Ethanol or Benzodiazepines to Prevent Alcohol Withdrawal in the ICU?
Ethanol or Benzodiazepines to Prevent Alcohol Withdrawal in the ICU?
Abstract & Commentary
By David J. Pierson, MD, Editor, Professor, Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle, is Editor for Critical Care Alert.
Synopsis: In this clinical trial of ethanol infusion vs scheduled diazepam administration in non-intubated trauma patients at high risk for alcohol withdrawal, fewer patients in the ethanol group were maintained in the target sedation range, but there were no other major differences.
Source: Weinberg JA, et al. J Trauma. 2008;64:99-104.
Trauma surgeons at the Regional Medical Center at Memphis carried out a randomized clinical trial comparing a continuous ethanol infusion with a protocol of scheduled diazepam administration for the prevention and control of severe alcohol withdrawal syndrome (AWS) among patients admitted to their ICU following trauma. They enrolled patients who consumed 5 or more drinks per day over the preceding 6 months, and excluded those with significant co-morbid conditions (including evidence of alcohol-related disease or neurologic dysfunction), intubated patients, and those who were unable to give informed consent. Patients received either a continuous infusion of 5% ethanol (starting at 50 mL/h) or regular doses of intravenous or enteral diazepam (starting at 5 mg every 6 h), according to protocols resembling those already in routine use in their unit. The study drug was titrated to a target score of 4 points ("calm and cooperative") on the 7-point Riker Sedation-Agitation Scale, where a score of 7 indicates dangerous agitation and 1 indicates unarousability. Patients were assessed for weaning from the protocol after 48 hours.
During the 18-month study period, 50 patients (26 receiving ethanol and 24 diazepam) were enrolled and completed the study. No significant differences were reported with respect to age, severity of injury, or cumulative opioid dose during the observation period. The patients in the alcohol infusion group had agitation scores different from the target score of 4 substantially more often (when assessed every 4 h) than those in the benzodiazepine group (p = 0.02), with the majority of deviations representing under- rather than over-sedation. One patient failed the ethanol protocol, with severe agitation despite infusion of 200 mL/h of 5% ethanol, and had to be treated with diazepam and haloperidol. Most patients in both treatment groups could be weaned from the AWS regimen at 48 h, although 3 in each group took up to 96 h.
Commentary
Intravenous ethanol continues to be used to prevent and treat AWS in a few centers—particularly, according to the authors of this article, by surgeons. This seemingly antiquated therapy has been subjected to little formal study, particularly in comparison with benzodiazepines, the use of which has been an evidence-based standard of care for many years. This small study found that, using the dosage regimens employed, patients achieved the target sedation goal more often and tended to be under-sedated less frequently when given diazepam than with intravenous ethanol. The authors comment that both regimens were generally effective, with only one treatment failure (in the ethanol group), but the study was underpowered to detect differences other than gross ones. Using only an assessment of agitation, rather than one incorporating measures of autonomic dysfunction such as tachycardia, hypertension, and diaphoresis (as in the more commonly used CIWA-Ar protocol-see reference), other differences in controlling the manifestations of AWS may have been missed.
Although the treatment regimens under investigation were intended to prevent and treat severe AWS, the incidence of AWS in the patients studied is not reported per se. Thus, even in this population of individuals for whom most clinicians would agree the risk of AWS was substantial, it is not clear how often the condition under investigation actually occurred. This increases the reader's uncertainty about the study's ability to detect differences between the two regimens if they had been present.
A final note of caution in accepting the authors' conclusion that essentially no differences between ethanol and diazepam could be demonstrated is that they studied a selected population of trauma patients in whom the potential adverse effects of ethanol infusion may have been less than for a broader population of alcohol-abusing patients. Only patients with no evidence for alcoholic liver disease or other signs of end-organ damage from excessive drinking were included. Only non-intubated patients, who were able to personally give informed consent, were enrolled. Whether intravenous alcohol might be effective or safe when used to prevent AWS in the broader ICU trauma population was not addressed in this study.
Reference
- Sullivan JT, et al. Br J Addiction. 1989;84:1353-1357.
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