title: Management of benzodiazepine-resistant alcohol withdrawal across a healthcare system: Benzodiazepine dose-escalation with or without propofol.
abstract: BACKGROUND
  Severe cases of alcohol withdrawal syndrome (AWS) may not resolve despite escalating doses of benzodiazepines (BZDs). Benzodiazepine-resistant alcohol withdrawal (RAW) is a subset of severe alcohol withdrawal defined by the requirement of ≥40mg of diazepam administered within one hour. Use of adjunct agents, such as propofol, may be beneficial to minimize BZD adverse effects and improve symptom control. While limited evidence suggests propofol as an effective adjunct in AWS through improved sedation, evidence is currently lacking for the addition of only propofol to BZDs for management of RAW.
  
  
  METHODS
  Retrospective review of adult patients from January, 2009 to March, 2012 with RAW. Patients were categorized into BZD dose-escalation only or BZD plus propofol. The primary endpoint was time to resolution of AWS. Secondary endpoints included safety outcomes associated with medication use.
  
  
  RESULTS
  Of 1083 patients with severe AWS, 66 RAW patients (n=33 BZD only, n=33 BZD plus propofol) met inclusion. Median time to AWS resolution was 5.0 and 7.0 days for BZD only vs. BZD plus propofol (p=0.025). Duration of mechanical ventilation, ICU and hospital length of stay were significantly higher with propofol (p=0.017, <0.001 and <0.001, respectively). Ten patients required intervention for management of propofol-induced adverse reactions.
  
  
  CONCLUSIONS
  The addition of propofol for RAW treatment is associated with significant increases in clinical care. While randomized, prospective evaluations are necessary to determine the cause of this association, our data suggests use of adjunctive propofol therapy in RAW is associated with longer and more complicated hospital admissions.
authors.affiliation: Department of Pharmacy, UPMC Presbyterian, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Wong
authors.affiliation: Department of Pharmacy, UPMC Presbyterian, 200 Lothrop Street, Pittsburgh, PA 15213, USA; Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, 3501 Terrace Street, Pittsburgh, PA 15213, USA.
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Benedict
authors.affiliation: Department of Pharmacy, UPMC Passavant, 9100 Babcock Boulevard, Pittsburgh, PA 15237, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Lohr
authors.affiliation: Department of Emergency Medicine, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15213, USA; Division of Medical Toxicology, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15213, USA.
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Pizon
authors.affiliation: Department of Pharmacy, UPMC Presbyterian, 200 Lothrop Street, Pittsburgh, PA 15213, USA; Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, 3501 Terrace Street, Pittsburgh, PA 15213, USA. Electronic address: slk54@pitt.edu.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Kane-Gill
mesh_terms: D000328:Adult; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D003975:Diazepam / Q000009:adverse effects / Q000627:therapeutic use*; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods*; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015742:Propofol / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
chemical_list: D001569:Benzodiazepines; D000431:Ethanol; D003975:Diazepam; D015742:Propofol
keywords: Alcohol withdrawal; Benzodiazepines; Propofol; Resistant alcohol withdrawal; Severe alcohol withdrawal