Fast Facts II

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

"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. subcutaneous glycopyrrolate

As defined by Dame Cicely Saunders, which of the following is one of the 4 essential domains of "total pain" (Fast Fact #417 Total Pain)? Neuropathy Nociception Social Financial Correct! Dame Saunders and other hospice and palliative care experts recognized that serious illness can fundamentally disrupt previously established expectations for a patient's future. Four essential domains or components of "total pain" have been described: psychological pain; social pain; spiritual pain; physical pain. The interaction of these four domains is often complex and dynamic. Clinicians ofter overlook non-physical sources of pain and consequently treatable suffering can get missed or overmedicated.

#417 Total Pain Introduction: Pain is a common, multi-dimensional symptom which compromises quality of life for many patients with serious illness (1,2). Understanding the concept of total pain and its dimensions should be a prerequisite for clinicians who care for patients facing a life-limiting illness (2). This Fast Fact discusses the concept of total pain along with, evaluation and management strategies. The concept of total pain: Nociception refers to neural encoding of impending or actual tissue damage (3). Pain refers to the subjective experience of actual or impending harm and is influenced by past experiences and expectations (3,4). A serious illness can fundamentally disrupt previously established expectations for the future. Dame Cicely Saunders, the founder of the modern hospice movement, recognized this and applied the term total pain as having physical, psychological, social, and spiritual components interacting upon one another (5-7). See the figure below used with the author's permission (2). While clinicians often focus on the physical pain component, the effect of a life-limiting illness on the spiritual, social, and psychological components often gets overlooked. Consequently, treatable suffering may get missed or overmedicated. The total pain experience - an interactive model: The interaction among total pain components is often complex, yet evident in patients with serious illnesses (2,8-15). For example, loss of hope can have a spiritual, existential, and psychological dimension which may compound the intensity of physical pain if the patient attributes pain with impending death. As suffering intensifies, the family's sense of helplessness may compel them to visit the patient less frequently. Thus, physical pain may exacerbate social and psychological pain from a perceived sense of abandonment (8,12). Clinicians cannot fully care for patients with life-limiting illnesses without assessing for all domains of total pain. Since no one person or discipline can manage total pain, interdisciplinary teams (IDTs) are vital to address total pain. Evaluation and management strategies of total pain: Listening to the patient's illness narrative with unhurried presence is key to developing a therapeutic presence that fosters assessment of all four domains (16). Elizabeth Kubler-Ross taught that dying people commonly yearn for love, touch, and communication (16). She stressed the importance of not just pharmacotherapies and interventional-based analgesics, but sitting, listening, and holding hands to enable care for all components of total pain (16). See the table below for an example of each component can be assessed and addressed.

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

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 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

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

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. Inability to titrate the opioid dose to meet the patient's pain needs because of associated sedation

#28 Subcutaneous Opioid Infusions

Background A parenteral opioid infusion is the standard of care for managing moderate-severe pain or dyspnea when the oral/rectal route is unavailable and/or frequent dose adjustments are needed. As death nears, the burden of maintaining intravenous (IV) access, especially in the home setting, can be enormous. An alternative delivery route supported by major pain societies such as European Association of Palliative Care is the subcutaneous (SQ) route for continuous infusions, Patient Controlled Analgesia (PCA), or intermittent bolus opioid injections. Drugs Morphine, hydromorphone (Dilaudid), fentanyl, and sufentanil can all be safely administered as SQ bolus doses or continuous SQ infusion. Methadone infusions cause frequent skin irritation; one case series reported successful use of methadone with concurrent dexamethasone infusion and frequent site rotation. Dosing equivalents Dose conversion ratios between the IV and SQ route for all the above listed opioids are not well established. For morphine, the ratio appears to be close to 1 mg IV = 1mg SQ. Pharmacokinetics SQ infusions can produce the same blood levels as chronic IV infusions. There is no data to suggest that cachectic, febrile or hypotensive patients have problems with drug absorption. Volume and Drug Choice The limiting feature of a SQ infusion is the infusion rate; in general, SQ tissue can absorb up to 3 ml/hr. At low opioid requirements morphine is generally the drug of choice based on availability and cost; a switch to hydromorphone is indicated for a high opioid requirement due its higher intrinsic potency (approximately 4-6 times as potent as morphine), thus the need for a smaller infusion volume. Administration Use a 25 or 27 gauge butterfly needle—place on the upper arm, shoulder, abdomen or thigh. Avoid the chest wall to prevent iatrogenic pneumothorax during needle insertion. The needle can be left indefinitely without site change unless a local reaction develops—typically, patients can keep the same needle in place for up to one week at a time. Toxicity Local skin irritation, itching, site bleeding or infection can occur. Of these, skin irritation is the most common, managed by a needle site change.

#68 Is it Pain or Addiction?

Background A very commonly requested educational pain topic by clinicians, surrounds differentiating the patient in pain from the patient with a substance abuse disorder. The key to proper assessment lies in understanding 1) the definitions of tolerance, physical and psychological dependence, 2) the components of an addiction assessment, and 3) the differential diagnosis of the symptom of "pain." Definitions Tolerance: the need to increase a drug to achieve the same effect. In clinical practice, significant opioid tolerance is uncommon. Tolerance may be present in the pain patient or the addict; by itself it is not diagnostic of addiction. Physical Dependence: development of a withdrawal syndrome when a drug is suddenly discontinued or an antagonist is administered. Most patients on chronic opioids will develop physical dependence; its presence cannot be used to differentiate the pain patient from the addict. Psychological Dependence (Addiction): overwhelming involvement with the acquisition and use of a drug, characterized by: loss of control, compulsive drug use, and use despite harm. Research suggests that opioids used to treat pain rarely leads to psychological dependence. Addiction (Substance Abuse) Assessment Assess for addiction in the domains presented in the list below (see Reference 1). Note: one positive item from the list does not establish a substance abuse disorder. Rather, the diagnosis rests on a pattern of behavior that includes several positive findings (see Reference 4). - Loss of control of drug use (has no partially filled med bottles; will not bring in bottles for verification). - Adverse life consequences - use despite harm (legal, work, social, family). - Indications of drug seeking behavior (reports lost/stolen meds, requests for high-street value meds). - Drug taking reliability (frequently takes extra doses, does not use meds as prescribed). - Abuse of other drugs (current/past abuse of prescription or street drugs). - Contact with drug culture (family or friends with substance abuse disorders). - Cooperation with treatment plan (does not follow-up with referrals or use of non-drug treatments). Differential Diagnosis The differential diagnosis for a patient reporting "pain" includes physical causes (broken leg, sciatica, pseudoaddiction - see Fast Fact #69); psychological causes (depression, anxiety, hypochondriasis, somatization disorder, etc.); spiritual causes (impending death, grief); substance abuse; and secondary gain/malingering/criminal intent (desire for attention, disability benefit, or financial gain from pain medications).

#133 Non-Oral Hydration in Palliative Care, prt II

Background At the center of the debate with regard to hydration in terminally ill patients is the desire to maintain comfort and avoid unnecessary/distressing procedures. There is no controversy that terminally ill patients should be encouraged to maintain adequate oral hydration for as long as possible. However there is debate and controversy around the use of parenteral hydration. This Fast Fact discusses medical decision-making about non-oral hydration in palliative care settings; Fast Fact #134 discusses techniques of hydration. Arguments Against Hydration Comatose patients do not experience symptom distress. Parenteral fluids may prolong dying. With less urine there is less need to void and use catheters. With less gastrointestinal fluid there can be less nausea and vomiting. With less respiratory tract secretions there can be less cough and pulmonary edema. Dehydration can help reduce distressing edema or ascites. Dehydration may be a "natural" anesthetic to ease the dying process. Parenteral hydration can be uncomfortable (e.g. needles/catheters) and limit patient mobility. Arguments For Hydration - Dehydration can lead to pre-renal azotemia, which in turn can lead to accumulation of drug metabolites (notably opioids), leading to delirium, myoclonus and seizures. Hydration can reverse these symptoms in some patients leading to improved comfort. - There is no evidence that fluids prolong the dying process. - Providing hydration can maintain the appearance of "doing something," even though there may be no medical value, and thus ease family anxiety around the time of death. Ethical/Legal Issues In the United States, the following ethical/legal standards exist: · Competent patients or their surrogates can accept or refuse hydration based on relevant information. - Non-oral hydration is considered a medical intervention, not ordinary care. As such, there is no legal or ethical imperative to provide it unless the benefits outweigh the burdens. Recommendation There is published medical literature to support both the use of, and the withholding of, non-oral hydration in patients near death; thus, there is no consensus on the single best approach to care. A Cochrane review of 6 relevant studies showed that sedation and myoclonus were improved with hydration in adult palliative care patients; however, discomfort from fluid retention was significantly higher in the hydration group and survival seemed to be the same between the groups. Key issues to be considered when determining the role of non-oral hydration include the following: - Expressed wishes of the patient or surrogate decision-maker regarding use of hydration. - Patient-defined goals; the presence of a specific goal may direct the clinician to use hydration as a means to improve delirium and potentially delay death. - Symptom burden: symptoms related to total body water excess may improve by withholding hydration, while delirium may lessen with hydration. - Burden to the patient and caregivers of maintaining the non-oral route of hydration. - Family distress concerning withholding hydration/nutrition. - When in doubt, a time limited hydration trial is an appropriate recommendation. Clinician Self-Reflection Finally, it is important to recognize that health care providers often have biases for or against non-oral hydration near the end-of- life. Self-reflection upon these biases is crucial to help patients and families make decisions that are based on the best interests and goals of the patient/family unit.

#252 Borderline Personality Disorder in Palliative Care

Background Borderline personality disorder (BPD) is identified by a pervasive pattern of instability of relationships, self-image, and mood, as well as marked impulsivity (1). The prevalence of BPD in the general population is 1-2%, and, despite the impression of a female predominance, evidence indicates that it occurs equally frequently in men and women (2). The stresses of serious illness may bring out these patients' most dysfunctional coping strategies, which can be uniquely challenging for medical professionals. This Fast Fact provides strategies for successful interactions with patients and patients' caregivers with BPD. Diagnosing BPD: The diagnosis of BPD requires a skilled clinical interview conducted by a knowledgeable examiner who has a longitudinal view of the affected patient. In the palliative care setting, certain behaviors and interactions with other individuals are clues to a BPD diagnosis if not previously established. - Individuals with BPD evoke strong emotional feelings in clinicians, including both negative emotions (anger, disgust, frustration, and anxiety) and over-identification, which may lead to attempts to "rescue" the patient. - Individuals with BPD have difficulty sustaining ambivalent feelings and may instead label clinicians as either "wonderful" or "terrible", a defense mechanism known as "splitting". - Individuals with BPD will go to great lengths to avoid real or imagined abandonment. They may demand multiple provider visits per day and become angry or withdrawn when demands for extra attention or special exceptions are not met. They are more likely to threaten legal action against providers when they perceive that their needs have not been met. - Impulsive behavior, including inappropriate use of prescribed medications, signing out against medical advice, and inconsistency in decision-making, occur commonly. - Defects in cognitive functioning, especially decision making, conflict resolution, and "effortful control" (the ability to inhibit or activate behavior to adapt to a situation) affect the ability to make reasoned decisions about medical care and sustain meaningful interactions with loved ones and medical staff. Strategies for working individuals with BPD (4, 5, 6, 9): Remember that the individual with BPD is suffering. Monitor your own feelings and refrain from responding emotionally or aggressively to verbal attacks and manipulation (See Fast Facts #59, 172 and 203). Begin encounters with a tactful assessment and acknowledgment of the individual's distress, and focus on specific problems. Address problem behaviors directly with statements such as "We want to continue to treat you, but if you threaten to hurt other people we will have to have you escorted out of the clinic". Recognize splitting behavior (when clinicians find themselves exuberantly praised or labeled as the 'only one who has ever been helpful' to the patient). Clinicians should avoid excessive familiarity and should instead identify themselves as part of a unified treatment team with a common plan. Set explicit limits on disruptive behavior such as angry outbursts or arm to self or property. A written treatment contract which specifies consequences may be helpful. Expect the individual to test the limits and be prepared to respond consistently. Clinician Self Care and Use of the Interdisciplinary Team Frequent debriefing with the interdisciplinary team and key clinicians (e.g., other consultants) where you have an opportunity to share the feelings you experience in working with a BPD patients is essential for practitioner self-care (See Fast Facts #167-170). Involve the treatment team in setting limits on behaviors (e.g., angry outbursts), visit frequency, and inappropriate use of medications. Carefully document all interactions with the patient or family member, including specific behaviors. Utilize consultants. A psychiatric consult-liaison service or the patient's own psychiatrist or psychologist, if the patient has one, should be involved in developing a plan for successful interaction the individual. If a patient's prognosis is long enough, consider requiring participation in psychological or psychiatric care as a condition of your continued involvement.

#191 Prognostication in Patients Receiving Dialysis

Background End stage renal disease (ESRD) is a highly prevalent and rapidly increasing condition. While dialysis prolongs life in patients with ESRD, life expectancy remains only a third to a sixth as long as similar patients not on dialysis. The overall one and five year mortality rates are 25% and 60%, respectively. Approximately 20% of ESRD patient deaths occur after a decision to stop dialysis, highlighting the importance of discussions of prognosis and goals of care with this chronically ill population. This Fast Fact reviews the current data regarding prognostication in patients receiving chronic hemo- and peritoneal dialysis. Note: renal transplantation reduces mortality and the following data do not consider patients with functioning kidney transplants. Prognostic Factors Several patient-specific factors influence prognosis: Age: For 1-year increments beginning at age 18, there is a 3 to 4% increase in annual mortality compared to the general population. 1 and 2 year mortality rates go from 10 and 12% at 25-29 years of age, to 25% and 42% at 65-69 years, to 39% and 61% at 80-84 years of age. Functional status: the relative risk of dying within 3 years of starting dialysis is 1.44 for those with Karnofsky Performance Status scores of <70 compared to a score ³70 (see Fast Fact #13). Albumin: a low serum albumin level, both at baseline and during the course of dialysis treatment, is a consistent and strong predictor of death. For example, the 1 and 2 year survival of patients with an albumin of >3.5 g/dL is 86% and 76% respectively, compared to 50% and 17% if less than 3.5. Surprise question: in a multivariate analysis, the likelihood of death in 6 months was significantly greater when nephrologists answered no to the question "would I be surprised if this patient died within 6 months?" Prognostic Tools It has long been recognized that patient comorbidity is strongly correlated with prognosis in ESRD. An age-modified Charlson Comorbidity Index (CCI), which stratifies patients based on medical comorbidities and age, has been successfully used to predict mortality in dialysis-dependent patients (8): For example, a 66 year old male on dialysis with a history of CHF, COPD, and diabetes with retinopathy would have a CCI score of 9 and a nearly 50% chance of dying within a year. Using this, a provider could discuss with the patient his prognosis and use this to facilitate further discussion regarding planning for the future, including end-of-life decisions. The Index of Coexistent Disease (ICED), a general illness severity index, has also shown predictive power in ESRD. The scale's complexity and length however (it entails asking over 100 questions) limit its clinical usefulness. Summary The age-modified CCI, in conjunction with other prognostic factors such as serum albumin and functional status, can be used to help facilitate discussions with dialysis-dependent patients and their families regarding goals of care and end-of-life planning.

#191 Prognostication in Patients Receiving Dialysis

Background End stage renal disease (ESRD) is a highly prevalent and rapidly increasing condition. While dialysis prolongs life in patients with ESRD, life expectancy remains only a third to a sixth as long as similar patients not on dialysis. The overall one and five year mortality rates are 25% and 60%, respectively. Approximately 20% of ESRD patient deaths occur after a decision to stop dialysis, highlighting the importance of discussions of prognosis and goals of care with this chronically ill population. This Fast Fact reviews the current data regarding prognostication in patients receiving chronic hemo- and peritoneal dialysis. Note: renal transplantation reduces mortality and the following data do not consider patients with functioning kidney transplants. Prognostic Factors Several patient-specific factors influence prognosis: Age: For 1-year increments beginning at age 18, there is a 3 to 4% increase in annual mortality compared to the general population. 1 and 2 year mortality rates go from 10 and 12% at 25-29 years of age, to 25% and 42% at 65-69 years, to 39% and 61% at 80-84 years of age. Functional status: the relative risk of dying within 3 years of starting dialysis is 1.44 for those with Karnofsky Performance Status scores of <70 compared to a score ³70 (see Fast Fact #13). Albumin: a low serum albumin level, both at baseline and during the course of dialysis treatment, is a consistent and strong predictor of death. For example, the 1 and 2 year survival of patients with an albumin of >3.5 g/dL is 86% and 76% respectively, compared to 50% and 17% if less than 3.5. Surprise question: in a multivariate analysis, the likelihood of death in 6 months was significantly greater when nephrologists answered no to the question "would I be surprised if this patient died within 6 months?" Prognostic Tools It has long been recognized that patient comorbidity is strongly correlated with prognosis in ESRD. An age-modified Charlson Comorbidity Index (CCI), which stratifies patients based on medical comorbidities and age, has been successfully used to predict mortality in dialysis-dependent patients (8):

#62 Early Diagnosis of Epidural Metastases

Background Epidural metastases are very common in patients with advanced cancer. Cancers most often associated with epidural spread include lung, prostate, breast, kidney, myeloma and melanoma. They are also common in testicular cancer, lymphomas, and Hodgkin's disease. Ovarian and pancreatic cancer rarely lead to epidural metastases. Tumor reaches the epidural space via contiguous spread from adjacent vertebral body metastases or, less commonly, from direct extension of tumor through the intervertebral foramina from adjacent tissue (e.g. retroperitoneal lymphoma or posterior lung cancer). The importance of early diagnosis Back pain is the herald symptom of epidural metastases; occurring, on average, many weeks to months prior to any neurological damage. That is, pain occurs long before there is any direct compression of the spinal cord, at a time when early diagnosis can be established and treatment started. Neurological deficits from spinal cord compression are a late finding of epidural metastases; serious damage is usually preventable by early diagnosis. Characteristics of pain from epidural metastases Pain from epidural metastases occurs due to vertebral body fracture, structural spine instability, periosteal or nerve root irritation. The various descriptions of pain from epidural metastases are protean. Most commonly, patients say it is 'dull' or 'aching,' often with a sensation of 'muscle spasm.' Pain typically worsens gradually, so that over a period of weeks patients require increasing analgesics and have a corresponding decrease in function. This is in contrast to benign compression fractures, where severe pain occurs suddenly, followed by slow improvement over weeks. If there is nerve root irritation, patients will describe neuropathic symptoms in a radicular pattern (e.g. burning or shock-like pain, and/or dysesthesias). The pain is usually located in the central back or paravertebral region and/or in a radicular distribution. Commonly missed radicular symptoms are tip of shoulder pain from C7-T1 metastases; lateral or anterior rib pain from thoracic metastases; anterior abdominal, flank or hip pain from T12-L2 metastases. Pain is often made worse by increasing the spinal cord load that occurs with standing, coughing or valsalva. Pain in the thoracic region is particularly worrisome due to the narrow spinal canal and minimal epidural space; patients with thoracic metastases often complain of increasing pain when recumbant. Diagnostic strategies The key to early diagnosis is a high index of suspicion. A good rule to use is that the cancer patient with progressive back or radicular pain, for more than 1-2 weeks, has epidural metastases unless proven otherwise; this is especially true in the high risk cancers (breast, prostate, lung, myeloma). Various protocols describing diagnostic approaches have been developed to aid clinicians (see references); all agree that in the setting of a normal neurological examination, early radiological imaging is essential for diagnosis and treatment planning. Rodichok et al demonstrated in 1981 that plain spine x-rays, in the region of back pain, can be an excellent first screening tool; MRI is the definitive diagnostic study and is necessary for planning radiation or surgical intervention. If neurological signs have become evident, emergent MRI is the diagnostic test of choice. Summary/Key Teaching Points: - Epidural metastases (tumor in the epidural space), occurs prior to actual spinal cord compression and neurological damage. - Pain will precede neurologic deficits by weeks to months. - Early diagnosis will preserve neurological function. - Progressive back or radicular pain is an indication for radiographic investigation to rule out epidural metastases, especially in high risk cancers

