title: Nitrous oxide-based versus nitrous oxide-free general anaesthesia and accidental awareness during general anaesthesia in surgical patients.
abstract: BACKGROUND
  Accidental awareness during general anaesthesia (AAGA) is when a patient unintentionally becomes conscious during a procedure performed with general anaesthesia and subsequently has explicit recall of this event. Incidence estimates for AAGA vary, with the most common estimate being one to two cases per 1000 general anaesthetics. Evidence linking nitrous oxide use and an increased risk of AAGA has come from observational studies data but the literature is contradictory, with some studies finding a protective effect of nitrous oxide.
  
  
  OBJECTIVE
  To assess the effect of general anaesthesia including nitrous oxide on the risk of AAGA in patients aged five years and over.
  
  
  METHODS
  We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and trial registers ((www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (www.who.int/ictrp/network/en/) and Current Controlled Trials (www.isrctn.com/)) for eligible studies on December 9 2015. In addition, we conducted forward and backward citation searching using key identified papers.
  
  
  METHODS
  We considered all randomized controlled trials (RCTs), including quasi-randomized studies and cluster-randomized studies, of participants aged five years or older receiving general anaesthesia for any type of surgery.We included trials in which participants receiving general anaesthesia that included nitrous oxide for maintenance at a concentration of at least 30% were compared with participants receiving no nitrous oxide during general anaesthesia. The intervention group must have received nitrous oxide in conjunction with an additional anaesthetic. We excluded studies where the depth of anaesthesia differed between the study arms. For inclusion in the review, studies needed to state in their methods that they planned to assess AAGA. We defined this as when a patient becomes conscious during a procedure performed with general anaesthesia and subsequently has explicit recall of this event.
  
  
  METHODS
  We used standard methodological procedures expected by Cochrane to identify studies. We extracted data and conducted 'Risk of bias' assessment using the Covidence database.
  
  
  RESULTS
  We included 15 studies. The total number of participants included in the analyses was 3520. Most studies were small with fewer than 120 participants, although two larger studies with 2012 and 671 participants were included. There was considerable variation in many of the study characteristics, including the anaesthetics used. The concentrations of nitrous oxide varied between 50% and 70%, and half of the studies used clinical signs and haemodynamic changes to monitor depth of anaesthesia.As it was not possible to blind the anaesthetist to the anaesthetic used, we rated all studies at high risk of performance bias and we therefore downgraded the quality of evidence by one level for risk of bias using the GRADE approach. Other types of bias were generally low, or were rated unclear due to missing information.No studies were designed to measure AAGA as the primary outcome, and were therefore statistically underpowered to answer this review question. Despite the inclusion of 3520 participants, only three awareness events were reported by two studies. In one study the event was due to technical failure. Due to the rarity of the events, we did not consider it appropriate to pool the data, and we therefore downgraded the quality of evidence by a further level for imprecision using GRADE.
  
  
  CONCLUSIONS
  It is not possible to draw any conclusions from this review. The included studies were mainly small (fewer than 120 participants) and there were limited estimates of effect, with only two studies reporting any events. We cannot therefore determine whether the use of nitrous oxide in general anaesthesia increases, decreases or has no effect on the risk of accidental awareness.
authors: Liverpool Reviews and Implementation Group, University of Liverpool, Sherrington Building, Ashton Street, Liverpool, UK, L69 3GE.
authors: Juliet
authors: J
authors: Hounsome
authors: Amanda
authors: A
authors: Nicholson
authors: Janette
authors: J
authors: Greenhalgh
authors: Tim M
authors: TM
authors: Cook
authors: Andrew F
authors: AF
authors: Smith
authors: Sharon R
authors: SR
authors: Lewis
mesh_terms: D000328:Adult; D000768:Anesthesia, General; D018685:Anesthetics, Inhalation; D002648:Child; D006801:Humans; D058926:Intraoperative Awareness; D011939:Mental Recall; D008875:Middle Aged; D009609:Nitrous Oxide; D016032:Randomized Controlled Trials as Topic; D013514:Surgical Procedures, Operative
chemical_list: D018685:Anesthetics, Inhalation; D009609:Nitrous Oxide