PT V Exam 2

Which Benzodiazepines are preferred for treating emergent SE?

Lorazepam, Diazepam, and Midazolam

Describe the clinical presentation of fibromyalgia?

"It hurts all over" - Worse with exertion, stress, changes in weather Numbness, tingling, burning, "crawling" Fatigue Light-headedness Headaches Flu-like symptoms IBS

What all is needed for the preparation step of RSI?

"SOAPME" - Suction, Oxygen, airway, pharmacology, monitoring, equipment Assess patient IV access Monitor - Pulse oximeter - BP - EKG Gather - Equipment for intubation - Medications for intubation - Pertinent patient history Pharmacy - Select medications - Draw up appropriate doses - Label medications

How much sodium bicarbonate is in 1 "amp" of bicarb?

1 "amp" of bicarb: = 50 mEq = 50 mmol = 50 mL

What are all of the steps of respiratory acidosis treatment?

1. Assess oxygenation: treat this first a. Clear airway obstructions/secretions b. Provide oxygen c. Bronchodilator d. Remove/reverse offending agents (opioids) 2. Assess acute, chronic, or acute on chronic 3. How much metabolic compensation? 4. Increase minute ventilation - often requires mechanical ventilation. 5. Consider cautious use of alkali therapy - Can restore responsiveness of bronchial muscles to β-adrenergic agonists. - Alkali treatments are rarely necessary - Rapid correction can eliminate respiratory drive → metabolic alkalosis. Bottom line: Treat the underlying cause(!)

What are the 3 steps in converting between opioids?

1. Calculate total daily dose of all current opioids used in the past 24 hours - May use a per dose conversion for acute pain 2. Use opioid conversion charts to determine dose of new agent. 3. If changing opioid agent, may use percentage of new dose to account for incomplete cross tolerance (chronic pain) - If pain controlled: 50 - 75% of new opioid dose - Pain NOT controlled: 75 - 100% of new opioid

What is the typical bowl protocol for opioid induced constipation in ICU patients?

1. Encourage fiber, fluids, mobility, constipating meds 2. Stool Softener and laxative (sennosides) 3. Add lactulose or MOM 4. Rule out impaction. If no impaction-bisacodyl supp, mag citrate solution, phos enema, other enemas

How do we calculate the SQ dose of insulin required after discontinuing IV insulin?

1. Estimate Total daily dose (TDD). 2. Calculate the average IV insulin rate (units/hr) over the past 6 hours. 3. Multiply average hourly rate by 24 to get 24 hour requirements. 4. Multiply by 0.75to get TDD. 5. Split 50% TDD basal, 50%TDD Nutritional bolus.

What are the 3 classifications of metabolic acid base disorders?

1. Hyperchloremic Metabolic Acidosis 2. Renal Tubular Acidosis - Type I (Distal or "classic" RTA) - Impaired hydrogen ion excretion - Type II (Proximal) - Defects in proximal tubular reabsorption of bicarbonate. - Type IV (Hyperkalemic Distal) - Hypoaldosteronism or generalized distal tubule defects. 3. Elevated Anion Gap Metabolic Acidosis - Organic acidosis (endogenous vs exogenous)

What are the 6 steps for starting an insulin drip?

1. Obtain baseline chemstrip and every 1 hours •Until glucose has been at goal range for 3 consecutive hours. • Then check capillary blood glucose every 2 hours. • If capillary glucose is out of goal range, then resume hourly checks. 2. Identify prescribed goal glucose range • 140-180 mg/dl for medical patients 3.Identify ordered "constant" •Range 0.01-0.12; Most common 0.04 •Lower the number the more insulin sensitive •Insulin 100 units in 100 ml obtained from pharmacy •Delivered to refrigerator 4.Calculate starting rate •(BG-60) x 0.04=Rate •Double check on constant tables(rates in ml/hr)-see example 5.Program infusion pump with calculated rate and document in flowsheet 6.Check Chemstrip in 1 hour

What are the 6 P's of Rapid Sequence Intubation (RSI)?

1. Preparation 2. Pre-oxygenation 3. Pretreatment and induction 4. Paralysis 5. Placement of the tube 6. Post-intubation management

1. ______________ blood reflects how much oxygen tissues are using. 2. ______________ blood reflects how well the blood is being oxygenated.

1. Venous 2. Arterial **Changes in tissue oxygen demand can significantly impact venous blood values.

Describe the timeline of the development of palliative care?

1.In the 1970's, Dr. Kϋbler-Ross advocated for at-home care for dying patients 2.In 1974, the first hospice service in the U.S. was funded by the National Cancer Institute 3.In 1977, the National Hospice Organization was established 4.In 1983, legislation was first enacted to provide for hospice care as a Medicare benefit 5.In 1993, hospice became a nationally guaranteed benefit in the U.S

What are the different ratios for blood products?

1:1:1 ratio for those with trauma Greater than 1:2 ratio of platelets to red cells showed reduced mortality in the first 48 hours for those with hemorrhage not caused by trauma

Can GCSE cause an epilepsy disorder?

30-60 minutes of GCSE = Neuronal damage in animal models Majority develop epilepsy following a prolonged seizure - Difficult to study in humans, but there is a similar correlation. Patients who develop epilepsy following prolonged GCSE - Less likely to experience remission - Have decreased cognitive and memory function - Increased incidence of mental retardation or neurologic deficits.

What is the typical pH of the urine?

4.6 to 6

Patients should receive aggressive treatment for seizures lasting > __ min

5 min *Average seizure is < 2 min. *Most seizures > 10 min will not stop without treatment.

What does the Surviving Sepsis Campaign recommend for BG control in sepsis patients?

A protocolized approach to manage BG in ICU patients with severe sepsis. - Commence insulin dosing when 2 consecutive BG levels are >180 mg/dl. - Should target an upper BG <180 md/dl. BG values should be monitored every 1-2 hours until rates are stable then every 4 hours. Glucose levels obtained with POC should be inter.

When is it appropriate to call 911 when someone is suffering from a seizure?

A seizure lasting longer than 5 minutes with no sign of slowing down. Difficulty breathing after the seizure. If the person is injured or experiencing any pain.

JS is a 30 y/o Caucasian male presenting to the ED via ambulance. According to the EMT, he has been having rhythmic jerking activity for about 7 minutes. What type of seizure is JS having? A. Convulsive Status Epilepticus B. Non-Convulsive Status Epilepticus C. Refractory Status Epilepticus

A. Convulsive Status Epilepticus

JS requires emergent therapy. The ED staff wants to administer a benzodiazepine immediately, however, they are unable to gain IV access. Which BZD would be the best option for JS? A. Midazolam B. Lorazepam C. Diazepam D. Clonazepam

A. Midazolam

What ventilator mode is a form of CMV that does the work of breathing but allows patient to initiate breath?

A/C - Assist/control

What anion gap value is considered elevated and what value is suggestive of significant organic acidosis?

AG > 12 is considered elevated (possible organic acidosis) AG >20 suggestive of significant organic acidosis

What is the formula for the delta ratio? - Known as gap-gap or delta gap - Calculate in high AG metabolic acidosis - Reveals the magnitude of the abnormality - Helps determine if mixed acid-base disorder are present

AG excess/HCO3 deficit = (Measured ACAG - 12) ÷ (24 - [HCO3-])

Which non-opioid analgesic is described here? Inhibit central prostaglandin synthesis - Analgesic and antipyretic effects - Negligible anti-inflammatory effects Used for mild to moderate pain Multiple dosage forms (oral, rectal, IV) - Changes to pediatric formulation Peak levels reached in 30 to 60 minutes Generally dosed every 4 to 6 hours Maximum daily dose of 4 grams for adults - 2-3 grams if elderly or liver damage

Acetaminophen

What law allows first responders (law enforcement, fire fighters, EMS) and family/friends to have and administer naloxone? Standing order as of 3/1/2016 to obtain naloxone from a pharmacy without a prescription - Training strongly encouraged but not required Numerous naloxone products available under the standing order

Act 139 : David's Law

What type of pain is described here? Protective, associated with tissue damage which resolves with resolution. Usually nociceptive, may be neuropathic.

Acute pain

How is intrinsic clearance effected in ICU patients? - Intrinsic metabolic activity-Important.

Acute phase reactants decrease Phase 1 & 2 - Example: Clindamycin, morphine Increased metabolism - Traumatic brain injury - Example: pentobarbital, phenytoin, lorazepam Protein supplementation Poor diffusion into the hepatocyte Slow dissociation from blood components Poor biliary transport Medications: low-extraction drugs

What are the different types of scoring systems used in the ICU?

Acute physiologic and chronic health evaluation (APACHE II) - Used when patients first present to determine how sick the patient is. Simplified acute physiology score (SAPS II) - Probability of death by looking at different organ systems. Multiple organ dysfunction score (MODS) - Looks at the number of organ systems that are failing. Sequential organ failure assessment (SOFA) - Used to identify sepsis patients. Logistic organ dysfunction score (LODS) Injury severity score (ISS) - Looks at severity of injury and trauma. Glasgow coma score (GCS) - Used for all admitted Pts. to assess mental status. Disease Specific Scoring Systems

What is defined as a dysregulation of the midbrain dopamine (pleasure) system due to unmanaged stress resulting in symptoms of decreased functioning, specifically: - Loss of control - Craving - Persistent use despite negative consequences.

Addiction

How is sodium chloride responsive metabolic alkalosis treated?

Adjust volume and chloride stores first Increased intravascular volume or sodium intolerant - Do NOT give fluids (NS) - will lead to fluid overload - Acetazolamide PO 250-350mg QD or BID (!!!) - Promotes bicarbonate diuresis and return pH down to normal. - PLUS potassium if K<3.5 mEq/L(!!) Decreased intravascular volume - Give normal saline

What are drugs that do not contain acetaminophen and those not classified as NSAIDs or opioid agents? - May enhance effects of NSAIDS and opioids - Many with documented benefits for treatment of neuropathic pain syndromes - Used in combination with opioids to effectively manage pain

Adjuvant Agents (Co-analgesics)

Compare advanced directives to a DNR.

Advance Directives: - Should be considered by everyone - Applies to all general medical treatments - Document usually requires patient signature Do Not Resuscitate (DNR): - Should be considered by those with risk factors for not surviving resuscitation. - Applies only in case of cardiopulmonary arrest. - Document does not require patient signature.

What are legal documents that allow patients to make end-of-life wishes known if unable to communicate? - Living will: guide to medical treatment desired and not desired at the end of life. - Medical power of attorney: person designated to make medical decisions. In effect only when patient is at end of life AND cannot communicate wishes or is unable to make medical decisions

Advance directives

What ADRs can occur with Lidocaine (Lidoderm®)?

Adverse reactions: local - Burning, blisters, dermatitis, erythema, irritation, papules, pruritis, vesicles, depigmentation.

GCSE incidence is highest in what age ranges?

Age <1 year and age >60 years.

What conditions that can occur during palliative care are described here? Acute onset of symptoms Associated with increased mortality Distressing to family and caregivers Confounds pain assessment and treatment Symptoms: - Restlessness, anxiety, sleep disturbance, irritability, reduced attention, altered arousal, emotionally labile, altered perception, memory impairment, disorganized thinking, incoherent speech.

Agitation and Delirium

What agents used for hypovolemic resuscitation are colloids?

Albumin 5%, 25% Dextran Hydroxyethyl starch - Leads to renal dysfunction

How does albumin affect anion gap?

Albumin contributes (~80% of AG) - Hypoalbuminemia results in falsely low AG Albumin-Corrected Anion gap (ACAG) - ACAG = AG + 2.5 * ([Normal Albumin] - [Measured Albumin]) **Normal Albumin = 4 g/dL

How should someone in palliative care with dyspnea caused by a bronchospasm with audible wheeze be treated?

Albuterol MDI 1-2 puffs q4-6h prn -OR- Albuterol nebulized 2.5 mg q2h prn No relief: Ipratropium MDI 1-2 puffs q4-6h prn -OR- Ipratropium nebulized 3 mg q4h prn No relief: opioids

What other abnormalities can be detected with labs that are other causes of seizures? - Laboratory tests are essential - Rule out underlying causes with GCSE!

All of the above can cause seizures Hypoglycemia Hypomagnesemia Hyponatremia Hypernatremia Hypocalcemia Renal failure

What neuropathic sensation is pain elicited by a nonnoxious stimulus (clothing, air movement, touch)? - Mechanical (induced by light pressure) - Thermal (induced by a nonpainful cold or warm stimulus)

Allodynia

What receptors does phenylephrine affect?

Alpha

What receptors does dopamine affect?

Alpha Beta 1 and 2 Dopamine

What receptors does epinephrine affect?

Alpha Beta 1 and 2

What receptors does norepinephrine affect and what dose is used for resuscitation ?

Alpha Beta 1 and 2 0.01-3 mcg/kg/min(!!!)

What drugs used to treat sodium chloride resistant or unclassified metabolic alkalosis are described here? - K+ sparing diuretics that inhibit the epithelial sodium channel in the DCT and collecting duct. - Use for Liddle syndrome

Amiloride and triamterene

What medications are effected by augmented renal clearance in ICU patients?

Aminoglycosides, vancomycin, ciprofloxacin, fluconazole, ranitidine, imipenam, Beta lactams (variable)

What agent used to treat metabolic alkalosis is converted by the liver into urea and free hydrochloric acid? - Dose based on ½ of the estimate of the total body chloride deficit (to avoid ammonia toxicity) assuming that 20 g ammonium chloride will provide 374 mEq (mmol) of H+ - 26.75% solution containing 100 mEq (mmol) of H+ in 20 mL - Further dilute the 20 mL of ammonium chloride with 500 mL of NS(!) - Maximum infusion rate of 1 mEq/min (mmol/min) to minimize risk of CNS toxicity(!!!) - Improvement is generally seen within 24 hours. Administer cautiously to patients with impaired kidney or hepatic function.

Ammonium chloride

By how much should you increase the dose of long acting opioids when increasing dose?

Amount of breakthrough used in past 24 hrs -OR- 25% of total daily dose

What is the anion gap?

Anion gap (AG) = unmeasured anions. - AG = unmeasured anions (UA) - unmeasured cations (UC) - AG = (Na+ + K+) - (Cl- + [HCO3-]) - Helps differentiate the type of metabolic acidosis Concentration of anions to cations, by rule, the concentrations should be relatively equal.

What agnate are used to increase gastric pH to prevent stress ulcers?

Antacids Sucralfate H-2 Receptor Antagonists PPIs

Name all of the Adjuvant Agents (Co-analgesics) that can be used to help treat chronic pain?

Antidepressants - Amitripyline, nortripyline, desipramine, duloxetine Anticonvulsants - Gabapentin, pregabalin, carbamazepine Skeletal muscle relaxants, antispasmodics - Cyclobenzaprine, tizanidine, diazepam, baclofen Bisphosphonates - Pamidronate, zoledronic acid Steroids - Dexamethasone, methylprednisolone Topical agents - Capsaicin, lidocaine

What are all of the other agents that can be used for neuropathic pain?

Antiepileptics - Lamotrigine - Carbemazepine - Phenytoin - Divalproic acid - Topiramate - Tiagibine - Zonisamide - Oxcarbazepine Dextromethorphan Mexiletine Memantine

What are the symptoms associated with opioid withdrawal syndrome?

Anxiety, nervousness, irritability. Salivation, lacrimation, rhinorrhea, diaphoresis, piloerection. Nausea, vomiting, cramps, insomnia.

Who is appropriate for palliative care?

Any patient with an end-stage chronic disease - Heart disease (i.e. NYHA class IV despite Rx) - Chronic lung disease - End-stage renal failure - Hepatic failure - Cancer - Dementia

How should capsaicin be applied?

Apply to affected area 3 to 4 times per day - Less than this will prevent total depletion, inhibition of synthesis, transport of substance P - Decreased efficacy and increased local discomfort Wear gloves to apply; wash hands with soap and water before and after application Recommended dose for DPN 0.075% QID

How should lidoderm be applied?

Apply to most painful area to intact skin (!!) Apply up to 3 patches up to 12 hours in a 24 hour period - Wearing up to 24h may provide additional pain relief; no significant effect on systemic levels Patches may be cut into smaller sizes (!)

What implications are associated with using sedation and analgesia for mechanical ventilation?

Appropriate ventilator adjustment should be completed before more sedation applied. Type of ventilator setting impacts depth and type of sedation.

What questions should be asked to determine if a patient is ready to be extubated?

Are they awake and conscious? Do they still have significant secretions that they can't clear? Are they tolerating a CPAP trial? Is a cuff leak present? Any upcoming procedures? Can they cough? Are they off vasopressors? Can they breath on their own? Is the underlying disease process resolving?

What agent used for metabolic alkalosis is similar to ammonium chloride: arginine is metabolized by the liver to produce H+ ions, with a conversion of 100 g to 475 mEq (mmol) of H+? Administer cautiously to patients with impaired kidney or hepatic function. - Impaired hepatic function: Can be used in patients with relative hepatic insufficiency (unlike ammonium chloride) because arginine combines with ammonia in the body to synthesize urea. - Impaired kidney function: Increases urea synthesis and associated BUN may be associated with severe hyperkalemia caused by arginine-induced shifts of potassium from ICF - ECF.

Arginine monohydrochloride

What serious ADRs are associated with Fosphenytoin? Considerations - Compatible in saline, dextrose, and LR - DOES NOT contain propylene glycol (!!)

Arrhythmias Hypotension

What serious ADRs can occur with phenytoin? Considerations - Only compatible in saline (microcrystals in glucose) - Contains propylene glycol

Arrhythmias Purple glove syndrome Hypotension

What lab tests can assess acid-base status and which one is preferred?

Arterial blood gas (ABG) - Always preferred! - Designated with an "a" (PaO2, PaCO2) Venous blood gas (VBG) - Designated with a "v" (PvO2, PvCO2)

What is the physicians role in communication in palliative care?

Articulating choices Likely benefits and burdens Helping patient/family to make medically appropriate decisions in keeping with their goals

What are the goals of palliative care for the family?

Assist with educating about the disease process and what to expect. Facilitate advance planning re: end-of-life issues/health care proxy. Assist with arrangements to care for patient at home if desired. Provide access to bereavement support

Why is it important to study pharmacokinetics in ICU patients?