#295 Opioid Induced Constipation - Part 2: Newer Therapies

Background Fast Fact #294 introduces OIC and discusses well-established treatments. This Fast Fact discusses emerging management approaches. In general, these agents are used for refractory OIC, which implies persistent and distressing symptoms despite exposure to typically effective doses of stimulant and osmotic laxatives. When exactly to use these emerging therapies remains largely empiric. 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. Typically, patients orally ingest the contents of IV ampules. Naloxone has a high first pass metabolism, so it is possible for patients who take it orally to have peripheral µ-opioid receptor antagonism without significant impact on central receptors which could lead to opioid withdrawal and loss of analgesia (2). In 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. Effective doses typically need to be at least 10% of equivalent daily morphine dose, so naloxone usually requires slow up-titration with max dosing of 12 mg daily (2). Methylnaltrexone bromide: Methylnaltrexone is a peripherally-acting µ-opioid receptor antagonist. It is a methylated form of naltrexone and formulated as a subcutaneous injection. It is less able to cross the blood brain barrier, reducing the risk of altering analgesia or inducing central opioid withdrawal. An industry-funded randomized controlled trial of chronic opioid users showed that weight based methylnatrexone dosing led to laxation in nearly half of subjects within 4 hours as opposed to 15% of placebo (4). A subsequent meta-analysis of 6 separate trials with methylnaltrexone demonstrated the number needed to treat (NNT) is 3 for OIC patients that have failed to respond to standard laxative therapy (5). Its use is limited by cost which averages $55 per dose, and it is also contraindicated when bowel obstruction is suspected or for patients with compromised bowel integrity. The most common side effects are nausea, diarrhea, and cramping - which can be severely painful. Naloxegol: Two oral peripheral acting µ-opioid receptor antagonists are available in the US: alvimopam, which is only approved for post-operative ileus, and naloxegol (pegylated naloxone), which has recently been approved for OIC in non-cancer patients. Two separate phase-three clinical trials showed an increase from 1 to >3 bowel movements per week in non-cancer patients on chronic opioids with daily dosed naloxegol compared to placebo. There was also a significant improvement in a subset of patients who had failed traditional laxative therapy as well (7). Both 12.5 mg and 25 mg have been studied; the 25 mg dose has a higher success rate but is associated with more abdominal pain, nausea, vomiting and diarrhea (7). Its current price is approximately $300 for 30 pills. 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. Two randomized controlled trials in non-cancer chronic opioid users demonstrated an increase in frequency of spontaneous bowel movements by week 8. Moreover, approximately 40% of subjects had a bowel movement at 24 hours, 60% within 48 hours, and 27% of subjects had > 3 bowel movements per week (8,9). The most studied dose is 24 mcg orally twice per day. Common side effects included nausea, diarrhea and abdominal distension. Curiously, lubiprostone does not appear to be effective for methadone induced constipation (10). Linaclotide has a different mechanism than lubiprostone, but is also a small intestinal secretogogue. It currently is approved for irritable bowel syndrome. Though there is interest in its efficacy in OIC, it has yet to be specifically studied in this population. Prucalopride is a serotonin receptor type-4 agonist which is available in Canada and parts of Europe and Asia to treat chronic constipation. It is a prokinetic agent which has shown promise for treating OIC in a phase 2 study (5). It is unclear if or when it will be released in the US. Practical Advice: 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. Patient and caregiver education about the importance of adherence to recommended therapy and guidance about signs and symptoms of OIC is essential to ensure effective treatment.

#98 Intrathecal Drug therapy For Pain

Background Intrathecal (IT) drug delivery can be an invaluable adjunct in the management of severe and refractory pain. While most of the evidence supporting the use of IT pain pumps in palliative care settings has been largely based on case series and consensus statements, one prospective randomized clinical trial of cancer patients with refractory pain, suggested that IT drug delivery may have better analgesia, less opioid-related side effects, and longer survival compared with oral opioids. Candidates for IT drug therapy: Appropriate patient selection is important to optimize the safety and effectiveness of IT therapy. Candidates for IT pumps should have: An established diagnosis of severe chronic pain classified as neuropathic, nociceptive, or mixed; Pain refractory to oral analgesics or are intolerant to oral analgesics; Failed or are not a candidate for nonpharmacologic or surgical treatments; Pain that is below the neck and ideally focal in location. Because multiple psychosocial factors can influence a patient's pain perception as well as their ability to manage a pump once implanted, a psychological evaluation should be considered for patients being evaluated for IT implantation. Epidural vs. Intrathecal Analgesia IT analgesia is distinguished from epidural analgesia by catheter location within the neuraxis (see Fast Fact #85). In the former, the catheter lies within the subarachnoid space, where small quantities of medication have direct access to spinal drug receptor sites. In the latter, larger doses of medication (necessitated by epidural fat and vascular uptake) must diffuse across the dura to reach these receptors. There are no published guidelines on when to use the IT versus epidural route. In general, implantable IT pumps are reserved for patients with a life expectancy > 3 months. Potential disadvantages of IT relative to epidural techniques may include: lack of reprogramming/refilling capabilities near the patient's home, payor constraints, infusion volumes too great for an implantable pump, and the need for frequent patient controlled analgesia. Potential advantages of IT - relative to epidural - techniques are: Superior analgesia in the presence of epidural pathology (e.g. metastatic disease, radiation fibrosis, vertebral compression), widespread pain, and pain poorly responsive to high-dose epidural therapy. Ease of catheter placement, particularly in the presence spinal pathology. Fewer catheter problems such as catheter migration, fibrosis, or tip occlusion. Lower dose requirements may reduce side effects and lower drug costs. Choice of System There exists a spectrum of IT system options - from a simple, percutaneous catheter/external pump to a totally implanted system. Life expectancy, performance status, and available professional expertise may also guide which system is selected. A trial of IT analgesia may be done to assess response to therapy and proper patient selection prior to implantation of a pump. Programmable pumps are often used and can allow patients to administer bolus doses for breakthrough pain. Drug Choice Arner and Arner (1985) demonstrated the following relative responsiveness of pain mechanisms to intraspinal opioids: continuous somatic pain > continuous visceral > intermittent somatic > intermittent visceral > neuropathic > cutaneous (ulcers or fistulas). First line treatment for somatic pain syndromes includes a single agent opioid (most often morphine or fentanyl) or ziconotide (a selective voltage-gated calcium channel blocker with a sole FDA indication as an analgesic in IT pumps). Bupivacaine or ziconotide may be added in combination with an opioid as second line therapy. For neuropathic pain, morphine with bupivacaine or ziconotide alone is recommended. Second line therapy may include a change to hydromorphone alone or the addition of clonidine. Complications and Side Effects Complications may occur from a) the procedure (e.g. post-spinal headache), b) medications (e.g. opioid-related respiratory depression, sedation, urinary retention, pruritis), and c) hardware (e.g. catheter kinking/disconnection/dislodgement, infection, granuloma formation at the catheter tip). Major contraindications to IT catheter placement include coagulopathy, infection at catheter insertion site, and sepsis. Ziconotide use has been associated with increased suicidality, worsening of mood disorders, confusion, somnolence, dizziness, and new onset psychosis. Frequency of adverse effects may be attenuated by slow titration. Patients receiving ziconotide should be closely monitored for psychological side effects. Ziconotide should be avoided in patients with pre-existing psychosis. - General Overview: In contrast to drugs administered systemically, drugs administered in the epidural space are extremely potent since the drug is delivered close to the site of action (opioid and alpha receptors in the spinal dorsal horn or local anesthetic blockade of nerve roots). -Because of this, systemic side effects such as nausea, sedation, and constipation, are minimized. In palliative care, epidural analgesia may be appropriate for patients with regional pain (e.g. pelvic pain from cervical cancer) and/or patients who do not tolerate or obtain relief from oral/parenteral drugs and non-drug therapies. -These indwelling epidural catheters, are tunneled under the skin, directed away from the spine, and covered it with clear adhesive dressing to reduce infection. Indwelling epidural catheters can remain in place for weeks to months and can be utilized in the home setting; however, longer catheter durations are associated with higher risks of serious adverse effects such as a deep epidural infection. Management Due to the proximity of drug delivery to its site of action, frequent assessment of pain relief, side effects, and signs or symptoms of technical complications (catheter dislodgement, epidural hematoma or abscess, pump malfunction, etc.) are necessary. This should be done every hour for the first 24 hours, then every 4 hours. Assess and document on the pain management flowsheet: - Patient's pain rating using patient-specific pain scale (e.g. 0-10), both at rest and with activity. - Level of sedation & respiratory rate, preferably by the same nurse during each shift. - Side effects: pruritis, nausea, urinary retention, orthostatic hypotension, motor block. - Sign of catheter insertion site infection or epidural abscess such as back pain, tenderness, erythema, swelling, drainage, fever, malaise, neck stiffness, progressive numbness, or motor block. - Changes in sensory/motor function that may indicate an epidural hematoma including unexplained back pain, leg pain, bowel or bladder dysfunction, motor block.

#294 Opioid Induced Constipation - Part 1: Established Management

Background Opioid induced constipation (OIC) affects 45-90% of patients (1, 2) and can cause significant morbidity. It is the most common reason patients avoid and/or discontinue opioids (3, 4) and can often result in an increase in hospital length of stay (5) and overall healthcare costs (6). Physiology OIC is mediated through several different mechanisms including ineffective GI motility, inhibition of mucosal transport of electrolytes and fluids, and interference with the defecation reflex (7). The greatest risk factor for developing OIC is duration of opioid therapy. 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). Non-pharmacologic Therapies Physical activity, scheduled toileting, fiber, and adequate fluid intake have been traditional non-pharmacologic mainstays for preserving GI regularity in constipation (8). However, there is no specific evidence in favor for any of these interventions to treat OIC and adherence may be challenging for chronically ill patients. Pharmacologic Therapies In general, patients with regular opioid exposure will require pharmacologic therapy to appropriately manage OIC. Both stimulant and osmotic laxatives have shown to be effective in treating OIC and are considered the cornerstone of treatment. Failure of oral pharmacologic therapy usually requires more invasive rectal based interventions or one of the newer treatment modalities (see Fast Fact #295). 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. This can sometimes be avoided by dividing the total dose into smaller more frequent doses (9). 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). While sorbitol and lactulose have shown similar efficacy, sorbitol tends to be more cost effective (13). Magnesium based compounds (milk of magnesia and magnesium citrate) are also effective, but the magnesium load can be dangerous for patients with renal insufficiency. 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. Consequently, most guidelines do not routinely recommend their use (11,15,16). Practical Advice A consistent bowel regimen is essential in preventing constipation in patients on chronic opioid therapy. Providers should educate their patients about the signs and symptoms of OIC and seek appropriate consultation in a timely manner. 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).

Which of the following is a true statement regarding the analgesic effects of pregabalin in comparison to gabapentin (Fast Fact #289 Pregabalin vs Gabapentin)? Gabapentin is approximately 3 times as expensive as pregabalin. In head to head trials, gabapentin has been shown to be a more effective analgesic for neuropathic cancer pain. Pregabalin can often be titrated to an effective dose range one week before gabapentin. Gabapentin is a controlled substance while pregabalin is not.

Background Pregabalin (Lyrica®) is a second generation antiepileptic drug that was developed after gabapentin (See Fast Fact #049). This Fast Fact will review pregabalin and its role in palliative care. A comparison between pregabalin and gabapentin is also available (See Fast Fact #289). Pharmacology Pregabalin binds to the alpha-2 (α-2δ) subunit of voltage-gated calcium channels in the CNS, subsequently inhibiting the release of excitatory neurotransmitters. Its oral bioavailability is ≥90% and can be taken with or without food. Peak plasma concentrations occur within 1.5 hours. Pregabalin does not bind to plasma proteins, undergoes negligible metabolism, and does not affect the major CYP450 enzymes in humans. It is unlikely to have significant drug interactions (1,2). Dosing Starting dose for pregabalin is 150 mg/day in two to three divided doses, and may be increased to 300 mg/day within 1 week. Maximum daily dose is 450 mg/day and 600 mg/day (in divided doses) for fibromyalgia and other neuropathic pain disorders, respectively. Dosing in Renal Impairment and Failure Pregabalin must be adjusted for patients with a CrCl <60 mL/min, as it is approximately 90% renally eliminated (2). Adverse Drug Reactions and Cautions Dizziness is the most commonly reported side effect, followed by somnolence which is the most frequent reason for discontinuation. Other side effects are dose-dependent and reversible — dry mouth, angioedema, peripheral edema, blurred vision, weight gain, and difficulty with concentration/attention (3). Correct! Answer A is wrong because pregabalin is 3 times more expensive than gabapentin, not the other way around. In one small randomized controlled trial, pregabalin was shown to be associated with statistically significant lower visual analogue pain scales for neuropathic cancer pain in comparison to gabapentin, placebo, or amitriptyline, making answer B incorrect. Pregabalin is a controlled V substance per the DEA; as of now gabapentin is not a controlled substance. Published medical data suggest pregabalin can be titrated to an effective dose range at 1-2 days; whereas it often takes 9 days or longer to titrate to gabapentin's usual effective dose range of 900-1,800 mg/day. In head to head trials, gabapentin has been shown to be a more effective analgesic for neuropathic cancer pain.

#415 General Inpatient Hospice Care

Background Questions regarding hospice resources commonly arise when caring for an actively declining, symptomatic hospice or hospice-eligible patient. This Fast Fact addresses questions and concerns regarding hospice general inpatient care (GIP) and distinguishes GIP from routine hospice care within the Medicare Hospice Benefit (MHB). GIP care is relatively common among MHB recipients; recent data suggests about a quarter of all MHB recipients receive GIP care (1). See Fast Facts #82, 87, 90, 139, and 140 for further information about the MHB including other levels of hospice care in the US. What is GIP Hospice Care? The Code of Federal Regulations regarding the MHB requires all hospice entities to be able to provide four levels of care to patients: GIP, routine (most hospice care at home or in long-term care is routine), continuous care (short term intensive symptom care, provided in the patient's own place of residence), and respite (short term facility-based care for family respite needs) (2). GIP is an inpatient care plan for a hospice patient who has short-term symptom management needs that cannot be provided adequately in any other setting. When is GIP appropriate? While GIP criteria can be individualized, at minimum it requires appropriate orders and documentation of acute symptom management needs. Importantly, anticipated survival of hours-to-days (i.e., imminent death) is not justification alone to meet GIP standards. GIP cannot be used for caregiver stress relief or respite. GIP is aimed at 'short term' admission (usually 5 days or less) for aggressive palliative interventions and discharge to a prior level of care when acceptable symptom control is achieved. Additional supporting evidence for GIP criteria include, but are not limited to (3,4): Analgesic needs that cannot be managed at home, such as complicated delivery mechanisms (e.g., subcutaneous, IV, epidural), frequent dose titration, and skilled nursing care with frequent monitoring. Symptom management for nausea, vomiting, respiratory distress, or terminal complications such as seizures or bleeding that would be uncontrollable with the resources available elsewhere. Advanced, open wounds requiring frequent dressing changes, frequent monitoring, or more than one person to complete. Severe delirium with behavioral manifestations not manageable elsewhere. Where is GIP provided? GIP most commonly occurs in a dedicated hospice inpatient unit, which could be located within a hospital, skilled nursing facility, or a freestanding facility. GIP occurs less commonly in regular hospital (33%) or skilled nursing facility beds (8%) (1). The facility must either be appropriately licensed to provide hospice care or have a contract with a hospice entity. GIP cannot be provided in a patient's own home, assisted living facility, or other long-term care facility where federal requirements for providing GIP care cannot be met. Regardless of site, additional GIP requirements include (2): 24-hour nursing care services with the ability for an RN to provide direct patient care on all shifts. Availability of spiritual and psychosocial care and assistance. A home-like atmosphere to preserve patient dignity and privacy. Ability to receive visitors at all times. Initiating GIP in patients who are already hospitalized Under some circumstances, appropriately selected hospitalized patients can receive GIP care even if they were not previously established on the MHB. The hospital must have an established partnership contract with a hospice agency. The patient can then be bureaucratically discharged from their original hospital stay and immediately readmitted as an enrolled hospice GIP patient, without ever leaving the hospital or even their bed (if the hospital does not have a hospice unit). The patient must meet GIP criteria as described above. For example, a terminally ill patient is admitted to a hospital with pneumonia. After 2 days, the family opts for hospice enrollment and signs onto the MHB. The patient has severe agitated delirium and cannot safely be discharged home. The hospital has a contract with a hospice agency to provide GIP, but no hospice unit. This patient can be "discharged" from their original hospital stay, and immediately readmitted as a hospice GIP patient for ongoing management of their delirium and comfort, without leaving their hospital bed. If they stabilize, they may need to be discharged to a different level/location of hospice care. GIP in a hospital is always complex from both a regulatory and practical standpoint. Logistic care issues are common such as questions regarding who the attending physician should be, the roles of hospice versus hospital unit nurses, and the role of the hospice medical director to name a few. Proactive, close collaboration between hospice and hospital personnel (including leadership, business administrators, and clinicians) is vital for these programs to be successful.

