title: Evaluation of adjunctive ketamine to benzodiazepines for management of alcohol withdrawal syndrome.
abstract: BACKGROUND
  Adjunctive medications to manage alcohol withdrawal syndrome (AWS) in patients not adequately responding to escalating doses of benzodiazepines (BZDs) are limited. The use of the N-methyl-d-aspartate antagonist ketamine, may serve as an effective adjunct agent; however, no published data currently exist for this practice.
  
  
  OBJECTIVE
  To determine the safety and efficacy of adjunct ketamine for management of AWS.
  
  
  METHODS
  The study was a retrospective review of adult patients from April 2011 to March 2014 who were administered ketamine specifically for management of AWS. Outcomes included changes in BZD requirements and ketamine-related adverse reactions.
  
  
  RESULTS
  Of 235 patients screened, 23 patients met study eligibility. Ketamine was initiated primarily with toxicology consultation for significant BZD requirements or delirium tremens. The mean time to initiation of ketamine from first treatment of AWS, and total duration of therapy were 33.6 and 55.8 hours, respectively. Mean initial infusion dose and median total infusion rate during therapy were 0.21 and 0.20 mg/kg/h, respectively. There was no change in sedation or alcohol withdrawal scores in patients within 6 hours of ketamine initiation. The median change in BZD requirements at 12 and 24 hours post-ketamine initiation were -40.0 and -13.3 mg, respectively. The mean time to AWS resolution was 5.6 days. There was one documented adverse reaction of oversedation, requiring dose reduction.
  
  
  CONCLUSIONS
  Ketamine appears to reduce BZD requirements and is well tolerated at low doses. Prospective dose range evaluations in the management of AWS would be helpful in determining its place as an adjunctive agent.
authors.affiliation: UPMC Presbyterian, Pittsburgh, PA, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Wong
authors.affiliation: UPMC Presbyterian, Pittsburgh, PA, USA University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA benedictnj@upmc.edu.
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Benedict
authors.affiliation: UPMC Presbyterian, Pittsburgh, PA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Armahizer
authors.affiliation: UPMC Presbyterian, Pittsburgh, PA, USA University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Kane-Gill
mesh_terms: D000430:Alcohol Withdrawal Delirium / Q000188:drug therapy; D001569:Benzodiazepines / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007649:Ketamine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D001569:Benzodiazepines; D000431:Ethanol; D007649:Ketamine
keywords: alcohol withdrawal delirium; alcohol withdrawal seizures; benzodiazepines; ketamine; toxicology