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of dexmedetomidine is the ability to produce sedation without respiratory depression. In some critically ill patients, night time sleep patterns are enhanced when patients are lightly sedated with dexmedetomidine. When compared to GABA agonists, dexmedetomidine resembles natural non‐REM‐type sleep.Postsynaptic activation of α2 receptors inhibits sympathetic activity, decreasing blood pressure and heart rate, having no effect on dopamine receptors or aspiration. According to the FDA, dexmedetomidine is indicated for initial sedation for the first 24 hours. Although not contraindicated, prolonged use of dexmedetomidine can lead to withdrawal effects like rebound hypertension, especially in higher doses. Hydromorphone (choice D) is an opioid receptor agonist used for severe pain. Hydromorphone is about 8–9 times more potent than morphine. Side effects of hydromorphone are pruritus, sedation, constipation, nausea, and vomiting. Adverse effects are more pronounced with excessive dosages and include respiratory and cardiovascular depression, dependency, and ileus. An overdose of hydromorphone resulting in loss of consciousness could result in aspiration, but it does not contribute to aspiration in usual therapeutic doses.Melatonin (N‐acetyl‐5‐hydroxytryptamine) is a mild hypnotic and generally well tolerated and regarded as safe with few adverse effects. It is synthesized in the pineal gland and its release helps regulate sleep and circadian rhythms. The anterior hypothalamus regulates melatonin which has its effects at MT2 and MT1 receptors. Melatonin (M) receptors are ubiquitous, found in the brain, retina, throughout the cardiovascular system, in the liver, gallbladder, colon, and skin. The MT1 receptor agonism is related to sleep onset. The most frequently reported adverse effects are daytime sleepiness, headache, dizziness, and hypothermia. Aspiration is not among reported adverse effects of melatonin, so choice E is incorrect.Answer: CAlexopoulou C, Kondili E, Diamantaki E, Psarologakis C, Kokkini S, Bolaki M, Georgopoulos D . Effects of dexmedetomidine on sleep quality in critically ill patients: a pilot study. Anesthesiology. 2014; 121(4):801–7.Besag FMC, Vasey MJ, Lao KSJ, Wong ICK . Adverse events associated with melatonin for the treatment of primary or secondary sleep disorders: a systematic review. CNS Drugs 2019; 33(12):1167–86.Herzig SJ, LaSalvia MT, Naidus E, Rothberg MB, Zhou W, Gurwitz JH, Marcantonio ER. Antipsychotics and the risk of aspiration pneumonia in individuals hospitalized for nonpsychiatric conditions: a cohort study. J Am Geriatr Soc 2017; 65(12):2580–6.DiBardino DM, Wunderink RG. Aspiration pneumonia: a review of modern trends. J Crit Care. 2015; 30(1): 40–8.Longnecker D ; Brown DL, Newman MF, Zapol W. Anesthesiology , Second Edition. New York: McGraw‐Hill Professional; 2012. 1748 p. p.