#228 Tapentadol

Background Tapentadol is a newly available oral analgesic, approved by the FDA in 2009 for the management of moderate to severe acute pain in adults. This Fast Fact reviews its pharmacology and use. Pharmacology Tapentadol is a centrally-acting, synthetic, oral mu-opioid receptor agonist which also inhibits norepinephrine and serotonin reuptake within the CNS. It is structurally and pharmacologically similar to tramadol (see Fast Fact #290 for more information on tramadol). Oral bioavailability ranges from 32% to 42%, with a half-life of 4 ½ hours. The drug is metabolized in the liver (97% by Phase-2 conjugation) and excreted in the urine. Tapentadol has no known pharmacologically active metabolites, no relevant CYP interactions, and no drug-drug interactions through cytochrome induction or inhibition (1). There are no dosing adjustments required in mild-to-moderate renal or hepatic impairment (Child class A or B); it has not been studied in patients with severe hepatic impairment (Child class C). Research Data The FDA approval was based on industry-coordinated, randomized controlled studies conducted in patients with osteoarthritis and after bunionectomy. In these studies 50 mg doses of tapentadol was shown to be non-inferior to 10 mg of oxycodone immediate-release in the treatment of pain, but the incidence of nausea, vomiting, dizziness, and constipation was significantly lower (2,3). In another single-dose study involving patients undergoing molar extraction, tapentadol 200 mg demonstrated improved analgesia but higher sedation than 60 mg of oral morphine (4). Total daily doses greater than 700 mg on the first day of therapy and 600 mg on subsequent days have not been tested, nor has tapentadol been studied in children. Tapentadol has not been tested in a randomized, controlled fashion for cancer pain nor in palliative care settings; however, prospective observational studies showed it to be well tolerated and effective for opioid naïve (doses 100 mg per day) and opioid tolerant patients (doses 350 to 450 mg per day) with moderate to severe cancer pain (5,6). There are not enough data to comment on whether the drug has a ceiling effect, nor its long-term safety and efficacy (the longest study is a 1 year safety study). It has not been comparatively studied against tramadol. Side Effects and Cautions Tapentadol's side effect profile is generally similar to opioids: nausea, vomiting, constipation, addiction, respiratory depression, pruritus, dizziness and drowsiness. A pooled analysis of randomized controlled trials suggest that gastro-intestinal side effects are likely milder than other opioids (7). As with tramadol, there is a theoretical increased risk of seizures, as well as serotonin syndrome if given with other serotonergic agents (e.g. antidepressants, drugs with monamine oxidase inhibitory effects). Abuse and addiction are possible as with any opioid agonist. An abstinence syndrome has not yet been described; in one study drug tapering was not required after 90 days of treatment (2). Dosing and Cost Tapentadol is available as 50, 75 and 100 mg immediate-release tablets and 50, 100, 150, 200, and 250 mg extended release tablets. The initial dose is 50-100 mg every 4 hours (although a second dose can be given one hour after the initial dose). The average wholesale pricing for tapentadol is approximately $5 to $7 per immediate release tab and $5 to $15 per extended release tablet. For comparison, tramadol costs $0.07/tab (50 mg), oxycodone costs $0.70 (15 mg tab), and morphine costs $0.18 (15 mg tab). Summary Tapentadol is a novel analgesic, with a 50 mg dose similar in efficacy to 10 mg of oxycodone. Currently its only clearly defined benefit over established opioids is its gentler GI side effect profile. Its cost, potential ceiling effect, safety concerns with drug interactions, and uncertainty about long-term efficacy and safety limit its current application.

#144 Palliative Care Issues in Heart Failure

Background The physical and psychological symptom burden in the dying heart failure (HF) patient is similar to that in the dying cancer patient. Symptom prevalence data in HF includes: pain (78%), dyspnea (61%), depression (59%), insomnia (45%), anorexia, (43%), anxiety (30%), constipation (37%), nausea/vomiting (32%), fatigue, difficulty ambulating, and edema. This Fast Fact reviews domains of medical management common to most end-stage HF patients. General Symptom Management Pain. Common causes include: peripheral edema, arthritis, diabetic neuropathy, and post-herpetic neuralgia. NSAIDs are generally contraindicated because they antagonize the effects of diuretics and ACE inhibitors, promoting fluid retention while decreasing glomerular filtration and impairing renal function. Opioids are the agents of choice for nociceptive and neuropathic pain because of efficacy, rapidity of onset and potential to relieve dyspnea. See Fast Facts #18, 28, 53, 54, and 72. Dyspnea. Reassess/optimize HF medications and assess for reversible causes, e.g. pleural/pericardial effusions, dysrhythmias, COPD exacerbation. See Fast Fact #27. Depression. Short-term psychotherapy can be helpful for mild-moderate depression, but patient participation and logistical issues can be problematic. Selective serotonin reuptake inhibitors (SSRIs) are the antidepressants of choice because they preserve ejection fraction, lack hypotensive/dysrhythmogenic effects, and have few drug interactions. Sertraline in particular may be the agent of choice in HF patients. Psychostimulants (see Fast Fact #61) may accelerate the treatment response to SSRIs. Note: as there exists no data on the safety of psychostimulants in HF, therapy should be initiated with caution. Heart Failure Pharmacotherapy Optimal drug use can improve symptoms and should be continued until the burden of administration outweighs benefits. Diuretic therapy can be crucial, but diuretic resistance is common. The following strategy can help overcome diuretic resistance: Optimize dose of oral loop diuretic (e.g. furosemide). Doses of up to 4000 mg/day have been found to be safe and effective. Change to intravenous or subcutaneous routes. IVboluses can produce symptom relief within minutes. Continuous infusions (3-200 mg/hr; 10-20 mg/hr in most patients) provide increased efficacy. Add a PRN oral thiazide diuretic (e.g. hydrochlorothiazide 25-100 mg/day or metolazone 5-20 mg/day. This can reestablish diuresis in a loop diuretic-resistant patient. Note: high dose and combination diuretics can result in electrolyte imbalances; consider electrolyte monitoring if death is not imminent. Inotropes Intravenous inotrope therapy (dobutamine, milrinone, dopamine) has a substantial record of use but a paucity of data in the home setting. Data suggest these agents may improve symptoms, but with an increased risk of dysrhythmic death. In hospitalized inotrope-dependent HF patients, discharge on inotropes may provide the opportunity for death to occur at home if desired by patient/family. Device therapies Decisions regarding previously implanted device therapies should be made in the context of goals of care. See Fast Facts #111,112 for a discussion of implantable devices and issues surrounding deactivation; Fast Fact #205 discusses ventricular assist devices. Prognostic Uncertainty Accurate prognostication is virtually impossible in HF (see Fast Fact #143). While this uncertainty is frustrating for physicians, it provides a basis for initiating end-of-life discussions. The American Heart Association released a scientific statement to help Clinicians best guide their patients: Initiate yearly "heart failure reviews" or advance care planning discussions. Utilize a HF hospitalization (which triples one-year mortality) as a bridge to either optimizing medical therapy or palliative care. Educate patients and families about the unpredictable, but usually terminal nature of HF, and the ever present danger of sudden cardiac death (even when feeling well). Ascertain specific goals of care (e.g. quality of life vs. length of life, living/dying at home vs. hospital) Assess options for achieving these goals (e.g. initiating/handling device therapies including when and how to deactivate, hospice vs. serial hospital/critical care unit admissions). Assess resuscitation preferences.

#53 Sublingual Morphine

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).

#290 Tramadol in Palliative Care

Background Tramadol is an important medication in palliative care. It 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. This Fast Fact will review tramadol's pharmacology, its benefits, and limitations. Note that tramadol has similarities with tapentadol which is discussed in Fast Fact #228. Pharmacology The analgesic effects of tramadol are likely due to mu-opioid agonist activity, and weak monoamine reuptake inhibition (specifically blocking norepinephrine and serotonin) in the CNS. Tramadol is a prodrug and must be metabolized via CYP2D6 to its pharmacologically active metabolite (O-desmethyl tramadol) (2). It is excreted 90% in the urine; therefore specific dosing adjustments are necessary in renal impairment (CrCl <30 mL/min). There are also dosing adjustments in the elderly and end-stage liver failure. Clinicians should be aware of tramadol's significant drug interactions with other CYP2D6 inhibitors (fluoxetine, paroxetine and amitriptyline) and CYP3A4 inhibitors (ketoconazole and erythromycin), which increase the risk of seizures and serotonin syndrome. Dosing Tramadol is available as both generic and proprietary formulations: a 50 mg immediate-release (IR) tablet and 100 mg, 200 mg, and 300 mg extended-release (ER) tablet (Ultram ER®). Immediate-release tramadol also comes formulated with acetaminophen. Tramadol should be started at 25 mg/day in the morning and increased by 25-50 mg every 3 days. The maximum daily dose of tramadol is 400 mg/day (50-100mg every 4-6 hours). In patients with renal impairment (CrCl <30 mL/min), the dosing interval is 12 hours with a maximum daily dose of 200 mg/day. The maximal recommended dose for adult patients with cirrhosis is 50 mg every 12 hours. For elderly patients over 75 years old, the total daily should not exceed 300 mg/day. Approximately 120 mg of oral tramadol is equivalent to 30 mg of oral morphine (3). Oral morphine tablets are roughly half the cost of tramadol IR tablets, and one-sixth the price of tramadol ER tablets. Adverse Drug Reactions Tramadol's adverse drug reaction profile is similar to other opioids, although it has a lower incidence of respiratory depression (4) and likely has a lower abuse potential. An early comparative study suggested that tramadol has less abuse potential than morphine (5) and more recent preclinical studies suggest that abuse-related behavioral effects of tramadol may be of lesser magnitude than other mu-opioid receptor agonists (6). However, there have been several reports of its abuse and misuse (7). Hence, in August of 2014 tramadol was made a Schedule IV controlled medication. Cautions Tramadol carries four specific cautions: 1. 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). 2. 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). 3. 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). 4. 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).

#182 Xerostomia

Background Xerostomia (dry mouth) is a common symptom at the end of life - affecting more than 75% of hospice patients - and is a cause of significant morbidity and diminished quality of life. Salivary Functions include hydration, lubrication, and antimicrobial defense of the oral mucosa. Decreased salivation can lead to oral pain; accelerated dental morbidity; oral infections, fissures, and ulcerations; halitosis; alteration in taste and enjoyment of food; chewing and swallowing difficulties; nutritional impairment; trouble producing intelligible speech; and denture-related problems. Etiologies - Medications with anticholinergic activity are the most common pharmacologic causes of xerostomia; these include many antiemetics, antihistamines, antipsychotics, antispasmodics, antidepressants (especially the tricyclics), and bronchodilators. Sympatholytics are also common culprits, including alpha-blockers (e.g. terazosin), alpha-2 agonists (e.g. clonidine), and beta-blockers (e.g. metoprolol). Medication-induced xerostomia may also result from direct interference with or damage to salivary tissue (as with some cancer chemotherapies). Opioids and benzodiazepines cause dry mouth, although the mechanisms are not known. - Radiation for head and neck malignancies. - Medical comorbidities such as HIV/AIDS, diabetes, renal failure, and Sjögren's syndrome. - Psychiatric comorbidities such as mood and anxiety disorders. - Dehydration from any cause including drug-induced. Treatment - Address underlying causes. Eliminate unnecessary drugs or substitute less drying ones. If this is not feasible, titrate to lowest effective dose or modify dosing schedule. Replacing immediate-release with controlled-release formulations of some drugs may help (e.g. with oxybutynin and tolterodine for overactive bladder). - Stimulate residual gland function. (a) Sugarless gums and candies can stimulate salivary reflexes. Products sweetened with xylitol are anticariogenic; those containing vitamin C may reduce salivary viscosity. (b) Cholinergic agonists such as pilocarpine and cevimeline. Therapeutic effect is rapid for drug-related xerostomia; latency is greater (often 8-12 weeks) for xerostomia related to radiotherapy. Pilocarpine is started at 5 mg po tid and can be titrated to 10 mg po tid. Cevimeline is dosed at 30 mg po tid. Urinary frequency, dizziness, and sweating are common side effects and may be attenuated with intake of dairy products. These agents are contraindicated in asthma, acute iritis, and narrow-angle glaucoma, and should be used with caution in COPD and cardiac disease. - Saliva substitutes. Most have limited efficacy; many patients find frequent sips of water more useful and convenient. Topical products containing olive oil, betaine, and xylitol have been found effective for medication-induced xerostomia (e.g. Xerostom® products). Newer products with enzyme systems such as lactoperoxidase, lysozyme, and glucose oxidase (e.g. Biotène® Oralbalance Dry Mouth Gel)—offer potential antimicrobial and moisturizing benefits. Due to limited duration of action, they may be particularly useful before eating, speaking, and sleeping. Recently, custom oral appliances with artificial saliva reservoirs have become available and may be particularly useful at night. - Encourage oral hydration. Humidifiers, especially during sleep, may also be helpful. - Optimize oral hygiene.

#360 The Surprise Question as a Prognostic Tool

Background: Clinicians have been encouraged to utilize the surprise question (SQ) — "Would I be surprised if this patient died within 12 months?" - to identify patients at high 1-year mortality risk. When clinicians answer "No - I would NOT be surprised if this patient died within 12 months," the SQ may help clinicians identify patients with unmet palliative care needs who could benefit from advance care planning discussions and/or a palliative care referral (1). This Fast Fact reviews the clinical utility of the SQ. Rationale of the SQ: As difficult as it is for clinicians to prognosticate accurately, multiple studies have shown that patients with incurable disease desire more prognostic information the sicker they get and prognosis is a major factor in preferences for rehospitalizations, life support, and CPR (2-4). Although, patients and surrogates often want temporal prognostic predictions (the clinician's estimated length of time he or she predicts the patient will live), clinicians are more accurate and willing to offer probabilistic predictions (the clinician's estimate, often in a percentage, of the chance of death in a set time frame, such as 1 year) (4-6). The SQ was designed as a clinical tool that generalist clinicians would utilize willingly and routinely to identify patients at risk of death in a year and thereby lead to more appropriate advance care planning, goals of care discussions, symptom management, and hospice referrals. Implementing the SQ Into Clinical Practice: The SQ can be helpful in identifying patients at risk of medical decline and death in a certain time frame when used as part of a larger prognostic assessment (19). Yet, considering the relatively high false positive rate of a "No" answer, it is not established if the SQ is a cost-effective tool nor an effective way to trigger a palliative care consultation on its own. A consensus panel of experts suggested that a "No" answer trigger generalist clinicians to perform a primary palliative care assessment or screening for unmet palliative care needs (20). Sentinel medical events like hospitalization, decline in performance status, or disease progression are reasonable triggers to implement the SQ into clinical practice. Note templates, medical rounding tools, and electric medical record prompts are potential system-based approaches to accomplish this. Reasonable components of the primary palliative care assessment triggered by a "No" include (20): - Assessment for distressing physical, psychological, social, or spiritual concerns. Identification of whether the patient completed an advance directive such as a health care power of attorney that is available in the medical records. Assessment of patient, family, and/or surrogate's understanding of the underlying illness, treatment options, and prognostic trajectory. Assessment of decision-making capacity. Engagement in honest conversations about prognosis and medical expectations. Elicitation of the patient's care preferences and values. Consideration of whether a hospice referral would be appropriate. Consideration of whether a palliative care consultation may be beneficial.

#189 Prognosis in Decompensated Liver Failure

Background: End stage liver disease (ESLD) and cirrhosis are characterized by symptom burden, decreased quality of life, hospitalizations, unpredictable exacerbations, and limited disease-directed therapies other than liver transplantation (1). It is a common cause of morbidity (15th) and death (11th) in the United States (2,3). This Fast Fact assimilates the evidence to help clinicians more accurately prognosticate in patients with ESLD and cirrhosis. Compensated vs decompensated ESLD: Patients with compensated chronic liver failure (meaning liver failure without evidence of current or prior ascites, variceal bleeding, encephalopathy, or jaundice) have a median survival of 12 years (4). Patients with decompensated cirrhosis or ESLD, have a far poorer median survival of about 2 years without transplantation (5). The Child's-Turcotte-Pugh (CTP) Score: It stratifies patients into three severity classes using two subjective and three objective parameters. Although the CTP was originally created to guide patient selection for portal decompression surgery, it now guides probabilistic prognosis estimates, transplant candidacy, and organ allocation (6-8). Patients who score 5-6 total points are "Class A"; 7-9 total points are "Class B"; and 10-15 points "Class C." The CTP is limited in its ability to differentiate disease severity and predict a specific mortality estimate. However, available evidence suggests that the 1-year median survival for Class A is nearly 100%, Class B is 80%, Class C is 45% (7,8); 5-year median survival for Class A is ~64%, Class B is 60-75%, Class C is 34-50% (9,10).Many experienced hepatologists have opined that the CTP does not accurately identify Class C patients with a high 90-day mortality. The MELD score was in part created to help clinicians identify patients at risk of dying <90 days more accurately.