Avoid adverse drug events - At least 40% of adverse drug reactions are preventable - Almost 30% of these events involve dosing errors - More harmful if in ICU, but not more frequent Increased incidence of drug interactions Individualize patient dosing needs Understand mechanisms of drug interactions and ADRs to prevent and anticipate their sequelae.

What patients should avoid taking Meperidine (Demerol®)?

Avoid in patients with renal impairment, increased intracranial pressure, hepatic dysfunction, MAOIs. Avoid in chronic pain, elderly.

What patients should not use TCAs for neuropathic pain?

Avoid: 2° or 3° heart block, arrhythmias, QT prolongation, recent MI, severe liver disease **Caution: closed-angle glaucoma, BPH, cardiovascular disease, urinary retention, constipation, liver dysfunction

After administering urgent therapy EEG monitoring is reviewed. EEG monitoring shows continued seizure activity. Which of the following would be appropriate therapy at this time? A. Additional dose of diazepam rectally B. Loading dose of midazolam followed by continuous infusion C. Continuous infusion fosphenytoin D. Corticosteroids followed by ketamine

B. Loading dose of midazolam followed by continuous infusion

JS requires emergent therapy. The ED staff wants to know which of the following would be the best option for initial therapy. Which of the following would be the best option for JS? A. Phenytoin IV B. Lorazepam IV C. Diazepam PO D. Propofol PO E. Phenytoin IM

B. Lorazepam IV

Why should a pharmacist be familiar with mechanical ventilation?

Basic knowledge is required for critical care pharmacists and helps to: - Participate fully during rounds - Understand sedation and analgesia plans - Assess the effectiveness of treatment regimens - Identify and address any potential complications - Manage route of medications

What objective measurements can be used to assess hypovolemic shock?

Bedside ultrasound - LV/RV size - IVC size/ collapsible Pulse Pressure/Stroke volume Variation Passive leg raise Fluid bolus Challenge Swan catheter - CVP, wedge pressure - Cardiac output - Systemic and pulmonary vascular resistance - Blood pressure - LV Ejection fraction - RV function

What pharmacologic therapy should be used as emergent treatment for SE lasting >5min? - Therapy used to immediately break the seizure activity - Must be rapid acting & non-oral Hyperpolarization of neurons - Prevent excitatory action -> stops depolarization - Produce sedation and hypnosis - Serious adverse effects include hypotension and respiratory depression.

Benzodiazepines (GABA-A agonists)

What types of ventilation are considered Non-invasive Positive Pressure Ventilation (NPPV)? - Requires a tight fitting mask over the nose/mouth or nose alone. - Used as a treatment or as supportive therapy to prevent intubation or re-intubation(!!!)

BiPAP - Bi-level Positive Airway Pressure - Two levels of pressure are used CPAP - Continuous Positive Airway Pressure - One continuous level of pressure applied

What is the formula for bicarbonate deficit? - Used to determine dose of sodium bicarbonate. Administer 25-50% as a bolus - Then replace the rest over 24-48 hours as continuous May mix 75 mEq with a liter of ½ NS or 150 mEq with 1 liter of sterile water - Results in relatively isotonic solutions - Drip rate: 0.5-1 mEq/kg/hr (after bolus)

Bicarbonate deficit = [0.5 x BW(kg)] x (Desired HCO3- - Current HCO3-)

What supportive pharmacologic therapy can be used to help treat status epileptics?

Blood gas (ABG) to monitor for metabolic acidosis - Administer sodium bicarbonate if pH < 7.2 Hypoglycemia -> treat blood glucose < 60 mg/dL - 50 mL of 50% dextrose x1 THEN - 1 mL/kg of 25% dextrose solution Thiamine 100 mg (adult) Pyridoxine 50-100 mg (infant) Antibiotics Naloxone

What is the difference between acid/alkalemia, and acid/alkalosis?

Blood → "emia" suffix - Acidemia: blood pH <7.35 - Alkalemia: blood pH > 7.45 Distinctly different than the pathophysiologic processes - "osis" suffix - Acidosis or Alkalosis - Respiratory or metabolic in nature - Based on main contributing physiologic process - What is the main determinant of CO2? Bicarbonate?

Can inhaled medications be used for patients on mechanical ventilation?

Both nebulizers and inhalers can be used! - Specific techniques may be required for inhalers in ventilated patients.

What BBW is associated with acetaminophen?

Boxed Warning: severe liver injury

What are the common causes of hypercapnic Acute Respiratory Failure (ARF)

Brain - Drugs - Metabolic - Brain infection - Trauma Nerves/muscles - Obesity hypoventilation - Drugs - Metabolic Upper airway - Trauma - Laryngeal edema Chest bellows - Obesity - Ascites - Pain - Pneumothorax - Rib fractures

What is a transitory exacerbation of pain that occurs on a background of otherwise stable pain in a patient receiving chronic opioid therapy?

Breakthrough Pain

What anatomic and physiologic problems can be caused by ARF?

Bronchial inflammation Mucosal edema Smooth muscle contraction Increased mucous production and viscosity Leads to: - Obstruction of airway gas flow - Increased airway resistance - Mismatch - Increased dead space

What opioid is a partial agonist?

Buprenorphine

What is the mnemonic to remember the causes of respiratory acidosis?

CANS CNS depression (stroke, narcotics, etc) Airway obstruction Neuromuscular disorders - Amyotrophic Lateral Sclerosis (ALS) - Neuromuscular Blocking agent (NMB) - Myasthenia Gravis (MG) Severe: PNA, PE, pulmonary edema

What mnemonic can be used to remember the causes of respiratory alkalosis?

CHAMPS CNS mediated hyperventilation (Pain, Trauma, Tumor) Hypoxia Anxiety Mechanical ventilation (over ventilation) Progesterone (pregnancy, cirrhosis) Salicylate intoxication or Sepsis

What mnemonic can be used to remember the causes of metabolic alkalosis?

CLEVER-PD Contraction (volume contraction or dehydration) Licorice ingestion Endocrine (Conn's, Cushing's, Bartter's) Vomiting Excess alkali administration Refeeding alkalosis Post hypercapnea Diuretic administration

What ventilator mode is when the ventilator does all work of breathing?

CMV - Controlled mechanical ventilation

What ADRs and DDIs are associated with H2RAs?

CNS adverse effects - Confusion, hallucinations, agitation, dizziness, headaches - Cimetidine>Ranitidine>Nizatidine>Famotidine Pneumonia Rapid IVP: hypotension and arrhythmias Pseudo-renal failure with cimetidine Thrombocytopenia: onset 4-7 days CYP-450 drug interactions: -3A4, 2D6, 2C19, 1A2 - Phenytoin, warfarin, amiodarone, colchicine, BZDs, CCBs - Cimetidine>>Ranitidine(low)>Nizatidine: Famotidine none

Acidity of extracellular fluid can be regulated by _________ or _____________.

CO2 or bicarbonate

Tolerance develops to all adverse effects associated with opioids EXCEPT ____________________________.

CONSTIPATION (!!)

What are the common causes of hypoxemic Acute Respiratory Failure (ARF)?

COPD Exacerbations Pneumonia Acute Respiratory Distress syndrome (ARDS) Pulmonary Embolism Heart failure

What is the difference between COX-1 and COX-2?

COX-1: Constitutive Present in most tissues Synthesizes PGs that regulate physiologic processes Especially important in - Gastric mucosa - Kidneys - Platelets - Vascular endothelium COX-2: Inducible in most tissues Induced mainly at sites of inflammation by cytokines Synthesizes PGs PGs mediate: - Inflammation - Pain - Fever

What ventilator mode is essentially the same as PEEP, but no set Vt is delivered?

CPAP - Continuous Positive Airway Pressure

What is the mnemonic to remember the causes of non-anion gap/hyperchloremic metabolic acidosis?

CURSED+AP C: Calcium Chloride/Cholestyramine U: Uretral Uretral diversion, Uretosigmoid or Uretoenteric fistula R: Renal tubular acidosis (i.e., caused by primary or secondary hyperparathyroidism) S: Small bowel fistula E: Extra chloride (saline) D: Diarrhea/Drug-induced Diarrhea (Magnesium) A: Adrenal insufficiency (Addison's)/Alimentation (TPN)/Acetazolamide and other carbonic anhydrase inhibitors P: Pancreaticduodenal fistula

COX-2 inhibitors increase risk of _________________. - Risk increased regardless of dose - Risk increased for both low risk and high risk patients

CV events

What condition is physical wasting, weight loss? - Not just the result of reduced food intake - Don't confuse with anorexia/

Cachexia

What pharmacological adjuncts are used when giving blood products to a hemorrhagic shock patient?

Calcium Procoagulant hemostatic adjuncts •Tranexamic acid •Recombinant factor VII •Prothrombin complex concentrate •Fibrinogen concentrate

What are the first steps in managing acute metabolic acidosis?

Calculate & assess anion gap vs non-gap Treat the underlying cause(!!!) Assess severity: Mild to moderate (pH 7.2-7.4): - Consider no additional therapy or PO alkali therapy Life threatening emergency (pH < 7.15-7.2 or [HCO3-] <8 mEq/L): - Assess treatment risks vs benefits - Dialysis is often required in severe cases - Administer IV alkali therapy

How is the total daily dose of basal insulin calculated when starting a patient on it?

Calculate TDD - 0.3-0.4 units/kg/day - 0.5-0.7 units/kg/day Adjust TDD - Past response to insulin - Presence of hyperglycemia inducing agents Basal insulin =50% of TDD - Long acting insulin (daily/BID) or intermediate acting insulin BID

How is neuropathic pain described?

Can be spontaneous or evoked May be constant and/or intermittent Description of pain: - Burning - Shooting - Electric shock-like - Lancinating - Crawling - Itching - Tingling - Numb

What type of pain is described here? Caused by the disease itself and/or procedures or treatments •Invasion of tissue, compression, obstruction •Biopsy, post-operative, chemo, radiation therapy

Cancer or malignant pain

What agent for neuropathic pain is an irritant derived from hot chili pepper? - Depletes substance P from sensory nerves Used for topical treatment of PHN, DPN, RA, OA, post-surgical pain - Onset of action: 14-28 days - Peak effect: 4-6 weeks continuous therapy Adverse reactions: stinging, itching, erythema, burning Available formulations:(!!) - Cream, gel, liquid, lotion, patch - Various strengths (0.025% to 8%)

Capsaicin

What are the main acid base pairs seen in the body?

Carbonic acid/bicarbonate - H2CO3/HCO3- - Most important one Monobasic/dibasic phosphate - H2PO4/HPO4 Ammonium/ammonia - NH4/NH3 Lactic acid/lactate - H6C3O2/H5C3O2-

How are the following factors affected with distributive shock? Cardiac index (2.4-4.7 l/min/m2) - Pump function PCWP (8-12 mm Hg) - Preload SVR (800-1400dynes.sec/cm5) - Afterload Mixed SvO2 - Tissue perfusion

Cardiac index (2.4-4.7 l/min/m2) - Pump function - High PCWP (8-12 mm Hg) - Preload - Low SVR (800-1400dynes.sec/cm5) - Afterload - Low Mixed SvO2 - Tissue perfusion - Low

ow are the following factors affected with cardiogenic shock? Cardiac index (2.4-4.7 l/min/m2) - Pump function PCWP (8-12 mm Hg) - Preload SVR (800-1400dynes.sec/cm5) - Afterload Mixed SvO2 - Tissue perfusion

Cardiac index (2.4-4.7 l/min/m2) - Pump function - Low PCWP (8-12 mm Hg) - Preload - High SVR (800-1400dynes.sec/cm5) - Afterload - High Mixed SvO2 - Tissue perfusion - Low

How are the following factors affected with hypovolemic shock? Cardiac index (2.4-4.7 l/min/m2) - Pump function PCWP (8-12 mm Hg) - Preload SVR (800-1400dynes.sec/cm5) - Afterload Mixed SvO2 - Tissue perfusion (!!!!!!!!!!!!)

Cardiac index (2.4-4.7 l/min/m2) - Pump function - Normal PCWP (8-12 mm Hg) - Preload - Low SVR (800-1400dynes.sec/cm5) - Afterload - Normal Mixed SvO2 - Tissue perfusion - Low

What cardiovascular and GI effects do opioids have?

Cardiovascular - Peripheral vasodilation - Inhibition of peripheral baroreceptors - Decreased peripheral resistance Gastrointestinal - Decreased gastric acid secretion and GI motility. - Decreased intestinal secretions and peristalsis. - Increased Sphincter of Oddi tone and biliary pressure.

What NSAID is COX-2 selective?

Celecoxib

What are the signs and symptoms associated with acute respiratory failure? Signs and symptoms of hypoxemia, hypercapnia, or both.

Change of mental status (agitation to somnolence) Bradypnea Cyanosis Diaphoresis, tachycardia, hypertension Increased work of breathing - Accessory muscles - Tachypnea - Dyssynchronous breathing pattern - Tripoding

What are some of the main possible causes of hypoglycemia in the hospital?

Change to NPO status Reduce oral intake DC of enteral feeding or PN DC of dextrose IV fluids Timing of premeal insulin altered Reduced/DC corticosteroids Reduced/DC vasopressors

What needs to be considered when treating chronic respiratory acidosis?

Chronic CO2 retention changes respiratory drive Oxygen worsens CO2 retention -> failure - If the patient is oxygenating well then don't go chasing numbers - Eliminates respiratory drive Must assess baseline status - Patient's can tolerate low PaO2 and elevated PaCO2 - Compensation: increased number of red blood cells, hemoglobin content, and 2,3-diphosphoglycerate Don't over correct! Bottom line: Treat the underlying cause!

What type of pain is described here? Persistent pain not associated with cancer Osteoarthritis, headaches, low back pain, phantom limb pain, peripheral neuropathy

Chronic non-malignant pain

What type of pain is described here? Pain that exists 3 to 6 months beyond onset or expected time of healing. Pathology does not explain presence/extent of pain; no adaptive purpose.

Chronic pain

Which H2RA is the only H-2RA FDA approved for SUP?

Cimetidine IV

Which opioid is described here? Low affinity for opioid receptors Better oral absorption vs. morphine (F=60%) Metabolized (10%) to morphine (CYP2D6) - Deficient in 8-10% of African-Americans - Amplified in 7% of Caucasians Effective anti-tussive Used for mild to moderate pain Formulations: - Tablet - Many combinations with APAP (tablet, oral solution, oral suspension) - Many combinations for cough/cold and migraine

Codeine

Which opioids are weak agonists?

Codeine Hydrocodone Tramadol Tapentadol

What opioid agents and doses should be initially used for moderate pain in adults?

Codeine - 30 - 60 mg Tramadol - 50 - 100 mg Hydrocodone - 5 - 10 mg Oxycodone - 5 mg

What are all of the formulations of Fentanyl?

Cogeners used in anesthesia - Alfentanil, sufentanil, remifentanil Available formulations - Injection PF (Sublimaze®) - Oral lozenge (Actiq®) - Buccal tablet (Fentora™) - Buccal soluble film (Onsolis™) - Sublingual tablet (Abstral®) - Sublingual spray (Subsys®) - Intranasal solution (Lazanda®) - Transdermal patch (Duragesic®)

What is palliative care of patients who are imminently dying (hours to days)? - Discontinue diagnostic/treatment efforts with negligible benefit or cause harm/decrease QOL - Nursing care (oral care, skin care, wound care, positioning) - Eating for pleasure if appropriate - Medications for rapid symptoms management - e.g. pain, anxiety/agitation, secretions, nausea

Comfort Care

What is essential to practice of palliative medicine? - Decreases anxiety - Improves well-being - Improves satisfaction with providers and health care - Improves outcomes

Communication

What term describes when there is an attempt by the body to maintain homeostasis (pH 7.38 to 7.42) by attempting to correct the primary acid-base disturbance?

Compensation

What is CI with duloxetine?

Concurrent or recent MAOI use and closed-angle glaucoma (!)

When should you consider increasing the dose of long acting opioids?

Consider increasing dose of long acting agent if: More than 2-3 breakthrough doses per 24 hrs. -OR- More than 25% total daily dose is used as breakthrough.

What are the pharmacologic principles of opioid use? - Should follow these in patients with opioid abuse and pain.

Consider loading dose Anticipate shorter duration of analgesia and higher requirements secondary to tolerance Consider the use of patient controlled analgesia Plan to taper upon discontinuation Treat for typical time frame of patients without substance abuse

When should NMBs be used for ARDS?

Consider use, but in select patients - ARDS Patients with ventilator dsynchrony , elevated Peak pressures, persistent hypoxia (!!)

What ADRs are associated with TCAs?

Constipation, dry mouth, blurred vision, urinary hesitancy, tachycardia, mental status changes, orthostatic hypotension, sedation, weight gain, falls

What indicates Refractory Status Epilepticus?

Continuous EEG (cEEG) activity after both emergent and urgent treatments have been given.

How is sodium chloride resistant or unclassified metabolic alkalosis treated?

Correct underlying or potentially contributing causes and treat concomitant electrolyte imbalances. - Exogenous corticosteroid therapy: decrease dose or switch to one with less mineralocorticoid activity. - Excess alkali intake, refeeding syndrome, high dose PCN: adjust therapy. - Severe potassium depletion (<3 mEq/L): PO or IV K+ supplementation. - Endogenous mineralocorticoid excess (e.g., Bartter's or Gitelman): - Spironolactone, amiloride, or triamterene. - No response to medication, consider surgery. - Liddle syndrome: amiloride or triamterene.

What structures in the brain are involved with perception of pain?

Cortical and limbic structures involved Thalamus - Information on location, intensity, quality of pain - Relays to the limbic system

What type of pharmacy specializes in the delivery of patient care services by pharmacists, as integral members of interprofessional teams, working to ensure the safe and effective use of medications in critically ill patients through interactions with prescribers, nurses, patients, families, and others?

