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. 2016 Aug 10;2016(8):CD011052.
doi: 10.1002/14651858.CD011052.pub2.

Nitrous oxide-based versus nitrous oxide-free general anaesthesia and accidental awareness during general anaesthesia in surgical patients

Juliet Hounsome  1 , Amanda Nicholson, Janette Greenhalgh, Tim M Cook, Andrew F Smith, Sharon R Lewis
Affiliations

Nitrous oxide-based versus nitrous oxide-free general anaesthesia and accidental awareness during general anaesthesia in surgical patients

Juliet Hounsome et al. Cochrane Database Syst Rev. .

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.

Objectives: To assess the effect of general anaesthesia including nitrous oxide on the risk of AAGA in patients aged five years and over.

Search 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.

Selection criteria: 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.

Data collection and analysis: We used standard methodological procedures expected by Cochrane to identify studies. We extracted data and conducted 'Risk of bias' assessment using the Covidence database.

Main 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.

Authors' 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.

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Conflict of interest statement

Juliet Hockenhull: none known

Amanda Nicholson: from March to August 2011, AN worked for the Cardiff Research Consortium, which provided research and consultancy services to the pharmaceutical industry. Cardiff Research Consortium has no connection with AN's work with Cochrane. AN's husband has small direct holdings in several drug and biotech companies as part of a wider balanced share portfolio. All AN's contributions to this review were prior to her work with Q Medical Technologies Limited, she conducted the work on this review whilst employed by Liverpool University.

From June 2015 AN has worked for Q Medical Technologies Limited, a firm which markets and distributes a range of medical devices. Q Medical Technologies do not sell any products that promote, or are specific to, nitrous‐oxide based anaesthesia. See Sources of support.

Janette Greenhalgh: none known

Tim M Cook: none known.

Sharon R Lewis: none known.

Andrew F Smith: none known.

Figures

1
1
Study flow diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Nitrous oxide ‐free vs Nitrous oxide‐based, Outcome 1 Accidental awareness.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD011052

