Causes and treatment of alcohol withdrawal symptoms
Common symptoms of alcohol withdrawal include autonomic hyperactivity, tremor, insomnia, nausea, vomiting, agitation, anxiety, grand mal seizures, and transient visual, tactile, or auditory hallucinations.5 These symptoms result, in part, from the effects of chronic alcohol exposure on brain γ–aminobutyric acid (GABA) and glutamate systems. Alcohol acutely enhances presynaptic GABA release through allosteric modulation at GABAA receptors and inhibits glutamate function through antagonism of N-methyl-d-aspartate (NMDA) receptors. Chronic alcohol exposure elicits compensatory downregulated GABAA and upregulated NMDA expression.
When alcohol intake abruptly stops and its acute effects dissipate, the sudden reduction in GABAergic tone and increase in glutamatergic tone cause alcohol withdrawal symptoms.6 Benzodiazepines, which bind at the benzodiazepine site on the GABAA receptor and, similar to alcohol, acutely enhance GABA and inhibit glutamate signaling, are the standard of care for alcohol withdrawal because they reduce anxiety and the risk of seizures and delirium tremens, which is a severe form of alcohol withdrawal characterized by disturbance in consciousness and cognition and hallucinations.5,6
Table
Benefits of symptom-triggered vs fixed scheduled therapy for alcohol withdrawal
| ST | FS | Benefits of ST | |
|---|---|---|---|
| Efficacy in alcohol withdrawal | Yes | Yes | |
| Flexibility in dosing with fluctuations in CIWA-Ar score | Yes | No | Less medication can be given overall if alcohol withdrawal signs resolve rapidly |
| Lower total benzodiazepine doses | + | – | Smaller chance of side effects such as oversedation, paradoxical agitation, delirium due to benzodiazepine intoxication, or respiratory depression |
| Fewer complications of higher benzodiazepine doses | + | – | Reduced risk of prolonged hospitalization, morbidity from aspiration pneumonia, or need to administer a reversal agent such as flumazenil |
| + = more likely; – = less likely CIWA-Ar: Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised; FS: fixed scheduled; ST: symptom-triggered Bibliography Amato L, Minozzi S, Vecchi S, et al. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev. 2010;(3):CD005063. Cassidy EM, O’Sullivan I, Bradshaw P, et al. Symptom-triggered benzodiazepine therapy for alcohol withdrawal syndrome in the emergency department: a comparison with the standard fixed dose benzodiazepine regimen [published online ahead of print October 19, 2011]. Emerg Med J. doi: 10.1136/emermed-2011-200509. Daeppen JB, Gache P, Landry U, et al. Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Arch Intern Med. 2002;162(10):1117-1121. DeCarolis DD, Rice KL, Ho L, et al. Symptom-driven lorazepam protocol for treatment of severe alcohol withdrawal delirium in the intensive care unit. Pharmacotherapy. 2007;27(4):510-518. Jaeger TM, Lohr RH, Pankratz VS. Symptom-triggered therapy for alcohol withdrawal syndrome in medical inpatients. Mayo Clin Proc. 2001;76(7):695-701. Weaver MF, Hoffman HJ, Johnson RE, et al. Alcohol withdrawal pharmacotherapy for inpatients with medical comorbidity. J Addict Dis. 2006;25(2):17-24. | |||
Factors influencing CIWA-Ar score
Vital signs monitoring. One limitation of the CIWA-Ar is that vital signs—an objective measurement of alcohol withdrawal— are not used to determine the score. Indeed, Mr. J presented with vital sign dysregulation. However, research suggests that the best predictor of high withdrawal scores includes groups of symptoms rather than individual symptoms.10 In that study, pulse and blood pressure did not correlate with withdrawal severity. Pulse and blood pressure elevations occur in alcohol withdrawal, but other signs and symptoms are more reliable in assessing withdrawal severity. This is clinically important because physicians often prescribe medications for alcohol withdrawal treatment based on pulse and blood pressure measures.1 This needs to be balanced against research that found a systolic blood pressure >150 mm Hg and axillary temperature >38°C can predict development of DTs in patients experiencing alcohol withdrawal.7
Lorazepam-induced disinhibition. Benzodiazepines affect functions associated with processing within the orbital prefrontal cortex,11 including response inhibition and socially acceptable behavior, and impairment in this functioning can result in behavioral disinhibition.12 This effect could account for the apparent paradoxical clinical observation of aggression in benzodiazepine-sedated patients.13 Because agitation is scored on the CIWA-Ar,1,10 falsely elevated scores caused by interpreting benzodiazepine-induced aggression as agitation could result in patients (such as Mr. J) receiving more lorazepam, therefore perpetuating this cycle.
Comorbid anxiety disorders also could falsely accentuate CIWA-Ar scores. For example, the odds of an alcohol dependence diagnosis are 2 to 3 times greater among patients with an anxiety disorder.14 Additionally, the lifetime prevalence of comorbid alcohol dependence for patients with GAD—such as Mr. J— is 30% to 35%.14,15
Alcohol withdrawal can be more severe in patients with alcohol dependence and anxiety disorders because evidence suggests the neurochemical processes underlying both are similar and potentially additive. Studies have shown that these dual diagnosis patients experience more severe symptoms of alcohol withdrawal as assessed by total CIWA-Ar score than those without an anxiety disorder.15 Although such patients may require more aggressive pharmacologic treatment, the dangers of higher benzodiazepine dosages may be even greater.