Critical Care Pharmacy

What type of resuscitation fluid is described here? Balanced electrolyte composition (!) Available as isotonic and hypertonic solutions(!) Pass freely between semipermeable membranes(!) - Expand total extracellular volume Potential to cause hemodilution Cheaper Chloride balanced vs chloride rich? - LR vs Normal saline

Crystalloids

What agent that can be used for fibromyalgia is a centrally-acting skeletal muscle relaxant; reduces somatic motor activity? Tricyclic compound structurally Usual dose 10-40mg per day Warnings and precautions similar to TCAs Adverse effects - Drowsiness, dizziness, dry mouth, anticholinergic effects similar to TCAs Dosage forms: IR tablet, ER tablet

Cyclobenzaprine (Flexeril®, Amrix®)

After receiving appropriate emergent therapy, JS ceased to have clinical convulsive seizure activity and the staff was able to place a peripheral IV. Which of the following would be the most appropriate therapy at this time? A. The seizure has stopped; no further drug therapy is needed, just continue supportive care B. Loading dose of midazolam followed by continuous infusion C. Give a dose of diazepam PR D. Give a dose of fosphenytoin IV E. Give a dose of lorazepam IV

D. Give a dose of fosphenytoin IV

What can be used to help remember all of the causes of delirium?

DELIRIUM Drugs Electrolyte or glucose abnormalities Liver failure Ischemia Renal failure Impaction of stool Urinary tract or other infection Metastasis to the brain

Describe the timeline for the pathogenesis of ARDS?

Days 0-7: - Exudative phase - Edema - Hyaline membranes Day 14: - Proliferative phase - INTERSTITIALS INFLAMMATION - INTERSTITIAL FIBROSIS Day 21: - Fibrotic phase - Fibrosis

Describe the pathophysiology of hemorrhagic stroke?

Decreased blood volume Decreased cardiac output Decreased oxygen delivery to tissues •Mountain of oxygen and catecholamine surge •End-organ damage •Failure of hemostatic mechanisms •Cell death Activation of the clotting cascade Coagulopathy

How is excretion altered in ICU patients? - Renal is primary excretory pathway

Decreased elimination Example: - Acute Kidney Injury - Chronic Renal failure - Hemodialysis - Continuous Renal Replacement Therapy Augment Renal Clearance (ARC) - At risk: <50 yrs old, no organ failure - Identify with measured urine creatinine clearance Example: - Burn patients - Trauma Patients - Traumatic brain injury

What did the PROSEVA trial determine about using the prone position for ARDS?

Decreased mortality compared to supine position in severe ARDS at day 28 and 90. Higher success rate of extubation in prone position at day 90. Increased ventilator-free days in prone position. Lower incidence of cardiac arrest in prone position. Decreased use of Nitric oxide in prone position.

How should patients with substance abuse be treated for pain?

Define mechanism of pain and treat primary problem Determine abuse history - Current, past, distant past, methadone maintenance Do not substitute non-opioids for opioids in severe pain; use a combination The use of mixed agonist-antagonist opioids is contraindicated - Nalbuphine, pentazocine, butorphanol Maintain maintenance opioid (if present) Follow pharmacologic principles of opioid use: Deal with substance abuse behavior as it is identified - Treatment agreements, urine drug screen The 4 A's of pain - Analgesia, ADLs, adverse effects, abuse issues

What are all of the causes of Xerostomia (Dry mouth) during palliative care?

Dehydration, mouth breathing, medications, infections, surgery, or XRT to mouth.

What are the 5 stages of emotions that effect dying people?

Denial Anger Bargaining Depression Acceptance

Describe the modulation step of pain signaling?

Descending inhibitory pathways Inhibitory substances released and bind to dorsal horn or peripheral neurons - Endogenous opioids, serotonin, norepinephrine, GABA Receptors: mu, delta, kappa, NMDA Wide variation in pain perception among patients

What medications can be used to help treat Anorexia/Cachexia associated with palliative care?

Dexamethasone (Decadron) Megestrol (Megace) Metoclopramide (Reglan) Dronabinol (Marinol) Mirtazipine (Remeron)

Which benzodiazepine is described here? Rapid onset (seconds) but short duration (high lipophilicity) Multiple routes of administration - IV or rectal(!) Administer 0.15 mg/kg - Up to 10 mg/dose - Rate of 5 mg/min May repeat every 5 min

Diazepam

What are the treatment goals for chronic non-cancer pain (CNCP)?

Diminish suffering including pain and associated emotional distress. Increase/restore physical, social, vocational, and recreational function. Optimize health, including psychological well-being. Improve coping ability and relationships with others.

Name all of the stool softeners and their doses and onset times.

Docusate 24-72 hr 100 mg q12h

How is succinylcholine dosed for RSI?

Dose: 1.5 mg/kg IV (infants: 2 mg/kg IV) - Use ACTUAL body weight - Rapid bolus; follow w/ 20-30 mL saline flush

Describe the dosing and pharmacokinetics of the Duragesic® Patch? - (Fentanyl patch)

Dosing - 25 mcg ≈ 45-90mg PO morphine/24 hrs - Typical interval every 72 hours, although some patients may require Q48 hour dosing - Strengths: 12.5mcg, 25mcg, 50mcg, 75mcg, 100mcg PK: - Onset of action 12 to 16 hrs - Steady state ~48 hours - T1/2 7-12 hours, effects up to 12 hrs after removal

How should phenytoin be dosed? - Also give rate

Dosing - LD: 20 mg/kg - May give an additional dose (5-10mg/kg) 10 minutes after LD. - Start maintenance doses within 12-24 hours of loading dose. Administration Rate - 50 mg/min (MAX!)

How should Pentobarbital be dosed when treating refractory status epileptics?

Dosing (IV) - LD: 5-15 mg/kg - May give additional 5-10 mg/kd - CI: 0.5-5 mg/kg/hr Administration Rate - < 50 mg/min

How is duloxetine dosed for neuropathic pain and at what CrCl should it not be given?

Dosing: 60 to 120mg daily - Not recommended for CrCL < 30 mL/min

What how is hepatic blood flow effected in ICU patients and how does this alter hepatic metabolism?

Drug delivery: - Shock states: late sepsis, hypovolemic shock (hemorraghic/non-hemorraghic), Myocardial infarction, and heart failure. - Iatrogenic: mechanical ventilation w/wo PEEP - Medications: Phenylephrine, norepinephrine, high dose dopamine, and vasopressin. - Inotropes (milrinone/dobutamin) may INCREASE HBF

What agent for neuropathic pain is a selective serotonin and norepinephrine reuptake inhibitor? Approved in 2004 Indicated for the treatment of: - Major depressive disorder - Generalized anxiety disorder - DPN - Fibromyalgia - Chronic musculoskeletal pain (Osteoarthritis or Low back)

Duloxetine (Cymbalta®)

What neuropathic sensation is an abnormal; spontaneous or touch-evoked, unpleasant sensation?

Dysesthesias

What problem is common at end of life? - Short of breath, uncomfortable awareness of breathing, feeling of being suffocated or smothered. - Usually accompanied by increased respirations. - Oxygen saturation cannot be depended upon to identify dyspnea.

Dyspnea

What are the mechanisms that cause neuropathic pain?

Ectopic impulse generation from neuroma Disinhibition: Ascending pathways - GABA inhibition lost - Mu receptors reduced; less sensitivity to mu agonists - Loss of spinal inhibitory neurons Descending pathways - Inhibition via alpha-2 receptors suspended - Serotonergic inhibition changed to facilitation

What causes altered protein binding in ICU patients?

Effect: albumin and AAG-bound concentration changes. Example: - Thermal injury - Increase AAG concentration and decrease albumin - Fraction of unbound acidic drugs increase for acidic drugs bound to albumin - Phenytoin, diazepam Fraction of unbound basic drugs decreased bound to AAG - Meperidine, propanolol, lidocaine

When screening a patient with possible GCSE, what all /observedshould be measured?

Electroencephalogram (EEG) - Monitors brain's electrical activity - Reveals seizure activity Serum drug concentration(s) - Obtain for those on chronic anticonvulsants - Is drug withdrawal was the cause? - Is a loading dose is needed? Determine if a CNS infection is present - Start antibiotics Drug and alcohol screen - Thiamine

What are the 3 main types of naturally occurring opioids in the body?

Enkephalins Endorphins Dynorphins

How should opioid induced constipation be prevented?

Ensure adequate fluid intake Encourage physical activity - Exercise, ambulation Avoid bulk-forming laxative - Psyllium, polycarbophil Usually requires stimulant laxative - Senna, bisacodyl All patients on chronic opioids should be on stimulant with stool softener (prevention) - Scheduled, not prn Peripherally-acting opioid antagonists also available - Methylnaltrexone, naloxegol, naldemedine

How should constipation be treated in palliative care?

Ensure adequate fluid intake Docusate sodium 100 mg PO BID (no opioids) Docusate sodium/sennosides PO BID (opioids) No bowel movement for 48 hrs add: Milk of magnesia 30-60 mL PO daily -OR- Bisacodyl 10 mg PO/PR daily No bowel movement in next 12 hrs: Magnesium citrate 8 oz. PO -OR- Fleet enema If opioid-induced: Methylnaltrexone weight-based dose QOD prn

What are the Updated Joint Commission Standards for treating pain?

Establish a clinical leadership team Actively engage medical staff and hospital leadership in improving pain assessment and management, including strategies to decrease opioid use and minimize risks associated with opioid use Provide at least one non-pharmacological pain treatment modality Facilitate access to prescription drug monitoring programs Improve pain assessment by concentrating more on how pain is affecting patients' physical function Engage patients in treatment decisions about their pain management Address patient education and engagement, including storage and disposal of opioids to prevent these medications from being stolen or misused by others Facilitate referral of patients addicted to opioids to treatment programs

What is the mortality rate with GCSE?

Estimated mortality in US - Between 22,000 and 42,000 per year - Up to 16% children - Neonates have higher mortality Outcome is affected by the time between onset of GCSE and the initiation of treatment and the seizure duration - Mortality significantly increases with increased duration. Mortality has decreased over past decade - Treating faster - Treating more aggressively

Which induction agent is described here? Ultrashort-acting non-barbiturate hypnotic - Rapid onset—30 to 60 secs - Duration: 3-12 minutes Gold standard Hemodynamic stability Hydrolyzed in liver and plasma Decreases ICP with minimal effects on cerebral perfusion - NO analgesia (!) ADE: Myoclonic jerks, ê cortisol production (adrenal suppression)

Etomidate

Describe the pathophysiology of fibromyalgia?

Exact mechanism is unknown Neuroendocrine system abnormalities - Hypothalamic-pituitary-adrenal (HPA) axis dysfunction - Inability to suppress cortisol Autonomic nervous system abnormalities - Alteration in physiologic response to stress and pain inhibition Sleep disturbances Potential genetic influence

What imbalance causes seizures?

Excitatory neurotransmission > inhibitory impulse = seizures. Excitatory: - Glutamate, calcium, sodium, substance P, and neurokinin B. Inhibitory: - γ-aminobutyric acid [GABA], adenosine, potassium, neuropeptide Y, opioid peptides, and galanin.

What mechanical devices can effect elimination in ICU patients?

Extra Corpeal Membrane Oxygenation (ECMO) Continuous renal replacement

What are the three mechanisms to maintain acid-base balance?

Extracellular buffering Ventilatory regulation Renal regulation

What boxed warning is associated with the vasopressors/inotropes that are used for resuscitation?

Extravasation - Administer through a central line if able - Peripheral okay for short term - Prefer phenylephrine

What is the mnemonic used for assessing ICU patients?

FASTHUG-MAIDENS F - Feeding A - Analgesia S - Sedation T - Thromboemboloic prophylaxis H - Hypo/Hyperactive delirium U - Ulcer prophylaxis G - Glucose control M - Medication reconciliation A - Anti-infectives I - Indication for medications D - Dose E - Electrolytes/lab values N- No duplication/interactions/adverse events S - Stop dates

What is respiratory failure defined as?

Failure in one or both gas exchange functions: Hypoxemic - Oxygenation- disorder of blood to oxygenate as it circulates in the alveolar capillaries - Ex: Pneumonia, Acute lung injury, pulmonary edema Hypercarbic - Carbon dioxide elimination - Ex: airflow obstruction, central respiratory failure, neuromuscular failure. Mixed In practice: - Pa02 <60mmhg or PaC02 >50 mmHg with PH<7.36 **May occur in patient without previous lung disease or may be superimposed on chronic respiratory failure

T or F: Repeated doses of an opioid cannot confer tolerance to other drugs in the same class.

False, repeated doses of an opioid will confer tolerance to other drugs in the same class. - Results in decreased effect of opioid Cross-tolerance between opioids is incomplete. Incomplete cross-tolerance likely due to: - Subtle differences in the molecular structure of each opioid. - Differences in the way each opioid interacts with the opioid receptors.

How should you apply knowledge of altered hepatic metabolism at bedside in Icu patients?

Familiarize when TDM should be implemented or considered. - Lidocaine, phenytoin pentobarbital Apply kinetic concepts to explain prolonged or exaggerated drug effect. Apply kinetic concepts to explain need for higher doses of infusions to achieve desired clinical outcome.

Which H2RA is the main one used for stress ulcer prophylaxis?

Famotidine (!!!)

Which induction agent is described here? - Short-acting, potent. - Minimal histamine release. - Hemodynamically stable - Sedation is rate- AND dose-dependent - Combined with other induction agents for analgesia ADE: muscle rigidity, grand mal seizures (rare)

Fentanyl

Which opioid is described here? Synthetic opioid agonist 100 times as potent as morphine More lipophilic than morphine Quicker onset than morphine (5 min) Hepatic metabolism and renal elimination - Inactive metabolites No histamine release Minimal effect on hemodynamics Used for moderate to severe pain

Fentanyl

What agents can be used for post-intubation care for sedation?

Fentanyl Propofol Dexmedetomidine Midazolam

What are all of the different agents that can be used as induction agents for RSI and their doses?

Fentanyl 5-15 mcg/kg IV Midazolam 0.1 mg/kg IV Ketamine 1-2 mg/kg IV Etomidate 0.3 mg/kg IV Propofol 2 mg/kg IV

What is a musculoskeletal connective tissue disorder? - Chronic, widespread pain and fatigue - Tenderness that is difficult to localize Often coexists with: - Sleep disturbances - Depression - Recurrent headaches - Mood disturbances

Fibromyalgia

What is used first line and second line for treating hypovolemic shock?

First Line - Fluid Resuscitation Second line - Vasopressor therapy

What is the most important step in treating hypovolemic shock? Goal - Increase preload and cardiac output - Achieve hemodynamic stability

Fluid resuscitation

What agent that can be used for fibromyalgia inhibits serotonin reuptake in the CNS? - Usual dose 20-80 mg daily - Use alone or in combination with TCA Adverse effects - Nausea, diarrhea, headache, sleep disturbances, sexual dysfunction

Fluoxetine (Prozac®)

For single doses of ibuprofen, give ibuprofen at least ___ hours before or at least ___ minutes after immediate release ASA (not enteric-coated). When taken concomitantly, ibuprofen attenuates the cardioprotective effect of ASA.

For single doses of ibuprofen, give ibuprofen at least 8 hours before or at least 30 minutes after immediate release ASA (not enteric-coated)

What agent is a prodrug of phenytoin that is rapidly converted after IV and IM administration? Dosing - LD: 20 mg PE/kg - May give an additional dose (5mg/kg) 10 minutes after LD - IM only if IV access is not available Administration Rate - 150 mg PE/min (MAX!) (!!)

Fosphenytoin

What is FiO2?

Fraction of inspired oxygen - Room air 21% - 60% or less is general goal to decrease oxygen toxicity.

How should someone in palliative care with dyspnea caused by mild CHF with respiratory distress be treated?

Furosemide 20-40 mg PO/IV x 1 dose Monitor for improvement - Diuresis - Oxygen saturation - Dyspnea Opioids

What type fo receptor are opioid receptors? - Opioid agonists lead to hyperpolarization of neurons, decreasing neuronal activity.

G-protein coupled receptors

What agents used for neuropathic pain mimic action of GABA alpha-2-delta subunit? Decrease the release of: - Glutamate, aspartate, substance P Considerable variation in pain relief

GABA analogues Gabapentin (Neurontin®) Pregabalin (Lyrica®)

Signals from what areas in the body can trigger the vomit center?

GI tract - Serotonin, acetylcholine, histamine, substance P Chemoreceptor trigger zone (CTZ) - Dopamine, serotonin Vestibular apparatus - Histamine, acetylcholine Cerebral cortex

What ADRs can occur with NSAIDs? - Used for mild to moderate pain

GI: dyspepsia, ulceration, bleeding, perforation. Heme: inhibit platelet aggregation. Renal: renal impairment, acute renal failure, sodium and water retention. CNS: decreased attention span, short-term memory loss, difficulty with calculations. Other: bronchospasm, skin reaction, tinnitus

What is the adequate trial period for each of the following agents for treating fibromyalgia? Gabapentin Lidocaine patch Opioids Tramadol TCAs

Gabapentin - 3 - 8 weeks Lidocaine patch - 2 weeks Opioids - 4 - 6 weeks Tramadol - 4 weeks TCAs - 6 - 8 weeks

What are the indications for Gabapentin (Neurontin®) and Pregabalin (Lyrica®)?

Gabapentin: - Adjunctive treatment for partial seizures - PHN Pregabalin (C-V): - Adjunctive treatment for partial seizures - PHN - DPN - Fibromyalgia

What ADRs are associated with each of the GABA analogues?

Gabapentin: •Dizziness •Somnolence •Dry mouth •Nausea •Ataxia •Fatigue Pregabalin: •Dizziness •Somnolence •Dry mouth •Blurred vision •Weight gain •Edema* •Difficulty concentrating ***December 2019 - FDA warned of serious breathing difficulties in patients with respiratory risk factors. - Opioids, CNS depressants, lung disease, elderly.

In metabolic acidosis what can cause SAG (Serum anion gap) to be high?

Gain of H+ (!!) **Normal SAG - Loss of HCO3- replaced by Cl- and/or gain of H+ - Severe diarrhea, biliary, or pancreatic drainage from a surgical drain or fistula

What neurotransmitter involved with neuropathic pain is the principle inhibitory neurotransmitter? - Endogeneous ___________________ hyperpolarizes neurons and decreases release of excitatory neurotransmitters (glutamate, aspartate, substance P).