#325 Uremic Calciphylaxis

Calciphylaxis is a poorly understood disorder in which calcification of small blood vessels causes painful ischemic skin and visceral lesions most often in patients with end-stage renal disease (ESRD). This Fast Fact will review its clinical presentation and offer recommendations for advance care planning and symptom management. Epidemiology: Calciphylaxis occurs in 4% of ESRD patients on peritoneal dialysis or hemodialysis and can occasionally occur in pre-dialysis renal disease ([i]). Risk factors include: female sex; Caucasian race; obesity; diabetes mellitus; hyperparathyroidism; albumin < 3; hypercoagulable states; and exposure to certain medications such as warfarin, iron, vitamin D, and corticosteroids (2-7). Pathophysiology: Uremia, calcium products, and reactive oxygen species (ROS) associated with ESRD are thought to increase vascular calcium deposition and fibrosis, leading to calciphylaxis (1,3). Over time this process likely precipitates arteriolar remodeling and progressive stenosis, causing ischemia and skin infarcts. The one-year mortality rate for calciphylaxis is estimated to be 45-80%, which may be even higher when ulcerative skin lesions are present (7,8). Ischemic complications and difficult to treat infections given incomplete antibiotic penetrance and poorly perfused tissues are potential mechanisms for the increased mortality risk. Clinical Presentation: Early signs include pain and a lace-like purplish discoloration of the skin (livedo reticularis). This is often followed by painful subcutaneous nodules or plaques that progress to necrotic ulcerations. Areas of greatest fat tissue — abdomen, buttocks, and inner thighs — are most commonly involved, although visceral organs, skeletal muscle, and heart muscle can also be affected (5, 9). Calciphylaxis can be challenging to distinguish from a vasculitis. Intact pulses, bilateral upper extremity involvement, and calcification seen on X-rays or CT scans are suggestive indicators of calciphylaxis. Diagnosis: Calciphylaxis is a clinical diagnosis. Laboratory findings are non-specific. In certain circumstances, a dermatology consult and/or skin biopsy may be needed. However, skin biopsy is usually deferred due to risk of pain, a false negative result, and poor wound healing (2,10). Imaging studies can support the diagnosis by identifying calcification, but they do not confirm a diagnosis and may lead to unnecessary discomfort (10). Treatment: No randomized control trials exist for the treatment of calciphylaxis. In general, most experts recommend a multi-modal approach involving adequate wound care, pain control, and treatment of hyperparathyroidism. This includes a low phosphate diet, use of non-calcium based phosphate binders (i.e., sevelamer), and cessation of vitamin D supplementation. In hemodialysis patients, calcimimetics (i.e. cinacalcet) and increasing dialysis frequency to 4 to 6 sessions per week may help but evidence is limited to case reports (3,11). Other less established options include sodium thiosulfate infusion during hemodialysis, oxygen therapy (10-15 liters via face mask 2 hours/day), and hyperbaric oxygen directed to the wound (3,5,12,13). Providing these therapies may be logistically challenging for hospice agencies. Pain Management: The mechanism of pain is poorly understood, but is thought to be due to ischemia and resultant nerve damage. No controlled studies have confirmed an optimal analgesic approach. However, case series suggest that combining aggressive wound care with an analgesia regimen consisting of opioids, ketamine, and non-opioid adjuvants (e.g., gabapentin or tricyclic antidepressants) can be effective (14). Fentanyl, buprenorphine and methadone do not have known renal metabolites and thus may be associated with less opioid toxicity. The use of topical ketamine or topical opioids, such as morphine-infused gels may offer local pain control with potentially less systemic side effects, but this has not yet been studied (see Fast Facts # 185). Amputation remains an option in cases of refractory pain. Advance Care Planning: Considering the one-year mortality risk, the diagnosis of calciphylaxis should prompt clinicians to engage patients and families in a larger discussion regarding advance directives, prognosis, and goals of care. A potential decision-point is whether to withhold or withdraw hemodialysis when calciphylaxis is diagnosed. Patients may not be aware that stopping dialysis is a viable care option unless raised by a clinician. Clinicians, however, should be aware that the decision to stop hemodialysis can be exceedingly complex and dependent upon a variety of factors such as patient-defined quality of life, symptom burden, prognosis, and care location preferences (see Fast Fact #163). While the Medicare Hospice Benefit (MHB) can provide important care resources and support for patients with calciphylaxis, MHB patients are typically unable to continue dialysis with a hospice admitting diagnosis of ESRD. Thus, even a discussion of hospice can be challenging to navigate for many clinicians. Given their skills in managing complex analgesic regimens and their multidisciplinary approach to clinical, psychological, spiritual, and social care, the involvement of a specialist palliative care team can be helpful when discussing withholding or withholding dialysis.

#187 Non-Tricyclic Antidepressant for Neuropathic Pain

Clinical Evidence Most randomized controlled trials of non-tricyclic antidepressants for pain have been for diabetic peripheral neuropathy or post-herpetic neuralgia. There have been a few well controlled studies in the treatment and prevention of chemotherapy induced peripheral neuropathy (CIPN) but limited good data in other neuropathic conditions. Selective Serotonin Reuptake Inhibitors (SSRIs): Fluoxetine is not effective for neuropathic pain. Paroxetine and citalopram have shown only mild benefit for HIV-related and diabetic neuropathy in small studies. Other SSRIs have not been evaluated. Serotonin Norepinephrine Reuptake Inhibitors (SNRIs): -Venlafaxine: Low doses of are predominantly serotonergic, but higher doses add substantial noradrenergic effects. Doses of 150-225 mg/day appear to have mild to moderate analgesic effect (30-50% reduction in pain) with a number needed-to-treat (NNT) of 4.6 in painful diabetic neuropathy (only one out of every 4-5 patients treated will benefit). In contrast, TCAs have shown a NNT of 2-3. Pilot data, in additional to one randomized controlled trial, support the use of extended release venlafaxine in preventing the onset of CIPN if given at doses of 25 mg to 75 mg a day one hour prior to chemotherapy infusion as well as 11 days after. One head-to-head trial showed venlafaxine 225 mg/day had the same tolerability as 150 mg/day of imipramine (a TCA), but venlafaxine was less effective for pain. Side-effects of venlafaxine include nausea, sedation, headache and dizziness. The usual starting dose is 37.5 mg daily, increasing weekly in 37.5 mg increments. Use of venlafaxine for analgesia is not FDA approved; a 75 mg tab costs approximately $3.70 (average US wholesale price). - Duloxetine: has been shown to have a mild to moderate analgesic effect in industry-sponsored trials in diabetic peripheral neuropathy (NNT 5.2). In addition, a randomized controlled trial showed relatively small but significant neuropathic pain relief compared with placebo. Onset of analgesia is at about 1 week, with maximum effect at about 4 weeks. A dose of 60 mg a day has been best studied for both diabetic peripheral neuropathy and CIPN; 60 mg BID may lead to increased analgesia but at the expense of an increased risk of nausea, sedation, constipation, sweating, and insomnia. Duloxetine has an FDA indication for use in diabetic peripheral neuropathic pain in the USA. A 60 mg tab costs approximately $3.50. Other Antidepressants Buproprion is a dopamine and norepinephrine reuptake inhibitor with mild analgesic effect according to one study involving 41 patients with a mix of neuropathic pain syndromes. Mirtazapine has a complicated pharmacology with unknown analgesic effects. Summary There are relatively well defined and preferred therapies for neuropathic pain including newer generation anticonvulsants (such as gabapentin), TCAs, and opioids in select patients. In patients with ongoing pain despite treatment with these agents, or who are intolerant to them, venlafaxine or duloxetine may be helpful. There are no comparative studies between non-tricyclics for neuropathic pain, thus an agent should be selected based on its side-effect profile, cost, and familiarity with use.

#142 Opioid-Induced Hyperalgesia

Clinical features of opioid hyperalgesia: HistoryIncreasing sensitivity to pain stimuli (hyperalgesia).Worsening pain despite increasing doses of opioids.Pain that becomes more diffuse, extending beyond the distribution of pre-existing pain.Can occur at any dose of opioid, but more commonly with high parenteral doses of morphine or hydromorphone and/or in the setting of renal failure. Physical ExaminationPain elicited from ordinarily non-painful stimuli, such as stroking skin with cotton (allodynia)Presence of other opioid hyperexcitability effects: myoclonus, delirium or seizures (see Fast Facts #57,58). Proposed mechanisms: Toxic effect of opioid metabolites (e.g. morphine-3-glucuronide or hydromorphone-3-glucronide). Central sensitization as a result of opioid-related activation of N-methyl-D-asparate (NMDA) receptors in the central nervous system. Increase in spinal dynorphin activity. Enhanced descending facilitation from the rostral ventromedial medulla. Activation of intracellular protein kinase C. Therapies: - Reduce or discontinue the current opioid. - Change opioid to one with less risk of neurotoxic effects: fentanyl or methadone (see Fast Fact #75). - Add an infusion of a non-opioid NMDA receptor antagonist such as ketamine (see Fast Fact #132). - Add a non-opioid adjuvant such as gabapentin, baclofen, acetaminophen or an NSAID. - Initiate epidural, intrathecal, regional or local anesthesia and taper/discontinue systemic opioids. - Increase hydration if clinically appropriate. Conclusion Opioids can lead to a paradoxical increase in pain. Opioid-induced hyperalgesia should be considered in any patient with increasing pain that is not responding to increasing opioids. Referral to pain/palliative care professionals is appropriate to help develop a management strategy.

#70 PRN Range Analgesic Orders

Considerations for writing and interpreting PRN range opioid orders: Avoid therapeutic duplication consisting of more than one type of PRN opioid by the same route. If PRN opioids from different routes are ordered, give clear indication for use (i.e., use oral route unless patient is NPO or vomiting, use IV route prior to dressing change) Avoid prescribing a dose based on pain ratings. While severe pain may require more aggressive analgesic treatment a nonlinear relationship has been demonstrated between opioid dose and the visual analog scale. There is high variability in individual responses to opioid doses. Reasonable range. A range order should be large enough to provide options for dose titration, but small enough to ensure safety. The maximum allowable difference for analgesic dose range orders should be no more than four times the lowest dose (eg. four times 2 mg is 8 mg). Patient's prior drug exposure. If the patient is opioid-naïve, the first dose administered should be the lowest dose in the range; if the patient is opioid tolerant or has received a recent dose with inadequate pain relief and tolerable side effects, utilize a dose on the higher end of the range. Prior response. Inquire about this patient's response to previous doses. How much relief did prior doses provide, and how long did it last? Did the patient experience side effects? Age. For very young or elderly patients, start low and go slow. Liver and renal function. If your patient has hepatic or renal insufficiency, anticipate a more pronounced peak effect and a longer duration of action. Pain severity. As a general rule, for moderate to severe pain increase the dose by 50-100%; do not increase by >100% at any time. To "fine-tune" the dose once pain is at a mild level, increase or decrease by 25%. Anticipated pain duration. Is the pain acute, chronic, or progressive (likely to worsen)? In other words, is the patient likely to require more or less analgesic over time? Kinetics. Know the onset, peak, and duration of action for the specific drug ordered. Unlike scheduled long-acting opioid formulations, doses of short-acting opioids can be increased at each specified dosing interval, Co-morbidities. Debilitated patients, or those with respiratory insufficiency, may be at more risk for hypoxia. Use of other sedating drugs. When other CNS depressants are administered in combination with opioids, the dose of each medication required to achieve the desired effect may be 30-50% less than if either drug was administered alone. Combination drugs. Limit doses of combination drugs: opioids with acetaminophen or an NSAID. Average adults should not receive more than 4000 mg of acetaminophen in 24 hours. If substantial upward dose titration is required or anticipated, use opioid-only preparations. Avoid administration of a partial dose. Partial doses at more frequent intervals may result in ineffective pain relief and create time delays in the ability to administer a full dose within the allowed range (i.e. giving oxycodone 5mg every hour when the order reads 5-15mg every 3 hours). Example: Opioid naïve patient arrives with the order 'Morphine sulfate 2-6 mg IV every 2h PRN pain.' Give 2 mg for first dose. Reassess within 30 minutes. If adequate relief, reassess within next 2 hours. If no side effects but inadequate relief - may give 4 mg more in 30 minutes or when time to peak effect has passed from first dose. Total dose therefore is 6 mg in a 2-hour period. Document patient response to PRN dosing: - Reassess pain relief, side effects and adverse events produced by treatment, and the impact of pain and treatment effects on patient function, once sufficient time has elapsed to reach peak effect: 15-30 minutes after parenteral drug therapy or 1 hour after oral administration of a PRN analgesic or non-pharmacologic intervention. - Reassessments may be done less frequently for patients with chronic stable pain or for patients who have exhibited good pain control without side effects after 24 hours of stable therapy

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

Correct! 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

A long-term kidney hemodialysis patient who does not have any urine output wants to know how long she would likely survive if she stopped dialysis. The best response would be to say that the average patient in her clinical situation who stops dialysis survives approximately (Fast Fact #191: Prognostication in End-stage Renal Disease Patients Receiving Dialysis): 1-3 days 5-12 days 2-3 weeks 1-2 months

Correct! A 2013 study of 1947 patients who discontinued dialysis found the mean survival was 7.4 days (range, 0-40 days) . Reference: O'Connor NR1, Dougherty M, Harris PS, Casarett DJ. Survival after dialysis discontinuation and hospice enrollment for ESRD.Clin J Am Soc Nephrol. 2013; 8 (12):2117-22. See Patient information from the National Kidney Foundation:

A long-term kidney hemodialysis patient who does not have any urine output wants to know how long she would likely survive if she stopped dialysis. The best response would be to say that the average patient in her clinical situation who stops dialysis survives approximately (Fast Fact #191: Prognostication in End-stage Renal Disease Patients Receiving Dialysis): 1-3 days 5-12 days 2-3 weeks 1-2 months

Correct! A 2013 study of 1947 patients who discontinued dialysis found the mean survival was 7.4 days (range, 0-40 days) . Reference: O'Connor NR1, Dougherty M, Harris PS, Casarett DJ. Survival after dialysis discontinuation and hospice enrollment for ESRD.Clin J Am Soc Nephrol. 2013; 8 (12):2117-22. See Patient information from the National Kidney Foundation: 5-12 days

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.

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. Tramadol has an increased risk of hypoglycemia compared with morphine

Which of the following is a true statement regarding the analgesic effects of pregabalin in comparison to gabapentin (Fast Fact #289 Pregabalin vs Gabapentin)? - Gabapentin is approximately 3 times as expensive as pregabalin. - In head to head trials, gabapentin has been shown to be a more effective analgesic for neuropathic cancer pain. - Pregabalin can often be titrated to an effective dose range one week before gabapentin. - Gabapentin is a controlled substance while pregabalin is not.

Correct! Answer A is wrong because pregabalin is 3 times more expensive than gabapentin, not the other way around. In one small randomized controlled trial, pregabalin was shown to be associated with statistically significant lower visual analogue pain scales for neuropathic cancer pain in comparison to gabapentin, placebo, or amitriptyline, making answer B incorrect. Pregabalin is a controlled V substance per the DEA; as of now gabapentin is not a controlled substance. Published medical data suggest pregabalin can be titrated to an effective dose range at 1-2 days; whereas it often takes 9 days or longer to titrate to gabapentin's usual effective dose range of 900-1,800 mg/day.

Which one of the following is correct regarding a celiac plexus block for cancer pain (Fast Fact #97: Sympathetic Blocks)? Transient hypertension is a potential side effect The definition of a successful celiac plexus block is when opioids are no longer needed for cancer pain. A decreased opioid dose requirement is a potential benefit Sympathetic blocks cannot be repeated

Correct! Answer choice A is incorrect as the main side effects are related to loss of sympathetic tone and include transient hypotension and increased intestinal motility resulting in diarrhea. Answer choice B is incorrect as a patient should anticipate a decrease in pain and opioid requirements after the procedure, but a complete resolution of pain in which opioids are no longer needed rarely occurs. Answer choice D is incorrect as a sympathetic block may be repeated. A decreased opioid dose requirement is a potential benefit #97 Blocks of the Sympathetic Axis for Visceral Pain: In the palliative care setting, the most common indication for interrupting the sympathetic axis via a "nerve block" is to control visceral pain arising from malignancies of the abdominal and pelvic viscera. Visceral pain is often described as a deep, squeezing pain that is difficult to localize and characterize. When it is recalcitrant to meticulous pharmacologic and behavioral therapy, or if the patient is intolerant to pharmacotherapy, consultation should be sought to either a pain specialist or interventional radiologist for consideration of neurolytic procedures. Potential advantages of a neurolytic procedure, compared to spinal and epidural anesthetic techniques (see Fast Fact #98), include cost savings and avoidance of hardware (e.g., catheters, tubes, pump), which can be cumbersome, are subject to malfunction, and pose an infection risk.

Which of the following is correct regarding oral opioid orders for cancer pain (Fast Fact # 74 Oral Opioid Orders- Good and Bad)? - When prescribing fentanyl transdermal patch, also prescribe a long-acting oral opioid at bedtime for anticipated nocturnal pain - Prescribe a short acting opioid for breakthrough pain - The fentanyl transdermal patch can be safely dose escalated every 24 hours - The peak effect of most available short acting opioids is typically 6 hours

Correct! Answer choice A is incorrect because only one long acting opioid should be written for at a time. Answer choice C is incorrect because the fentanyl transdermal patch can only be safely dose escalated every 3 days. Choice D is incorrect because the peak effect of short acting opioids is typically 1-2 hours.

Mr. K, a 68 year old male with a history of metastatic melanoma, presents with arm pain due to a humerus metastasis. He has no other known sites of bone lesions and no associated neurologic deficits. You recommend radiation therapy and advise him on the process. Choose the best answer (Fast Fact # 66 and # 67: XRT for palliation): A standard radiation prescription for bone metastases is 800 cGy x 10 treatments Bones can only tolerate lower radiation doses than solid organs such as liver or kidneys Each radiation treatment will last 2-3 hours One of the most anticipated side effects is fatigue

Correct! Answer choice A is incorrect, a standard course is 300cGy x 10 treatments. Answer choice B is incorrect because bone and peripheral nerves typically can tolerate a much larger total radiation dose as compared to liver and kidneys. Answer choice C is incorrect because each daily treatment will typically last minutes.

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. No further testing is necessary

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

Correct! 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. Xerostomia (dry mouth)

As defined by Dame Cicely Saunders, which of the following is one of the 4 essential domains of "total pain" (Fast Fact #417 Total Pain)? Neuropathy Nociception Social Financial

Correct! Dame Saunders and other hospice and palliative care experts recognized that serious illness can fundamentally disrupt previously established expectations for a patient's future. Four essential domains or components of "total pain" have been described: psychological pain; social pain; spiritual pain; physical pain. The interaction of these four domains is often complex and dynamic. Clinicians ofter overlook non-physical sources of pain and consequently treatable suffering can get missed or overmedicated. The total pain experience - an interactive model: The interaction among total pain components is often complex, yet evident in patients with serious illnesses (2,8-15). For example, loss of hope can have a spiritual, existential, and psychological dimension which may compound the intensity of physical pain if the patient attributes pain with impending death. As suffering intensifies, the family's sense of helplessness may compel them to visit the patient less frequently. Thus, physical pain may exacerbate social and psychological pain from a perceived sense of abandonment (8,12). Clinicians cannot fully care for patients with life-limiting illnesses without assessing for all domains of total pain. Since no one person or discipline can manage total pain, interdisciplinary teams (IDTs) are vital to address total pain.

Which antidepressant medication has shown effectiveness in treating chemotherapy-induce peripheral neuropathy per a 2013 randomized controlled trial (Fast Fact #187 Non-tricyclic Antidepressants for Neuropathic Pain)? Bupropion Duloxetine Venlafaxine Fluoxetine

Correct! Despite several trials assessing a multitude of different adjuvant analgesics (e.g. gabapentin, pregabalin, etc), the only non-opioid adjuvant analgesic to show efficacy in treating the pain associated with chemotherapy-induced peripheral neuropathy is duloxetine at a dose of 60 mg by mouth once a day. Of note, although venlafaxine has shown some efficacy in preventing chemotherapy-induced peripheral neuropathy, no trial to date has shown its efficacy in treating chemotherapy-induced peripheral neuropathy after the onset of the symptom.

