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pre‐existing nerve injury, placement in anesthetized adults, and anticoagulation. While none of the above medications alone are absolutely contraindicated (choices B, C, D, and E), a patient receiving more than one antithrombotic medication should not receive an epidural or spinal anesthetic technique (choice A). Non‐steroidal anti‐inflammatory medications are not contraindicated if used alone.Answer: AHorlocker TT, Vandermeuelen E, Kopp SL, Gogarten W, Leffert LR, Benzon HT. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence‐Based Guidelines (fourth edition). Reg Anesth Pain Med. 2018; 43(3):263–309.

      16 Patient is a 65‐year‐old woman admitted to the ICU for TBI with past medical history of mitochondrial disease and lupus. Patient has been on long‐term steroids. Patient is agitated and you suspect she has increased ICP. You are about to intubate the patient for airway protection. What would be the best choice for induction and intubation?PropofolEtomidate (Amidate)Lorazepam (Ativan)FentanylNo induction, topicalize with benzocaine and plan for awake fiberoptic intubationCritically ill patients are often intubated emergently, and a rapid sequence technique is preferred if clinically deteriorating. Typically, clinicians combine sedative and paralytic agents although judgment is needed before deciding to use either class of drug. Fentanyl will provide a stable induction and can be used with succinylcholine for a rapid sequence intubation (choice D). Propofol lowers ICP and is also acceptable in traumatic brain injured patients. But in the setting of mitochondrial disease, it should be avoided as propofol infusion syndrome is thought to result from inhibition of mitochondrial enzymes in mitochondria and on mitochondrial membranes (choice A). A single low dose of propofol may be acceptable; however, it can cause vasodilation and hypotension and is not the best choice here. Etomidate, a sedative‐hypnotic, is often used because it has relative cardiac stability when compared with propofol. Caution should be used with even a single dose of etomidate (Amidate) because it can cause adrenal insufficiency by inhibition of 11β‐hydroxylase (choice B). Long‐acting benzodiazepines such as lorazepam (Ativan) can delay a post intubation neurovascular exam and its use should be avoided (choice C). Awake fiberoptic intubation is unlikely to be tolerated in an agitated patient (choice E).Answer: DNiezgoda J, Morgan PG. Anesthetic considerations in patients with mitochondrial defects. Paediatr Anaesth. 2013; 23(9):785–93.Footitt EJ, Sinha MD, Raiman JA, Dhawan A, Moganasundram S, Champion MP. Mitochondrial disorders and general anaesthesia: a case series and review. Br J Anaesth. 2008; 100(4):436–41.

      17 About 5 hours ago, a 35‐year‐old woman with a history of depression and anxiety, ingested an unknown amount of alcohol (ethanol), 20 tabs of alprazolam (Xanax), and methocarbamol (Robaxin). She is arousable to sternal rub. Blood pressure is 100/60 mmHg, heart rate is 68/min, respiratory rate is 8/min, and temperature is 36 °C. Which is the most appropriate intervention?IntubationGastric lavageFlumazenil (Anexate)Fomepizole (Antizol)Activated charcoalSince the patient ingested several medications, the best intervention is intubation and supportive care (choice A). Activated charcoal is not likely to be effective since the presentation is delayed, so activated charcoal and gastric lavage are not indicated (choices B, E). Flumazenil (Anexate) is an antidote for benzodiazepines but is contraindicated in a patient with chronic use of alprazolam. Flumazenil may precipitate withdrawal seizures in this case. It would be difficult to treat subsequent seizures after flumazenil since benzodiazepine receptors would be blocked (choice C). Benzodiazepine overdose may cause respiratory depression but risks of reversing benzodiazepines in chronic use outweigh potential benefits as it may precipitate seizure. Fomepizole (4‐methylpyrazole, Antizol) competitively inhibits the first enzyme in the metabolism of ethylene glycol and methanol (alcohol dehydrogenase) which prevents their metabolism to toxic acids. The slower rate of metabolite production allows the liver to process and excrete the metabolites as they are produced; however, it is not indicated in acute ethanol toxicity. Do not give fomepizole in acute alcohol intoxication because fomepizole will compete for alcohol dehydrogenase (choice D) and impair metabolism. Methocarbamol (Robaxin) is a muscle relaxant.Answer: ABrent J, McMartin K, Phillips S, Aaron C, Kulig K ; Methylpyrazole for Toxic Alcohols Study Group. Fomepizole for the treatment of methanol poisoning. N Engl J Med. 2001; 344(6):424–9.Seger DL. Flumazenil‐‐treatment or toxin. J Toxicol Clin Toxicol 2004; 42(2):209–16.Chyka PA, Seger D, Krenzelok EP, Vale JA ; American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. Position paper: single‐dose activated charcoal. Clin Toxicol (Phila). 2005; 43(2):61–87.