Gamma-aminobutyric acid (GABA)

What ADRs can occur with Proton Pump Inhibitors? - Similar ADE rates among PPIs

Gastrointestinal - Diarrhea, nausea, vomitting abdominal pain Headaches (3-5%) Rash Acute interstitial nephritis - Rash, fever, arthralgias - Oliguric ARF, eosinophilia, pyuria, hematuria Hypomagnesemia with chronic use (3 months) - PPIs may change intestinal absorption of Mg Pneumonia-CAP, HAP, VAP C-difficile diarrhea Hip fractures - PPIs > H2RAs

What physical exams are used for evaluating pain?

General: appearance (pallor, grimacing, diaphoresis), vital signs (increased BP, HR) Site of pain: tenderness Neurological: sensory deficits Musculoskeletal: posture, gait, range of motion, muscle tone

What type of status epileptics is described here? - Repeated primary or secondary generalized seizures - Involve both hemispheres of the brain - Associated with a persistent postictal state

Generalized convulsive status epilepticus (GCSE) *This is what we will focus on for the exam.

What are all of the predisposing factors for addiction?

Genetics Grief/trauma Exposure Poor coping skills or lack of access to skill learning

What are the goals of the pre-oxygen phase of RSI and what are the methods used to accomplish them?

Goals: - Establish O2 reservoir - Maximize time for intubation - Prevent need for bag-mask ventilation Methods: - 3-5 minutes of 100% O2 via face mask - 4 (or 8) vital capacity breaths on 100% O2

What agents for preventing stress ulcers are described here? Preponderance of efficacy and safety data - Extensive data with intravenous dosage form - Data with oral formulations is lacking Intermittent vs. Continuous infusions No advantage to pH monitoring vs. no pH monitoring Tachyphylaxis with CI Renal dosing required Cost effective-generics available

H-2 Receptor Antagonists (H2RAs)

What pharmacologic agents can be used to treat agitation and delirium in palliative care?

Haloperidol 0.5-1 mg IV q1h until symptoms resolve - Schedule required dose divided q6-8h Risperidone 0.5-1 mg PO q12h Olanzapine 2.5-5 mg PO daily Quietapine 50 mg PO q12h Benzodiazepine can be added to above - Never alone: worsens delirium and cognitive impairment.

What are all of the barriers to the treatment of pain?

Healthcare system - Failure to make pain relief a priority - Failure to provide clinicians with tools and training - Lack of accountability for pain management - Fragmented patient care - Limited access to pain specialists and therapy - Inconsistent reimbursement Healthcare professional - Clinicians attitude, beliefs, behaviors. - Inappropriate or exaggerated concerns. - Regulatory scrutiny, adverse effects, addiction. - Inadequate or inaccurate clinical knowledge. - Understanding of pharmacology, misconceptions about pain. Patient and families - Inability to communicate - Reluctance to report pain - Low expectations for relief - Fear of what the pain means - Fear of adverse effects - Fear of addiction - Financial barriers

What ADRs can occur with acetaminophen?

Hepatotoxicity, hepatic necrosis, skin rash, blood dyscrasias.

Name all of the semisynthetic opioids.

Heroin Hydromorphone Oxycodone Hydrocodone

What are all of the therapy options for ARDS?

High-flow nasal oxygen Tidal volume - Use 6mL/kg per predicted bodyweight Plateau airway pressure Positive end-expritory pressure Recruitment maneuvers Neuromuscular blockade Prone position Inhaled NO (Pulmonary vasodilator) Fluid management Renal replacement therapy Antibiotics Glucocorticoids Extracorporeal membrane oxygenation (Lung dialysis)

What risks are associated with increasing gastric pH when trying to prevent stress ulcers?

Higher gastric pH is associated with: - Gastric microbial growth - Tracheobronchial colonization - Nosocomial pneumonia - Clostridium difficile Increased risk of death Osteoporosis Neutropenia

What all is needed to have good communication in palliative care?

Honesty Willingness to talk about dying Sensitive delivery of bad news Listening Encouraging questions

Which hospital is providing better care?? Why? Hospital A: - Mortality rate = 45% - Predicted mortality rate= 58% Hospital B: - Mortality rate = 20% - Predicted mortality rate = 14%

Hospital A because their mortality rate is lower than their predicted mortality rate.

What pharmacologic treatment options are used once the seizure activity is broken for urgent treatment of SE? - Prevents further seizure activity after emergent therapy's activity stops. - Attain rapid therapeutic levels of antiepileptic drug therapy.

Hydantoins (Historically preferred tx) Barbituates Valproate Levtiracitam Lacosamide Midazolam **Newer data is revealing that others may be as effective

How is sodium chloride responsive metabolic alkalosis treated if the patient has persistent alkalosis or if initial pH >7.60? - Severe and symptomatic - Unresponsive to conventional fluid & electrolyte management - These agents are rarely used in practice

Hydrochloric acid - Preferred for those with renal failure, liver failure, or decompensated CHF Ammonium chloride Arginine monohydrochloride Hemodialysis using a low-bicarbonate dialysate

Which opioid is described here? Moderate affinity for opioid receptors Good oral absorption Used for mild to moderate pain Recently rescheduled from CIII to CII Formulations: - Combination with APAP (4g/day limit) - Max of 325mg APAP per dosage unit - Tablet, oral solution, elixir - Combination with ibuprofen (tablet) - Combination products for cough/cold - ER tablet, ER capsule

Hydrocodone

What processes in the body produce the acids and bases needed to maintain proper pH? - Hydrogen (H+) - Bicarbonate (HCO3-) - Non-volatile Acids - Carbonic Acid (H2CO3)

Hydrogen (H+) - Cellular metabolism produces large quantities Bicarbonate (HCO3-) - Kidney's maintain serum bicarbonate levels - Reabsorb or excrete bicarbonate as needed - Excrete ammonium (NH4+) Non-volatile Acids - Produced by dietary digestion and tissue metabolism Carbonic Acid (H2CO3) - Maintained in equilibrium with CO2 - CO2 produced from the catabolism of carbohydrate, protein, and fat.

What opioid is described here? Semi-synthetic opioid agonist Similar efficacy and duration to morphine Peak effects in 0.5 - 1.5 hours Duration 4 - 5 hours (T½ 2.5 hours) - Extensive liver metabolism, renal elimination - Lacks clinically significant active metabolites - Preferred in renal impairment Minimal effect on hemodynamics Used for moderate to severe pain Available as injection, PF injection, IR tablets, ER tablet, oral liquid, suppository

Hydromorphone (Dilaudid®)

What neuropathic sensation is an exaggerated pain response to a mildly noxious (mechanical or thermal) stimulus?

Hyperalgesia

What can central sensitization can lead to?

Hyperalgesia: increased response to stimuli Allodynia: pain to innocuous stimuli Persistent pain: pain after transient stimuli Referred pain: pain in uninjured tissue

What neuropathic sensation is an increased sensitivity to stimulation?

Hyperesthesia

What is the clinical presentation of metabolic acidosis?

Hyperkalemia Low serum CO2 and low [HCO3-] Mild to moderate acidemia: pH 7.2-7.4 - Usually asymptomatic Severe acidemia: pH <7.15-7.20, plasma HCO3-<8 mEq/L (mmol/L) - Symptoms: - Dyspnea - Hyperventilation with deep, rapid respirations (to increase CO2 excretion) Compensation: hyperventilation leading to decreased PaCO2.

What ADR with succinylcholine is one of the most severe? Can be caused in the following patients: - Burn Pts - Crush injury - Denervation - ALS or MS - Intra-abdominal sepsis Because of this ADR, succinylcholine is CI in: - Conditions with up-regulation of ACh-receptors (see table) - Known/suspected hyperkalemia - Personal/family hx of malignant hyperthermia

Hyperkalemia - Typical K+ increase < 0.5 mEq/L - Up to a 5mEq/L K+increase in certain settings

Describe the typical clinical presentation of respiratory acidosis?

Hyperkalemia(!!) Moderate (PaCO2 of 50-55 mm Hg) to severe (PaCO2 >80 mm Hg) hypercapnia. Hypoxia is often present (PaO2 <70 mm Hg). - Can be severe and life-threatening when PaO2 <40 mm Hg. Usually symptomatic May complain of neurologic symptoms - Altered mental status, abnormal behavior, seizures, stupor, confusion, difficulty thinking, etc. Mild to moderate acidosis: - pH 7.2-7.4 - PaCO2>50-55 mmHg - Up to 80mmHg Stimulates a stress-like response: - Increased catecholamines - Corticosteroid hormone levels - Increased cardiac output and pulmonary artery pressure Severe acidosis: - pH<7.15-7.20 - PaCO2>80 mmHg - Cardiac output declines and vascular resistance decreases - refractory hypotension Compensation: Increased HCO3- reabsorption - Takes 12-24 hours to have a significant effect

What laboratory signs can indicate hypovolemic shock?

Hypernatremia and hyperchloremia Elevated BUN:SCr ratio Elevated base deficit Lactic acid CBC - Hemoglobin ABG - Low oxygen - Acidosis (resp/metabolic)

What neuropathic sensation is a delayed and explosive pain response to a noxious stimulus?

Hyperpathia

Describe the clinical presentation of respiratory alkalosis?

Hypokalemia (!) Decreased free calcium - Increased albumin binding due to decreased competition from H+ ions. Mild to moderate alkalemia: pH 7.4-7.6 - Usually relatively asymptomatic - Hyperventilation or symptoms related to decreased PaCO2 or decreased cerebral blood flow: light-headedness, confusion, seizures, nausea/vomiting, etc. Severe alkalemia: pH>7.60 - Cardiac arrhythmias - Neuromuscular irritability Compensation: decreased HCO3- reabsorption - Occurs if respiratory alkalosis persists for > 6-12 hours

What is the typical clinical presentation of metabolic alkalosis?

Hypokalemia(!) Decreased free Calcium - Increased albumin binding due to decreased competition from H+ ions. Mild to moderate alkalemia (pH 7.4-7.6) - Usually relatively asymptomatic - May have symptoms related to underlying cause of disorder: - Muscle weakness with hypokalemia - Postural dizziness or orthostatic hypotension with volume depletion. Severe alkalemia: pH>7.60 - Cardiac arrhythmias - Particularly in patients with heart disease, hyperventilation, hypoxemia. - Neuromuscular irritability with tetany or hyperactive reflexes. - Due to secondary decreased free calcium Compensation: hypoventilation resulting in increased PaCO2

How does Type I Renal tubular acidosis(RTA) affect potassium and urinary anion gap? - Type I RTA (distal): impaired H+ excretion

Hypokalemic (!) Unable to attain maximal urinary acidification Urinary anion gap positive (!)

What serious ADRs can occur with Pentobarbital when treating refractory SE?

Hypotension Respiratory depression Cardiac depression Parlytic ileus

What serious ADRs can occur with Propofol?

Hypotension Rhabdomyolysis Metabolic Acidosis Renal failure Cardiac failure Respiratory depression PRIS (High dosing: > 4 mg/kg/hr and/or > 48 hours)

What does the sniffing test detect?

Hypovolemia by showing IVC collapse on an ultrasound.

What is the most appropriate glucose lowering agents for critical ill ICU patients? - Most potent glucose lowering agent - Rapidly effective - Easily titratable - No real contraindications

IV insulin

What are the principles of chronic pain?

Identify and treat underlying cause if possible. Expecting complete absence of pain may be unrealistic. Individualize treatment to patient and underlying cause of chronic pain. Functional impairment or diminished QOL are candidates for pharmacological therapy. Risks and benefits of all pharmacologic interventions should be reviewed. Use the least invasive method for drug administration. Greater pain reduction achieved with multi-modal therapy. Initiate low doses and titrate with frequent assessment. For episodic pain, use rapid-onset, short-acting analgesics. For continuous pain, provide analgesics around the clock. Patients prescribed long-acting analgesics should also have rapid-onset, short-acting analgesics for breakthrough pain. Consider rotation to different opioid as tolerance increases.

In what situations should the provider be called when adjusting an insulin drip?

If glucose is less than 70 mg/dL - HOLD insulin infusion, initiate hypoglycemia protocol, and call for instructions on when to resume insulin infusion and at which "constant". If exogenous calories are held (TPN, tube feeds, dextrose containing IVF), then decrease insulin infusion by 50%, resume hourly capillary glucose checks, and call MD for new insulin constant orders. If glucose less than 130 mg/dL contact physician for consideration of constant reduction. If insulin rate less than 0.5 units/hr notify physician for further instructions.

What are the short term goals for treating status epileptics?

Immediate termination of seizure activity (electrical and physical) Prevent clinically adverse effects Prevent recurrent seizure activity

What are other risk factors for constipation in patients taking opioids? - Other than the opioids lol

Immobility Low fiber diet Dehydration Other medications - Anticholinergics, calcium salts, lithium, verapamil

What are the different types of breakthrough pain?

Incident pain (most common) - Occurs with activity or movement - Can be predictable or unpredictable End of dose failure - Occurs prior to scheduled dose of analgesic - More gradual onset and longer duration Idiopathic pain - No known cause - Lasts longer than incident pain

What are the indicators for VAP?

Increase Ventilatory requirements - Increase PEEP, FIO2 Hyperthermia/hypothermia Leukopenia/leukocytosis New antibiotic after 4 days ICU stay Gram stain evidence of purulent secretions or pathogenic pulmonary culture

What are the goals of palliative care for the healthcare team/system?

Increase caregiver satisfaction Reduce unnecessary procedures, interventions, ICU transfers, etc. Support smooth transitions between care settings (potentially reducing hospital days)

What should gastric pH be increased to to prevent stress ulcers in ICU patients?

Increase gastric pH to >3.5

What is the MOA of Phenytoin? Onset of action (IV): about 0.5 - 1 hours - Not fast enough for emergent treatment!

Increased efflux or decreased influx of sodium ions across the cell membranes in the motor cortex

What are the indications for mechanical ventilation?

Indications: - Acute respiratory failure/apnea - Coma/inability to protect airway - Acute exacerbation of COPD - Ventilatory dysfunction secondary to neuromuscular disorders.

What is considered the "gold-standard" for estimating caloric requirements? - - Needs a closed ventilatory circuit Many hospitals do not have the technical capabilities

Indirect Calorimetry

What are the principles of pain management?

Individualize the route, dosage, and schedule - Optimal dose varies widely among patients - Give each analgesic an adequate trial Administer analgesics on a regular schedule if pain is present most of the day Follow patients closely to assess response Anticipate, recognize and treat adverse effects Do not use placebos to assess pain Monitor for the development of tolerance and treat appropriately Expect physical dependence and prevent withdrawal Be alert to the psychological state of the patient - Do not diagnose addiction based on dependence alone

What type of agents are given as rapid IV push immediately before paralyzing agent? - Facilitates intubation through reducing patient movement and induce muscle relaxation. - Success rate increased to 98% while reducing complications. Ideally provides: - Rapid loss of consciousness - Analgesia - Amnesia - Stable hemodynamics

Induction Agent(s)

What types of inhaled medication can be given to patients on mechanical ventilation?

Inhaled antibiotics can be used - Typically used to help clear tracheal/bronchial secretions Inhaled mucolytics - 3-7.5% NaCl - Acetylcysteine - Sodium bicarbonate Inhaled pulmonary vasodilators - Nitric Oxide - Epoprostenol Inhaled beta agonist - Albuterol - Levalbuterol Inhaled anticholinergics - Ipratropium

What effect do opioids have when they bind to an opioid receptor?

Inhibit transmission of nociceptive input from periphery to the spinal cord (ascending pathways). Activate descending inhibitory pathways that modulate transmission in the spinal cord.

What is used for initial fluid resuscitation in hypovolemic shock patients and how much?

Initial - 250 - 1,000 mL boluses - Assess - Repeat Choice of fluid Crystalloid - Isotonic - Hypertonic Colloid

What are the different multidimensional tools used for assessing pain

Initial Pain Assessment Tool - Diagram for location of pain and scale to rate pain Brief Pain Inventory (BPI) - Questions on pain over past 24 hours McGill Pain Questionnaire (MPQ) - Three dimensions of pain - Sensory, affective, evaluative - 102 words in 20 groups - Short-form also available

What does that American College of Critical Care Medicine-Guidelines recommend for when to administer insulin and what dose should be given for treating hyperglycemia in ICU patients?

Insulin infusion (1 unit/ml) should be used to control hyperglycemia after priming new tubing with a 20ml waste volume. - Subcuntaneous (SC) insulin may be acceptable in the ICU if BG goals maintained. Suggest that a BG >150 should trigger initiation of insulin therapy. (!!) Titrate to keep BG<150 for most adult ICU patients, maintain less than 180 mg/dl (!!) Use a protocol that achieves a low rate of hypoglycemia - BG <70 mg/dl associated with an increase mortality. (!) Lower glucose targets (110-140 mg/dl) may be appropriate in selected patients. - Targets <110 mg/dL are not recommended.

Which induction agent is described here? NMDA-antagonist - dissociative anesthesia - Analgesic, amnestic, anesthetic Dissociation occurs at threshold of 1-2 mg/kg IV - 4-10mg/kg IM (more emesis) Onset: 30 seconds Duration: 5-15 minutes Catecholamine reuptake inhibition (Increases HR, BP, CO, ICP) Maintains respiration and airway reflexes ADE: Emergence delirium (30%)—Premed: midazolam 0.07 mg/kg - Emesis (highest in adolescents ~9yo) CI: schizophrenia (schizoaffective); <3 months - CVD

Ketamine

What are all of the alternative therapies that can be used to treat refractory status epilepticus?

Ketamine - potentially neurotoxic (NMDA activity) Corticosteroids Inhalational anesthetics - require specialized training - Isofluorine Vagal nerve stimulator Ketogenic diet Hypothermia Electroconvulsive therapy (ECT) Surgical management - Before age 12 (still have neuroplasticity)

What diagnostic tests are used to evaluate pain?

Labs, imaging (CT, MRI), procedures

Name all of the osmotic laxatives and their doses and onset times. - And also where in the GI they work.

Lactulose 24-48 hr 15-30ml q12-24hr Osmotic, colon PEG 48-96 hr 17g q12-24hr Osmotic, GI tract Sorbitol 8-24 hr 15-30 ml q12-24 Osmotic, colon Mag hydroxide 30 min 30 ml q12-24 hr Colon, osmotic,perstalsis

Describe what colloid solutions for resuscitation are.

