Hospitalists and alcohol withdrawal: Yes, give benzodiazepines but is that the whole story?

With 17 million Americans reporting heavy drinking (5 or more drinks on 5 different occasions in the last month) and 1.7 million hospital discharges in 2006 containing at least 1 alcohol-related diagnosis, it would be hard to imagine a hospitalist who does not encounter patients with alcohol abuse. Estimates from studies looking at the number of risky drinkers among medical inpatients vary widely—2% to 60%— with more detailed studies suggesting 17% to 25% prevalence. Yet despite the large numbers and great costs to the healthcare system, the inpatient treatment of alcohol withdrawal syndrome remains the ‘‘ugly stepsister’’ to more exciting topics, such as acute myocardial infarction, pulmonary embolism and procedures. We hospitalists typically leave the clinical studies, research, and interest on substance abuse to addiction specialists and psychiatrists, perhaps due to our discomfort with these patients, negative attitudes, or belief that there is nothing new in the treatment of alcohol withdrawal syndrome since Dr Leo Henryk Sternbach discovered benzodiazepines in 1957. Many of us just admit the alcoholic patient, check the alcohol-pathway in our order entry system, and stop thinking about it. But in this day of evidence-based medicine and practice, what is the evidence behind the treatment of alcohol withdrawal, especially in relation to inpatient medicine? Shouldn’t we hospitalists be thinking about this question? Hospitalists tend to see 2 types of inpatients with alcohol withdrawal: those solely admitted for withdrawal, and those admitted with active medical issues who then experience alcohol withdrawal. Is there a difference? The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) defines early alcohol withdrawal as the first 48 hours where there is central nervous system (CNS) stimulation, adrenergic hyperactivity, and the risk of seizures. Late withdrawal, after 48 hours, includes delirium tremens (DTs) and Wernicke’s encephalopathy. This is based on studies done in the 1950s, where researchers observed patients as they withdrew from alcohol and took notes. The goal in treatment of alcohol withdrawal is to minimize symptoms and prevent seizures and DTs which, prior to benzodiazepines, had a mortality rate of 5% to 20%. Before the US Food and Drug Administration (FDA) approval of the first benzodiazepine in 1960 (chlordiazepoxide), physicians treated alcohol withdrawal with ethanol, antipsychotics, or paraldehyde. (That is why there is a ‘‘P’’ in the mnemonic ‘‘MUDPILES’’ for anion gap acidosis.) The first study to show a real benefit from benzodiazepine was published in 1969, when 537 men in a veterans detoxification unit were randomized to chlordiazepoxide (Librium), chlorpromazine (Thorazine), antihistamine, thiamine, or placebo. The primary outcome of DTs and seizures occurred in 10% to 16% of the patients, except for the chlordiazepoxide group where only 2% developed seizures and DTs (there was no P value calculated). Further studies published in the 1970s and early 1980s were too small to demonstrate a benefit. A 1997 meta-analysis of all these studies, including the 1969 article, confirmed benzodiazepines statistically reduced seizures and DTs. Which benzodiazepine to use, however, is less clear. Long-acting benzodiazepines with liver clearance (eg, chlordiazepoxide or diazepam) versus short-acting with renal clearance (eg, oxazepam or lorazepam) is debated. While there are many strong opinions among clinicians, the same meta-analysis did not find any difference between them, and a small 2009 study found no difference between a short-acting and long-acting benzodiazepine. How much benzodiazepine to give and how frequently to dose it was looked at in 2 classic studies. Both studies demonstrated that symptom-triggered dosing of benzodiazepines, based on the Clinical Institute Withdrawal Assessment (CIWA) scale, performed equally well in terms of clinical outcomes, with less medication required as compared with fixeddose regimens. Based on these articles, many hospitals created alcohol pathways using solely symptom-triggered dosing. The CIWA scale is one of multiple rating scales in the assessment of alcohol withdrawal. The CIWA-Ar is a modified scale that was designed and validated for clinical use in inpatient detoxification *Address for correspondence and reprint requests: Kathleen M. Finn, MD, Clinician Educator Program, Massachusetts General Hospital, 50 Staniford St, Suite 503B, Boston, MA 02114; Tel.: 617-643-4053; E-mail: Kfinn@partners.org