      5 Which commonly prescribed medications in the intensive care unit is most likely to cause an unstable arrhythmia and sudden death?Fentanyl, opioid analgesicMeperidine (Demerol), opioid analgesicHaloperidol (Haldol), typical antipsychoticDexmedetomidine (Precedex), alpha 2 agonistPropofol, short‐acting lipophilic intravenous general anestheticHaldol (choice C) has a proven association with torsade de pointe and sudden death. Prolonged QT intervals can be congenital or acquired as in a patient receiving haldol, methadone, atypical antipsychotics, or antidepressants. Long QT associated with polymorphic ventricular tachycardia (PMVT) is called torsade de pointes. Factors that increase the QT and risk for torsades are rapid administration of QT prolonging drugs, coexisting myocardial ischemia, older age, recent dysrhythmia, hypomagnesemia, or hypokalemia. The first‐line treatment of acquired QT prolongation with torsade de pointes is 2–4 gm intravenous magnesium followed by infusion 1 gm/h, replacement of potassium if needed, cardioversion or isoproterenol for bradycardia or pauses. PMVT without long QT can also be seen in acute coronary syndromes.Fentanyl infusions typically in the range of 50–200 mcg/h are used for sedation and pain control. Adverse effects of fentanyl include tolerance, constipation, hyperalgesia, and dependence. Fentanyl can cause hypotension; however, it is not associated with life‐threatening arrhythmias (choice A). Similarly, meperidine (Demerol) is an opioid analgesic. Adverse effects of meperidine include respiratory and circulatory depression, lightheadedness, constipation, nausea, vomiting, and dependence. Meperidine does not have a known association with life‐threatening arrhythmias (choice B).Common side effects of the sedative‐anxiolytic dexmedetomidine (Precedex) are sinus bradycardia and hypotension. Dexmedetomidine also provides some analgesic effects. It is a centrally acting sympatholytic alpha 2 agonist but it does not prolong the QT interval (choice D).Propofol (choice E) is a hypnotic agent for induction of anesthesia or for sedation. It produces sedation through GABA potentiation. Some of the more serious adverse effects or propofol are hypotension from reduced systemic vascular resistance or direct myocardial depression and propofol infusion syndrome (PRIS). PRIS is a metabolic derangement manifested by metabolic acidosis, renal injury, and rhabdomyolysis. However, propofol is not usually associated with life‐threatening arrhythmias or sudden death.Answer: CRay WA, Chung CP, Murray KT, Hall K, Stein CM. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med. 2009; 360(3):225–35.Huffman JC, Stern TA. QTc prolongation and the use of antipsychotics: a case discussion. Prim Care Companion J Clin Psychiatry. 2003; 5(6):278–81.Milbrandt EB, Kersten A, Kong L, Weissfeld LA, Clermont G, Fink MP, Angus DC. Haloperidol use is associated with lower hospital mortality in mechanically ventilated patients. Crit Care Med. 2005; 33(1):226–9; discussion 263‐5.Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, Shintani AK, Thompson JL, Jackson JC, Deppen SA, Stiles RA, Dittus RS, Bernard GR, Ely EW. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA. 2007; 298(22):2644–53.Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, Rocha MG ; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009; 301(5):489–99.Biesenbach P, Mårtensson J, Lucchetta L, Bangia R, Fairley J, Jansen I, Matalanis G, Bellomo R. Pharmacokinetics of magnesium bolus therapy in cardiothoracic surgery. J Cardiothorac Vasc Anesth. 2018; 32(3):1289–94.Ling X, Zhou H, Ni Y, Wu C, Zhang C, Zhu Z . Does dexmedetomidine have an antiarrhythmic effect on cardiac patients? A meta‐analysis of randomized controlled trials. PLoS One 2018; 13(3):e0193303.

      6 A 120 kg 82‐year‐old man with a past medical history of colon cancer, diabetes, and renal insufficiency is admitted to the ICU after a colectomy. Postoperatively, he had bilateral transversus abdominis (TAP) blocks placed. His creatinine clearance is estimated to be 52 mL/min. Which of the following factors increase his risk for local anesthetic toxicity?Renal insufficiencyAdvanced ageMale sexObesityDiabetesLocal anesthetic toxicity (LAST) is a life‐threatening event resulting from inadvertent intravascular administration or excessively dosed local anesthetic medications. The underlying mechanisms of LAST are multifactorial, but primarily manifest with cardiovascular and neurologic deterioration. The risk factors for LAST are extremes of age (choice B), pregnancy, low body weight, and pre‐existing cardiovascular disease. The anesthetic medications should be based on ideal body weight. Renal insufficiency (choice A), gender (choice C), and diabetes (choice E) do not affect the likelihood of LAST. Obesity (choice D) could contribute if the dosage was based on actual rather than ideal body weight.Answer: BEl‐Boghdadly K, Pawa A, Chin KJ. Local anesthetic systemic toxicity: current perspectives. Local Reg Anes. 2018; 11:35–44.Neal JM, Barrington, MJ, Fettiplace MR, Gitman M, Memtsoudis SG, Mörwald EE, Rubin DS, Weinberg G The third American society of regional anesthesia and pain medicine practice advisory on local anesthetic toxicity: executive summary 2017. Regional Anesth. Pain Med. 2018; 43(2):113–23.

      7 A 112 kg patient with a history of anxiety disorder has been admitted to the ICU. He is intubated and he is on multimodal sedation including a hydromorphone drip 3 mg/h for 7 days. To manage his ongoing sedation and acute pain needs, in addition to the current medications, including IV Tylenol, what is your next best action?Start a ketamine drip to provide dissociative analgesia, 5 mcg/kg/min.Start low‐dose ketamine drip at 1–2 mcg/kg/min after a bolus and start to decrease hydromorphone (Dilaudid) by 20%.Increase the hydromorphone (Dilaudid) drip to 4 mg/h to provide both sedation and analgesia.Add lorazepam (Ativan) drip and increase the hydromorphone (Dilaudid) to 4 mg/h.Start a propofol infusion, switch hydromorphone (Dilaudid) to equianalgesic fentanyl.Higher doses of ketamine infusions contribute to the unwanted side effects including agitation, hallucinations, and somnolence. These psycho‐mimetic effects are particularly worrisome in a patient who may be unable to communicate these effects. For this reason, choice A is incorrect. Sub‐anesthetic doses of ketamine when added to a multimodal pain approach are opioid sparing and may attenuate unwanted side

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