Large molecules - Protein - Starch Remain in the intravascular space - Exert high oncotic pressure Potential to trigger anaphylactic reaction

What environmental factors can effect absorption in ICU patients?

Less blood flow due to decreased perfusion. Decreased intestinal surface area due to intestinal atrophy. Decreased GI motility Alteration of pH

What are the 3 levels of hypoglycemia? - If any of these levels of hypoglycemia occur, modify treatment regimen

Level 1 - Glucose less than 70 mg/dl. Level 2 - Glucose less than 54 mg/dl. Level 3 - Severe event characterized by altered mental status and/or physical function.

What anti-epileptic agent is described here? Mechanism of Action - Exact MOA unknown Dosing (IV) - LD: 1000-3000 mg IV Administration Rate - 2-5 mg/kg/min Serious adverse events - Increased blood pressure - CNS - Behavioral problems, Headache, Drowsiness - Vomiting Considerations - Minimal drug interactions - Not hepatically metabolized

Levetiracetam

What agent for neuropathic pain is in a transdermal patch? - Indicated for PHN - 10 x 14cm transdermal patch Contains 700mg _____________ that acts predominately locally - Only ~3% absorbed systemically Improves pain scores, QOL, allodynia

Lidocaine (Lidoderm®)

What agents and doses are given in the pretreatment phase of RSI?

Lidocaine - 1.5mg/kg IV (Rarely used anymore) Opioid (Fentayl) - 1-3mcg/kg IV Atropine - 0.02mg/kg (No longer recommended) Defasciculating agent

What non-pharmacologic treatment options can be used for fibromyalgia?

Lifestyle Modification - Stress Management - Cognitive Behavioral Therapy, Relaxation Training, Group Therapy, Biofeedback - Hypnotherapy - Exercise (Cardiovascular and resistance training) Alternative Therapies - Herbal remedies, Acupuncture, Tai-chi Chiropractic therapy, electrotherapy, massage therapy, ultrasound, trigger point injections

How do you apply knowledge of distribution changes at bedside for ICU patients?

Loading doses of antimicrobials and or need for therapeutic drug monitoring Consider lower doses or monitoring for protein bound medications

What is the safety mechanism on PCA pumps? - Max amount of drug patient can receive per hour - = basal rate + drug from available PCA doses.

Lockout interval (per hour) Example regimens: - Morphine 2mg q10min prn - 1-hour lockout = 12mg - Morphine 2mg/hr and 1mg q15min prn - 1-hour lockout = 6mg

Which benzodiazepine is described here? Drug of choice for IV administration! (!!!!) - IV administration preferred - Rapid onset (2-3 min) - Administer 0.1 mg/kg Up to 4 mg/dose (Max dose for bolus)(!!) Rate of 2 mg/min Repeat every 5-10 minutes(!) - Dilute 1:1 with saline Contains propylene glycol

Lorazepam

What agents are effected the most by low albumin and AAG-bound concentration changes in ICU patients?

Low liver extraction drugs - Fentanyl, diltiazem, nicardipine, haloperidol, milrinone, propofol.

What effect does using COX-2 inhibitors have on GI and CV risk? - Selectively inhibit COX-2 isoenzyme - Similar efficacy to nonselective NSAIDs

Lower risk of GI effects Increased cardiovascular risk Nonselective NSAIDs increase risk of GI complications - Risk differs among individual agents.

What is the mnemonic to remember anion gap metabolic acidosis causes?

MUDPILES Methanol, metformin, malignancy Uremia (advanced/chronic kidney failure, AKI) Diabetic ketoacidosis (DKA) Paraldehyde, propylene glycol, propofol Isoniazid (INH), Iron, Infection Lactic acidosis, linezolid Ethylene glycol, ethanol Salicylates, sepsis, starvation ketosis, seizures

Describe the metabolism of acetaminophen?

Majority conjugated with glucuronide and sulfate and excreted in urine. Minority metabolized through CYP450 to toxic N-acetyl-para-benzoquinonimine(NAPQI). - Conjugated with glutathione, further metabolized and excreted in urine. - NAPQI accumulates in APAP overdose.

What is a massive transfusion and when should it be used?

Massive transfusion is defined as - Replacement of >1 blood volume in 24 hours, or - >50% of blood volume in 4 hours (adult blood volume is approximately 70 mL/kg), or - in children: transfusion of >40 mL/kg (blood volume in children over 1 month old is approximately 80 mL/kg) A Massive Transfusion Protocol should be used in critically bleeding patients anticipated to require massive transfusion(!!)

What DDIs can occur with omeprazole?

May inhibit CYP-450 2C19 Diazepam, Phenytoin, Warfarin, Cyclosporine - Less likely with esomprazole Not noted with lansoprazole or pantoprazole Inducers may decrease levels of all PPIs

How can MAP be used to determine systemic vascular resistance?

Mean arterial pressure minus central venous pressure divided by cardiac output.

What are the patient risk factors indicating the need for stress ulcer prophylaxis?

Mechanical ventilation>48 hrs Coagulopathy NPO Vasopressors Corticosteroids Septic shock Hepatic/renal failure Trauma Burns *If a multiple risk factors consider stress ulcer prophylaxis and discontinue when risk factors no longer present

What risks are associated with Rapid Sequence Intubation (RSI)?

Medication side effects Prolonged intubation Emergent or crash airway - Cricothyrotomy - Tracheotomy Hypotension/cardiac arrest

What are all of the potential causes of constipation during palliative care? - Can cause significant physical discomfort - Goal of treatment is comfort, not a particular frequency of bowel movements.

Medications - Opioids - Anticholinergics - Antidepressants - Diuretics - Antacids - Calcium channel blockers - NSAIDs - Iron Bowel obstruction Electrolytes - Hypercalcemia - Hypokalemia Abdominal tumor Dehydration Reduced physical activity Limited mobility

Which medications are effected the most by an altered hepatic blood flow in ICU patients?

Medications with liver extraction of E>0.7 most affected - Lidocaine, beta-blockers, morphine, midazolam

Name all of the synthetic opioids

Meperidine Fentanyl series Methadone

Which opioid is described here? Synthetic opioid agonist Similar absorption to morphine Quicker onset compared to morphine but shorter duration - 5 min onset IV, duration 2 to 4 hours Metabolized to active, toxic metabolite, eliminated renally (T1/2 15 to 30 hours) - Normeperidine: excitation, hallucinations, seizures Generally do not use due to neurotoxicity Only for acute post-op pain or rigors (!!!!) Limit use to less than 48 hours and less than 600 mg in 24 hours - Increased risk of adverse effects Available as injection, tablet, oral solution

Meperidine (Demerol®)

What acid-base disorder is most commonly diuretic associated? - Chronic may be steroid (mineralocorticoid) associated - Liver and kidney failure may also contribute - Treat the underlying cause - Choose treatment based on sub-classification

Metabolic alkalosis

What are the different causes of agitation and delirium during palliative care?

Metabolic causes Bowel obstruction Infection CNS events Medications - Opioids, chemotherapy, corticosteroids Inadequate pain control

Which opioid is a Phenylheptamine? - Synthetic opioid agonist, lipophilic - Also NMDA antagonist - Excellent oral bioavailability (F>85%) - Onset of action 0.5-1 hour - Accumulates with repetitive dosing - Peak effect 3-5 days with continued dosing - Duration 4-8 hours, 22-48 hours with repetitive dosing - Half life 8-59 hours - Inactive metabolites

Methadone

What agent for opioid induced constipation is described here? - If nothing else works. Quaternary amine does not cross blood brain barrier(!) Indication - Opioid regimen for 2 weeks and laxative regimen for 3 days Dose 12 mg subq every other day Efficacy - Less constipation compared to placebo Safety Increased risk bowel perforation

Methylnaltrexone

Which benzodiazepine is described here? Extremely short half-life - Maintenance doses given as continuous infusion Multiple possible routes of administration - IV, IM, buccal, intranasal (!!!) - More reliable IM absorption than other benzos - Buccal requires small fluid volume (2-5 mL) Administer 0.2 mg/kg - Up to 10 mg/dose (!)

Midazolam

Which induction agent is described here? Sedative, amnestic, muscle relaxant - NOT analgesic Onset: 60-90 seconds Duration: 1-4 hours Not routinely used Less cardiorespiratory depression vs. other benzos - Decreases BP; Increases HR - Use lower dose in hypovolemic, elderly, or traumatic brain injury patients (0.05 mg/kg) Does NOT contain propylene glycol(!)

Midazolam

What anti-epileptic agent is described here? Mechanism of Action - Enhancement of the inhibitory effect of GABA Onset of action (IV) - About 3 to 5 minutes Dosing - LD: 0.2 mg/kg - CI: 0.05 - 2 mg/kg/hr - Titrate by 0.05 - 0.1 mg/kg/hr Q3-4H Administration Rate - 2 mg/min Serious adverse events - Hypotension - Respiratory Depression Considerations - Tachyphylaxis after prolonged use - Active metabolite - Rapid redistribution - Renally eliminated - Does NOT contain propylene glycol

Midazolam infusion

What agents can be administered if Refractory Status Epilepticus occurs? - Immediately start additional agents. Consider continuous infusions (if not initiated) - Administer bolus doses prior to start - Switch agents if the infusion choice fails

Midazolam, propofol, & pentobarbital

What agent is indicated for fibromyalgia only (in US)? - Contraindications, precautions, adverse effects similar to duloxetine Dosing - Day 1: 12.5mg once - Days 2-3: 12.5mg BID - Days 4-7: 25mg BID - After day 7: 50mg BID - May increase to 200mg/day based on response - Requires adjustment for renal dysfunction (CrCL < 30 mL/min use 25mg BID) (!!)

Milnacipran (Savella®)

What are the long term goals for treating status epileptics?

Minimize or avoid pharmacoresistant epilepsy Avoid neurologic sequelae

What is MV or Ve?

Minute ventilation - Respiratory rate x Vt

What are the goals with the pretreatment step of RSI?

Mitigate adverse physiologic reactions to intubation - Sympathetic "pressor response" - Bronchospasm - Increased intracranial pressure (ICP) - Muscle fasciculation Begins 2-3 minutes PRIOR to induction/paralysis - "LOAD" - Not routinely done in practice

What is methadone indicated for?

Moderate to severe pain Detox, maintenance treatment opioid addiction - Methadone can be dispensed in community setting for analgesic purposes only. - Treatment for addiction only permitted by registered treatment programs

What non-pharmacologic therapy is used for treating status epileptics?

Monitor vital signs Protect airway - Maintain ventilation - Maintain oxygen saturation (SaO2) - give 100% O2 - Intubate if needed - Assisted ventilation to correct respiratory acidosis Treat hyperthermia aggressively - Cooling blanket & rectal acetaminophen EEG Monitoring

What ADRs can occur with opioids?

More serious - Respiratory depression - Apnea - Respiratory arrest - Circulatory depression - Hypotension - Shock - Hypersensitivity - Dysphoria Less serious - Somnolence - Dizziness - Nausea, vomiting - Constipation - Diaphoresis - Dry mouth - Urinary retention - Pruritus

What opioid is described here? Naturally occurring opioid agonist Pharmacokinetics - Adequate absorption (F=30%) - Peak: 20 min (IV), 1 hour (PO, except SR) - Duration: 4-5 hours (T1/2 2-4 hours) - Metabolism: Extensive liver metabolism (Conjugation) - Elimination: Kidney (90%) - (Requires adjustment for renal impairment) (!!!) Used for moderate to severe pain

Morphine

Name all of the naturally occurring opioids.

Morphine Codeine

Which opioids are strong agonists?

Morphine Hydromorphone Oxycodone Fentanyl Methadone Meperidine Oxymorphone

Name all of the long acting opioids?

Morphine (MS Contin, Kadian, Avinza, Embeda) Oxycodone (Oxycontin, Xtampza ER) Hydromorphone (Exalgo) Oxymorphone (Opana ER) Fentanyl (Duragesic) Tramadol (Ultram ER) Tapentadol (Nucynta ER) Hydrocodone (Zohydro ER, Hysingla ER) Methadone

What opioid agents and doses should be initially used for severe pain in adults

Morphine - 15 - 30 mg Hydromorphone - 4 - 8 mg Oxymorphone - 5 - 10 mg Oxycodone - 10 - 20mg

What sublingual opioids are used for palliative care? - Possible when using concentrated oral opioid solutions. - Administer a few drops at a time to allow for absorption.

Morphine 20 mg/mL, oxycodone 20 mg/mL

What metabolites are produced from morphine? - 50% to 80% of metabolites renally eliminated

Morphine 3-glucuronide (M3-G) (45-55%) - Devoid of analgesic activity (may actually induce hyperalgesia). - Postulated to affect confusion, agitation, and dysphoria. Morphine 6-glucuronide (M6-G) (10-15%) - Equal affinity to parent drug for mu1 receptor - Fourfold greater affinity for mu2 receptor

What did the NICE-SUGAR trial discover about glycemic control in the ICU?

Mortality: 27.5% vs. 24.9% - intensive vs. conventional. No difference in median length of ICU or hospital stay, number of days of mechanical ventilation, RRT, positive blood cultures, or RBC transfusions. - Don't need super strict glucose control for best results, just keep glucose between 140-180ish.

How is xerostomia treated in palliative care?

Mouth swabbing Sialogogues Artificial saliva

What opioid receptors are effected by mixed agonist-antagonists? - Butorphanol

Mu - Antagonist Kappa - Agonist

What opioid receptors are effected by partial agonists? - Buprenorphine

Mu - Partial activation Kappa - Antagonist

What opioid receptors are activated with full agonists?

Mu and Kappa

What opioid receptors are blocked by opioid antagonists? - Naloxone

Mu, Delta, and Kappa

What are all of the potential causes of dyspnea at the end of life?

Muscle dysfunction/deconditionin Pleural effusion Pulmonary disease Pneumonia PE CHF Tumor Anxiety or depression Anemia

What ADRs are associated with succinylcholine?

Muscle fasciculation - myalgias - Hyperkalemia, Decreased CPK Bradycardia/hypotension Mild increase in ICP Malignant hyperthermia - Treat with Dantrolene (1-2 mg/kg IV)

GCSE is largely caused by glutamate acting on what postsynaptic receptors? - Activation leads to neuronal depolarization - Sustained depolarization lead to neuronal death

N-methyl-D-aspartate (NMDA) ε-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA)/kainate

What are all of the different disease specific scoring systems?

NIH Stroke Scale King's College Criteria RIFLE Criteria HEP Score MELD Score CHA2DS2-VASc HAS-BLED HINCHEY Classification

What are the 3 main classifications of metabolic alkalosis?

NaCl Responsive (Urine Cl <10 Meq/L) - GI Disorders - Vomiting - Gastric drainage - Diuretic Therapy - Correction of chronic hypercapnia - Cystic fibrosis NaCl Resistant (Urine Cl >20 Meq/L) - Excess Mineralocorticoid activity - Hyperaldosteronism - Cushing Syndrome - Profound potassium depletion - Magnesium Deficiency - Liddle syndrome - Estrogen therapy - Excess black licorice Unclassified - Alkali administration - Milk-Alkali syndrome - Massive blood or plasma transfusion - Nonparathyroid hypercalcemia - Carbohydrate refeeding after starvation - Large doses of penicillin

What opioid antagonist is described here? - 0.4-2mg every 2-3 minutes to max 10mg - Short half life, may need to repeat doses every 20-60 minutes - Completely metabolized through first pass - Given IV, IM, SC, intranasal, ET tube - Can reverse opioid toxicity acutely

Naloxone (Narcan®)

What opioid antagonist is described here? Long half life Used 3 times/week in maintaining drug-free state in opioid dependence Tablet, suspension for IM injection (ER) Can be used to reverse opioid toxicity acutely

Naltrexone (ReVia®, Vivitrol™)

What are the different methods for administration of oxygen supplementation for ARF? - Most patients with ARF require supplemental oxygen

Nasal cannula Various masks - Air entrainment face mask - Aerosol face mask - Reservoir face mask - Resuscitation bag-mask unit

What are the different ventilation methods?

Nasal cannula BiPAP Endotracheal intubation

What dosage form of opioids is not FDA approved? Achieve rapid but erratic plasma levels - Peak reached in 10 minutes - Range 10 - 30 minutes Bioavailability 3 - 35% Small number of small studies conducted - Generally show benefit for patients. - No major benefit compared to opioids via other routes of administration. Generally well tolerated - Avoids first pass metabolism - May cause fewer side effects

Nebulized Opioids

What neuromuscular blocker reversal agent is described here? Acetylcholinesterase inhibitor Renal dose adjustment recommended Time to recovery: 10-20 minutes after admnistration - Defined as train of four ratio 0.9 - Slow and inconsistent antagonism of NMB effects Side effects - Bradycardia, bronchospasm, increased secretions, atelectasis - May need atropine, glycopyrrolate Cannot reverse deep neuromuscular blockade and require a degree of spontaneous recovery of muscle function before being administered.

Neostigmine

What agents are quaternary ammonium compounds that mimic structure of ACh? - Depolarizing vs non-depolarizing Allow complete airway control - Higher success (100% vs 82%) - Less aspiration and airway trauma Enable lower doses of sedative - Better hemodynamic stability

Neuromuscular Blocking Agents (NMBAs)

When should a neuromuscular blockade be preformed for mechanical ventilation with regards to sedation and analgesia?

Neuromuscular blockade can only be used with certain settings? - Sedation and analgesia must be optimized FIRST(!!)

What type of pain is described here? Aberrant nerve signals Central sensitization Serves no purpose Burning, tingling, prickling, shooting, shock-like, numb

Neuropathic

What is pain that typically arises as a consequence of a lesion or disease affecting the somatosensory system? - May affect up to 7-8% of the population - Often described as chronic pain - Often under-recognized and difficult to treat

Neuropathic Pain

What type of pain is described here? Response to noxious stimuli Actual or potential tissue injury Normal process Localized, sharp, dull, aching, cramping

Nociceptive

What type of NMBAs are competitive antagonists of ACh at neuromuscular junctions? - Higher doses = faster onset, longer duration - Reversible Alternatives to succinylcholine Long-acting vs intermediate-acting

Non-Depolarizing NMBAs

What preventative measures can be used to prevent VAP?