References

References to studies included in this review

Aceto 2002 {published data only}
    1. Aceto P, Valente A, Adducci E, Gorgoglione M, Cosmo G. Implicit memory, dream and auditory evoked responses during anaesthesia. Acta Medica Romana 2002;40(1):21‐9.
    1. Aceto P, Valente A, Gorgoglione M, Adducci E, Cosmo G. Relationship between awareness and middle latency auditory evoked responses during surgical anaesthesia. British Journal of Anaesthesia 2003;90(5):630‐5. [PUBMED: 12697591] - PubMed
Albertin 2005 {published data only}
    1. Albertin A, Casati A, Bergonzi PC, Moizo E, Lombardo F Torri G. The effect of adding nitrous oxide on MAC of sevoflurane combined with two target‐controlled concentrations of remifentanil in women. European Journal of Anaesthesiology 2005;22(6):431‐7. [PUBMED: 15991505] - PubMed
Arellano 2000 {published data only}
    1. Arellano RJ, Pole ML, Rafuse SE, Fletcher M, Saad YG, Friedlander M, et al. Omission of nitrous oxide from a propofol‐based anesthetic does not affect the recovery of women undergoing outpatient gynecologic surgery. Anesthesiology 2000;93(2):332‐9. [PUBMED: 10910478] - PubMed
Crawford 1998 {published data only}
    1. Crawford MW, Lerman J, Sloan MH, Sikich N, Halpern L, Bissonnette B. Recovery characteristics of propofol anaesthesia, with and without nitrous oxide: a comparison with halothane/nitrous oxide anaesthesia in children. Paediatric Anaesthesia 1998;8(1):49‐54. [PUBMED: 9483598] - PubMed
Dedola 2008 {published data only}
    1. Dedola E, Albertin A, Poli D, Colla L, Gandolfi A, Martani C, et al. Effect of nitrous oxide on desflurane MACBAR at two target‐controlled concentrations of remifentanil. Minerva Anestesiologica 2008;74(5):165‐72. [PUBMED: 18414359] - PubMed
ENIGMA {published data only}
    1. Chan MT, Gin T. Perioperative outcome after nitrous oxide anaesthesia: an ENIGMA trial. Hong Kong Medical Journal 2014;20(S3):S34‐5. [PUBMED: 25001034] - PubMed
    1. Graham AM, Myles PS, Leslie K, Chan MTV, Paech MJ, Peyton P, et al. A cost‐benefit analysis of the ENIGMA Trial. Anesthesiology 2011;115(2):265‐72. [PUBMED: 21681081] - PubMed
    1. Leslie K, Myles PS, Chan MTV, Forbes A, Paech MJ, Peyton P, et al. Nitrous oxide and long‐term morbidity and mortality in the ENIGMA trial. Anesthesia and Analgesia 2011;112(2):387‐93. [PUBMED: 20861416] - PubMed
    1. Leslie K, Myles PS, Chan MTV, Paech MJ, Peyton P, Forbes A, et al. Risk factors for severe postoperative nausea and vomiting in a randomized trial of nitrous oxide‐based vs nitrous oxide‐free anaesthesia. British Journal of Anaesthesia 2008;101:498‐505. [PUBMED: 18682411] - PubMed
    1. Myles PS, Chan MT, Leslie K, Peyton, P, Paech M, Forbes AA. Effect of nitrous oxide on plasma homocysteine and folate in patients undergoing major surgery. British Journal of Anaesthesia 2008;100(6):780‐6. [DOI: ; PUBMED: 18400808] - PubMed
Girardi 1994 {published data only}
    1. Girardi G, Rossi R, Cellai MP, Pieraccioli E, Novelli GP. Anesthesia with isoflurane in air and with isoflurane and nitrous oxide [Italian]. Minerva Anestesiologica 1994;60:321‐8. [PUBMED: 7984314] - PubMed
Handa 2010 {published data only}
    1. Handa T, Koike S, Kohkita Y, Ihara Y, Fukuda KI, Ichinohe T, et al. Frequency and content of dreams during propofol anesthesia in patients undergoing mandibular sagittal split ramus osteotomy. [Japanese]. Journal of Japanese Dental Society of Anesthesiology 2010;38(1):29‐34.
Handa Tsutsui 2007 {published data only}
    1. Handa‐Tsutsui F, Kodaka M. Effect of nitrous oxide on propofol requirement during target‐controlled infusion for oocyte retrieval. International Journal of Obstetric Anesthesia 2007;16(1):13‐6. [PUBMED: 17125991] - PubMed
Heath 1996 {published data only}
    1. Heath KJ, Sadler P, Winn J H, McFadzean WA. Nitrous oxide reduces the cost of intravenous anaesthesia. European Journal of Anaesthesiology 1996;13(4):369‐72. [PUBMED: 8842658] - PubMed
Lindekaer 1995 {published data only}
    1. Lindekaer AL, Skielboe M, Guldager H, Jensen EW. The influence of nitrous oxide on propofol dosage and recovery after total intravenous anaesthesia for day‐case surgery. Anaesthesia 1995;50(5):397‐9. [PUBMED: 7793542] - PubMed
Ngan Kee 2002 {published data only}
    1. Ngan Kee WD, Khaw KS, Ma KC, Wong ASY, Lee BB. Randomized, double‐blind comparison of different inspired oxygen fractions during general anaesthesia for Caesarean section. British Journal of Anaesthesia 2002;89(4):556‐61. [PUBMED: 12393355] - PubMed
Singh 2011 {published data only}
    1. Singh GP, Prabhakar H, Bithal PK, Dash HH. A comparative evaluation of nitrous oxide‐isoflurane vs isoflurane anesthesia in patients undergoing craniotomy for supratentorial tumors: A preliminary study. Neurology India 2011;59(1):18‐24. [PUBMED: 21339653] - PubMed
Sukhani 1994 {published data only}
    1. Sukhani R, Lurie J, Jabamoni R. Propofol for ambulatory gynecologic laparoscopy: Does omission of nitrous oxide alter postoperative emetic sequelae and recovery?. Anesthesia and Analgesia 1994;78(5):831‐5. [PUBMED: 8160978] - PubMed
Vanacker 1999 {published data only}
    1. Vanacker B. Comparative study of the effect of desflurane with nitrous oxide vs desflurane without nitrous oxide on postoperative nausea and vomiting in female patients undergoing breast surgery [abstract]. British Journal of Anaesthesia 1998;80 Suppl 1:134.
    1. Vanacker BF. The impact of nitrous oxide on postoperative nausea and vomiting after desflurane anesthesia for breast surgery. Acta Anaesthesiologica Belgica 1999;50(2):77‐81. [PUBMED: 10418646] - PubMed

