Clinical Scenario:
It’s the age old story, chronic alcoholic evaluated for an
unrelated issue, cleared from that issue only to now have developed alcohol
withdrawal. The patient in question is a middle aged male with heavy alcohol
use history who was transferred from another center for specialist evaluation.
After being cleared by the consultant, he is now 24 hours from his last drink
and looks decidedly not well. He is tremulous, tachycardic, anxious, and
vomiting. You recognize his alcohol withdrawal, but despite treatment, he
rapidly worsens requiring very high doses of benzodiazepines and an ICU
admission. What adjunct therapies are available for severe alcohol withdrawal?
Alcohol abuse is an exceedingly common problem and
alcohol-related ED visits are encountered daily across the country. Annually, around 500,000 episodes of acute
alcohol withdrawal require treatment. The symptoms typically begin to manifest
within hours to days after cessation of alcohol and typically peak at 2 – 3
days. The clinical course of alcohol
withdrawal varies widely among patients.
Chronic alcohol use leads to down-regulation of GABA receptors and up-regulation
of NMDA glutamate receptors. Additionally, GABA receptor expression is
suppressed. In the active drinker, this allows patients to maintain a normal
level of consciousness despite blood alcohol levels that would incapacitate a
nondrinker. Withdrawal is therefore, associated with a decrease in GABAergic
activity and an increase in glutaminergic activity. The increase in excitatory
activity and loss of inhibitory activity results in the symptom complex of
alcohol withdrawal. Symptoms include autonomic hyperactivity, tremor, insomnia,
nausea/vomiting, hallucinations (commonly visual or tactile in addition to auditory),
psychomotor agitation, anxiety, generalized tonic-clonic seizures.
Benzodiazepines are the standard of care for alcohol withdrawal. Adjunct
therapies of old have targeted adrenergic symptoms, not so much the underlying
disease. These include beta-blockers and calcium channel blockers. Other more
targeted therapies like gabapentin are hindered by prolonged onset of action.
Adjuncts that make a bit more sense pharmacologically and are gaining
popularity include barbiturates, ketamine, and dexmedotomidine. Let’s look at some of that data.