Non-invasive ventilation Daily sedation interruption with spotaneous breathing trials Early moblization Intermittent subglottic suctioning Elevate head of bed 30-45 degrees Good hand hygiene Other Approaches - Selective decontamination of the oropharynx - Perform oral care with chlorhexidine - Administer prophylactic probiotics

What are the different pharmacologic approaches to treating pain? - 3 types of approaches (!!!)

Non-opioids Opioids Adjuvant agents (co-analgesics)

What can be used to treat secretions?

Non-pharm: - Position patient on side or semi-prone - Suction not always effective, can be disturbing - Reduce fluid intake Pharm: - Scopolamine - Hyoscyamine - Glycopyrrolate - Atropine

What type of status epileptics is described here? - Approximately 25% of SE - Fluctuating or continuous "epileptic twilight" state - Altered consciousness and/or behavior

Nonconvulsive status epilepticus (NCSE)

What neurotransmitters involved with neuropathic pain are key neurotransmitters in descending inhibitory pain pathways? - Increasing availability may promote pain inhibition centrally.

Norepinephrine and serotonin

What is normal blood pH? - Very narrow range!

Normal blood pH = 7.4 (7.38 to 7.42)

What solutions are crystalloids?

Normal saline Lactated ringers D5W

What is the current recommendation for using corticosteroids for treating ARDS?

Not routinely recommended. Consider in patients in patients with Sepsis+ARDS or PNA+ARDS.

What are the different unidimensional tools used for assessing pain?

Numeric rating scale (NRS) - 0 (no pain) to 10 (worst imaginable pain) Visual analog scale (VAS) - 10 cm line; 0 (no pain) to 10 (worst imaginable pain) Categorical scales - Faces pain scale - Verbal descriptors

What are the risk factors for developing stress ulcers in the ICU?

ONE Major Independent risk factor: - Respiratory failure (Mechanical ventilation>48 hrs) - Coagulopathy (Plt <50,000/mm + INR >1.4) - Thermal injury - Spinal cord/head trauma TWO minor risk factors: - Renal failure - Septic shock/severe sepsis - High dose corticosteroids >250 mg Hydrocortisone - History of GIB or perforation within past year

What gender is affected by Fibromyalgia more?

Occurs 6x more often in females Onset in early-middle adulthood - Ages of 20 to 55 * Possible genetic link as it tends to be familial

What are the risk factors for Postherpetic Neuralgia (PHN)?

Older age Greater severity of the acute phase: - Prodrome - Rash - Pain Chronic diseases - DM, respiratory conditions Immunocompromised patients

When is neuromuscular blocker reversal indicated? Rarely indicated in this population - Other options: bougie, escalation of intervention to a surgical airway - Most commonly after OR anesthesia

Only indication would be in cannot intubate, cannot ventilate situations where a nondepolarizing NMBA has been administered. - Elective intubation for procedures

What agents usually have no effects unless opioids present? - Bind to opioid receptors, but do not activate them - Reverse respiratory depression in 1-2 minutes Can induce a withdrawal syndrome in patients taking chronic full opioid agonists.

Opioid Antagonists

What agents that can be used to treat dyspnea in palliation are described here? - Reduce the subjective sensation of breathlessness. - Titrate _____________ to patient comfort. - Decreased respiratory rate is normal result of dying process.

Opioids

What are all of the different possible routes of admission for opioids?

Oral (preferred) - Most convenient, cost-effective, flexible - Peak drug effects occur in 1 to 2 hours - Except for SR preparations Intramuscular (PAINFUL) - Variable and/or inconsistent absorption - 30-60 minute lag time to peak, rapid fall-off - Can lead to neuropathy, abscesses - Not recommended (!!!) Intravenous - Most rapid onset of effect - Improved effectiveness, titration - Options: - Bolus, continuous infusion, PCA Subcutaneous - Alternative to oral or IV route - Intermittent injection or continuous infusion - Volume that can be injected/infused limited Rectal - Alternative to injections in NPO patients - Avoids first pass metabolism - Can give CR morphine and CR oxycodone tablets rectally. Transdermal - Continuous administration without pump or needle - May cause less constipation than oral controlled-release opioid Intraspinal - Administered directly into epidural or intrathecal (subarachnoid) space

What agent for opioid induced constipation is effective as long as patient not on high doses or chronic steroids around the clock?

Oral naloxone

What opioid is described here? Semi-synthetic opioid agonist Analgesic potency comparable to morphine Higher oral bioavailability (F=60-90%) Used for moderate to severe pain Formulations: - Tablets, capsules, oral solution, concentrated oral solution, CR/ER tablet/capsule - Combination products with APAP, ASA, IBU - Combination with naloxone and naltrexone

Oxycodone

What opioid is described here? Semi-synthetic opioid Poor bioavailability; food increases absorption, but given on empty stomach Slightly longer T1/2 than morphine:7-9h Undergoes glucuronidation to active metabolites; may accumulate in renal dysfunction Co-administration of ethanol with ER product dramatically affects AUC - Varying degrees of increases in AUC, but ethanol use is contraindicated during therapy with oxymorphone ER. Formulations: IR tablet, ER tablet, injection

Oxymorphone (Opana®)

What ventilator mode is when positive pressure is maintained on the airway during expiratory phase?

PEEP - Positive End Expiratory Pressure

What is the PQRST method for assessing pain?

PQRST Palliative/provocative factors Quality Radiation Severity Temporal factors

What ventilator mode is when pressure delivered at the beginning of initiated breath?

PS - Pressure Support

What is the most common cause of long-term disability? _________ is the most common reason individuals seek medical attention. "An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage"

Pain *9 out of 10 Americans have regular pain

What do patients and families ideally want with palliative care?

Pain and symptom control Avoid inappropriate prolongation of the dying process Achieve a sense of control Relieve burdens on family Strengthen relationships with loved ones

What are all of the factors that are assessed when assessing pain?

Pain characteristics - Onset and duration, location(s), quality, intensity, associated symptoms, exacerbating/alleviating factors. Management strategies - Past and current medications (Rx, OTC, herbals), nonpharmacologic treatments. Relevant medical history - Prior illnesses, surgeries, accidents, coexisting acute or chronic diseases, prior pain issues and treatment. Impact of pain on patient's life - Work, daily activities, relationships, sleep, appetite. Patient expectations and goals for treatment - Pain intensity, daily activities, quality of life, desire and expectations for pharmacologic treatment.

What tests can be used to diagnose neuropathic pain?

Pain interview/questionnaire - Pain description/level, occurrence/triggers, area(s) affected. Past medical history Blood tests Electrodiagnostic tests - Electromyography (EMG), nerve conduction velocity (NCV) testing. Quantitative sensory testing (QST)

Why is the accurate assessment of pain difficult? - Objective is to obtain information to help identify cause of pain and guide management.

Pain is subjective Multidimensional Assessment can depend on multiple factors

What is the most common type of peripheral neuropathy? - 16-34% of patients with diabetes Characterized by diffuse damage to peripheral nerves causing debilitating symptoms - Pain, sleep disturbance, anxiety, impaired function - Typically affects feet/lower extremities; symmetrical and worse at night. Peripheral neuropathy and/or pain may precede diagnosis of diabetes

Painful Diabetic Neuropathy (PDN)

What type of care provides relief from pain and other symptoms? - Affirms life and regards dying as normal process - Intends neither to hasten nor postpone death - Integrates psychological and spiritual aspects - Offers support system to patient and family - Uses a team approach to address needs of the patient and family - Enhances quality of life - Applicable early in course of illness

Palliative Care

What is the difference between palliative care and hospice?

Palliative Care: - No time limits (At any stage of illness) - Advanced directives encouraged - Treatment may include active therapies Hospice: - Short life expectancy (< 6 months) - DNR status generally required - Beyond point of active therapies - Chemotherapy, radiation, dialysis, surgery

Which Non-Depolarizing NMBAs is described here? Long time to onset Increases HR and BP (vagolytic effect) Histamine release - bronchospasm/anaphylaxis Active metabolites Accumulates - Renal dosing required - CrCl 10-50: 50% of dose - CrCl <10: do not administer NOT recommended for RSI (!!!)

Pancuronium

What neuropathic sensation is an abnormal; spontaneous, intermittent, painless sensation?

Paresthesias

What is PCA?

Patient-Controlled Analgesia (PCA) Programmable pump for IV opioids - Also subcutaneous Provides small dose constantly and/or very frequently - Continuous infusion (basal rate) - prn dose (PCA dose) Patient uses button to obtain prn dose

Are patients fully conscious during Rapid Sequence Intubation (RSI)? - Why or why not?

Patients are sedated and then paralyzed to allow for an easier intubation. - Prevention of adverse outcomes - Autonomic nervous system response - Increased HR, BP, and wall shear stress - Elimination of protective airway reflexes - Coughing, gagging, increased secretions, laryngospasm - Elimination of discomfort and recall - Better control of the cervical spine

What is PIP or Ppeak?

Peak inspiratory pressure - Pressure in the large airways

What are the different blood pressure goals for hypovolemic shock caused by the following reasons? - Penetrating Trauma - Blunt trauma - Brain injury - Other

Penetrating Trauma - SBP 50-70 mm Hg - Once hemorrhage controlled may resume MAP 65 Blunt Trauma - Initial SBP 80-90 - Once hemrrohage controlled may resume MAP 65 Brain Injury - Initial SBP 100-110 mg Hg, MAP>70 mm Hg Other hypovolemic shock - MAP 65 mm Hg - Some cases lower MAP 55-60 mm Hg considered - If known: BP low at baseline - Liver cirrhosis - ESRD - CHF advanced

What opioids are mixed agonist-antagonists?

Pentazocine Butorphanol Nalbuphine

What are the other risk factors for opioid abuse?

Personal or family history of alcohol or drug abuse Younger age Presence of psychiatric conditions

What factors can effect drug distribution in ICU patients?

Ph Changes - Causes: Shock, Renal failure, Respiratory failure - Effect: Ionized state changes Fluid shifts - Cause: Increase capillary permeability, Oncotic pressure decrease, crystalloids/colloids, third spacing - Effect: Increased volume of distribution (up to 3x) Plasma protein binding - Cause: Decrease alpha-1 acid glycoprotein (AAG) and albumin. - Effect: Change in free highly protein bound drugs and increase in Vd.

What are the 2 phases of GCSE? - GCSE - Generalized Convulsive Status Epilepticus

Phase I: Seizure activity markedly increases plasma epinephrine, norepinephrine, and steroid concentrations. - Hypertension, tachycardia, and cardiac arrhythmias. Muscular contractions and hypoxia cause lactic acid release - Severe acidosis that maybe accompanied by hypotension and shock Rhabdomyolysis with secondary hyperkalemia and acute tubular necrosis can occur. Airway can be obstructed - Cyanosis or hypoxemia Phase II: Seizures exceeding 30 min EEG ictal discharge and clonic motor activity become continuous - Patient begins to decompensate. Patient can become hypotensive. Autoregulation of cerebral blood flow begins to fail. Compensatory mechanisms are no longer able to meet body's demand.

What anti-epileptic agent is described here? Mechanism of Action - Depresses the sensory cortex, decrease motor activity, alter cerebellar function. Onset of action (IV) - About 5 minutes - Highest concentrations in 12 to 60 min Dosing (IV) - LD: 20 mg/kg - May give two additional doses (10-20 mg/kg) - Start maintenance dose within 12-24 hours of loading dose Administration Rate - 50-100 mg/min Considerations - Contains propylene glycol, but can be administer more rapidly than phenytoin - IM dosing is possible but absorption is too slow to be effective

Phenobarbital

What agents can be used for post-intubation care for transient/post hypotension?

Phenylephrine Ephedrine Norepinephrine Epinephrine

What are the 4 domains of palliative care?

Physical Psychological Spiritual Social

What is defined as a state of adaptation manifested by a drug class-specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood levels, and/or administration of an antagonist?

Physical Dependence

What are the different non-pharmacologic approaches for treating pain?

Physical approaches - Stretching, heat/cold, acupuncture, massage Psychological approaches - Cognitive-behavioral therapy, hypnosis, relaxation, biofeedback, distraction. Surgical approaches

What are all of the different physical and emotional/psychological causes of anxiety in palliation? - Anxiety: A state of apprehension and fear resulting from the perception of a threat to oneself. - Can be confused with delirium

Physical: •Uncontrolled pain •Dyspnea, hypoxemia •Weakness •Insomnia •Pre-existing anxiety disorder •Drug-related Emotional/psychological: •Family, finances •Denial, fear, anger, guilt •Isolation, inadequate support •Uncertainty •Depression •Delirium

What social issues are associated with palliative care?

Placement - Home - Assisted living - Skilled nursing facility Homecare services Hospice

What is Pplat?

Plateau pressure - Pressure at the alveolar level

What complications can occur with ventilators?

Pneumothorax Hypotension Stress ulcers Increased risk of VTE Stridor VAP

What issues are associated with sliding scale insulin?

Poor control of hyperglycemia ( no basal) Insulin stacking Hypoglycemia NOT Preferred (!!)

What type of neuropathic pain is described as pain that is a direct consequence of peripheral nerve damage sustained during a herpes zoster attack? - Results in decreased QOL, physical functioning, and psychological well being. May affect nerve tissue in skin ± spinal cord Conventionally defined as dermatomal pain persisting 90+ days after acute rash appears 20% of patients report pain at 3 months

Postherpetic Neuralgia

What precautions and ADRs are associated with Duloxetine (Cymbalta®)?

Precautions •Risk of suicide •Serotonin syndrome/NMS •May increase blood pressure, HR •May increase glucose •Risk of bleeding •Hepatoxoticity (!!) •Should not be abruptly discontinued Adverse Effects •Nausea •Dizziness •Headache •Somnolence •Fatigue •Constipation •Dry mouth •Hyperhidrosis

What is the volume of blood in the ventricles at the end of diastole? (End diastolic pressure) Increased in: - Hypervolemia - Valve regurgitation - Heart failure

Preload

What prevention strategies are used to prevent VAP during ventilation?

Prevention strategies (ventilator bundles) - Elevated head of bed (30-45 degrees) - Continuous suctioning - Oral care (chlorhexidine)

What are the risk factors for developing VAP in the ICU?

Prolonged Intubated - >72 hours Early enteral feeding Witnessed aspiration Paralytic agents Underlying illness Extremes of age

Name all of the medications that can be used for N/V with palliative care?

Promethazine (Phenergan) Ondansetron (Zofran) Metoclopramide (Reglan) Lorazepam (Ativan) Dexamethasone (Decadron)

What processes occur in the proximal tubule and the distal tubule to help regulate pH?

Promixal tubule - Bicarbonate is freely filtered at the glomerulus - Reabsorbed; primarily in the proximal tubule Distal tubule - Excretes hydrogen ion - Recirculates bicarbonate - Generates and excretes Ammonium (NH4+)

What are the goals of palliative care for the community?

Promote use of advance directives Educate about end-of-life issues Promote practical use of resources

What measures are NOT recommended to prevent VAP in adults in the ICU?

Prone position Stress ulcer prophylaxis Early parenteral nutrition

What agent used for refractory SE is described here? Mechanism of Action - CNS depression through agonism of GABA receptors and possible reduced glutamatergic activity through NMDA receptors Onset of action (IV) - About 9 - 51 seconds Dosing - LD: 1-2 mg/kg - CI: 20 mcg/kg/min Administration Rate - 30 - 200 mcg/kg/min, continuous infusion Considerations - Requires mechanical ventilation - Adjust caloric intake (1.1 kcal/mL)

Propofol

Which induction agent is described here? Dosing 1-2 mg/kg IV Onset: 15-45 seconds Duration: 5-10 minutes Significant hypotension - Reduced preload, afterload and cardiac contractility - Reduced CPP - Limits use in unstable critically ill patients Bronchodilation - Reactive airway patients

Propofol

What medications can cause lactic acidosis? Also caused by: - Tissue hypoperfusion - Inability to meet metabolic oxygen demand - Physiologic processes

Propofol Infusion Syndrome (PRIS) Metformin Sodium Nitroprusside (cyanide toxicity) Nucleoside Reverse Transcriptase Inhibitors (NRTI) - Didanosine, stavudine, zidovudine Propylene glycol toxicity

What are the pros and cons to using sodium bicarbonate for acute metabolic acidosis? - 8.4% concentration(!)

Pros: Effective for emergencies Predictable response Dose calculations available Helps vasopressors work Cons: Over-correction Very concentrated Intracellular acidosis Must be careful when adding to IVF

What agents for stress ulcer prophylaxis are the most potent inhibitors of gastric acid secretion? Consistent pH control, no tachyphylaxis. Favorable side effect profile. Most trials studied enteral PPIs for SUP - Paucity of trials with IV PPIs Use in stress ulcer prophylaxis increasing Cost effective with nominal pricing contracts

Proton Pump Inhibitor

Why is fentanyl sometimes given for pretreatment in RSI?

Provides analgesia Lessens pressor response - Limits ICP increase - More effective than lidocaine Agent of choice: - CAD, HTN emergencies, AAA, CVA, ICP, IOP

What clinical features are associated with ADRS?

Pts at risk Onset of dyspnea, tachypnea, respiratory alkalosis gas exchange abnormality within 12-48 h of inciting event The inflammatory process and alveolar flooding lead to severe ventilation-perfusion mismatch. Generally, a marked reduction in lung compliance S/S of underlying disorder may predominate early Most patients with ARDS develop diffuse alveolar infiltrates and progress to respiratory failure within 48 hours of the onset of symptoms, may take up to 7 days Course can be variable - not all require vent Generally resp failure is HYPOXEMIC

What diagnostic tests can be used to identify acute respiratory failure?

Pulse oximetry - Can be used to rapidly evaluate oxygenation in patient with respiratory distress - Estimation of arterial oxyhemoglobin saturation Arterial blood gas - Pa02, PaCO2, pH Electrolytes, hematocrit, drug levels Chest xray CT Chest

What are the different classes of opioids based on receptor binding?

Pure agonists: - High affinity, binding and full activation of mu opioid receptors. - Ceiling to analgesia only limited by adverse effects Partial agonists: - High affinity, binding and partial activation of mu opioid receptors. - Ceiling effect to analgesia and respiratory depression. Mixed agonist-antagonists: - Affinity, binding and activation of kappa receptors and inactivation of mu receptor. - Ceiling to analgesic effects. - May cause acute withdrawal in patients on opioid agonists. Pure antagonists: - High affinity, binding and inactivation of all opioid receptors. - No intrinsic pharmacologic effect. - Interfere with agonists activity.

