Morning Report: EtOH Withdrawal

Here’s Dr. Kincade with today’s Morning Report!

ETOH Withdrawal

Case:

A 45yo M presents to the ED for EtOH detoxification. Drinks 1L of vodka daily. Last drink 18 hours prior. VS: HR:150 beats/min, BP: 172/84 mm Hg, diaphoretic and has a severe tremor. The patient denies illicit drug use and alcohol withdrawal seizures or delirium tremens. He receives 1 liter of intravenous normal saline and an intravenous dose of 5 mg of diazepam. Fifteen minutes later, his tremor is worsening and her vital signs have failed to improve.

Background/Epidemiology:

-Recognized in ancient times

-Major cause of mortality and morbidity

-Mortality from DTs 2-3% down from 52% in 1912

-Complications responsible for 21% ICU admits

Pharmacology:

-etoh rapidly absorded w/ high vol distribution

-eliminated primarily via liver (lung, kidneys, sweat account for small amounts)

-Metabolized by ADH->acetaldehyde which is metab by aldehyde dehydrogenase-> acetate->acetyl CoA-> Drebs cycle for metab to CO2 and H2O

-Gen metabolization rate 20mg/dL/h

Pathophysiology:

-no ethanol receptors

-potentiates GABA (inhibitory) and antagonizes glutamate (excitatory) at NMDA receptor in CNS

-long term etoh alters structure of GABA receptor dec sensitivity to etoh (decreased GABA tone)

-long term antagonism ->up regulation NMDA receptor and altered structure->resistant to antagonism of etoh-> req higher etoh doses (increased NMDA tone)

-in w/drawal, loss of GABA and potentiation of NMDA -> hyperexcitation

-may have “kindling”: diff to tx w/d Sxs due to BZD resistance

Differential Dx:

-intox (cocaine)

-serotonin syndrome

-anticholinergic syndrome

-NSM

-Thyroid dysfunction

-sepsis

-trauma

-hypoglycemia

-acute psychosis

Dx: per DSM-5 Criteria, 2 or more of the following needed to Dx AWS

Mneumonic: THIN SAAP

Tremor

Hallucinations

Insomnia

Nausea/vomiting

Seizures

Autonomic hyperactivity

Anxiety

Psychomotor agitation

CIWA-Ar (Clinical Institute Withdrawal of Alcohol Scale, Revised)

Score < 8: safely manage as outpt

Treatment:

-First line for mild to severe AWS: BZD, substantiated in the research

-BZD: dec w/d severity, dec rates delirium, dec seizure

-Can give oral, IM, or IV route

Valium: onset 1-5 min, long ½ life, active metabolites that increase duration of action

-If refractory or for severe withdrawal Sxs can increase dose to 20mg, 50mg, up to 100mg Q15 min

Ativan: onset 10-20 min, better IM v valium; preferred if pt w/ severe liver dz due to elimination via kidneys

-For severe withdrawal can increase dose to 2mg , 4mg, 8mg, 16mg Q 15-20 min

Versed: short acting
Librium, can give orally, slow onset limits use in acute setting

References:

Picciotto MR. Common aspects of the action of nicotine and other drugs of abuse. Drug Alcohol Depend. 1998;51(1-2):165- 172. (Review) 5. Moore M, Gray MG. Delirium tremens: a study of cases at the Boston City Hospital, 1915–1936. New Engl J Med. 1939;220(23):953-956. (Observational; 2375 patients)

Moore M, Gray MG. Delirium tremens: a study of cases at the Boston City Hospital, 1915–1936. New Engl J Med. 1939;220(23):953-956. (Observational; 2375 patients)

Alldredge BK, Lowenstein DH, Simon RP. Placebo-controlled trial of intravenous diphenylhydantoin for shortterm treatment of alcohol withdrawal seizures. Am J Med. 1989;87(6):645-648. (Prospective randomized double-blind placebo-controlled trial; 90 patients) 48. Rathlev NK, D’Onofrio G, Fish SS, et al. The lack of efficacy of phenytoin in the prevention of recurrent alcohol-related seizures. Ann Emerg Med. 1994;23(3):513-518. (Prospective randomized double-blind trial; 147 patients) 49. D’Onofrio G, Rathlev NK, Ulrich AS, et al. Lorazepam for the prevention of recurrent seizures related to alcohol. N Engl J Med. 1999;340(12):915-919. (Randomized doubleblind trial; 229 patients)

Rathlev NK, D’Onofrio G, Fish SS, et al. The lack of efficacy of phenytoin in the prevention of recurrent alcohol-related seizures. Ann Emerg Med. 1994;23(3):513-518. (Prospective randomized double-blind trial; 147 patients)

D’Onofrio G, Rathlev NK, Ulrich AS, et al. Lorazepam for the prevention of recurrent seizures related to alcohol. N Engl J Med. 1999;340(12):915-919. (Randomized doubleblind trial; 229 patients)

Cagetti E, Liang J, Spigelman I, et al. Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABAA receptors. Mol Pharmacol. 2003;63:53-64. (Animal study; rats)

EB Medicine: Alcohol Withdrawal Syndrome