There are approximately 8 million alcohol dependent people in the United States. Nearly 500,000 episodes of withdrawals occurred requiring pharmacological treatment.1 Chronic ethanol use induces an insensitivity to the Gamma-aminobutyric acid (GABA) receptor such that more inhibitor is required to maintain a constant inhibitory tone. In addition, alcoholism can cause an up-regulation of N-methyl-D-aspartate (NMDA) receptor.2 Therefore, a continuous dependence on alcohol is required to maintain equilibrium and prevent the occurrence of alcohol withdrawal syndrome (AWS).3
Benzodiazepines (BZDs) are GABA agonists and considered the preferred class for the management of AWS. However, some patients do not respond to BZDs, despite escalating doses.4 A small number of drugs (e.g. dexmedetomidine, propofol, etc.) have also been used with variable results.4,5 Ketamine is one other drug that has been used in the literature with some efficacy. It is classified as an anesthetic with NMDA antagonism activity.6
The authors of this study sought to evaluate whether the addition of ketamine to BZD is safe and effective for the management of patients with AWS at the University of Pittsburgh Medical Center health system. The study was a retrospective cohort of adult ICU patients receiving ketamine infusions from April 2011-March 2014.7 All patients less than 18 years of age or who were initiated on ketamine for reasons other than AWS management were excluded. An AWS treatment protocol utilizing the Withdrawal Assessment Scale (WAS) was used. The WAS is a validated tool derived from the Clinical Institute Withdrawal Assessment (CIWA) tool and indicates severity of AWS on a scale from 0 to 96.8 The decision to initiate BZDs was based on symptoms when the WAS score, completed every 4 hours, was greater than 10. Lorazepam or chlordiazepoxide were the preferred agents in the WAS protocol. Study outcomes include changes in BZD requirements and ketamine-related adverse reactions.
Ketamine was initiated for significant BZD requirements or delirium tremens. Out of 235 patients screened, 23 patients met the inclusion/exclusion criteria. Ketamine was initiated 34 hours after the first treatment of AWS and 12 hours after the occurrence of resistant alcohol withdrawal (RAW) defined as a BZD-equivalent requirement of 40 mg of diazepam administered in 1 hour for the management of AWS.9 For patients not receiving diazepam, a BZD dose equivalent was applied.10
Ketamine loading dose used was 0.3 mg/kg. Ketamine was continued for approximately 56 hours and was effective in decreasing BZD requirements 12 or 24 hours post–ketamine initiation (p = 0.110 and 0.330, respectively). The mean time to AWS resolution was 5.6 days. Furthermore, the initiation of ketamine was not associated with changes in sedation scores. Only one documented adverse event occurred from ketamine therapy, which was oversedation requiring dose adjustment.
Limitations of the study include the fact that the CIWA and the WAS have not been verified in the ICU population because they were originally studied in outpatient or general ...