What non-pharmacologic measured can be used for dyspnea during palliative care?

Pursed-lip breathing Fan Repositioning

What is a procedure used to quickly secure a definitive airway to minimize aspiration risk and airway events? - Impending loss of airway - Unstable - Critically ill and at risk for aspiration

Rapid Sequence Intubation (RSI)

How is hemorrhagic shock treated before the patients arrives at the hospital?

Rapid control of bleeding •Tourniquet application proximal to the site of bleeding •Saves lives without risking amputation Fluid resuscitation •Large-bore peripheral vascular access •Administration of red cells and plasma •Practical to administer small volumes of crystalloids Rapid transport to hospital

What is the main idea of treatment for managing chronic metabolic acidosis?

Rarely life threatening Treat the underlying cause Correct over time Remove causative factors - Administer PO alkali therapy if unable to remove factors Assess for RTA - Replace K+ and Mg2+ Replace renal and/or GI losses over time

What is the ratio of bicarbonate to carbonic acid for physiologic pH? - It's all about the ratio!

Ratio for physiologic pH is 20/1 Examples: pH = 6.1 + log(20/1) = 7.4 pH = 6.1 + log(40/2) = 7.4 pH = 6.1 + log(10/0.5) = 7.4

How should SE in pregnancy be treated? Pregnant women typically have increased Vd and Cl - Vitamin B6 levels may be low

Recommended initial emergent therapy and urgent control therapy. - Lorazepam and Fosphenytoin Known birth defects with first trimester exposure to AED's - Valproate sodium, Phenobarbital, Phenytoin - Could consider levetiracetam as an alternative Pregnant + Eclampsia - Magnesium Sulfate is superior to antiepileptics

What outcomes do critical care pharmacists improve?

Reduced medication errors Reduce cost and waste of medications Improved fluid management Reduced frequency of adverse drug reactions Reduced ventilator-associated pneumonia (VAP) occurrences Less central line infections Reduced time to antibiotic delivery

What is central sensitization associated with?

Reduction in central inhibition Spontaneous dorsal horn neuron activity Recruitment of other neurons Expansion of dorsal horn fields

What are the goals for the patient with palliative care?

Relieve distressing symptoms Facilitate advance planning re: end-of-life issues Ensure good communication Reduce unnecessary procedures, interventions, ICU transfers, etc. Support smooth transitions between care settings

What are the goals of treating pain?

Relieve pain Improve function Minimize adverse effects

What are the disadvantages to using antacids for stress ulcer prophylaxis? - Dose:30-60 mL q1-2 hrs with PH monitoring

Require frequent dosing-high demands on nursing. High volume may pre-dispose patients to aspiration pneumonia. Gastrointestinal disturbances. Electrolyte imbalances (magnesium and aluminum). Metabolic alkalosis. Numerous drug interactions (Digoxin, quinolones, Fe). Not cost effective.

What important information should be known regarding intraspinal administration of opioids? - Dosing? - Which opioids?

Requires preservative free products. (!) Epidural doses are 1/10th that of IV doses; intrathecal doses are 1/10th that of epidural doses(!) - i.e. morphine 10mg IV = 1mg epidural = 0.1mg intrathecal. Morphine and fentanyl used primarily - Morphine: longer duration of action - Fentanyl: quicker onset Other agents: local anesthetics, clonidine Systemic adverse effects still possible

What effect does opioids have on the respiratory system, skin, and smooth muscle?

Respiratory - Depression of respiratory center in brain. - Severe respiratory depression rare at standard doses in absence of pulmonary disease. - Opioid naïve patients at greater risk. - Patients on concomitant benzos or other CNS-depressants. - Respiratory rate not always reliable indicator of depth of respiratory suppression. Skin (histamine release) - Pruritus, urticaria, flushing, rash Smooth muscle - Decreased tone in bladder, uterus

Which type of compensation occurs faster, respiratory compensation or metabolic compensation? Metabolic compensation: increase or decrease HCO3- or H+ ions by the kidneys.

Respiratory - Occurs within minutes Metabolic - Occurs within ~24-48 hours

What acid-base disorder is described here? Not enough ventilation to meet demands - Fail to excrete enough CO2 Commonly caused by respiratory diseases - Can tolerate high level CO2 (90-100 mmHg) if O2 maintained Non-respiratory pathology plays a role Mechanical malfunctions - Dead space ventilation - Inadequate ventilator settings CO2 narcosis results in hypoactive mental status - Headache, confusion, stupor Cardiac output increases (moderate) or decreases (severe)

Respiratory Acidosis

What acid-base disorder is caused by the following? Hyperventilation CO2 exhalation exceeds production - Elevated minute volume - Increased CO2 production Naturally occurs in normal pregnancy and persons living in high altitudes

Respiratory Alkalosis

What are the goals of treating hypovolemic shock?

Restoring or maintaining normothermia Minimize coagulopathy Stop Bleeding or volume loss Establish blood pressure goal Fluid challenge - Controversial - Type of fluid - Timing - Quantity

Describe the typical day for pharmacists in the ICU?

Review patients - Assessment of problems - Active meds and medication list - Lab value - Microbiology - Imaging Participate in morning rounds Review orders during rounds Provide formal consults Attend committee meetings, develop protocols, and provide drug information responses Respond to code blues, medical emergencies

What problems/complications can occur with blood transfusions?

Risks and complications of large volume resuscitation with blood products: •Volume overload (careful monitoring of filling pressures, response to volume, diuresis etc) •Over-transfusion (monitor Hb regularly, titrate according to needs) •Hypothermia (monitor temp, use fluid warmers and other measures to reduce heat loss) •Dilutional coagulopathy of clotting factors and platelets (regular and early monitoring of coagulation, involvement of haematology for replacement therapy ) •Transfusion related acute lung injury (consider use of filters, leukodepletion) •Excessive citrate causing metabolic alkalosis and hypocalcaemia (monitor pH and ionised calcium, replace calcium as necessary) •Hyperkalaemia (use of younger blood, monitor regularly, may require specific therapy) •Disease transmission (use of products only on a needed basis only, standard blood banking precautions etc) If uncross-matched / O neg blood •Hemolytic disease of newborn if RhD mismatch •Difficulty with cross-matching future blood product •Difficulty with matching solid organs

Which Non-Depolarizing NMBAs is described here? Onset similar to succinylcholine Non-vagolytic; no histamine release No active metabolites Preferred alternative to succinylcholine in RSI (!!!!) Only NMBA that has reversal agent

Rocuronium

Name the Non-Depolarizing NMBAs?

Rocuronium Vecuronium Pancuronium

What ventilator mode is commonly considered a weaning mode? - Patient increasingly takes over work of breathing

SIMV - synchronized intermittent mandatory ventilation

Why are scoring systems used in the ICU?

Scoring systems help with... - Predicting patient outcomes - Predicting patient mortality - Comparing quality of care - Comparing stratification for clinical trials Use this information to decide how sick patients are at a given moment and to trend when then are improving or getting worse. Scoring systems can be used to decide when certain therapies are indicated or should be discontinued.

What TCAs have fewer anticholinergic and sedative effects? Shown effective in: DPN, PHN, cancer-related neuropathy Generally require ⅓ to ½ depression dose Starting dose: 10 to 25mg at bedtime - Titrate by 10 to 25mg/wk to max of 150mg Adequate trial: - 6 to 8 weeks with at least 1 to 2 weeks at max tolerated dose

Secondary amines: desipramine, nortriptyline

What problem in palliative care is distinct from dyspnea? As level of consciousness decreases, patients lose ability to swallow secretions Air movement over secretions produces gurgling or rattling noise - "Death rattle" No evidence this disturbs patients Disturbing to family and visitors - Fear patients is choking to death

Secretions

How should the following ADRs associated with opioids be managed? Sedation Nausea/ vomiting Pruritus Respiratory depression

Sedation: - Eliminate non-essential sedating meds - Switch opioid agents - Psychostimulant (i.e. methylphenidate) Nausea/ vomiting: - 5-HT3 antagonist, phenothiazines, metoclopramide Pruritus: - Diphenhydramine, hydroxyzine Respiratory depression - Naloxone 0.4mg q1-3 minutes IV/IM/SC to maximum of 10mg

Name all of the stimulant laxatives and their doses and onset times.

Senna 6-10 hr 2 tab qHS Bisacodyl 30 min 10 mg PRN

What causes peripheral sensitization?

Sensitized nociceptors - Inflammatory mediators, intense, repeated, or prolonged noxious stimuli - Lower threshold for activation - Increased rate of firing Nerve impulses generated more readily and more often. Role in central sensitization, hyperalgesia, allodynia.

What can occur as a result of organ hypoperfusion? - Causes cellular dysfunction and death Determined by: - Clinical signs - Hemodynamics - Biochemical signs

Shock

What agents can be used to treat anxiety in palliative care?

Short-acting benzodiazepines: Alprazolam - 0.25-2mg PO q6-8h Lorazepam - 0.25-2mg PO/SL q6-8h (conc. oral solution 2 mg/mL) Longer-acting benzodiazepines Clonazepam - 0.25-0.5mg PO q8-12h Diazepam - 2-10mg PO q8-12h Nonsedating neuroleptic Haloperidol - 0.2-4mg PO/IM/IV q4-6h prn

What are the signs of impending death?

Sign/Symptom -- Hours Preceding Death Secretions (death rattle) - 57 hours Respirations with mandibular movement - 7.6 hours Cyanosis/mottling - 5.1 hours Lack of radial pulse - 2.6 hours

Describe the process of transmission of a pain signal?

Signal travels from the periphery to spinal cord. - Impulses travel via afferent neurons to the dorsal horn - Release of excitatory hormones (glutamate, aspartate) and neuropeptides (substance P) at synapses - Impulse moves toward brain - Release of inhibitory hormones (GABA) and neuropeptides (endogenous opioids). - Inhibit transmission to the brain. Spinal cord to the brain - From dorsal horn, stimuli travel to the brain via ascending tracts.

What is the difference between C-fibers and A-delta fibers?

Signals from nociceptors travel via: - C-fibers (unmyelinated): dull, aching, poorly localized - A-delta fibers (myelinated): sharp, localized

What physical properties of the drugs themselves can be effected in ICU patient?

Size Solubility Lipophilicity pKa Stability Enteral nutrition

Name all of the different dosage forms and formulations of morphine?

Solution for injection - Also available preservative free (PF) Immediate release tablet Oral solution Concentrated solution Controlled/extended release tablets, capsules Rectal suppository Combination with naltrexone

What drug used to treat sodium chloride resistant or unclassified metabolic alkalosis is described here? - Competitive antagonist of the mineralocorticoid receptor - Directly inhibits aldosterone stimulation of the H+ ion pump - Use for Bartter's or Gitelman syndrome

Spironolactone

What are the 4 different stages of GCSE?

Stage 1 - (0-30 min) Stage 2 - (30-60min) Stage 3 - (>120 min) Refractory Stage 4 (>24 hour) Super-refractory

What is defined as any seizure lasting longer than 30 min OR Recurrent seizures without an intervening period of consciousness between seizures.

Status epilepticus

What are the 8 steps to evaluating acid-base disorders?

Step 1: Carefully evaluate the patient - Medical history, History of present illness, vitals, medication history, labs Step 2: Determine the "emia" - Strictly evaluate pH from labs Step 3: Determine the primary "osis" - Predominant disorder is typically in the direction of the "osis" - Evaluate pCO2 & [HCO3-]. Compare to normal values. - Determine which explains the pH shift Step 4: If it is a respiratory "osis", determine if it is chronic (>2-3 days) or acute (<2-3 days) Step 5: Evaluate compensatory response. - Unexpected or "abnormal" compensation indicates concomitant disorder Step 6: Calculate the Anion Gap, corrected for albumin (ACAG) - May also correct for lactate Step 7: If the ACAG is elevated, calculate the Delta Ratio Step 8: If ACAG is normal with a metabolic acidosis & the cause is unknown, calculate a urinary anion gap (UAG)

What medications are mainly used in patients with opioid induced constipation?

Stimulant: Senna Bisacodyl

Describe transduction. - First step of experiencing pain.

Stimulation Conversion of energy from a noxious stimuli (thermal, mechanical, chemical) into electrical energy - Nerve impulse Nociceptors: sensory receptors sensitive to tissue trauma. - Free endings of nerve fibers. Injury also causes cell breakdown and release of neurotransmitters - Byproducts and mediators of inflammation - Prostaglandins, substance P, bradykinin, histamine, serotonin, cytokines - Some substances will activate nociception - Most sensitize nociceptors Signals from nociceptors travel via C-fibers and A-delta fibers.

When should the infusion of HCl for the treatment of metabolic acidosis be stopped? Dose based on the estimated base deficit. - Dose HCl (in mEq or mmol) = [0.5 L/kg × BW (in kg)] × (desired [HCO3-] - observed [HCO3-]). The dose of hydrochloric acid is usually infused IV over 12 to 24 hours. Improvement usually seen within 24 hours of initiating therapy. ABGs and serum electrolytes should be drawn every 4 to 8 hours.

Stop infusion when the arterial pH decreases to 7.50

What variables can contribute to causing hyperglycemia in ICU patients?

Stress Critical illness Vasopressors Corticosteroids Enteral feeds TPN

What stroke volume variation and pulse pressure variations are indicative of volume responsiveness?

Stroke volume variation - PPV of > 12% is associated with volume responsiveness Pulse pressure variation - Measured over the 20 second cycle. - SVMax - SVMin/SV mean Normal < 15 % - >15% patient may be volume responsive

What is the formula for cardiac output?

Stroke volume x heart rate

What is defined as any use of an illegal drug, or the intentional self-administration of a medication for a non-medical purpose such as altering one's state of consciousness?

Substance Abuse

What DDIs can occur with methadone?

Substrate: major 3A4, minor 2C9, 2C19, 2D6 Inhibitor: moderate 2D6, weak 3A4

What depolarizing NMBA non-competitively binds ACh receptors à initial membrane depolarization? - Longer degradation time than ACh Paralysis in ~60 sec. DOA: 3-5 min - Prolonged in pseudocholinesterase deficiency (genetic, hepatic/renal failure, pregnancy, cocaine). - Repeat doses prolong paralysis - May increase bradycardia/hypotension DOC for RSI(!!!!!)

Succinylcholine

What are all of the different agents that can be used to cause paralysis for RSI? - Given quickly after giving induction agents?

Succinylcholine Rocuronium Vecuronium

Which agent for preventing ulcers in the ICU is described here? No pH monitoring required Minimal risk of aspiration pneumonia Not available intravenously Requires spacing from enteral feeds Feeding tube occlusion Can cause: - Aluminum toxicity - Hypophosphatemia - Constipation Drug interactions via chelation: - Quinolones, digoxin, warfarin, quinidine, levothyroxine, azoles Dose: 1-2 g q4-8hours

Sucralfate

What NMB reversal agent is a modified y-cyclodextrin that rapidly reverses the effects of non-depolarizing NMBA? - Forms a stable 1:1 complex resulting in encapsulation of the drugs - Decrease free NMBA available - Dose 16 mg/kg IV x1 - Renal elimination - Not recommended in renal failure Time to recovery: 3 minutes Side effects - Bradycardia 5% - 40% less than neostigmine - Dose dependent increase in aptt and PT/INR

Sugammadex

What is the reversal agent for Rocuronium?

Sugammadex 16 mg/kg

What are the benefits to using PCA?

Superior pain relief with less sedation Less sedation during daytime hours; improved sleep patterns Decrease delays between request for analgesia and relief Fewer postoperative complications Lower potential for overdose

What is the benefit of using H2RAs instead of sucralfate for preventing stress ulcers?

Superiority of H2RAs - Meta-analysis demonstrates rate of overt GIB compared to antacids. - RCT demonstrates less clinically significant GIB compared to sucralfate. Sucralfate and antacids further limited by: - Adverse effects (electrolyte distrubances, feeding tube occulusions, aluminum toxicity. - Drug interactions (FQ). - Frequency of administrations.

What opioids can be used rectally for palliative care? - Rapid absorption; avoids first pass metabolism(!!)

Suppositories - Morphine, hydromorphone, APAP available - Potential to compound others CR tablets - Administering CR morphine or CR oxycodone rectally maintains the time release properties(!!) - Place inside a gelatin capsule(!!)

What is the formula used to calculate Tris-Hydroxymethylaminomethane [Tromethamine(THAM)] dose?

THAM dose (mL) = 1.1 x BW(kg) x (Desired [HCO3-]- Current [HCO3-])

Is palliative care the same as hospice?

There is a lot of overlap between the two. - There are many common treatment issues with palliative care and hospice but... Hospice is a Medicare benefit and is subject to certain limitations. Palliative care is not a guaranteed benefit in the same way - allows more liberal use.

What is Vt?

Tidal volume - Amount of air in and out in a ventilatory cycle

What do the treatment guidelines recommend for treating painful; diabetic neuropathy (PDN)?

Tight glucose control First line: pregabalin or duloxetine Alternative first line: gabapentin TCAs also effective Use of opioids not recommended as first or second line

Why is atropine sometimes given for pretreatment in RSI? - NO LONGER RECOMMENDED

To prevent bradycardia caused by airway manipulation and succinylcholine. - Historically used in pediatrics May be more beneficial with repeated doses of succinylcholine (i.e. OR setting)

Why is lidocaine sometimes given for pretreatment in RSI?

To prevent rise in ICP by - Preventing cough - Blunting pressor response May reduce reactive bronchospasm in asthma

What is defined as a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more opioid effects over time? Common with chronic use of opioids Related to alterations in mu receptors - Shorter duration of analgesia - Decrease in effectiveness of each dose

Tolerance

What agents can be used to treat Postherpetic Neuralgia (PHN)?

Topical treatments: *Lidocaine 5% patch (FDA approved) Capsaicin cream Capsaicin patch Oral treatments: Gabapentin *Pregabalin (FDA approved) TCAs Morphine and oxycodone Tramadol

What are the 2 different approaches for applying chemistry to acid-base physiology? - Both methods are equally correct!