Choose the functional status scale below that best matches the following descriptor. This functional scale was formalized in 1982. Published evidence has validated its usefulness in prognosticating overall survival for adults receiving chemotherapy for a variety of solid tumors. Scores greater than 2 on this scale have been correlated with a prognosis of 3 months or less in patients with solid cancers in the pre-immunotherapy era (Fast Fact #416 Functional Status Assessment in Serious Illness). Eastern Cooperative Oncology Group (ECOG) Performance Scale Edmonton Functional Assessment Tool (EFAT) Karnofsky Performance Status (KPS) Palliative Performance Scale (PPS)

Correct! ECOG is a 5-point global functional scale with 0 set as a normal functional status without any noted limitations and 4 being a moribund functional status. Higher scores have been correlated with shorter survival in many malignant conditions. ECOG does not appear to correlate with anticipated survival as accurately in non-malignant illnesses. EFAT is a more involved scale that assesses 10 different domains and is most commonly utilized in research, not clinical settings. KPS is a 100 point scale that evaluates functional status; scores 50 or less have correlated with a shorter prognosis in patients with cancer. PPS is a modernized version of the KPS and is commonly utilized in hospice or palliative care units as a prognostic tool for patients with comfort-focused goals of care. Eastern Cooperative Oncology Group (ECOG) Performance Scale

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): 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. 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. 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.

Which one of the following statements about intravenous (IV) hydration in the last week of life is TRUE (Fast Fact #133 Non Oral Hydration in Palliative Care): maintaining IV hydration will improve pain management maintaining IV hydration will prevent dry mouth stopping IV hydration will lead to painful muscle cramps stopping IV hydration will lessen dyspnea associated with renal failure

Correct! For many years it was considered standard practice that all dying patients in the hospital setting receive intravenous fluids, with the thinking that such care improved symptoms of the dying process. However scant data exists to support this claim for most patients. It is true that in settings where fluid accumulation is a problem, such as in renal, liver or heart failure, intravenous hydration can worsen dyspnea

A 2012 systematic review identified these three clinical factors as having the strongest association with a 6-month or less prognosis in elderly patients with advanced dementia (Fast Fact #150 Dementia Prognosis): Malnutrition, feeding issues, and dysphagia Karnofsky performance status, creatinine levels, and age Presence of pressure ulcers, urine or fecal incontinence, and a FAST staging score Need for supplemental oxygen, Mini-Mental Status Examination (MMSE) score, and Charlson Comorbidity Index score

Correct! Identifying reliable and verifiable clinical factors which correlate with a prognosis of < 6 months has been difficult in advance dementia. This has made it challenging for clinicians to successfully identify patients who are appropriate for enrollment in hospice. Although the NHPCO guidelines utilize a FAST score of 7c or worse as an indicator for hospice enrollment for dementia, a 2012 systematic review found that malnutrition, feeding issues, and dysphagia had the strongest association with death in 6 months or less. Malnutrition, feeding issues, and dysphagia

Which one of the following represents potential "splitting" behavior (Fast Fact #252 Borderline Personality): A family that expresses concern that the clinician is not being aggressive enough A family that expresses anger when told that there are no further disease modifying treatments. A patient who requests a second opinion A patient who says "you are the only clinician who has ever been helpful"

Correct! Individuals with BPD have difficulty sustaining ambivalent feelings and may instead label clinicians as either "wonderful" or "terrible", a defense mechanism known as "splitting". A patient who says "you are the only clinician who has ever been helpful"

"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

Correct! 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.

When a referring clinician wants to broach the subject of a palliative care specialty consultation with a patient and family, which one is the best suggested phrases to use (Fast Fact #42 Broaching the Topic of Palliative Care Consultation with Patients and Families): II Palliative care clinicians have special expertise in managing dying patients. Palliative care clinicians work together as an interdisciplinary team. Palliative care clinicians can help you and your family deal with the changes brought on by your illness. Palliative care clinicians are most useful when there is nothing more that can be done.

Correct! Many clinicians struggle to find the right words to introduce the concept of palliative care to their patients, fearful of provoking anxiety or anger. Option c) is a neutral statement that can apply to any palliative care consultation, no matter what the diagnosis or prognosis. In contrast, option a) is linked to the dying process, which does not fit the broad role for palliative specialists. Option b) is correct, but is not specific to palliative care, as other clinicians work in teams and option d) is a false statement, since there is never a time when "nothing more can be done".

All of the following are examples of real-time mindfulness exercises which may help reduce healthcare professional burnout EXCEPT (Fast Fact # 316 Mindfulness): Self-guided body scan in which the clinician attends to bodily sensations and natural reactions without altering the perceptions. Anticipating the triage order of the next 3 inpatient consultations while examining a patient. Purposefully taking 4-5 long deep breaths, paying particular attention to exhalations during a difficult patient encounter. Prior to seeing a new patient, mentally visualize close loved ones while sitting in a relaxed chair in the clinician workroom and acknowledge the emotions associated with these loved ones.

Correct! Mindfulness has been defined as "paying attention on purpose, in the present moment, and nonjudgmentally, to the unfolding of experience moment to moment." Although mindfulness techniques with the most robust clinical evidence supporting them require time-intensive training, recently several easy-to-perform, quick mindfulness techniques have been described in the medical literature as being potentially effective in mitigating burnout. Answer A is a description of a known mindfulness technique called a body scan. Answer D is a modified description of Loving-Kindness Meditation. Answer C is a commonly advocated technique of utilizing a short succession of deep breaths to interrupt the "Flight or Fight" stress response. Answer B provides an example of future thinking that may distract the clinician by taking him or her out of the present moment and perhaps compound the present level of stress experienced during the patient encounter. Examples of Mindfulness Exercises (2,12): Body Scan: led- or self-guided meditation focused on recognizing bodily sensations and the natural reactions without trying to alter the perceptions, but rather employing unbiased concentration. Loving-Kindness Meditation: focused attention on warm, loving feelings for close loved ones followed by redirection of those feelings towards the self and larger circles of others. Walking Meditation: relaxed, leisurely gait with direct focus on the experience and feelings associated with the movement. Mindful Movement: disciplined, relaxing movement coupled with attention centered on the physical experience and emotional response to the actions rather than focus on the activity itself. Practical Real-Time Mindfulness Approaches: Concentrating on the present moment by setting aside electronic devices and avoiding the distractions of multitasking. In the thick of a difficult situation, complete a brief breathing exercise by taking four to five long deep breaths focusing on the relaxing effects of purposeful deep breathing. Take the few moments during hand washing to focus attention on the sensations of the water's temperature and scent of the soap. In a relaxed and comfortable position such as a desk chair in a quiet clinician workroom, mentally visualize close loved ones and the emotions associated with them. Then, perceptually transition those feelings to other family, friends, and colleagues. While relaxed in a chair, respite room, or in the hospital chapel, sequentially concentrate on the position and sensations of the body starting with the feet and gradually transition focus superiorly. Summary Stress and burnout are significant concerns within the healthcare community. While the most evidence-based mindfulness educational programs are comprehensive and time intensive, mindfulness activities made simple to learn and easy to access may mitigate the effects of burnout.

Which of the following statements is TRUE regarding the Screener and Opioid Assessment for Pain Patients (SOAPP) and the Opioid Risk Tool (ORT) screening tools for potential opioid misuse (Fast Fact #244: Screening for Opioid Misuse and Abuse)? Only the SOAPP tool has been validated in cancer patients Scores above a certain threshold on the SOAPP tool are diagnostic for opioid misuse. The ORT tool is best designed for lower risk clinical settings such as a primary care clinic. Family history of chronic pain is one of the 5-item yes/no questions on the ORT tool

Correct! Neither the SOAPP or the ORT has been validated in cancer patients nor in patients with advanced illnesses so (a) is incorrect. Both the SOAPP and ORT tools are designed to identify high-risk patients appropriate for close monitoring, but neither are diagnostic tools so answer (b) is correct. Answer c is correct because clinicians administering the ORT tool can be misled by patients with a history of opioid misuse who downplay past behavior, therefore it's use in higher risk clinical settings such as a pain management clinic with a high prevalence of addiction would be less than ideal. Family history of substance abuse, not chronic pain, is one of the 5 items screened for on the ORT tool.

A 43 year-old cyclist is intubated in the ICU after sustaining multiple fractures and brain trauma after being hit by an intoxicated driver. She has multiple skull fractures with bilateral intraparenchymal hemorrhage. Her Glasgow Coma Scale (GCS) remains 2/15 after 2 weeks in the ICU. Her pupils don't respond to light and she does not withdraw to noxious stimulus but still has EEG activity and some brain stem reflexes; she does not meet brain death criteria. The power of attorney for health care and family reach consensus that she would not want to continue pursuing life-prolonging therapies, and request that all artificial life-support be discontinued. They request that her organs be donated in accordance with her wishes. 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. 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.

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

Correct! 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.

Choose the best answer regarding the pharmacologic properties of tapentadol in comparison to traditional opioids such as morphine or oxycodone (Fast Fact #228 Tapentadol). Opioids like morphine have a centrally acting analgesic effect in the brain and spinal cord; tapentadol has a peripheral analgesic effect in the soft tissues. Opioids like morphine are stronger inhibitors of norepinephrine and serotonin reuptake than tapentadol. Tapentadol has no mu-opioid receptor activity, while traditional opioids are mu-opioid receptor agonists. Randomized controlled trials suggest that tapentadol may have less gastro-intestinal side effects, such as constipation or nausea, than traditional opioids.

Correct! Tapentadol is a centrally-acting, synthetic, oral mu-opioid receptor agonist which also inhibits norepinephrine and serotonin reuptake within the CNS. Therefore, answers A-C are incorrect. Structurally it is quite similar to a traditional opioid, although it tends to be costlier. A pooled analysis of randomized controlled trials suggest that gastro-intestinal side effects are likely milder with tapentadol than other opioids (Etropolski M, Kuperwasser B, et al. Safety and tolerability of tapentadol extended release in moderate to severe chronic osteoarthritis or low back pain management: pooled analysis of randomized controlled trials. Adv Ther 2014; 31:604-620). Randomized controlled trials suggest that tapentadol may have less gastro-intestinal side effects, such as constipation or nausea, than traditional opioids.

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.

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.

Correct! 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.

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. Prognosis of the underlying serious illness is an important patient selection factor

You are caring for a dying lung cancer patient who is receiving a morphine intravenous infusion for bone pain and dyspnea. The patient has not been eating or drinking the past four days and is sleeping most of the time. Over the next 24-48 hours the patient becomes less responsive, with an irregular breathing pattern, and a bluish discoloration of her feet. What is the most appropriate action to take (Fast Fact #39 Inpatient Naloxone)? Discontinue the morphine infusion and administer a one-time dose of naloxone 0.4 mg Discontinue the morphine infusion and administer a one-time dose of naloxone 0.04 mg Discontinue the morphine infusion and only administer naloxone if oxygenation as measured by pulse-oximetry falls below 88%. Continue the morphine infusion at its current dose

Correct! The patient is actively dying as evidenced by her declining functional status without reversible cause, which has now progressed to breathing changes and mottling. The morphine infusion is appropriate for management of her underlying pain. There is no rationale to discontinue or reduce the current morphine dose as any dose reduction may result in inadequate symptom control at the end of life. Administering naloxone is not appropriate in this patient.

As you near the end of a clinical work day, you notice a physician colleague on a computer purchasing international airline tickets. You excitedly ask your colleague about his travel plans, but your colleague replies that he is purchasing the tickets for an ill patient, not for his own travel. Your colleague then states that he still has regretful feelings for not traveling overseas to visit his own mother prior to her death. Therefore, he feels compelled to purchase these airline tickets for his patient so that the patient can visit certain family members prior to her death. What would be the best response (Fast Facts #167-170, 172 Health Professional Burnout)? Nominate your colleague for a patient service award for going 'above and beyond' for an ill patient. Offer to coordinate a money collection with other clinicians involved in the patients care to off-set the financial cost of the airline ticket purchase Discuss with your colleague that he may be exhibiting signs of burnout and may need professional counseling Advise your colleague to call the patient's relatives and advise them to come to visit the patient instead.

Correct! There are several 'red flags' in this case that should alert the clinician to boundary issues and health professional burnout symptoms among their colleagues. First, expensive gift-giving to a patient is a recognized warning sign for boundary blurring between clinician and patient. Also, there is concern that the colleague may be making this airline purchase to address his own's emotional needs, rather than a therapeutic need of the patient. Boundary blurring is a recognized sign of health professional burnout and it is also a risk factor for health professional burnout. Helping the colleague to recognize this would be the most appropriate response as would encouraging the colleague to seek out professional counseling. Discuss with your colleague that he may be exhibiting signs of burnout and may need professional counseling

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).

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

Correct! 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.

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

Correct! 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. Introduction Dyspnea is defined as a subjective sensation of difficulty breathing. This Fast Fact reviews key elements in the assessment and treatment of dyspnea near the 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). Family/Team Discussions While there is no evidence that proper symptom management for terminal dyspnea hastens death, the course and management of terminal dyspnea, especially when opioids are used, should be fully discussed with family members, nurses and others participating in care to avoid confusion about symptom relief vs. fears of euthanasia or assisted suicide (see Fast Fact #8).

#164 Informed Consent in Palliative Care - Part 1

Definition Informed consent is a process, not a signature, whereby a physician discloses key information to help patients make a choice among healthcare options. The informed consent process requires that three conditions be met: a) the patient is able to make a voluntary choice, b) the patient is informed (see below), and c) the patient has the capacity to make medical decisions. Legal Standard The legal standard of informed consent varies between states. Some use: what a reasonable patient would want to know; in other states the standard is, what a reasonable physician should provide. A failure to meet the legal standard may meet the threshold for liability. Information No matter which legal standard is operational, the consensus among national medical and ethical organizations is that following information should be provided to meet the spirit of the informed consent doctrine: - The patient's diagnosis, if known; - The nature, purpose, risks and benefits of a proposed treatment or procedure; - The nature, purpose, risks and benefits of alternative treatments or procedures; - The risks and benefits of not receiving or undergoing a treatment or procedure. Emergency Exception to Informed Consent—physicians may proceed with treatment in emergency situations when all of the following criteria are met: - Life threatening emergency and time is of the essence. - Patient is not decisional and no legal surrogate decision maker is available. - Reasonable person would consent to the emergency treatment. Summary The purpose of the informed consent doctrine is to promote autonomy of the individual in medical decision making (Meisel 1996). However, the informed consent process is often viewed by physicians as being counter to an equally desirable social goal - a physician's responsibility for a patient's well-being and promotion of health.

A 74 year old woman with metastatic breast cancer is seen in palliative care clinic with recent onset diarrhea. She notes three days of liquid stool and worsening diffuse abdominal pain. One month ago, the patient was treated for clostridium difficile infection shortly after her last dose of systemic chemotherapy. One week ago, she presented to the clinic with worsening L sided chest pain attributed to tumor invasion into her L chest wall. At that time she was given prescriptions for dexamethasone and an increased dose of oxycodone. She reports that since then her pain has improved but her po intake for liquids and solids has greatly diminished. She denies nausea, vomiting, fevers, melena, or bloody stools.Which of the following is the most likely cause of her diarrhea? Constipation Recurrent clostridium difficile infection Chemotherapy side effect Bacterial gastroenteritis

Diarrhea is a common symptom in patients with serious illness including cancer. This patient's recent increased opioid dose combined with her decreased fluid intake place her at significant risk for constipation (answer a). When patients are severely constipated, "overflow diarrhea" can occur in which liquid stool is all that is able to pass around the area of impaction. While recurrent c.difficile infection (answer b) is possible, the onset of diarrhea shortly after an opioid dose increase and decreased oral intake makes constipation more likely. Chemotherapy-induced diarrhea (answer c) is unlikely as the patient stopped this treatment weeks prior to the onset of this symptom. Bacterial gastroenteritis (answer d), while also possible, is less likely given the lack of other signs and symptoms of infection and the patient's high risk for constipation. Constipation

Opioids for Chronic Pain in Patients with History of Substance Use Disorders - Part 2: Management and Monitoring

Fast Fact #311 discussed the assessment and initiation of opioid therapy in patients with a history of a substance use disorder (SUD). This Fast Factwill highlight expert suggested strategies for opioid monitoring in this patient population. Patient Monitoring: Adherence checklists, electronic drug monitoring databases, and individual/group counseling can reduce opioid abuse in high-risk patients (1). Only one clinician and pharmacy should be utilized in providing opioids. Regular follow up visits should be scheduled to assess the "Four A's of Pain" before and after every intervention (2,3): analgesia (pain relief);activities of daily living (functional status);adverse effects; aberrant drug-taking behaviors. Aberrant Drug Behaviors are not all the same, each behavior should be evaluated based on the specific patient and situation. Clinicians should assess the degree of risk involved with the aberrant drug behavior. Considerations include the extent of the aberrant behavior, including whether it has persisted despite attempts to correct it, if the patient is actively using, the type of substance (opioids, alcohol, methamphetamine, cocaine, cannabis), as well as level of abuse (daily intoxication, binge use). General Strategies Ask patients if they are using other substances or using their opioids to get high or emotionally cope with stressors. Remind patients that these are routine questions asked to all patients. Schedule more frequent visits, provide shorter-term prescriptions, and readdress opioid agreements. Intensify non-opiate pain strategies. Patients who are using illegal drugs or alcohol. In addition to the general strategies, consider the type of substance: If cannabis or alcohol, perform a patient specific assessment: is there evidence of loss of control or adverse consequences? Taper opioids or intensify monitoring depending on the scenario. If cocaine, methamphetamine, or heroin, consider patient's prognosis. Either taper and discontinue opioids or negotiate use in a highly structured environment and/or ongoing addiction treatment. 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. Opioid Diversion: Opioid diversion is a serious public health threat with legal ramifications. Patients actively using controlled substances have a higher risk for diversion. Voluntary diversion occurs when a patient prescribed a controlled substance knowingly transfers it to another person. This can range from "sharing" one or two pills with others to patients selling some or all of the prescribed medications. Treatment teams should inform patients at the beginning of treatment that sharing medication is not permitted, and lost or stolen medications will not be replaced. Patients who share medications in small amounts (e.g. giving a pill to a spouse who has acute pain) should be re-educated on the dangers involved and be reminded of opioid agreements/clinic policies. Suspected diversion of large amounts of medication should be verified by calling the patient in for a pill count and UDS in the middle of the prescribing period. Clinicians should discontinue opioid therapy in patients with whom they have a reasonable degree of suspicion for diversion. Consideration should be given to notification of local police. Involuntary diversion occurs when a controlled substance is stolen from a patient without their knowledge. This happens more frequently in patients with unstable housing and/or family dynamics. Clinicians should discuss safety strategies with patients (e.g. lock boxes) and perform pill counts. Clinicians should utilize the help of social workers in determining if exploitation of a vulnerable adult is occurring which could necessitate the involvement of police or adult protective services. Consider weaning opioids if involuntary diversion continues given negative public health effects or placing the patient in a more supervised setting such as a nursing home or an inpatient hospice. Admission to the hospital to monitor pain management can be a useful management step in situations in which clinicians are suspicious for voluntary or involuntary diversion.