References to studies excluded from this review

Chowdhury 2014 {published data only}
    1. Chowdhury T, Prabhakar H, Bithal P K, Schaller B, Dash H H. Early cognitive decline in pituitary surgery: Is nitrous oxide the culprit?. Future Neurology 2014;9:579‐85.
    1. Chowdhury T, Prabhakar H, Kumar Bithal P, Dash HH. To assess the effects of two anesthetic techniques (with and without nitrous oxide) on cognitive function in patients undergoing transsphenoidal pituitary surgery. Journal of Neurosurgical Anesthesiology 2011;23(4):436.
ENIGMA‐II {published data only}
    1. Leslie K, Myles PS, Kasza J, Forbes A, Peyton PJ, Chan MTV, et al. Nitrous oxide and serious long‐term morbidity and mortality in the evaluation of nitrous oxide in the gas mixture for anaesthesia (ENIGMA)‐II trial. Anesthesiology 2015;123(6):1267‐80. [PUBMED: 26501387] - PubMed
    1. Myles PS, Leslie K, Chan MT, Forbes A, Peyton PJ, Paech MJ, et al. The safety of addition of nitrous oxide to general anaesthesia in at‐risk patients having major non‐cardiac surgery (ENIGMA‐II): a randomised, single‐blind trial. Lancet 2014;384(9952):1446‐54. [PUBMED: 25142708] - PubMed
Goto 1997 {published data only}
    1. Goto T, Saito H, Shinkai M, Nakata Y, Ichinose F, Morita S. Xenon provides faster emergence from anesthesia than does nitrous oxide‐ sevoflurane or nitrous oxide‐isoflurane. Anesthesiology 1997;86(6):1273‐8. [PUBMED: 9197295] - PubMed
Goto 1997a {published data only}
    1. GotoT, Saito H, Nakata Y, Uezono S, Ichinose F, Morita S. Emergence times from xenon anaesthesia are independent of the duration of anaesthesia. British Journal of Anaesthesia 1997;79(5):595‐9. [PUBMED: 9422897] - PubMed
Inada 1999 {published data only}
    1. Inada T, Shingu K, Nakao S, Nagata A. Effects of nitrous oxide on haemodynamic and electroencephalographic responses induced by tetanic electrical stimulation during propofol anaesthesia. Anaesthesia 1999;54(5):423‐6. [PUBMED: 10995137] - PubMed
Kang 2013 {published data only}
    1. Kang DH, Lee SH, Kim SJ, Choi JI, Jeong CW, Jeong SW, et al. Anesthetic requirements and stress hormone responses in chronic spinal cord‐injured patients undergoing surgery below the level of injury: nitrous oxide vs remifentanil. Korean Journal of Anesthesiology 2013;65(6):531‐8. [DOI: 10.4097/kjae.2013.65.6.531; PUBMED: 24427459] - DOI - PMC - PubMed
Liu 2014 {published data only}
    1. Liu N, Guen M, Boichut N, Genty A, Herail T, Schmartz D, et al. Nitrous oxide does not produce a clinically important sparing effect during closed‐loop delivered propofol‐remifentanil anaesthesia guided by the bispectral index: a randomized multicentre study. British Journal of Anaesthesia 2014;112(5):842‐51. [DOI: 10.1093/bja/aet479; PUBMED: 24486835] - DOI - PubMed
Luginbuhl 2005 {published data only}
    1. Luginbuhl M, Petersen‐Felix S, Zbinden AM, Schnider TW. Xenon does not reduce opioid requirement for orthopedic surgery. Canadian Journal of Anesthesia 2005;52(1):38‐44. [PUBMED: 15625254] - PubMed
Nakata 1999 {published data only}
    1. Nakata Y, Goto T, Ishiguro Y, Terui K, Niimi Y, Morita S. Xenon suppresses the hypnotic arousal in response to surgical stimulation. Journal of Clinical Anesthesia 1999;11(4):305‐9. [PUBMED: 10470632 ] - PubMed
Ochiai 1999 {published data only}
    1. Ochiai N, Tashiro C, Okutani R, Murakawa K, Kinouchi K, Kitamura S. Improved oxygen delivery to the fetus during cesarean section under sevoflurane anesthesia with 100% oxygen. Journal of Anesthesia 1999;13(2):65‐70. [PUBMED: 14530942] - PubMed
Rocca 2000 {published data only}
    1. Rocca G, Montecchi C, Baisi F, Monaco S, Romboli D, Gasparetto A. N2O‐free sevoflurane anesthesia. Clinical evaluation. [Italian]. Minerva Anestesiologica 2000;66(9):611‐9. [PUBMED: 11070960] - PubMed
Ropcke 2001 {published data only}
    1. Ropcke H, Wirz S, Bouillon T, Bruhn J, Hoeft A. Pharmacodynamic interaction of nitrous oxide with sevoflurane, desflurane, isoflurane and enflurane in surgical patients: measurements by effects on EEG median power frequency. European Journal of Anaesthesiology 2001;18(7):440‐9. [PUBMED: 11070960] - PubMed

