title: Long-term effects of and physiological responses to nitrous oxide gas treatment during alcohol withdrawal: a double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Nitrous oxide gas (N2O) has been proposed to be effective in the treatment of the alcohol withdrawal syndrome (AWS). This has not been proved, however, in studies performed according to good clinical practice guidelines. Moreover, previous studies have not measured end tidal N2O concentrations or physiologic responses during N2O treatment. We have recently reported that in a double-blind, randomized, controlled setting, N2O was not superior to placebo in relieving AWS symptoms. In this previous study, we did not find significant differences between the treatments either in the Clinical Institute Withdrawal Assessment of Alcohol scores or in the total use of benzodiazepines (diazepam and temazepam). The aim of the present study was to characterize other effects and side effects of the N2O treatment using several objective measures and to study the possible long-term efficacy of the treatment.
  
  
  METHODS
  A total of 105 inpatients who had AWS and were admitted to the A-Clinic detoxification center were included in the study. The subjects were randomly assigned to one of the following three treatments: (1) N2O/oxygen (from 30 to 70% in oxygen), (2) air/oxygen (30%/70%), and (3) medical (normal) air. During the single 45-min treatment period, end-tidal N2O, carbon dioxide, and oxygen concentrations were measured. The physiologic responses were studied by measuring heart rate, blood pressure, pulse oximetric saturation, frontal muscle electromyographic activity, and plethysmographic pulse amplitude. Long-term effects were studied by measuring craving with the Obsessive-Compulsive Drinking Scale; severity of dependency with Severity of Alcohol Dependence Data; and liver enzymes with aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase 3 and 6 months after the treatment.
  
  
  RESULTS
  Patients in the N2O group demonstrated significantly higher facial muscle electromyographic activity and higher pulse amplitude than the air-treated subjects. Self-reported side effects between the gas treatments, however, did not differ between the groups. Regarding long-term effects of the treatments, there were no differences between the groups.
  
  
  CONCLUSIONS
  Contrary to previously published data, N2O treatment did not decrease craving or liver enzymes during the 6-month follow-up. At the concentration used, N2O treatment produced signs of arousal instead of strong sedation.
authors.affiliation: National Public Health Institute, Department of Mental Health and Alcohol Research, Helsinki, Finland. hannu.alho@ktl.fi
authors.forename: Hannu
authors.initials: H
authors.lastname: Alho
authors.forename: Taina
authors.initials: T
authors.lastname: Methuen
authors.forename: Markku
authors.initials: M
authors.lastname: Paloheimo
authors.forename: Nuria
authors.initials: N
authors.lastname: Strid
authors.forename: Kaija
authors.initials: K
authors.lastname: Seppä
authors.forename: Juha
authors.initials: J
authors.lastname: Tiainen
authors.forename: Mikko
authors.initials: M
authors.lastname: Salaspuro
authors.forename: Risto
authors.initials: R
authors.lastname: Roine
mesh_terms: D000437:Alcoholism / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D016739:Behavior, Addictive / Q000097:blood / Q000188:drug therapy / Q000523:psychology; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D006801:Humans; D016014:Linear Models; D008099:Liver / Q000201:enzymology; D009609:Nitrous Oxide / Q000009:adverse effects / Q000627:therapeutic use*; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D013995:Time
chemical_list: D009609:Nitrous Oxide