Which one of the following is an appropriate opioid analgesic order (Fast Fact #70 PRN Range Orders)? Oxycodone immediate release 5 mg PO q2h prn for back pain + Morphine immediate release 15 mg PO q2h prn for abdominal pain Morphine immediate release 15 mg po q2 hours prn for partially controlled pain, 30 mg q 2hour for uncontrolled pain Morphine 4 mg IV q6h prn Hydromorphone 0.2 mg IV q2h prn, reassess in 30 minutes, if inadequate relief without side effects, may give 0.4 mg more in 30 minutes

Hydromorphone 0.2 mg IV q2h prn, reassess in 30 minutes, if inadequate relief without side effects, may give 0.4 mg more in 30 minutes. Answer choice A is incorrect because there should not be therapeutic duplication consisting of more than one type of PRN opioid by the same route. Answer choice B is incorrect since the order contains vague parameters (partially controlled or uncontrolled) which can be interpreted differently by different health care providers, patients and families. Answer choice C is incorrect because morphine has a duration of action of only 2-4 hours.

Which of the following is a recognized pharmacologic benefit of IV acetaminophen (Fast Fact #302 IV vs PO Acetaminophen)? IV acetaminophen has higher mean cerebrospinal fluid concentrations than oral acetaminophen. IV acetaminophen has a longer duration of action than oral acetaminophen. IV acetaminophen has a lower number needed to treat (NNT) for a 50% reduction in post-operative pain compared with oral acetaminophen at equivalent dosing. IV acetaminophen has been shown to be a more cost-effective way to manage terminal fevers in comparison to oral acetaminophen

IV acetaminophen has higher mean cerebrospinal fluid concentrations than oral acetaminophen. Peak analgesic effect of IV acetaminophen may only be 10 minutes vs 1 hour for oral acetaminophen. This is likely due to the higher CSF concentrations with IV over oral acetaminophen. Hence, there has been great interest in IV acetaminophen as a better peri-operative analgesic when quick and controlled analgesic onset is desired. B is wrong because the duration of action is essentially equivalent between oral and IV. Both the high cost and recent trials which have shown that IV acetaminophen did not have a lower NNT in comparison to oral acetaminophen in achieving 50% analgesia (in fact oral acetaminophen NNT was 3.8 compared with 5.3 for IV acetaminophen), have dampened some of the excitement about IV acetaminophen as a perioperative analgesic. IV acetaminophen has not been well studied for use in the terminally ill. Safety IV acetaminophen can be safely administered at doses of 1000 mg in patients who weigh over 50 kg, with a maximum daily limit of 4000 mg. For patients and children over 2 years, who weigh less than 50 kg, the dose is weight based at 15 mg/kg. Given its favorable first pass effects, the theoretical risk of hepatotoxicity with IV acetaminophen is believed to be low. A review of the literature suggests that when hepatotoxicity occurs, it is mostly due to dosing errors and can be potentiated by malnutrition (11). Of note, IV acetaminophen overdose has no validated nomogram for treatment decision-making. The most common side effects are similar to oral acetaminophen and include nausea, vomiting, and insomnia (12). Cost IV acetaminophen costs more than 20 times the equivalent dose of oral acetaminophen. Therefore, there is controversy whether IV acetaminophen is a cost-effective analgesic.

#326 Illness Trajectories: Description and Clinical Use

Illness trajectories can provide a framework for addressing patient and family expectations of what will happen with regards to their anticipated health. Distinct illness trajectories have been recognized in the medical literature (see Figure 1). This Fast Fact will review the medical evidence of these trajectories as well as their utility as a patient teaching tool. General Evidence: A large observational study, described distinct illness trajectories at the end of life for frailty/dementia, cancer, and organ failure (1). Subsequent research has cast some controversy about the validity of these findings, particularly whether hospitalizations may have a more significant role on the pattern of decline than the specific illness itself (2-4). Organ failure: A more erratic trajectory with punctuated periods of decline likely correlating with acute exacerbations (1). Each exacerbation may result in death but is often survived with gradual deterioration in health and functional status. Timing of death is less certain than in cancer. Perhaps as a result, patients with congestive heart failure (CHF) and chronic obstructive pulmonary disorder are more likely to die in the hospital and less likely to receive hospice services nor understand the likely progression of their illness (9-12). Other take home points regarding the organ failure trajectory include: - The functional decline for CHF has been shown to be particularly heterogeneous (2,13). Some hypothesize this may be related to co-morbidities and/or research methodologies (13). - Often prognosis is more centered around patient specific goals regarding acceptance or not of repeat hospitalizations and treatment of potentially reversible complications. - Although observational studies have shown inconsistent findings, elderly end stage renal disease patients who forgo initiating hemodialysis may be more likely to have an illness trajectory similar to sudden death - stable function for months with a rapid end of life deterioration (14-16). Sudden Death or Decline: An abrupt change from normal physical function to either death or significant medical disability, often as a result of trauma or an acute cardiopulmonary/neurologic event. Many times there is little or no prior interaction with the health system nor a recognizable pattern of functional decline preceding the event (1,9). Thus, intense displays of shock or anger are common from family members when clinicians break bad news. See Fast Fact #305. Loved ones are at increased risk for depression and complicated grief as they adjust to the new medical reality after the event (17,18). Clinical Use: Although there is no known published data assessing the effectiveness of utilizing the illness trajectories as a clinical teaching tool, describing or even diagramming these illness trajectories with patients and families may be a concise communication technique to set expectations and offer guidance regarding the anticipated impact of chronic illness on daily life. Clinicians should be aware of the significant variability in the medical literature regarding the validity of these illness trajectories as well as the limitations in the way functional decline is measured between studies. Therefore, it is vital that illness trajectories be reevaluated as the condition evolves. In particular, certain patterns such as an abrupt functional decline or frequent hospitalizations may indicate the need to readdress goals of care.

#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) Example: Change 90 mg q12 Extended Release Morphine to Morphine by IV continuous infusion Calculate the 24 hour current dose: 90mg q 12 = 180 mg Morphine/24 hours Use the oral to parenteral equianalgesic ratio: 30 mg PO Morphine = 10 mg IV Morphine Calculate new dose using ratios: 180/30 x 10 = 60 mg IV Morphine/24 hours or 2.5 mg/hour infusion 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. Calculate the 24 hour current dose: 90 Q12 x 2 = 180 mg PO Morphine/24 hrs Use the equianalgesic ratio: 30 mg PO Morphine = 7.5 mg PO Hydromorphone Calculate new dose using ratios: 180/30 X 7.5 = 45 mg oral Hydromorphone/24 hours. 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. Calculate the 24 hour current dose: 90 Q12 x 2 = 180 mg PO Morphine/24 hrs Use the equianalgesic ratio of PO to IV morphine: 30 mg po Morphine = 10 mg IV Morphine Calculate new dose using ratios: 180/30 x 10 = 60 mg IV Morphine/24 hours Use the equianalgesic ratio of IV Morphine to IV Hydromorphone: 10 mg Morphine = 1.5 mg Hydromorphone Calculate new dose using ratios: 60/10 x 1.5 = 9 mg IV Hydromorphone/24 hours Reduce dose 50% for cross-tolerance: 9 x 0.5 = 4.5 mg/24 hours = 0.2 mg IV continuous infusion 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

#234 Prognosis of Anoxic-Ischemic Encephalopathy

Introduction Cardiac arrest, experienced by approximately 450,000 Americans annually, has a very poor survival rate (see Fast Fact #179). Some patients who initially survive cardiopulmonary resuscitation remain comatose, demonstrating obvious impairments in consciousness and neurologic function. This syndrome, called anoxic-ischemic encephalopathy (AIE, also known as 'anoxic brain injury,' or 'hypoxic-ischemic coma'), can result in outcomes ranging from full recovery to permanent unconsciousness to death. This Fast Fact discusses prognostic factors in adults with AIE after cardiac arrest. "Neurologic Outcome" A challenge in interpreting the literature on AIE is the use of variable or imprecise definitions of a 'poor neurologic outcome.' The American Academy of Neurology practice parameter paper defines poor outcome as: death, persistent unconsciousness (such as a vegetative state), or severe disability requiring full nursing care after 6 months (6). This is the definition used in this Fast Fact. Predictors of Neurologic Outcome A review of the current literature reveals that data obtained by careful neurologic exam, electrophysiologic studies, and biochemical markers are most predictive of outcome (see below). Other factors not strongly predictive of outcome include: age, sex, cause of arrest, type of arrhythmia, total arrest time, duration of CPR, geographic location of arrest, elevated body temperature, elevated intracranial pressure, concurrent respiratory failure, and early brain imaging findings (3,6,7,8). Note: the data below assume patients are not receiving medications which would significantly confound their neurologic examination such as high-dose barbiturates. In all cases, specialist neurologic examination and input is advised. Strong Indicators of Poor Outcome (false positive rates of 0% based on current literature): Absent pupillary light reflexes 24 hours after CPR, or 72 hours after CPR for those who initially had intact papillary light reflexes (3,6,7). Absent corneal reflexes 72 hours post-CPR (6,7). Short-latency Somatosensory Evoked Potentials (SSEP, an electrophysiologic study): bilateral absence of the N20 potentials on SSEP of the median nerve in AIE patients greater than 24 hours post-CPR (1,6,7,8). Neuron-Specific Enolase (NSE, a blood test): serum NSE > 33 mcg/L on day 1 to 3 (6,7,8). While this biomarker is promising, it has not been studied in large trials, nor is the assay itself standardized, so its current clinical role remains undefined (7). Moderate Predictors of Poor Outcomes (these all predict a poor outcome, but not as invariably as the above factors based on current literature): Clinical exam findings: no spontaneous eye movements or absent oculocephalic reflexes at 72 hours post-arrest (3,6,7). No, or extensor-only, motor response to painful stimuli at 72 hours also implies a very poor chance of recovery (3,6). Electroencephalogram findings: certain findings can be strongly associated with poor outcomes but are highly subject to institutional/technician variability. Myoclonic status epilepticus within 1 day of cardiac arrest is the most predictive of a poor outcome (3,6,7,8).

#27 Dyspnea at End-of-Life

Introduction Dyspnea is defined as a subjective sensation of difficulty breathing. This Fast Fact reviews key elements in the assessment and treatment of dyspnea near the 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). Nebulized morphine has been reported to provide benefit in uncontrolled case reports, however a controlled trial demonstrated no greater efficacy or lower rate of side effects compared to subcutaneous morphine. Treatment with oxygen Oxygen is often, but not universally, helpful. When in doubt, a therapeutic trial, based on symptom relief, not pulse oximetry, is indicated in dying patients. A well-designed randomized, controlled trial of oxygen vs ambient air, delivered by nasal cannula, in normoxic patients with advanced illness and dyspnea showed no benefit of oxygen over ambient air delivered by nasal cannula. Patients generally prefer nasal cannula administration than a mask, especially in setting of imminent death when agitation from the mask is commonly seen. There is little reason to go beyond 4-6 L/min of oxygen via nasal cannula in the actively dying patient. Request a face-tent for patients who are claustrophobic from a mask. Treatment with other drugs Anti-tussives can help with cough (see Fast Fact #200), anit-cholinergics (e.g. scopolamine) will help reduce secretions, anxiolytics (e.g. lorazepam) can reduce the anxiety component of dyspnea. Other agents that may have specific disease modifying effects include diuretics, bronchodilators, and corticosteroids. Family/Team Discussions While there is no evidence that proper symptom management for terminal dyspnea hastens death, the course and management of terminal dyspnea, especially when opioids are used, should be fully discussed with family members, nurses and others participating in care to avoid confusion about symptom relief vs. fears of euthanasia or assisted suicide (see Fast Fact #8).

#42 Broaching the Topic of a Palliative Care Consultation with Patients and Families

Introduction Palliative care consultative services are becoming commonplace in academic and community hospitals and clinics. Patients and families may have negative perceptions of palliative care and hospice - viewing such a discussion as signaling that the physician is "giving up on the patient" and that the reality of impending death must be faced. For the attending physician, the decision to convey to a patient and family that a consultation is needed can provoke anxiety. Physicians may fear such a discussion will provoke anxiety, anger or a sense of hopelessness. First, decide why you want assistance from the palliative care team. Typically, physicians seek assistance in four domains: 1) pain and non-pain symptom assessment and management; 2) assistance in making difficult decisions, usually about continued use or withdrawal of potentially life-prolonging treatments such as feeding tubes, antibiotics, dialysis, or ventilators; 3) assistance in planning for the most appropriate care setting to meet patient/family goals for end-of-life care; and 4) providing psychological support to patients, families and the health care team. Second, contact the palliative care team. Discuss your reason(s) for consultation along with pertinent details of the patient's history and family support structure. Describe both what your goals are for the consultation, as well as what the family's/patient's goals may be. This is a good time to discuss any concerns you have about using the term palliative care with the patient or family. Third, engage the patient/family in a discussion of the current medical condition and goals of care. Introduce the topic of a consultation by saying: To best meet some of the goals we've been discussing (fill in with the goals mentioned by the family/patient) I'd like to have some consultants from the Palliative Care Team visit with you. You can follow this by saying, They are experts in treating the symptoms you are experiencing (fill in symptom). They are also good at helping your family deal with all the changes brought on by your illness; they can answer your questions about (fill in previously discussed patient questions). Finally, emphasize your continued involvement: You and I will talk about the recommendations of the palliative care experts. I'll make sure all your questions are answered. This can help relieve fears of abandonment. If a patient or family reacts negatively to the suggestion for a consultation, explore their concerns. Someone may have mentioned palliative care and this may have negative connotations to them. Ask, What experience do you have with hospice/palliative care? What are your concerns? It may be important to discuss that palliative care is compatible with aggressively treating the underlying disease. Emphasize the positive aspects of what palliative care can do, rather than focusing on how the palliative care team will help them accept death and dying. After all, the goal of palliative care is to achieve the best possible quality of life through relief of suffering, control of symptoms and restoration of functional capacity, while remaining sensitive to the patient and family's values. Palliative Care guides the patient and family as they face disease progression and changing goals of care, and helps those who wish to address issues of life completion and life closure.

#42 Broaching the Topic of a Palliative Care Consultation with Patients and Families

Introduction Palliative care consultative services are becoming commonplace in academic and community hospitals and clinics. Patients and families may have negative perceptions of palliative care and hospice - viewing such a discussion as signaling that the physician is "giving up on the patient" and that the reality of impending death must be faced. For the attending physician, the decision to convey to a patient and family that a consultation is needed can provoke anxiety. Physicians may fear such a discussion will provoke anxiety, anger or a sense of hopelessness. This Fast Fact provides tips for beginning a discussion leading to a visit by a palliative care consultation team. First, decide why you want assistance from the palliative care team. Typically, physicians seek assistance in four domains: 1) pain and non-pain symptom assessment and management; 2) assistance in making difficult decisions, usually about continued use or withdrawal of potentially life-prolonging treatments such as feeding tubes, antibiotics, dialysis, or ventilators; 3) assistance in planning for the most appropriate care setting to meet patient/family goals for end-of-life care; and 4) providing psychological support to patients, families and the health care team. Second, contact the palliative care team. Discuss your reason(s) for consultation along with pertinent details of the patient's history and family support structure. Describe both what your goals are for the consultation, as well as what the family's/patient's goals may be. This is a good time to discuss any concerns you have about using the term palliative care with the patient or family. Third, engage the patient/family in a discussion of the current medical condition and goals of care. Introduce the topic of a consultation by saying: To best meet some of the goals we've been discussing (fill in with the goals mentioned by the family/patient) I'd like to have some consultants from the Palliative Care Team visit with you. You can follow this by saying, They are experts in treating the symptoms you are experiencing (fill in symptom). They are also good at helping your family deal with all the changes brought on by your illness; they can answer your questions about (fill in previously discussed patient questions). You should not say that the reason you are asking Palliative care to be involved is "that there is nothing more to do" or because "I have nothing more to offer." Talk about the positive goals Palliative Care can help you and the patient achieve. Finally, emphasize your continued involvement: You and I will talk about the recommendations of the palliative care experts. I'll make sure all your questions are answered. This can help relieve fears of abandonment. If a patient or family reacts negatively to the suggestion for a consultation, explore their concerns. Someone may have mentioned palliative care and this may have negative connotations to them. Ask, What experience do you have with hospice/palliative care? What are your concerns? It may be important to discuss that palliative care is compatible with aggressively treating the underlying disease. Emphasize the positive aspects of what palliative care can do, rather than focusing on how the palliative care team will help them accept death and dying. After all, the goal of palliative care is to achieve the best possible quality of life through relief of suffering, control of symptoms and restoration of functional capacity, while remaining sensitive to the patient and family's values. Palliative Care guides the patient and family as they face disease progression and changing goals of care, and helps those who wish to address issues of life completion and life closure.

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

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 - Sarcopenia: diffuse muscle loss often associated with an increase in fat mass and abdominal circumference (2). - Anorexia: appetite reduction which can be psychogenic (anorexia nervosa) or secondary to an underlying(cannabinoids), #314 (mirtazapine), and #315 (olanzapine). - 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% (4,5). - 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). 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 (4,5). 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 (6-13). 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 (3,6-8). 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 (3). 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 (17) 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 (18-20). 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 (17). 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 (21,22). 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 (5,23).

#416 Functional Status Assessment in Serious Illness

Karnofsky Performance Status (KPS) Introduced in 1949, KPS is a commonly used 100-point scale that evaluates functional status in oncology settings (16). It can be administered reliably by a clinician without specialized training (ICC 0.787) and quickly (few minutes) in an office setting (17). It looks at patient's baseline activity levels, disease related disability, and dependence on caregivers to determine a numerical value of function on a scale of 0-100, with 0 being dead, and 100 no functional limitation (18). A KPS score 50 percent or less predicts a median life expectancy of two months for patients with a progressive underlying cancer (19). Eastern Cooperative Oncology Group (ECOG) Performance Scale One of the most used functional assessment tools in oncology, it was derived from KPS for its relative ease of use before being formalized in 1982 by ECOG (20). It is a 5-point global functional scale with 0 set as normal function without limitation and 4 being a moribund functional status. It only takes a few minutes to administer with 3-4 basic questions evaluating dependence on caregivers and ability to walk and perform self-care (20,21). This scale has good inter-operator reproducibility >0.8 (22), but there is growing literature that patient's self-reported ECOG and clinician ECOG do not always align (23). Of note, most efficacy trials of systemic cancer therapy have been limited to patients with an ECOG of 0 and 1 (20). ECOG ≥ 2 has been correlated with a prognosis of < 3 months in patients on chemotherapy for solid cancers, at least in the pre-immunotherapy era (24-29). In general, there is significant correlation of ECOG status and overall survival for adults receiving chemotherapy for a variety of solid tumors (24-29); but like KPS, it has correlated poorly with prognosis in non-malignant illnesses (20). Palliative Performance Scale (PPS) Commonly used in hospice settings or palliative care units, the PPS is a modernized version of KPS that also incorporates oral intake and level of consciousness. It has been shown to be a validated clinical assessment and prognostic tool in patients already identified as having palliative care goals (30). See Fast Fact #125 for more information. Edmonton Functional Assessment Tool (EFAT) was introduced in 2001 to evaluate functional status in palliative care inpatient units (31). It is reliable (ICC 0.97) (32), but because it evaluates 10 domains (communication, mental status, respiratory function, pain, mobility, balance, walking, ADLs, fatigue, and motivation), it can take up to 15 minutes for a clinician to complete (31). Therefore, it may be more applicable to research rather than clinical settings. Conclusion Given the association of functional status with quality of life and prognosis, clinicians should routinely implement functional assessment into the clinical care of patients with life-limiting illnesses. While there are insufficient data to broadly recommend any scale, clinicians should be familiar with validated functional assessment scales which can be applied to the relevant underlying illness.

