typically, there are two main models for utilizing social workers to address palliative care needs: 1) utilizing the unit or clinic generalist social worker or 2) utilizing the IDT social worker with specialized training and experience. A specialized palliative social worker is preferred and offers greater expertise relative to the serious illness context of the IDT, patient and family.

Opioid-induced constipation

Stimulant Laxatives: Senna and bisacodyl are the main stimulant laxatives available in the US and work by increasing enteric muscle contraction and GI motility. The onset of action for oral senna and bisacodyl is around 6-12 hours. Starting dose for senna is two 8.6 mg tabs; bisacodyl is one 10mg tab. However, higher doses are usually needed for OIC. Senna can be safely dosed up to 12 tabs daily and bisacodyl up to 30 mg (9). Both medications are relatively inexpensive. Because stimulant laxatives cause intestinal contractions their use can be limited by abdominal cramps and pain. Osmotic Laxatives: These include non-absorbable sugar molecules such as polyethelyne glycol (PEG), lactulose, and sorbitol, as well as poorly absorbed salt-based molecules like milk of magnesia and magnesium citrate. Osmotic laxatives have limited intestinal absorption leading to an increase in colonic intraluminal water through oncotic pressure. With increased intraluminal volume and distension, reflex peristalsis subsequently occurs. Additionally, the increase in intraluminal water also leads to softer stool and allows for easier intestinal transit. The starting daily dose for PEG is 17 g, for lactulose is 15 ml, and 30 ml for 70% sorbitol solution. Osmotic laxatives will have a linear effect on bowel function with dose increases; the maximum effective daily dose of PEG is 68 g (10), lactulose is 60 ml, and for sorbitol is 150 ml. The onset of action for osmotic laxatives tends to be variable ranging from 12 to 48 hours, but when used regularly patients will have a more consistent effect. Osmotic laxatives generally do not lead to a loss of fluids or electrolytes as they only bind to orally taken fluid. With this, PEG requires 125 ml of fluid per 17 g dose (11) and similarly ~200 ml is recommended with every 30 ml of lactulose (12). Major side effects from osmotic laxatives include abdominal cramping, pain, and flatulence. Lactulose and sorbitol tend to have more of these side effects than PEG (11). Rectal Based Laxatives: Unfortunately, there is a lack of clinical research to support rectal based laxatives, but anecdotally they are often used for refractory constipation. Stimulant suppositories such as bisacodyl and rectal vault lubricants such as glycerin are inexpensive. Their onset is usually within 10-15 minutes and can be dosed daily (9). Warm tap water and milk of molasses enemas (12) can be dosed more frequently (up to every two hours). They work by causing rectal distension and reflex defecation. Other enema formulations, such as phosphate or saline enemas, should be used with caution in renal insufficiency due to concern for electrolyte shifts. Manual Evacuation: Digital stimulation and manual disimpaction may be necessary if fecal impaction is suspected. Due to the discomfort associated with manual evacuations, these are often interventions of last resort and may require pre-medication with pain medications and/or anxiolytics. Ineffective Therapies: Docusate sodium not demonstrated efficacy in randomized controlled studies for OIC compared with placebo (14). Bulk forming laxatives (psyllium or fiber) require at least 1.5 L of water to be effective and can actually lead to worsened constipation with inadequate fluid intake. Practical Advice: A scheduled stimulant laxative regimen such as Senna 2 tabs twice daily should be prescribed at the onset of regular opioid use regardless of opioid dosing. The goal for the bowel regimen should be an unforced bowel movement at least every other day. If a patient has not had a bowel movement in 48 hours, increasing stimulant laxative dose and/or adding an osmotic laxative is appropriate. Failure of oral laxative therapy usually requires rectal based interventions and/or one of the newer treatment modalities (see Fast Fact #295). Opioid Antagonists Since the majority of symptoms associated with OIC are secondary to stimulation of µ-opioid receptors in the gut, opioid antagonists offer an attractive pharmacologic rationale for OIC (1). Naloxone: Until recently, naloxone was the only available opioid antagonist for OIC treatment. n a small, non-controlled study, 80% of chronic opioid users had bowel evacuation in 1-4 hours after naloxone administration. Unfortunately, over two-thirds reported a 10-15% loss of analgesia and nearly one-third had withdrawal symptoms (3). Therefore, if used, it is recommended to start at a low dose of 0.8 mg twice daily. Methylnaltrexone bromide: Methylnaltrexone is a peripherally-acting µ-opioid receptor antagonist. It is less able to cross the blood brain barrier, reducing the risk of altering analgesia or inducing central opioid withdrawal. The most common side effects are nausea, diarrhea, and cramping - which can be severely painful. Other Agents Lubiprostone: Lubiprostone is a selective chloride channel-2 activator that acts locally on the small intestine to increase fluid secretion and GI motility. It is FDA approved for OIC. Linaclotide has a different mechanism than lubiprostone, but is also a small intestinal secretogogue. It currently is approved for irritable bowel syndrome. Of the pharmacologic interventions described above, methylnatrexone has been the best studied and shown to be the most efficacious. It is reasonable to give methylnaltrexone after failure of oral laxatives (see Fast Facts #294) in OIC, and potentially can be used prior to using more invasive rectal based interventions.