EtOH Withdrawal: Ketamine, Precedex, and Other Pearls

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    EtOH Withdrawal: Ketamine, Precedex, and Other Pearls

    Case:

    Unk-FrequentFlyer is rushed back to you in the cardiac room by Unk-Intern. He was found in the back corner of the B side shortly after 7am sign out. The patient is in florid alcohol withdrawal, combative, hallucinating, and of course does not have an IV. What’s your game plan?

     

    Initial Sedation:

    This patient requires sedation prior to securing IV access. He is too strong and agitated to attempt IO. What do you reach for?

    Benzos: Which one? As far as I’m concerned there is only one answer: Midazolam (1). The dose is 0.2mg/kg IM prn. The time to maximum plasma concentration for midazolam 17.5 mins vs diazepam 33.8 mins (2).  Time to sedation for Midazolam and Lorazepam are 13.9 min and 135.3 min respectively (3). Diazepam should not be used IM as the absorption is slow and erratic.

    Ketamine: Dissociative dose ketamine can be used for many instances of excited delirium (1, 4). Dose is ~5mg/kg IM

     

    Management of EtOH Withdrawal

    Follow the protocol by Weingart

    The patient in our case is requiring increasingly large doses of benzos and you wonder, are there any other therapies that can be utilized to avoid intubating this patient and starting a propofol drip?

    Phenobarbital: This is actually included in the protocol above, but in practice I personally have never used it. Phenobarbital has dual activity through an increase in the duration of GABA-receptor opening and inhibition of glutamate receptor activity. Combination therapy with benzodiazepines, particularly in the setting of benzodiazepine resistant withdrawal or DT, is efficacious and supported in the literature (8). One study showed that use of Phenobarbital in combination with benzos decreased the use of mechanical ventilation (9). When used in combination with benzos, patients must be monitored closely for respiratory suppression, hypotension.

    Ketamine: Ketamine is a NMDA antagonist, which may have a role in alcohol withdrawal, as alcohol use results in upregulation of NMDA receptors. In 2015 Wong evaluated the use of ketamine (bolus and infusion) in addition to benzos for the management of EtOH w/d. No change in sedation or alcohol withdrawal scores was found, but ketamine reduced the amount of benzodiazepines received, from 40 mg to 13.3 mg (5)

    Precedex: The use of Precedex in EtOH w/d is controversial. Dexmedetomidine is a centrally acting alpha-2-agonist that reduces sympathetic output, while providing titratable sedation without affecting airway reflexes. There are several studies evaluating its use as adjuvant to standard therapy that showed reduced benzo requirement (5). The literature seems to support Precedex as adjuvant to standard therapy, however it does not address the underlying pathophysiology of alcohol withdrawal (5,6). As such, Precedex should be used with caution, as its effects can mask worsening withdrawal.

    Haldol: Should not be used as it lowers seizure threshold (7)

    Baclofen/beta blockers/ethanol: Have all been studied and are not indicated for the treatment of alcohol withdrawal

     

    Sources:

    (1) Reuben Strayer

    (2)Hung, Dyck, Varvel et al. Comparative absorption kinetics of intramuscular midazolam and diazepam. Can J Anaesth 1996;43:5 pp 450-5.

    (3)Nobay, Simon, Levitt et al. A Prospective, Double-blind, Randomized Trial of Midazolam versus Haloperidol versus Lorazepam in the Chemical Restraint of Violent and Severely Agitated Patients. Acad Emerg Med 2004;11:744-749.

    (4) https://www.aliem.com/2015/05/ketamine-for-excited-delirium-syndrome/

    (5)Wong A, Benedict NJ, Armahizer MJ, Kane-Gill SL. Evaluation of adjunctive ketamine to benzodiazepines for management of alcohol withdrawal syndrome. Ann Pharmacother 2015;49(1):14–9 Jan.

    (6) Dixit, Deepali, et al. “Management of acute alcohol withdrawal syndrome in critically ill patients.” Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 36.7 (2016): 797-822.

    (7)Blum, Kenneth, et al. “Enhancement of alcohol withdrawal convulsions in mice by haloperidol.” Clinical toxicology 9.3 (1976): 427-434.

    (8)Long, Drew, Brit Long, and Alex Koyfman. “The emergency medicine management of severe alcohol withdrawal.” The American journal of emergency medicine 35.7 (2017): 1005-1011.

    (9)Hayanga, Awori, and Eric Weiss. “A strategy of escalating doses of benzodiazepines and phenobarbital administration reduces the need for mechanical ventilation in delirium tremens.” Critical care medicine 35.7 (2007): 1809-1810.

     

     

     

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