#08 Morphine and Hastened Death

Main Teaching Points 1) Many physicians inaccurately believe that morphine has an unusually or unacceptably high risk of an adverse event that may cause death, particularly when the patient is frail or close to the end of his or her life. In fact, a large study of opioid use at the end of life from the US National Hospice Outcomes Project, as well as a systematic review of various other countries, found no difference in survival with absolute opioid dose or change in opioid dose. Furthermore, morphine-related toxicity will be evident in sequential development of drowsiness, confusion, then loss of consciousness before respiratory drive is significantly compromised. 2) Many physicians inappropriately call this risk of a potentially adverse event, a double effect, when it is in fact a secondary, unintended consequence. The principle of double effect refers to the ethical construct where a physician uses a treatment, or gives medication, for an ethical intended effect where the potential outcome is good (eg, relief of a symptom), knowing that there will certainly be an undesired secondary effect (such as death). An example might be the separation of conjoined twins knowing that one twin will die so that the other will live. Although this principle of "double effect" is commonly cited with morphine, in fact, it does not apply, as the secondary adverse consequences are unlikely. 3) When offering a therapy, it is the intent in offering a treatment that dictates whether it is ethical medical practice: a) if the intent in offering a treatment is desirable or helpful to the patient and the potential outcome good (such as relief of pain), but a potentially adverse secondary effect is undesired and the potential outcome bad (such as death), then the treatment is considered ethical: b) If the intent is not desirable or will harm the patient and the potential outcome bad, the treatment is considered unethical 4) All medical treatments have both intended effects and the risk of unintended, potentially adverse, secondary consequences, including death. Some examples are total parenteral nutrition, chemotherapy, surgery, amiodarone, etc. 5) Assisted suicide and euthanasia are not examples of "double effect." The intention in offering the treatment in assisted suicide and euthanasia is to end the patient's life. 6) If the intent for using morphine in the scenario is to relieve pain and not to cause death, and accepted dosing guidelines are followed: a) the treatment is considered ethical, b) the risk of a potentially dangerous adverse secondary effects particularly hastening death is minimal, and c) the risk of respiratory depression is vastly over-estimated.

Which of the following medications is least likely to be associated with myoclonus (Fast Fact #114 Myoclonus)? imipenem oxycodone phenobarbital midazolam

Myoclonus can result from multiple etiologies, ranging from metabolic derangements to focal CNS damage such as stroke. Many medications can result in myoclonus, including opioids, antiepileptic drugs, anti-depressants and antibiotics. When possible, the underlying cause should be identified and addressed. In the case of drug toxicity, the medication should be discontinued if not essential to therapy, or changed to a different agent if possible. At the end of life, if the causative agent cannot be reversed, refractory myoclonus can be treated with benzodiazepine medications (such as Midazolam). Although not relevant in the patient described above, midazolam has been an implicated cause of myoclonus in preterm infant population. midazolam

#143 Prognostication in Heart Failure

NYHA Classification The NYHA classification remains the major gauge of disease severity. Based on data from SUPPORT, Framingham, IMPROVEMENT, and other studies, 1-year mortality estimates are: Class II (mild symptoms): 5-10%. Class III (moderate symptoms): 10-15%. Class IV (severe symptoms): 30-40%. General Predictors of Shorter Prognosis: Cardiac hospitalization (triples 1-year mortality; nearly 1 in 10 die within 30 days of admission). Intolerance to neurohormonal therapy (i.e. beta-blockers or ACE-inhibitors) is associated with high 4 month mortality Elevated BUN (defined by upper limit of normal) and/or creatinine ≥1.4 mg/dl (120 μmol/l). Systolic blood pressure <100 mm Hg and/or pulse >100 bpm (each doubles 1-year mortality). Decreased left ventricular ejection fraction (linearly correlated with survival at LVEF ≤ 45%). Ventricular dysrhythmias, treatment resistant. Anemia (each 1 g/dl reduction in hemoglobin is associated with a 16% increase in mortality). Hyponatremia (serum sodium ≤135-137 mEq/l). Cachexia or reduced functional capacity. Orthopnea. Co-morbidities: diabetes, depression, COPD, cirrhosis, cerebrovascular disease, and cancer Hospice Eligibility Guidelines The National Hospice and Palliative Care Organization's 1996 guidelines for heart disease admission criteria include: a) symptoms of recurrent HF at rest (NYHA class IV) and b) optimal treatment with ACE inhibitors, diuretics, and vasodilators (contemporary optimal treatment now includes β-blockers, aldosterone antagonists, and device therapies). The NHPCO guide indicates that an ejection fraction < 20% is "helpful supplemental objective evidence," but not required. The NHPCO guidelines also assert that each of the following further decreases survival: treatment resistant ventricular or supraventricular arrhythmias, history of cardiac arrest in any setting, history of unexplained syncope, cardiogenic brain embolism, and concomitant HIV disease. Bottom Line Meticulous application of medication and device therapies can and will continue to change HF prognosis. HF follows an unpredictable disease trajectory, one which is highly mutable by application of evidence-based therapies, yet still marked by a high incidence of sudden death. The 1996 NHPCO criteria are not accurate predictors of 6-month mortality. Several models have recently been developed to aid in determining short- and long-term mortality in HF patients. These models await independent, prospective validation in unselected ambulatory HF patients and will need periodic updating to control for continually evolving standards of HF care. At present, accurate prognostication remains problematic.

#150 Prognostication in Dementia

Natural history of dementia Olson (2003) classifies dementia into four functionally defined categories: mild, moderate, severe, and terminal. 'Terminal dementia' is defined as loss of communication, ambulation, swallowing, and continence. Others use the term "end-stage" or "advanced" making interpretation of prognostic data challenging. Many prognostic factors have been associated with shortened survival: male gender, age, diabetes mellitus, CHF, COPD, cancer, cardiac dysrhythmias, peripheral edema, aspiration, bowel incontinence, recent weight loss, dehydration, fever, pressure ulcers, seizures, shortness of breath, low oral intake, not being awake for most of the day, low Body Mass Index, and recent need for continuous oxygen. A 2012 systematic review found that malnutrition, feeding issues, and dysphagia were the strongest associated factors with 6 month mortality in elderly patients with advanced dementia. Simply being admitted to the hospital with acute illness and end-stage or terminal dementia is associated with a particularly poor prognosis: the six month mortality after hospitalization for pneumonia was 53% compared with 13% for cognitively intact patients. For patients with a new hip fracture, 55% of end-stage dementia patients died within 6 months compared with 12% for cognitively intact patients (Morrison 2000). Prognostic Systems (see table below): The National Hospice and Palliative Care Organization (NHPCO) recommends the Functional Assessment Staging (FAST), a 7-step staging system, to determine hospice eligibility. The FAST identifies progressive steps and sub-steps of functional decline. NHPCO guidelines state that a FAST stage 7A is appropriate for hospice enrollment, based on an expected six month or less prognosis, if the patient also exhibits one or more specific dementia-related co-morbidities (aspiration, upper urinary tract infection, sepsis, multiple stage 3-4 ulcers, persistent fever, weight loss >10% within six months). Luchins (1997) studied the relationship of FAST to survival in 47 patients enrolled in hospice with advanced dementia and one or more dementia-related co-morbidities. The median survival for all patients was 6.9 months; 38% survived beyond six months. Of note, 41% of patients did not demonstrate dementia progression in a manner that allowed for assigning a FAST stage. For those patients who could be assigned a FAST stage (n = 12), and who were at stage 7C or greater, mean survival was 3.2 months. The Mortality Risk Index (MRI), a composite score based on 12 risk factor criteria obtained from using the MDS (Minimum Data Set), has been suggested as an alternative to FAST. Mitchell (2004) developed and then validated the MRI by examining data from over 11,000 newly admitted nursing home patients. Among patients with a MRI score of ≥ 12, 70% died within 6 months (mean survival time not reported). Compared to FAST Stage 7C, the MRI had greater predictive value of six month prognosis. The MRI as only been evaluated in newly admitted nursing home residents; it has yet to be validated in the community setting or for previously established long-term nursing home residents. Medical Interventions Estimation of prognosis in severe/terminal dementia is in part dependent on the goals of care and decisions regarding the level of intervention that will be provided to treat acute medical problems such as urosepsis and malnutrition. Summary Although many prognostic risk factors have been identified there is no gold standard to help clinicians determine a less than six months prognosis with any degree of certainty. The criteria adopted by NHPCO for hospice eligibility is based on very limited research and lacks important studies to determine FAST scale reliability and validity among referring physicians and hospice staff. The MRI is a promising new scale but more research is needed. Physicians can best help their patients by working with families to help them establish goals of care and levels of medical intervention that are most consistent with current medical research and family/patient preferences.

#328 Naloxone for Outpatients at Risk of Opioid Overdose

Opioid Overdose in Palliative Care Patients: Previous studies have suggested that opioid overdoses are infrequent for patients receiving palliative care (2). In recent years, however, palliative care clinicians have been more routinely involved in the outpatient treatment of cancer pain and, in some instances, may also manage pain in long-term cancer survivors and/or non-cancer pain (2-4). 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 (2). Pharmacology: Naloxone is an opioid antagonist indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. A needle-free formulation which is FDA approved for the emergency treatment of an opioid overdose is available via a pre-filled, single dose intranasal spray. 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 (9). 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 (8). In some states, it is available in pharmacies without a prescription. In a study of patients who received naloxone by paramedics, intranasal naloxone was found to be noninferior to intravenous naloxone regarding the reversal of sedation and respiratory rate (10). Indications For Outpatient Naloxone Prescribing: Co-prescribing of naloxone with prescription opioid medications is still the exception rather than a rule, especially in the palliative care setting. There is a concern that bystanders may administer naloxone inappropriately in seriously ill patients when physiological changes related to disease progression are mistakenly thought to be related to an overdose. The final decision about co-prescribing naloxone should be individualized based on a patient's risk profile, prognosis, care preferences, and the availability of an informed caregiver. 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 (6,11): - Daily morphine equivalent doses of > 100 mg/day (12,13) - Methadone as a prescribed analgesic (14) - Benzodiazepines and/or antidepressants in combination with opioids (15) - History of unintentional or intentional overdose (16) - History of a substance use disorder including alcohol or tobacco (17) - History of chronic pulmonary, renal, or hepatic disease (12) - A recent history of incarceration (18)

When a referring clinician wants to broach the subject of a palliative care specialty consultation with a patient and family, which one is the best suggested phrases to use (Fast Fact #42 Broaching the Topic of Palliative Care Consultation with Patients and Families): Palliative care clinicians have special expertise in managing dying patients. Palliative care clinicians work together as an interdisciplinary team. Palliative care clinicians can help you and your family deal with the changes brought on by your illness. Palliative care clinicians are most useful when there is nothing more that can be done.

Palliative care clinicians can help you and your family deal with the changes brought on by your illness. Correct! Many clinicians struggle to find the right words to introduce the concept of palliative care to their patients, fearful of provoking anxiety or anger. Option c) is a neutral statement that can apply to any palliative care consultation, no matter what the diagnosis or prognosis. In contrast, option a) is linked to the dying process, which does not fit the broad role for palliative specialists. Option b) is correct, but is not specific to palliative care, as other clinicians work in teams and option d) is a false statement, since there is never a time when "nothing more can be done"

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

Peripheral opioid receptor antagonism 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.

#313 Thirst in Palliative Care

Physiology Thirst is the desire to drink fluids in response to a water deficit. Social customs, dry mouth, accompanying food intake, fluid availability, and palatability all serve as cues to drink. Seriously ill patients encountered by hospice and palliative care clinicians are at risk for thirst due to dehydration, electrolyte disturbances, hypotension, xerostomia, and immobility which can impede access to water. Patients with heart failure (HF), with end stage renal disease (ESRD), on mechanical ventilation, and taking certain medications (e.g. anti-hypertensives, tolvaptan, diuretics, or SSRIs) are also at increased risk. While opioids cause xerostomia, whether or not they cause thirst is controversial (1,2). Thirst vs. xerostomia Thirst is the desire to drink, while xerostomia is subjective or objective dry mouth. While xerostomia can contribute to thirst, not all patients with dry mouth experience thirst. Similarly, thirsty patients may not have xerostomia present. Research studies often use xerostomia as a surrogate for thirst, making it difficult to evaluate the prevalence and treatment efficacy for either symptom independently. It is important that clinicians evaluate for xerostomia or thirst as independent symptoms and determine if reversible causative factors are involved. Thirst in dying patients Around 80-90% of dying patients report significant thirst (4,5). Given its high prevalence, providers should routinely assess for thirst among dying patients who are able to report the symptom. The use of artificial or medically-assisted hydration to alleviate symptoms of dehydration amongst the terminally ill remains controversial. The concern that dehydration-related symptoms, including thirst, can cause discomfort is weighed against the concern that iatrogenic over-hydration can lead to pain and dyspnea from fluid retention. Studies of thirst in dying patients conclude there is little relationship between artificial hydration and thirst (5-8). Instead, daily oral care and sips of oral fluid administered for comfort can improve thirst (5-9) and should be routinely offered (see Fast Fact #133). Concerned family and friends may be distressed that their loved one is experiencing thirst at the end of life, which can prompt requests for artificial nutrition or hydration. While these requests should be considered on a case by case basis, reassurance that artificial hydration is unlikely to alleviate thirst and comes with significant risks should be provided. Patients with ESRD: Thirst and xerostomia are associated with higher inter-dialytic weight gain (IWG) which in turn increases cardiovascular morbidity and mortality (10,11). Increasing the frequency of dialysis from three times per week to daily is the only change to dialysis that has conclusively shown to reduce thirst scores, but this has obvious practical limitations (12). Angiotensin converting enzyme inhibitors have been associated with a reduction in thirst scores and IWG, but this benefit does not seem to last beyond six months (13-16). Frequent gum chewing and saliva substitutes used more than six times per day may alleviate thirst for at least several weeks after initiation (17-18). Patients in the ICU Significant thirst has been reported in over 70% of critically ill patients (19). An "ICU bundle" of oral swab wipes, sterile ice-cold water sprays, and a lip moisturizer has been shown to decrease thirst intensity, thirst distress, and dry mouth in ICU patients (20). Summary: Education, emotional support, oral care, and sips of fluid should be offered instead. Patients with ESRD, HF, and intubated ICU patients may have specific interventions which can improve thirst.

#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 - -All equianalgesic ratios/formulas are approximations; clinical judgment is needed when making dose or drug conversions. --The FDA Prescribing Information indicates that their table should only be used when converting from another opioid to transdermal fentanyl. --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. --When in doubt, go low and slow, using prn breakthrough doses generously while finding the optimal dosage of a long-acting drug. --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).

Choose the most accurate statement regarding outcomes of patients who underwent cardiopulmonary resuscitation (CPR) for cardiopulmonary arrest in the hospital (Fast Fact #179 CPR Survival in the Hospital Setting). The rising prevalence of rapid response teams explains the significant improvement in survival rates to hospital discharge over the last 2 decades. Cardiac arrhythmia is the most common cause of cardiopulmonary arrest in hospitalized patients in the United States. Sepsis is associated with an improved chance of survival to hospital discharge. Roughly 1 in 6, or 15%, survive the hospitalization.

Roughly 1 in 6, or 15%, survive the hospitalization. Correct! Despite the rising prevalence of "rapid response teams", there is no convincing evidence these teams have improved survival rates. In fact, there is no convincing evidence that survival from CPR in hospitalized patients has changed much at all in the last several decades. This is likely because the cause of cardiopulmonary arrest is usually associated with an advanced, incurable chronic illness in hospitalized patients rather than an easily reversible acute cardio-pulmonary event such as an isolated arrhythmia. Hence, A&B are both incorrect. The presence of sepsis has been found to be a poor prognostic indicator in hospitalized patients who underwent CPR per a 1998 meta-analysis, so C is incorrect. Depending on the rigor of CPR event definition, immediate survival was 41-44% and survival to discharge was 13-15%. Of the five studies reporting discharge information, 78% of 93 survivors returned to their home. Factors associated with survival to discharge were: myocardial infarction, coronary heart disease, and hypertension. Factors predicting a failure to survive to discharge: - Sepsis the day prior to the CPR event - Serum creatinine >1.5 mg/dl - Metastatic cancer - Dementia or dependent status - Survival 20 minutes after CPR was 44%, but only 17% of all CPR patients survived to discharge. The survival to discharge for ventricular fibrillation and pulseless ventricular tachycardia was 34% and 35%, respectively, but only 10% for asystole and pulseless electrical activity. - Pre-CPR, 84% of patients came from home. Among survivors, 51% returned home, the remainder being discharged to another hospital, a rehabilitation facility, or a nursing home. Two percent were discharged to hospice care. - Neurological function of survivors was assessed using a five point scale (1 = good performance to 5 = brain death). Pre-CPR, 68% were in category 1, falling to 59% at discharge. In other words, 86% of category 1 patients remained at this level if they survived CPR, whereas 14% had neurological decline. - Overall functional performance was assessed using a similar five point scale (1 = good to 5 = brain death). Overall performance declined: 49% of survivors were category 1 pre-CPR compared to only 37% after CPR, a 25% decline in overall function. Summary CPR for hospitalized patients is associated with poor outcomes, as the cause of arrest is usually associated with advanced chronic illness rather than an easily reversible acute cardio-pulmonary event (e.g. isolated arrhythmia). The AHA recommends the widespread use of advance directive for all patients admitted to the hospital as well as "frank" discussions about prognosis and survival rates from CPR. When talking with patients about CPR, physicians can say roughly 15%, or 1 in 6 patients, who undergo CPR in the hospital may survive to discharge. However, specific co-morbidities will reduce the chance of survival, and surviving patients are at risk for a range of CPR-related complications including permanent neurological and functional impairment.