Additional references

Alkire 2004
    1. Alkire MT, Gorski LA. Relative amnesic potency of five inhalational anesthetics follows the Meyer‐Overton rule. Anesthesiology 2004;101(2):417‐29. [PUBMED: 15277925] - PubMed
ASA 2006
    1. American Society of Anesthesiologists Task Force on Intraoperative Awareness. Practice advisory for intraoperative awareness and brain function monitoring. Anesthesiology 2006;104(4):847‐64. [PUBMED: 16571982] - PubMed
Avidan 2008
    1. Avidan MS, Zhang L, Burnside BA, Finkel KJ, Searleman AC, Selvidge JA, et al. Anesthesia awareness and the bispectral index. The New England Journal of Medicine 2008; Vol. 358, issue 11:1097‐108. [PUBMED: 18337600] - PubMed
Avidan 2011
    1. Avidan MS, Jacobsohn E, Glick D, Burnside BA, Zhang L, Villafranca A, et al. Prevention of intraoperative awareness in a high‐risk surgical population. The New England Journal of Medicine 2011;365(7):591‐600. [PUBMED: 21848460] - PubMed
Brice 1970
    1. Brice DD, Hetherington RR, Utting JE. A simple study of awareness and dreaming during anaesthesia. British Journal of Anaesthesia 1970; Vol. 42, issue 6:535‐42. [PUBMED: 5423844] - PubMed
Cook 2008
    1. Cook TM. Anesthesia awareness and the bispectral index. The New England Journal of Medicine 2008;359(4):430; author reply 430‐1. [PUBMED: 18655251] - PubMed
Covidence [Computer program]
    1. Covidence. www.covidence.org. Covidence, 2014.
Davidson 2011
    1. Davidson AJ, Smith KR, Blusse van Oud‐Alblas HJ, Lopez U, Malviya S, Bannister CF, et al. Awareness in children: a secondary analysis of five cohort studies. Anaesthesia 2011;66(6):446‐54. [PUBMED: 21501128] - PubMed
De Vasconcellos 2013
    1. Vasconcellos K, Sneyd JR. Nitrous oxide: are we still in equipoise? A qualitative review of current controversies. British Journal of Anaesthesia 2013;111(6):877‐85. [PUBMED: 23801743] - PubMed
Egger 1997
    1. Egger M, Smith GD, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ 1997;315:629‐634. - PMC - PubMed
Errando 2008
    1. Errando CL, Sigl JC, Robles M, Calabuig E, Garcia J, Arocas F, et al. Awareness with recall during general anaesthesia: a prospective observational evaluation of 4001 patients. British Journal of Anaesthesia 2008;101(2):178‐85. [PUBMED: 18515816] - PubMed
Ghoneim 2009
    1. Ghoneim MM, Block RI, Haffarnan M, Mathews MJ. Awareness during anesthesia: risk factors, causes and sequelae: a review of reported cases in the literature. Anesthesia and Analgesia 2009;108(2):527‐35. [PUBMED: 19151283] - PubMed
Guyatt 2008
    1. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck‐Ytter Y, Schünemann HJ. What is “quality of evidence” and why is it important to clinicians?. BMJ 2008;336(7651):995‐8. [PUBMED: 18456631] - PMC - PubMed
Higgins 2011a
    1. Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928. [PUBMED: 22008217] - PMC - PubMed
Higgins 2011b
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Hopkins 2005
    1. Hopkins PM. Nitrous oxide: a unique drug of continuing importance for anaesthesia. Best Practice & Research. Clinical Anaesthesiology 2005;19(3):381‐9. [PUBMED: 16013688] - PubMed
Imberger 2014
    1. Imberger G, Orr A, Thorlund K, Wetterslev J, Myles P, Möller AM. Does anaesthesia with nitrous oxide affect mortality or cardiovascular morbidity? A systematic review with meta‐analysis and trial sequential analysis. British Journal of Anaesthesiology 2014; Vol. 112, issue 3:410‐26. [PUBMED: 24408738] - PubMed
Isik 2007
