is a 70 kg, 60‐year‐old man undergoing paravertebral nerve block due to multiple rib fractures in the ICU. Patient is hemodynamically stable before the block; however, becomes hypotensive and tachycardic 15 minute after the procedure is finished. You are suspecting local anesthetics toxicity. What would be the most appropriate treatment at this time? Vasopressin bolus followed by infusionDiltiazem (Cardizem) 5 mg bolus followed by infusionLipid emulsion 20% 100 mL follow by infusionPropofol 100 mgLorazepam (Ativan) 2 mgLocal anesthetic systemic toxicity (LAST) can occur after inadvertent intravascular injection or increased vascular uptake of a local anesthetic (LA) agent. The mechanisms for the clinical responses seen are multifactorial, mostly affecting the central nervous and cardiovascular systems. Neurologic manifestations such as tinnitus, seizures, or confusion are most common but the cardiovascular effects can be devastating. LA medications accumulate in mitochondria and cardiac tissue with greater affinity relative to plasma and can manifest with profound shock and cardiac instability.LA exerts its action at voltage‐gated sodium channels, blocks calcium channels, and at higher concentrations inhibits other channels, enzymes, and receptors including the carnitine‐acylcarnitine translocase receptor in mitochondria. This is the basis for treatment of LAST with lipid emulsion. Bupivacaine is more likely to cause cardiovascular collapse because it is more lipophilic and has a greater affinity for the voltage‐gated sodium channels. Factors that increase the likelihood of toxicity are extremes of age, comorbidities, higher total dose of LA medication, and site of injection. The highest incidence of LAST is with paravertebral blocks.Treatment of LAST includes 20% lipid emulsion which acts as a “lipid sink.” Recommended dose is 100 mL over 2–3 minutes for patients at least 70 kg (1.5 mL/kg), followed by infusion of 250 mL over 20 minutes. The bolus can be repeated, and the infusion rate doubled if clinically not improved (choice C).Further care includes supportive measures such benzodiazepines for treatment of seizures. Lorazepam (Ativan) can be administered if the patient is showing signs of seizure activity (choice E). Beta‐blockers, calcium channel blockers (diltiazem), and vasopressin should be avoided (choices A and B). Epinephrine if needed should be administered at lower doses (less than 1 mg/kg). Propofol is not the best choice and can exacerbate hypotension (choice D).Answer: CNeal JM, Neal EJ, Weinberg GL. American Society of Regional Anesthesia and Pain Medicine Local Anesthetic Systemic Toxicity checklist: 2020 version. Reg Anesth Pain Med. 2020:rapm‐2020‐101986. doi: 10.1136/rapm‐2020‐101986. Epub ahead of print.El‐Boghdadly K, Pawa A, Chin KJ. Local anesthetic systemic toxicity: current perspectives. Local Reg Anesth. 2018; 11:35–44.15 A 65‐year‐old polytrauma patient in the ICU with blunt cerebrovascular injury and rib fractures has severe pain which affects patient's respiratory efforts. Patient has a new lower extremity venous thromboembolic event. You place a pain consult for possible epidural anesthesia. Considering your plan for a neuraxial block, which of the following therapies should be avoided?Ketorolac (Toradol) and subcutaneous heparinASAEnoxaparin (Lovenox)Heparin infusionAcetaminophen IV (Ofirmev)Because neuraxial techniques are increasingly used to manage pain in the ICU, intensivists need to understand the guidelines for management of anticoagulation as it affects the placement of epidural catheters. Serious complications associated with neuraxial anesthesia are epidural hematomas, epidural abscess, and nerve injuries. Absolute contraindications include patient refusal and severe coagulopathy. Relative contraindications are sepsis, thrombocytopenia, 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