#189 Prognosis in Decompensated Liver Failure Part II

The Model for End-stage Liver Disease (MELD) Score (11-12): It was developed in 2000 and then updated in 2008 to reflect the addition of serum sodium levels (MELD-Na). It is validated in patients 12 years and older as an independent predictor of survival in patients with cirrhosis (alcoholic and non-alcoholic), acute liver failure, and acute hepatitis. It is also used by the United Network of Organ Sharing (UNOS) for prioritizing allocation of liver transplantation. It relies on laboratory values alone (serum creatinine, total bilirubin, Na, 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. The formula to calculate MELD score is complex. Online calculators are available (13). Other variables: Many factors which are not accounted for by CTP and MELD-Na greatly affect prognosis in patients with ESLD including age, persistent alcohol use, unmanaged hepatitis B/C, and medical comorbidities such as peripheral vascular disease and heart failure. Therefore, clinician judgement, the rate of decompensation, the likelihood of transplantation and the presence of one or more of the following complications may have more prognostic value than the CTP or MELD score alone. - Hepatorenal syndrome (HRS) -caused by renal arterial underfilling. Patients with type-1 HRS (rapid and severe renal failure) have a median survival of 2 weeks with few patients surviving more than 10 weeks even with renal replacement therapy (14,15). Median survival with type-2 HRS (chronic, less severe with serum creatinine usually 1.5-2 mg/dL) is 3-6 months (14,15). If the patient survives to transplant, renal function can improve quickly and significantly (16). - Ascites— presence of excessive peritoneal fluid from portal hypertension resulting in activation of renin angiotensin aldosterone system—suggests a mortality of 50% at 2 years (17). - Variceal hemorrhage—enlarged veins secondary to portal hypertension that are at risk for rupture and bleeding. There is a 20% of death within 6-weeks following of each bleeding episode (18). - Hypotension isa well-recognized and dangerous complication of ESLD stemming from portal hypertension. It is associated with an increased 6-month mortality risk in cirrhosis. - Hepatocellular carcinoma (HCC) -Chronic inflammation during the progression towards cirrhosis is a risk factor for HCC. Median survival of HCC without treatment is 8 months (19). Patients with Class B or Class C cirrhosis are rarely eligible for disease-directed HCC therapy (19).

When disclosing medical error to a patient or family, which answer below best reflects recommended practice (Fast Fact #194 Disclosing Medical Error)? Optimal timing for the medical error disclosure discussion would be after discharge from the hospital so that the clinicians can appropriately assess the harm that ensued from the error. Clinicians involved in the case are often too close to the error, therefore it is better to ask a medical administrator or a trusted colleague who reviewed the case to disclose the error. Inviting trainees involved in the medical care to the medical error disclosure discussion is not advised as it exposes the trainee to excessive liability. Apologizing is only professional for system- based medical errors, not individual-based medical errors. The institution's risk management team should be notified at the time the medical error is identified.

The institution's risk management team should be notified at the time the medical error is identified. Discussing Error - Preparation Whoever committed the error (attending physician, advance practice provider, or resident), the clinician with the final responsibility for the patient's care should lead the discussion. Invite trainees to attend - this is an important learning opportunity. Limit the discussion to just those healthcare professionals directly involved. Have the discussion in a timely manner - as soon as possible after the error is identified - but make sure the appropriate people are there (including an incapacitated patient's legal decision maker). Set aside ample time and have the meeting in a distraction-free environment. Review the pertinent facts of the case so that you are prepared to answer any detailed questions that the patient/family might have. Discourage other consultants/ancillary staff from discussing the error with the patient/family - multiple accounts of the events will likely confuse rather than clarify. Notify and seek the advice of your institution's risk manager. In addition to informing you of policies and procedures specific to your institution, they will then be aware of the case should legal inquiries be made. Note: while it is wise to seek risk management input, remember that discussing errors with patients/families is a clinical task - part of clinicians' obligation to openly share medical information - not a legal task. Discussing Error - Content (see Fast Facts #6, 11 for general breaking bad news principles) Be clear, concise, and honest. Avoid medical jargon or lengthy explanations. Give the patient and family time for questions, emotional reactions, or silence. If you believe the adverse outcome was a result of error (either individual or system-wide), specifically apologize for the error and its outcome. If the outcome was unanticipated, but not clearly avoidable express regret and sorrow. Avoid blame: "I am sorry this has happened" is not an admission of error or liability. Commit yourself and your institution to investigating and remedying any individual or systematic deficiencies. Commit to providing ongoing, appropriate care, including comfort-oriented care for a dying patient. Involve the appropriate services as indicated such as chaplaincy, social work, and consultants including palliative care. Document your discussion; refer legal inquiries to your institution's risk manager. Summary Discussing error requires professionalism and openness, sometimes at the expense of vulnerability. Not only is it an ethical imperative, it is a requisite skill that is key to maintaining a healthy clinician-patient relationship.

Which one of the following statements is TRUE (Fast Fact 164 and 165 Informed Consent Part 1 and 2): Clinicians are allowed by law to provide any necessary emergency treatment without informed consent. Informed consent for treatment is not necessary if transported following a 911 call. Starting antibiotics in the Emergency Room does not require informed consent unless the patient is a minor. The legal standard of informed consent varies between states.

The legal standard of informed consent varies from state to state, Some use: what a reasonable patient would want to know; in other states the standard is, what a reasonable physician should provide (check with your local ethics committee). Informed consent is always required for medical testing and treatment except in cases where the situation meets all criteria for the "emergency exception" - Life threatening emergency and time is of the essence. - Patient is not decisional and no legal surrogate decision maker is available. - A reasonable person would consent to the emergency treatment.

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.

There are lower dose requirements associated IT pumps which may reduce side effects and drug costs. 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.

#97 Blocks of the Sympathetic Axis for Visceral Pain

Types of Nerve Blocks The following have an established record in well-selected patients: Celiac plexus block (CPB). Used for upper abdominal pain - most commonly from pancreatic cancer. It is also appropriate for pain involving the GI tract from the distal third of the esophagus to the transverse colon, the liver and biliary tract, the adrenals, and mesentery. There have been over 25 controlled studies assessing the utility of a CPB. The data suggest CPB can improve analgesia, decrease opioid consumption, and decrease opioid-induced adverse effects compared with conventional analgesic treatments. Splanchnic nerve block: The splanchnic nerves are formed by sympathetic pre-ganglionic fibers from T5 to T12 of the thoracic spine. Visceral pain from structures innervated by the celiac plexus can be treated with a splanchnic nerve block as well. Hence, a splanchnic nerve block can be a viable alternative to CPB when there are regional distortions of the celiac plexus anatomy (e.g., tumor burden, adenopathy, or prior surgery). Superior hypogastric plexus block (SHPB). Applicable to malignant pain of the gastrointestinal tract from the descending colon to the rectum, as well as the urogenital system. There is less robust data evaluating SHPB for visceral pain, with one study showing a decrease in pain intensity and less morphine consumption when SHPB was utilized. Ganglion impar block (GIB). The ganglion impar innervates distal structures of pelvis including the vulva, rectum, anus, sacrum, perineum, and coccyx. A study of 15 patients found a 3-point reduction in visual analogue pain scales lasting 3 months with a reduction in opioid dose consumption. Inferior hypogastric plexus block: the inferior hypogastric plexus innervates the pelvis, perineum, and genitals. Because it is more difficult to access and prone to complications due to its presacral location, it is utilized less frequently than a GIB. Several smal studies have shown a short-term benefit in select patients with pelvic or genital pain. Pain improvement from neurolysis typically lasts 3 to 6 months, at which point the procedure can be repeated if indicated. Complications & Side Effects Side effects - referable to loss of sympathetic tone - include transient hypotension (30-60% of cases) and increased intestinal motility leading to diarrhea which is usually temporary. However, often the diarrhea is preferred over opioid induced constipation. Complications include needle injury to visceral, neural, and vascular structures; pain at the injection site; and failure to obtain an analgesic response. Contraindications to these procedures include bleeding diathesis and local infection. Post-Procedural Management Crucial to the success of sympatholysis is proper patient selection and technical skill. Sympathetic blocks are not a panacea and generally do not obviate the need for ongoing pharmacological management of residual pain. However, in select patients they can substantially improve analgesia and quality of life and may allow for opioid dosage reduction. Note: attempts at post-block opioid reduction should be done with care to avoid unmasking existing nociceptive/neuropathic pain and precipitating opioid withdrawal.

#383 Kennedy Terminal Ulcer

What is a Kennedy Terminal Ulcer (KTU)? The KTU was first coined in 1989 to describe a skin wound that occurs despite best preventative measures and results from the moribund functional status and underlying skin failure associated with the dying process (1). - Timing: KTUs can develop and appear within a matter of hours, in comparison to usual pressure ulcers which develop over approximately 5 days (2). The seemingly sudden appearance has led them to be referred as the "3:30 Syndrome": in the early AM, clinicians note intact healthy skin, hours later a few small blackish spots appear that may resemble "specks of dirt", then by mid-afternoon, flat, black blisters emerge that may continue to expand in size (1,4). - Location: Primarily the sacral region but KTUs are also seen in other bony prominences, such as the elbows, shoulders, and heels (5,6). - Description: 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 (3). Who is at risk? While the etiology of the KTU is not fully determined, they occur primarily in adult or pediatric patients in the final 2 weeks of life (2,3,6). Hence, anyone who is actively dying is felt to be at risk of developing skin failure and KTUs (2,3).Skin failureis a term, not well defined, that has been used in the published literature to conceptualize the overall breakdown process of the skin as an organ system that is associated with the end-stages of a chronic, progressive illness and/or multi-organ failure, even when excellent skin care is provided (5). Instead of the wound developing from preventable pressure on an isolated part of the body, KTUs are felt to occur from the failure of the skin as an organ system (5). Both skin failure and the KTU often go undiagnosed or may be misdiagnosed as a usual pressure ulcer. The most distinguishing factors of a KTU is the quickness of the wound development, usually occurring in a day or less, in the setting of a terminal illness. How does a health care professional prevent a KTU?. A prevention strategy that is similar for all pressure ulcers and aims to reduce moisture and friction on bony prominences is recommended by many experts. This includes a) turning moribund patients every 2 hours as tolerated; b) keeping skin over bony prominences dry and clean; c) the use of pressure-relieving devices such as high-specification (cubed, soft, or pressure redistributing) foam mattresses; d) placing pillows under the knee to reduce sheer forces on the sacrum whenever the head of the bed is elevated; and e) the use of pressure-relieving dressings (e.g. Mepilex) (9,10). Even if all these measures are followed, unfortunately, KTUs may still occur in actively dying patients (3). How should a KTU be managed? While KTU management is similar to any pressure ulcer, there a few unique elements. - Emotional support and KTU counseling for caregivers are vital. Since KTUs can appear with little warning, caregivers may perceive this wound as a sign of care neglect or even abuse, which without the proper education from clinicians, could create complicated feelings of guilt, mistrust, or anger (3). - KTUs can often be signs of impending death. Hence, addressing the signs, symptoms, and expectations of imminent death in the context of the KTU counseling is important (11). - Individual judgement is needed to determine the need for frequent repositioning in dying patients. By minimizing pressure to the localized area for patients, frequent repositioning can reduce discomfort in many patients with a prognosis of several days to a week. Yet, many patients with a prognosis of only hours to days may experience more discomfort than benefit from repositioning. Also, family members may wish to avoid repositioning so that their love one can rest in peace. Transparent and ongoing communication with family members is vital. - If the patient grimaces or moans with repositioning, pre-medicating with an as needed analgesic is an alternative to discontinuing repositioning (10). - Nursing experts suggest that more than one person be utilized to assist with repositioning. Lowering the head of the bed and utilizing slide sheets is also recommended (10). - While KTUs are usually irreversible, the use of pressure-relieving surfaces and pressure-relieving dressings is still advised to reduce pain associated from friction (3,4,6). - KTUs and the associated tissue death from skin failure can lead to malodor. The use of charcoal infused dressings or topical metronidazole have been described to manage this odor (2).

Patients with which type of illness are more likely to utilize hospice services in comparison to other chronic illnesses, likely because of a more predictable trajectory of physical decline and psycho-spiritual distress (Fast Facts #326 Illness Trajectories). Cancer Congestive heart failure Dementia Stroke

Wrong! A study of Medicare patients showed that cancer patients were more likely to utilize hospice services in comparison to other chronic illnesses and that the more predictable illness trajectory is a likely factor in the increased hospice utilization of cancer patients. Reference: Lunney JR, Lynn J, Hogan C. Profiles of Older Medicare Descendents. JAGS. 2002;50:1108-1112. Cancer

All of the following laboratory findings are independent predictors of a shorter survival in advanced heart failure EXCEPT (Fast Fact #143 CHF Prognosis): Anemia Elevated BUN Hypomagnesemia Hyponatremia

Wrong! Anemia, elevated BUN/creatinine and low sodium are all common in heart failure and are independent survival prognostic factors.

Choose the best answer regarding the clinical utility of the surprise question - "Would I be surprised if this patient died within 12 months" (Fast Fact #360 The Surprise Question as a Prognostic Tool): No answers have stronger predictive value than yes answers Responses are more accurate in non-cancer illness such as congestive heart failure and dementia than they are in cancer patients It has only been studied and validated in nursing home settings No answers to the surprise question during sentinel events such as hospitalizations should trigger a standardized assessment for unmet palliative care needs.

Wrong! Answer choice A is wrong since "Yes" answers (meaning the clinician would be surprised if the patient died in < 12 months) have a predictive value of 93% while the positive predictive value of "no" answers may only be 37%. Answer choice (b) is wrong as the pooled accuracy of the surprise question for cancer patients appears to be slightly higher than non-cancer patients. Answer choice (c) is wrong because it has been studied and validated in general inpatient settings, high-risk primary care clinics, pediatric patients, advanced kidney disease, emergency departments, cancer clinics, and nursing home settings.

"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

Which of the following is a moderate to strong indicator of a poor neurologic outcome from anoxic brain injury (Fast Fact #234 Prognosis from Anoxic Brain Injury): - Myoclonic status epilepticus within 1 day of CPR - Duration of cardiopulmonary resuscitation - Cause of cardiopulmonary arrest - Presence of fever 48 hours after CPR

Wrong! Neither cause of cardiopulmonary arrest, total arrest time, duration of CPR, nor fever have been strongly associated with neurologic outcomes. However, the presence of myoclonic status epilepticus within 1 day of CPR or 1 day after rewarming from the hypothermia protocol has been associated with poor neurologic outcomes.

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.

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. Cancers most often associated with epidural spread include lung, prostate, breast, kidney, myeloma and melanoma. They are also common in testicular cancer, lymphomas, and Hodgkin's disease. Ovarian and pancreatic cancer rarely lead to epidural metastases. Tumor reaches the epidural space via contiguous spread from adjacent vertebral body metastases or, less commonly, from direct extension of tumor through the intervertebral foramina from adjacent tissue (e.g. retroperitoneal lymphoma or posterior lung cancer).

Fast Fact #127 All of the following are recognized reasons clinicians should transparently address addiction concerns with their patients EXCEPT (Fast Fact #127 Substance Abuse in the Palliative Care Patient): The diagnosis of addiction enables clinicians to prescribe methadone as an analgesic for cancer pain. Recovery from addiction can better enable patients to accomplish end-of-life work Recovery from addiction can lead to improvement in quality of life for patients and their families Acknowledgement of addiction can help restore the patient's damaged social supports

Wrong! When methadone is utilized as an analgesic it does not require any extra licensing beyond a standard DEA license. Therefore, the diagnosis of "addiction" would not make easier for a clinician to prescribe methadone as an analgesic. Answer b-d are recognized potential benefits of directly addressing addiction concerns with patients. Background The spectrum of substance use disorders (SUDs) is characterized by increasing degrees of craving, compulsive use, loss of control, and continued use despite harm (see Fast Fact #68). Addiction is understood to be a disease with complex genetic, neurobiological, psychosocial, and behavioral determinants. If not properly managed an SUD can: 1) complicate the diagnosis and treatment of psychological (e.g. depression) and physical (e.g. pain) symptoms; 2) compromise compliance with the palliative treatment plan; 3) impair a stressed social support network; 4) weaken trust in patient-physician/nurse relationships; and 5) promote the use of opioids to cope with emotional distress and decision-making - "chemical coping." Substance Use Disorders and Pain Management Patients with a current or past history of an SUD are particularly challenging. Patients who are in recovery are often fearful of using opioids, even in the setting of severe pain near the end-of-life. Conversely, the ability to complete a pain assessment and use opioids effectively is challenging in patients with an active SUD. Listed below are suggested management techniques in patients with a past or current SUD. - Complete a thorough substance use history. Distinguish between those who have active SUDs from those who are at-risk or in recovery. Validated tools such as the Opioid Risk Tool are available for risk stratification. Explain to patients why your knowledge of this information is important for their care. Be empathic and nonjudgmental. - Encourage participation in recovery programs (e.g. 12-step) if the patient is willing and physically able. Consider consultation with an addictions/mental health professional. - Formalize a treatment plan and coordinate it with all other involved health professionals. - Consider use of a written opioid agreement with carefully defined patient and provider expectations; this may give motivated individuals a sense of control over their SUD. - -- - Components of an opioid agreement include: establishing a single opioid prescriber, using a single pharmacy, employing pill counts and periodic urine drug testing (see Fast Fact #110). - Use non-opioid analgesics and non-pharmacological measures to their full potential; poorly controlled pain can increase substance abuse behaviors (see Fast Fact #69). - Use opioids at appropriate doses and at appropriate intervals. Titrate long-acting opioids to minimize the need for short-acting opioids. Note: opioid-tolerant patients may need larger than 'usual' doses. - Address anxiety with counseling, antidepressants and, if necessary, judicious use of anxiolytics; this has been shown to reduce illicit drug use in a hospice population (8). - Monitor closely; frequent contact allows for close patient observation and prescription of limited quantities of opioids. - Careful monitoring will usually distinguish whether deteriorating function is due to substance abuse or disease progression. - Recognize that addiction is a chronic, relapsing illness - and respond with increasing structure and compassion. - Develop system policies for identifying and appropriately treating patients with substance abuse.

Which one of the following is not required to say that a patient has decision-making capacity (Fast Fact #55 Decision-making capacity): able to reason, to weigh treatment options can express a choice among treatment options is oriented to person, place and time understands the significance of information relative to personal circumstances

is oriented to person, place and time The three criteria patients must meet to demonstrate decision making capacity include: Understand the information (e.g. be able to relate what they have been told and what it means) Ability to make a rational Evaluation of the burdens, risks, benefits, and alternatives to the proposed health care Communicate a choice (implies ability to communicate)