      18 Which of the following is a true statement regarding flumazenil (Anexate)?It exerts a clinical effect by competitive antagonism at mu receptor.It is a competitive inhibitor at GABA A receptors.Flumazenil does not contribute to seizure activity in benzodiazepine tolerant patients.It is a relatively long‐acting medication.Flumazenil consistently reverses respiratory depression caused by benzodiazepine overdose.Mu receptors are specific transmembrane neurotransmitter receptors that couple G proteins and are activated by opioids and are not affected in the presence of flumazenil (choice A). Naltrexone (Vivitrol) is a competitive antagonist to mu receptors. Flumazenil (Anexate) is structurally similar to midazolam and is a nonspecific competitive antagonist of the benzodiazepine receptor (GABAA) in the central nervous system (CNS) (choice B). Flumazenil has a limited role in the management of benzodiazepine overdose, purportedly to avoid the need for procedure (i.e., intubation), and is contraindicated in the presence of a known seizure disorder or benzodiazepine dependence. It can reverse the effect of benzodiazepines in the CNS and precipitate seizures making choice C incorrect. Flumazenil rapidly undergoes hepatic metabolism to inactive metabolites and its half‐life is not long, about 40–80 minutes, thus the duration of effect of a long‐acting benzodiazepine or a large benzodiazepine dose can exceed that of flumazenil making choices D and E incorrect. However, in the right scenario, flumazenil as a reversal and rescue medication can be lifesaving. The recommended initial dose in adults is 0.2 mg IV given by slow push over 1–2 minutes. Doses can be repeated 0.2 mg, but one must watch for a maximum dose of 2 mg.Answer: BKreshak AA, Cantrell FL, Clark RF, Tomaszewski CA. A poison center's ten‐year experience with flumazenil administration to acutely poisoned adults. J Emerg Med. 2012; 43(4):677–82.Weinbroum AA, Flaishon R, Sorkine P, Szold O, Rudick V. A risk‐benefit assessment of flumazenil in the management of benzodiazepine overdose. Drug Saf 1997; 17(3):181–96.Shalansky SJ, Naumann TL, Englander FA. Effect of flumazenil on benzodiazepine‐induced respiratory depression. Clin Pharm 1993; 12(7):483–7.Seger DL. Flumazenil‐‐treatment or toxin. J Toxicol Clin Toxicol 2004; 42(2):209–16.Murray L Little M Pascu O Hoggett KA. Toxicology Handbook. 3rd Edition. eBook ISBN: 9780729584951.

      19 A 40‐year‐old man with a history of depression is admitted to the ICU after laparotomy and lysis of adhesions. He was using a fentanyl PCA but developed autonomic dysfunction, confusion, and muscular rigidity. The PCA was stopped because it was suspected that he was exhibiting serotonin syndrome . When stable, you will need to rethink the pain management plan. What is the best course of action?Stop fentanyl PCA and order tramadol (Ultram)Continue fentanyl PCA and add methadone (Dolophine)Stop fentanyl PCA and order meperidine (Demerol)Stop the fentanyl PCA and order a morphine PCAStop the fentanyl PCA and order oxycodoneSome opioids including fentanyl, methadone, and demerol act as serotonergic agents that contribute to the development of serotonin syndrome. Medications in this class of opioids are the synthetic and semisynthetic opioids. Serotonin syndrome results from over‐dosage or coadministration of narcotics with serotonin reuptake inhibitor antidepressants (SSRIs). Synthetic piperidine opioids are pro‐serotonergic in their own right and can act as serotonin reuptake inhibitors. This class of narcotics includes fentanyl, methadone, oxycodone, meperidine (Demerol), and tramadol (choices B, C, and E). Morphine is not in this class and does not inhibit serotonin reuptake (choice D) and is the correct answer. Clinical manifestations of serotonin syndrome results from increased postsynaptic stimulation of 5‐hydroxytryptamine, 2A and 1A serotonin receptors in the central and peripheral nervous system. Since this patient has a history of depression and is receiving a synthetic opioid, serotonin syndrome is suspected.Answer: Dvan Ewijk CE, Jacobs GE, Girbes ARJ. Unsuspected serotonin toxicity in the ICU. Ann Intensive Care. 2016; 6(1):85.Pathan H, Williams J. Basic opioid pharmacology: an update. Br J Pain. 2012; 6(1):11–16.Pedavally S, Fugate JE, Rabinstein AA. Serotonin syndrome in the intensive care unit: clinical presentations and precipitating medications. Neurocrit Care. 2014; 21(1):108–13.

      20 A

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