Toni Manougian, MD, MBA1 and Bardiya Zangbar, MD2 1 Department of Critical Care Anesthesiology, New York Medical College, Westchester Medical Center, Valhalla, NY, USA 2 Division of Trauma and Acute Care Surgery, New York Medical College, Westchester Medical Center, Valhalla, NY, USA All of the choices are false regarding thoracic epidural catheters except choice A. Pulmonary function is unaffected by thoracic epidural analgesia in patients with normal function. However, severe pulmonary disease is a relative contraindication for brachial plexus blocks. Brachial plexus blocks such as an interscalene block affect ipsilateral hemi‐diaphragmatic excursion and reduce functional residual capacity and pulmonary function as much as 40%. Interestingly, the recurrent laryngeal nerve may also be blocked and can cause complete airway obstruction in a patient with existing vocal cord palsy. A blockade at the T5‐L1 level will increase gastric secretions, peristalsis, and enhanced gastric motility due to increased parasympathetic activity and sympathetic splanchnic blockade making choice B incorrect answer. Renal blood flow is auto‐regulated and unaffected by epidural analgesia. When thoracic epidural catheters are used, indwelling urinary catheters are not always required. Lumbar epidural analgesia however, can cause urinary retention, especially when blocking S2 to S4 spinal segments. Therefore, lumbar epidural catheters are more likely to affect bladder function than thoracic epidurals (choice C). One of the major benefits when choosing neuraxial analgesia (NA) is to blunt the sympathetic stress response. NA reduces oxygen consumption and decreases levels of vasopressin, catecholamines, cortisol, and glucose (choice D). Choice E is incorrect, because blocks at the T1‐4 level result in sympathetic blockade and profound cardiovascular effects. Blocks at T1‐T4 result in hypotension from both bradycardia and decreased cardiac contractility. Answer: A Mian A, Chaudhry I, Huang R, Rizk E, Tubbs RS, Loukas M. Brachial plexus anesthesia: A review of the relevant anatomy, complications, and anatomical variations. Clin Anat. 2014; 27(2):210–21. Basse L, Werner M, Kehlet H. Is urinary drainage necessary during continuous epidural analgesia after colonic resection? Reg Anesth Pain Med. 2000; 25(5):498–501. The patient is exhibiting signs of a dystonic reaction and his symptoms are best treated with benztropine. Dystonic reactions are an unwanted effect after administration of neuroleptic medications. Dystonic reactions can occur immediately, or be delayed hours to days. Classic features of dystonic reaction to medications such as haloperidol are cholinergic symptoms such as increased salivation and spasmodic or sustained involuntary contractions of muscles in the face, neck, trunk, pelvis, extremities, or larynx. Dystonic reactions, while not usually life threatening, are distressing for patients and families. Benztropine, an anticholinergic agent, is used for symptomatic improvement (choice A). While some symptoms can be improved with benzodiazepines, this class of medication may worsen his confusion, blunt his respiratory drive, and contribute to ICU delirium, so choice B is not the best answer. Metoclopramide (Reglan) exerts an antiemetic effect by antagonist activity at central D2 receptors in the chemoreceptor trigger zone and may potentiate the dyskinesia symptoms, so choice C is incorrect. Dantrolene (Ryanodex) is used in reversal of malignant hyperthermia and has no primary role in treatment of dystonic reactions (choice D). While haloperidol (Haldol) is associated with neuroleptic malignant syndrome, the side effects manifested is mental status change in the form of agitated delirium with confusion or catatonic signs and mutism. Other symptoms include muscular rigidity which can be demonstrated by moving the extremities and is characterized by “lead pipe rigidity” or stable resistance through all ranges of movement. Hypothermia is common and extremely high temperatures greater than 40 °C is common. Autonomic dysfunction in the form of tachycardia with hypertension and tachypnea along with dysrhythmias may occur. In the scenarios of induced neuroleptic malignant syndrome, dantrolene can be an antidote. Quetiapine (Seroquel) is a second‐generation antipsychotic and known to be rare in causing extrapyramidal side effects and has no role in treatment of dystonic side effects (choice E). Answer: A Digby G, Jalini S, Taylor S. Medication‐induced acute dystonic reaction: the challenge of diagnosing movement disorders in the intensive care unit. BMJ Case Resp. 2015; 2015:bcr2014207215 Goff DC, Arana GW, Greenblatt DJ, Dupont R, Ornsteen M, Harmatz JS, Shader RI. The effect of benztropine on haloperidol‐induced dystonia, clinical efficacy and pharmacokinetics: a prospective, double‐blind trial. J Clin Psychopharmacol 1991; 11(2):106–12. Narcotic first regimens are common but undesirable because their adverse effects include ileus, delayed extubation, tolerance, and opioid‐induced hyperalgesia. Narcotics also place patients at risk for withdrawal. For most patients, especially those you plan to extubate soon or those at risk for complications, narcotic infusions are not the first choice. A stepwise approach including multimodal analgesia with acetaminophen, intermittently dosed narcotics and ketamine (0.5 mg/kg IVP × 1 followed by 1–2 mcg/kg/min infusion) is recommended. The goal is to minimize opioid therapy when managing postsurgical adult patients in the ICU (conditional recommendation, very low quality of evidence) and ketamine can be used as an IV adjunct. Gabapentin is also available as part of stepwise approach. Acetaminophen and pain‐dose ketamine infusions are excellent analgesics and can be added to an intermittently dosed narcotic plan as needed, making choice B the best answer. Choices A, C, and D are also incorrect because they rely on opioid infusions and do not represent the best stepwise approach. It is especially important to avoid continuous narcotic infusions in patients at high risk for opioid toxicity, such as those with sleep apnea or at patients at risk for ileus. Although dexmedetomidine (Precedex) has some pain effects as an alpha 2 agonist, its primary effect is sedation and would not be the best choice for pain in combination with propofol. The patient is calm and does not need two sedative agents, so choice (E) is also incorrect. Answer: B Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJC, Pandharipande PP, Watson PL, Weinhouse GL, Nunnally ME, Rochwerg B, Balas MC, van den Boogaard M, Bosma KJ, Brummel NE, Chanques G, Denehy L, Drouot X, Fraser GL, Harris JE, Joffe AM, Kho ME, Kress JP, Lanphere JA, McKinley S, Neufeld KJ, Pisani MA, Payen JF, Pun BT, Puntillo KA, Riker RR, Robinson BRH, Shehabi Y, Szumita PM, Winkelman C, Centofanti JE, Price C, Nikayin S, Misak CJ, Flood PD, Kiedrowski K, Alhazzani W. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018; 46(9):e825–73. Antipsychotic medications such as haloperidol and quetiapine are used to manage delirium. These medications can increase the QTC interval but also antagonize dopamine signaling, which affects the swallow mechanism and increases the risk of aspiration. Therefore, choice C is correct. Both clonidine (choice A) and dexmedetomidine (choice B) are useful adjuncts in pain management because of their effects at central α2 receptors. Clonidine blocks sympathetic outflow, reduces arterial blood pressure, and ameliorates symptoms of alcohol and opiate withdrawal but does not increase aspiration risk. When used in epidural pain catheters, clonidine produces analgesia at the presynaptic and post junctional alpha 2 receptors. Dexmedetomidine (Precedex) produces centrally mediated sympatholytic sedation, anxiolysis, and analgesia. A transient increase in blood pressure during the loading dose of dexmedetomidine may occur, followed by hypotension which may be concerning for patients needing strict blood pressure control. A valuable characteristic 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: C Alexopoulou 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. Haldol (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: C Ray 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. Local 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: B El‐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.
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Analgesia and Anesthesia
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