title: Nitrous oxide may not increase the risk of cancer recurrence after colorectal surgery: a follow-up of a randomized controlled trial.
abstract: BACKGROUND
  Even the best cancer surgery is usually associated with minimal residual disease. Whether these remaining malignant cells develop into clinical recurrence is at least partially determined by adequacy of host defense, especially natural killer cell function. Anesthetics impair immune defenses to varying degrees, but nitrous oxide appears to be especially problematic. We therefore tested the hypothesis that colorectal-cancer recurrence risk is augmented by nitrous oxide administration during colorectal surgery.
  
  
  METHODS
  We conducted a 4- to 8-year follow-up of 204 patients with colorectal cancer who were randomly assigned to 65% nitrous oxide (n = 97) or nitrogen (n = 107), balanced with isoflurane and remifentanil. The primary outcome was the time to cancer recurrence. Our primary analysis was a multivariable Cox-proportional-hazards regression model that included relevant baseline variables. In addition to treatment group, the model considered patient age, tumor grade, dissemination, adjacent organ invasion, vessel invasion, and the number of nodes involved. The study had 80% power to detect a 56% or greater reduction in recurrence rates (i.e., hazard ratio of 0.44 or less) at the 0.05 significance level.
  
  
  RESULTS
  After adjusting for significant baseline covariables, risk of recurrence did not differ significantly for nitrous oxide and nitrogen, with a hazard ratio estimate (95% CI) of 1.10 (0.66, 1.83), P = 0.72. No two-way interactions with the treatment were statistically significant.
  
  
  CONCLUSIONS
  Colorectal-cancer recurrence risks were not greatly different in patients who were randomly assigned to 65% nitrous oxide or nitrogen during surgery. Our results may not support avoiding nitrous oxide use to prevent recurrence of colorectal cancer.
  
  
  CONCLUSIONS
  The risk of colorectal cancer recurrence was similar in patients who were randomly assigned to 65% nitrous oxide or nitrogen during colorectal surgery.
  
  
  BACKGROUND
  Current Controlled Clinical Trials NCT00781352 http://www.clinicaltrials.gov.
authors.affiliation: Outcomes Research, The Cleveland Clinic, Cleveland, Ohio, USA. DS@OR.org.
authors.forename: Edith
authors.initials: E
authors.lastname: Fleischmann
authors.forename: Corinna
authors.initials: C
authors.lastname: Marschalek
authors.forename: Katja
authors.initials: K
authors.lastname: Schlemitz
authors.forename: Jarrod E
authors.initials: JE
authors.lastname: Dalton
authors.forename: Thomas
authors.initials: T
authors.lastname: Gruenberger
authors.forename: Friedrich
authors.initials: F
authors.lastname: Herbst
authors.forename: Andrea
authors.initials: A
authors.lastname: Kurz
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Sessler