Traditional approach: - Focus is on bicarbonate and CO2 - Simple, easy to remember - Useful for every clinician Stewart approach: - Focus is on strong ion disassociation - Not as widely used in clinical practice

What agent for neuropathic pain is an opioid agonist that also inhibits reuptake of norepinephrine and serotonin? - Improves pain, allodynia and function scores in neuropathic pain - May need ________________ or other opioid for acute pain control until neuropathic agent reaches peak effect

Tramadol (Ultram®)

Which opioid is described here? Synthetic codeine analog Unique dual mechanism - Weak mu opioid receptor agonist - Weak inhibitor of serotonin, norepinephrine reuptake Good oral absorption (F=75%) Hepatic metabolism and renal elimination - Half life: 6 hours - Requires adjustment for renal impairment, liver disease Dose: 50 to 100mg q6h (max 400mg/day) Used for mild to moderate pain (C-IV) Duration of action: 6 hours Formulations: tablet, ER tablet, variable release capsule, tab with APAP

Tramadol (Ultram®)

What route of opioid admission for palliative care is described here? - Only long-acting agent without PO administration - May cause less constipation and sedation compared to PO morphine (!!!)

Transdermal opioids

What are the 4 processes associated with experiencing pain?

Transduction Transmission Perception Modulation

How should someone in palliative care with complaints of dyspnea be treated?

Trial of oxygen 2-6 L/min; reassess q2h Opioids: - Morphine 10 mg PO q2-4h prn -OR- - Morphine 3 mg IV/SQ q2-4h prn No relief: - Lorazepam 0.5 mg PO/SL/IV q4h prn

What agents that can be used for neuropathic pain provide benefit through effects on norepinephrine and serotonin? - Also block sodium channels in periphery First-line for many neuropathic pain syndromes No difference between agents - Choice depends on adverse effect profiles

Tricyclic Antidepressants

What pharmacologic agents can be used to treat fibromyalgia?

Tricyclic antidepressants (TCA) compounds - Amitriptyline, cyclobenzaprine Anticonvulsants - Pregabalin*, gabapentin Selective serotonin norepinephrine reuptake inhibitors (SNRI) - Milnacipran*, duloxetine* Selective serotonin reuptake inhibitors (SSRI) - Fluoxetine Opioids - Tramadol

What agent for metabolic acidosis is a sodium-free proton acceptor? - Developed to overcome some of sodium bicarbonate's limitations - Combines with protons and carbonic acid to form bicarbonate and cationic buffer. - Does positively affect intracellular pH (raises) - Renally eliminated: Not recommend for CrCl < 30 mL/min(!!) - Not commonly used in practice; has not shown superiority to NaHCO3(!)

Tris-Hydroxymethylaminomethane [Tromethamine(THAM)]

T or F: Chemical dependency is an illness influenced by biologic AND genetic factors.

True

T or F: GI risk with COX-2 inhibitors is no better than a nonselective NSAID + PPI.

True

T or F: Mechanical ventilation will impact caloric requirements.

True

T or F: Mortality can be decreased with tight glucose control when a patient is in the hospital.

True!

T or F: Generally during the dying process, fluids and nutrition are not needed.

True, patients generally do not feel hungry or thirsty. Fluids can also be given subcutaneously if needed (hypodermoclysis) - Add hyaluronidase to the infusion (!!!!) - Can administer fluids at up to 60 mL/hr Adverse effects: fluid overload - Cerebral edema, headaches, peripheral/pulmonary edema, CHF, ascites, pneumonia, increased respiratory secretions, excess fluid in GI tract.

T or F: Most GCSE occur in individuals with no history of epilepsy.

True. 5% of adults & 10-25% of children with epilepsy will develop GCSE. Most occur due to anticonvulsant withdrawal OR A metabolic disorder or concurrent illness

What are all of the possible causes of nausea and vomiting during palliative care?

Tumor - Brain - GI tract Medications - Opioids - Chemotherapy - Antibiotics Hypercalcemia Increased intracranial pressure Vestibular disturbances Anxiety Constipation

What patients would need to be transitions to SQ insulin after recieving IV in the ICU?

Type I DM Type II DM on insulin PTA New hyperglycemia requiring >2 units/hr of insulin

What type of renal tubular acidosis(RTA) is described here? Hypokalemic Fanconi syndrome or sodium-bicarbonate co-transporter disorder - Can't reabsorb filtered bicarbonate Administer high doses of PO bicarbonate daily

Type II RTA (proximal)

What type of renal tubular acidosis(RTA) is described here? Whole kidney, hyperkalemic(!!) - Hyporenin, hypoaldosteronism - Elderly or patients with CKD - Urine pH<5.5, urinary anion gap positive Often exacerbated by agents that can interfere with the renin-angiotensin-aldosterone axis - β-adrenergic blockers - Angiotensin-converting enzyme (ACE) inhibitors - Angiotensin receptor blockers - Nonsteroidal anti-inflammatory drugs (NSAIDs) Limit daily potassium intake or PO Bicarbonate - Often resolves by correcting the hyperkalemia

Type IV RTA

What is the formula for urinary anion gap and what causes it to be positive or negative?

UAG = [Na+] + [K+] - [Cl-] Negative UAG: - Infusion with large volumes of Saline - Diarrhea - Proximal Renal Tubular Acidosis (RTA) Positive UAG: - Renal Failure - Distal RTA - Hypoaldosteronism

What challenges are associated with palliative care?

Understanding of palliative care concepts Symptom management Communication Psychological and emotional issues Social issues Advance care planning

How should you apply knowledge of how exertion is altered in ICU patients at bedside?

Use appropriate up to date literature for correct dosing or refer to institutional policy. - Avoid Package insert and caution with tertiary references Know the mode of CRRT and find specific dosing. Recognize patients with augmented renal clearance and use primary literature to find appropriate dosing.

With what patients should you use caution with when giving Tramadol?

Use caution in patients with seizure history - Lowers seizure threshold - Seizure risk increases with doses >400 mg/day Use caution in patients on other medications that affect serotonin - Increased CNS depression, serotonin syndrome

Is sodium bicarbonate always used for treating acidosis? - Why or why not?

Use for acidosis treatment is CONTROVERSIAL - Reserved for EMERGENCIES *Bolus dosing is reserved for emergent situations (ACLS) - 1 mEq/kg rapid IV injection.

What type of opioids can be administered as nebulizer opioids and how often is it given?

Use nonpreserved injectable solution (!!) Place opioid in 2 mL of normal saline - Morphine: 2.5 to 10 mg - Hydromorphone: 0.25 to 1 mg - Fentanyl: 25 mcg Administer q4h and adjust to effect

What is sliding scale insulin?

Use of meal time insulin (short acting) as the only insulin for managing hyperglycemia.

How is hypovolemic shock treated?

VIP Ventilate/ Non-invasive ventilation Infuse Pump

What anti-epileptic agent is described here? Mechanism of Action - Increased GABA availability to neurons - Enhances or mimics GABA's action at the postsynaptic receptor sites Dosing (IV) - LD: 20-40 mg/kg - May give an additional dose (20mg/kg) 10 minutes after LD Administration Rate - 3-6 mg/kg/min Serious Adverse events - Hyperammonemia - Pancreatitis - Thrombocytopenia - Hepatotoxicity Considerations - Caution in patients with traumatic head injury - May be the preferred agent in patients with glioblastoma multiforme

Valproate sodium

What do the different delta ratio values mean? - AG excess/HCO3 deficit = (Measured ACAG - 12) ÷ (24 - [HCO3-])

Value < 1 shows concomitant non-gap metabolic acidosis. Value between 1 & 2 shows only the high anion gap acidosis. Value > 2 shows concomitant metabolic alkalosis or appropriately compensated chronic respiratory acidosis.

Describe the pathogenesis of Postherpetic Neuralgia?

Varicella zoster virus is a highly contagious double stranded DNA virus of the herpes family. During primary infection, virus gains entry into the sensory dorsal root ganglia. Viral reactivation occurs with decrease immunity in advanced age. Reactivated virus replicates and migrates down the sensory nerve leading to the dermatomal distribution of pain. As a result, uninhibited and amplified activity in unmyelinated primary afferents leads to PHN.

What receptors does vasopressin affect?

Vasopressin receptors

Which Non-Depolarizing NMBAs is described here? Slower onset than rocuronium Non-vagolytic; no histamine release Active metabolites Often requires "priming" dose - 0.01 mg/kg during pre-oxygenation phase, then - 1.5 mg/kg given 3 min later for paralysis

Vecuronium

What is V/Q or VDS/Vt?

Ventilation / perfusion - Ratio describing air flow compared to blood circulation in the same area(s) of the lung.

What should be monitored in a patient receiving a blood transfusion?

Vitals Urine output Laboratory •Platelet, PT, aPTT, fibrinogen normalization •Hemoglobin and hematocrit trends •Acid base status •BMP, CBC •Liver function tests •Serum creatinine Clinical status •Glasgow Coma Scale

What should be monitored in patients after administering vasopressors?

Vitals •Blood pressure (prefer arterial pressure) •Body temperature •Oxygen saturation •Respiratory rate •Heart rate Urine output •Normal 0.5 - 1.5 mL/kg/hr Objective •Swan/CVP •Ultrasound Clinical status •Glasgow Coma Scale

What is asthenia?

Weakness and fatigue

When should IV insulin be transitioned to SQ basal bolus insulin? - How should it be timed with respect to discontinuing the IV drip?

When patient begins to eat and BG levels are stable. Because of short half life of IV insulin subcutaneous basal insulin should be administered at least 1-2 hours prior to discontinuing the drip. - If short-acting insulin also administered, IV insulin may be able to stopped sooner, e.g after 1 hour.

How is fibromyalgia diagnosed? - American College of Rheumatology (ACR) Criteria

Widespread Pain Index (WPI) Score - Endorsement of 19 body regions in which pain has been experience in past week - Scale: 0-19 Symptom Severity (SS) Score - Evaluation of fatigue, waking unrefreshed, cognitive symptoms, S and somatic (physical) symptoms - Such as headache, weakness, bowel problems, nausea, dizziness, numbness/tingling, hair loss - Scale: 0-12 Clinical diagnosis - WPI of at least 7 and SS scale score of at least 5, OR - WPI of 3-6 and SS scale score of at least 9

Do Gabapentin and Pregabalin need to be adjusted for renal impairment?

Yes!!!

What agent should pediatric patients with SE receive? - Pharmacokinetic differences, adverse effects and treatment specific syndromes should be considered. - Weight based dosing different from adults. - Possible hepatotoxicity with valproate sodium

Young children with SE should receive IV pyridoxine(!)

What are the 2 available Herpes Zoster Vaccinations? - How are they different from each other?

Zostavax: •Live •SC •Single dose •FDA approved for 50+ years •ACIP: 60+ years old Shingrix: •Recombinant, adjuvanted •IM •2 dose series (2-6 months) •FDA/ACIP: 50+ yrs including h/o shingles or already had Zostavax

What is the formula for mean arterial pressure? (MAP)

[(2 x diastolic pressure) + systolic pressure]/ 3

What is the formula for [H+] using pH?

[H+] = 10^(-pH)

What is the formula for electroneutrality? - To maintain electroneutrality: cations = anions

[Na+] + [K+] + [UCs] = [Cl-] + [HCO3-] + [UAs] Common unmeasured cations (UC): Mg2+, Ca2+, & sometimes K+ Common unmeasured anions (UA): proteins (sometimes albumin), sulfates (SO42-), phosphates (PO43-), organic anions.

Prolonged seizures lead to _________________ (Decreased/Increased) inhibitory GABA-A-receptor density

decreased *Decrease response to both endogenous GABA and GABA agonists

For chronic pain patients can be provided majority of opioids needed to control pain in _______ acting formulation - Provides steady state, basal amount of opioid

long Also provide prn opioid for breakthrough pain in addition to long acting opioid - Each breakthrough dose is 10 to 20% of total daily dose of long acting opioid. - Generally administered q2-6h prn pain (depending on duration of action).

Ventilation driven by ___________________.

minute volume - Minute volume = respiratory rate (breaths per minute) x tidal volume (mL per breath) Rate and depth of ventilation can be varied independently(!!)

What are the 3 types of opioid receptors, and what happens when they are activated?

mu: Analgesia (mu-1), sedation, vomiting, respiratory depression, pruritus, euphoria, anorexia, urinary retention, dependence, reduced GI motility. delta: Analgesia, spinal analgesia kappa: Analgesia, sedation, dyspnea, psychomimetic effects, miosis, respiratory depression, euphoria, dysphoria

What subcutaneous opioids are used during palliative care? - Place in subclavicular region, anterior chest wall, or abdominal wall (#25 or #27 gauge butterfly). - Change site every 3-7 days. - Rate of administration ~1-2 mL/hr maximum of 10 mL/hr (adjust solution concentration)

nGenerally use morphine, hydromorphone, or fentanyl

Diagnosis of GCSE should not be made until a clinician has ____________________________________.

observed a seizure

How is respiratory alkalosis treated?

pH <7.50 typically doesn't require treatment (mild) Correct hypovolemia (IV fluids) Rebreathing device (paper bag) for hyperventilation O2 therapy for severe cases (correct hypoxemia) Mechanical ventilation settings - Add rebreather (allows "rebreathing" expired gas from lungs) Bottom line: Treat the underlying cause!

What is the Henderson-Hasselbalch equation?

pH = pK + log ([base]/[acid]) - K = dissociation constant - pK = negative logarithm of the dissociation constant Ex. for carbonic acid/bicarbonate pH = 6.1 + log([base (HCO3-)]/[acid (H2CO3)])

Tolerance to __________________ and __________________________ develops as rapidly as tolerance to analgesic effect. Can be overcome by increasing the dose Cross-tolerance does exist between full agonists, but is NOT complete - Switching to another opioid may be helpful - Adjust dose of new opioid as necessary (usually downward)

respiratory and CNS depression

What effects do opioids have on the CNS?

•Analgesia •Sedation •Mental clouding/confusion •Euphoria, tranquility •Nausea, emesis •Hypothermia •Miosis •Myoclonus •Inhibition of GnRH and CRH release •Increase in prolactin secretion

What ADRs are associated with the vasopressors?

•Arrhythmias •Tachycardia •Bradycardia •Peripheral/gut ischemia

Describe the pathophysiology of hypovolemic shock?

•Decreased intravascular volume •Compensation •Reperfusion

Describe the resuscitation step at the hospital for a hemorrhagic shock patient? - Goal to restore intravascular volume

•Delay fluid administration until time of hemostasis •Minimize crystalloid infusions •Maximize infusion of blood products

What are the signs and symptoms associated with hemorrhagic shock?

•Extensive thirst •Tachycardia •Hypotension •Decreased urine output •Tachypnea •Altered mental state •Anxiety •Flush, dry skin with decreased turgor

What are all of the different blood products that can be used for hemorrhagic shock?

•Fresh Frozen Plasma •Platelets •Red blood cells •Cryoprecipitate

What diagnostic tests indicate hemorrhagic shock?

•Hemoglobin and hematocrit - decreased •Platelet count - decreased •Fibrinogen - decreased •Prothrombin time - increased •Activated partial thromboplastin time - increased •Serum lactate - increased

What are the different types of shock?

•Hypovolemic •Distributive (septic) (Most common) •Cardiogenic •Obstructive

How do you apply using absorption knowledge at the bedside for ICU patients?

•IV route Preferred in most situations if critically ill •If other route chosen, you need to justify

What are the 3 main steps to treating hemorrhagic shock at the hospital?

•Identification of the bleeding source •Avoid and correct hypothermia •Resuscitation

What is the ideal resuscitation fluid? - Doesn't exist!

•Increases intravascular volume •Has a chemical composition similar to extracellular fluid •Is metabolized and excreted without accumulation in tissues •Doesn't produce adverse effects •Is cost-effective

How should pregabalin be dosed for neuropathic pain?

•Initial dose 25-150mg/day •Give BID or TID •Titrate within 1 week •PHN - max 600mg/day •DPN - max 300 mg/day •Fibromyalgia - max 450mg/day •Taper over 1 week if discontinued

How should gabapentin be dosed for neuropathic pain?

•Initial dose: 100-300 mg PO at bedtime or 100-300 mg PO TID •Titrate dose by 100-300 mg every 1-7 days as tolerated •Give BID to QID •Target dose 1800 mg/day - Max dose 3600 mg/day •Taper over 1 week if discontinued

Name all of the Phenylpiperidine opioids.

•Meperidine •Fentanyl •Alfentanil •Sufentanil •Remifentanil •Diphenoxylate •Loperamide

Name all of the Phenanthrene opioids.

•Morphine •Hydromorphone •Oxycodone •Oxymorphone •Levorphanol •Codeine •Hydrocodone

What are all of the different neuropathic pain syndromes?

•Painful diabetic neuropathy (PDN) (!!!) •Postherpetic neuralgia (PHN) (!!!) •Chemotherapy induced neuropathy •HIV sensory neuropathy •Phantom limb pain •Trigeminal neuralgia •Spinal cord injury pain •Central post-stroke pain •Central pain syndrome •Painful radiculopathies

Name the TCAs used for neuropathic pain?

•Secondary amines: desipramine, nortriptyline •Tertiary amines: amitriptyline, imipramine

What are the signs and symptoms associated with hypovolemic shock?

•Severe hypotension •Tachycardia •Tachypnea •Skin that is cold and clammy •Altered mental status •Decreased urine output •Dry mucous membranes •Increased thirst •Decreased pulse pressure •Weak •Pale skin •Visual bleeding quantity - Urine, stool, oral, surgical/trauma site

What are the goals of ventilating hypovolemic shock patients?

•Stabilize the patient •Maintain oxygen saturations •Correct acidosis

What are the usual transfusion reactions and problems that occur with blood transfusions?

•Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) •Acute / delayed haemolytic transfusion reaction •Non-febrile haemolytic transfusion reaction •Bacterial / viral infection •Anaphylaxis if IgA deficient •GVHD •Storage lesion effects

What are all of the potential causes of hemorrhagic shock?

•Trauma •Obstetric/gynecologic emergencies •Vascular causes •Antithrombotic therapy •Coagulopathies

What medications should be administered after fluid resuscitation fails for hypovolemic shock?

•Vasopressors •Inotropes •Norepinephrine, dopamine, epinephrine, phenylephrine and vasopressin