    1. Isik B, Tuzuner T, Tezkirecioglu M, Oztas N. Nitrous oxide sedation and bispectral index. European Journal of Dentistry 2007;1(4):240‐5. [PUBMED: 19212474] - PMC - PubMed
Lampe 1990
    1. Lampe GH, Wauk LZ, Donegan JH, Pitts LH, Jackler RK, Litt LL, et al. Effect on outcome of prolonged exposure of patients to nitrous oxide. Anesthesia and Analgesia 1990;71(6):586‐90. [PUBMED: 2240628] - PubMed
Lennmarken 2002
    1. Lennmarken C, Bildfors K, Enlund G, Samuelsson P, Sandin R. Victims of awareness. Acta Anaesthesiologica Scandinavica 2002;46(3):229‐31. [PUBMED: 11939910] - PubMed
Leslie 2010
    1. Leslie K, Chan MT, Myles PS, Forbes A, McCulloch TJ. Posttraumatic stress disorder in aware patients from the B‐aware trial. Anesthesia and Analgesia 2010;110(3):823‐8. [PUBMED: 19861364] - PubMed
Leslie 2011
    1. Leslie K, Myles PS, Chan MT, Forbes A, Paech MJ, Peyton P, et al. Nitrous oxide and long‐term morbidity and mortality in the ENIGMA trial. Anesthesia and Analgesia 2011;112(2):387‐93. [PUBMED: 20861416] - PubMed
Leslie 2013b
    1. Leslie K, Myles P, Devereaux PJ, Forbes A, Rao‐Melancini P, Williamson E, et al. Nitrous oxide and serious morbidity and mortality in the POISE trial. Anesthesia and Analgesia 2013;116(5):1034‐40. [PUBMED: 23337413] - PubMed
Mashour 2009
    1. Mashour GA, Tremper KK, Avidan MS. Protocol for the "Michigan Awareness Control Study": A prospective, randomized, controlled trial comparing electronic alerts based on bispectral index monitoring or minimum alveolar concentration for the prevention of intraoperative awareness. BMC Anesthesiology 2009;9:7. [PUBMED: 19891771] - PMC - PubMed
Mashour 2010
    1. Mashour GA, Esaki RK, Tremper KK, Glick DB, O'Connor M, Avidan MS. A novel classification instrument for intraoperative awareness events. Anesthesia and Analgesia 2010;110(3):813‐5. [PUBMED: 19713251] - PubMed
Mashour 2011
    1. Mashour GA, Orser BA, Avidan MS. Intraoperative awareness: from neurobiology to clinical practice. Anesthesiology 2011;114(5):1218‐33. [PUBMED: 21464699] - PubMed
Mashour 2012
    1. Mashour GA, Shanks A, Tremper KK, Kheterpal S, Turner CR, Ramachandran SK, et al. Prevention of intraoperative awareness with explicit recall in an unselected surgical population: a randomized comparative effectiveness trial. Anesthesiology 2012;117(4):717‐25. [PUBMED: 22990178] - PMC - PubMed
Messina 2008
    1. Messina AG, Ward MJ, Pace NL. Anaesthetic interventions for prevention of awareness during surgery. Cochrane Database of Systematic Reviews 2008, Issue 3. [DOI: 10.1002/14651858.CD007272] - DOI - PMC - PubMed
Myles 2004
    1. Myles PS, Leslie K, McNeil J, Forbes A, Chan MT. Bispectral index monitoring to prevent awareness during anaesthesia: the B‐Aware randomised controlled trial. Lancet 2004;363(9423):1757‐63. [PUBMED: 15172773] - PubMed
Myles 2007
    1. Myles PS, Leslie K, Chan MT, Forbes A, Paech MJ, Peyton P, et al. Avoidance of nitrous oxide for patients undergoing major surgery: a randomized controlled trial. Anesthesiology 2007;107(2):221‐31. [PUBMED: 17667565] - PubMed
Myles 2014a
    1. Myles, PS, Leslie K, Chan MTV, Forbes A, Peyton PJ, Paech MJ. The safety of addition of nitrous oxide to general anaesthesia in at‐risk patients having major non‐cardiac surgery (ENIGMA‐II): a randomised, single‐blind trial. The Lancet 2014;384(9952):1446‐54. [PUBMED: 25142708] - PubMed
NICE 2012
    1. National Institute of Health and Clinical Excellence. Depth of anaesthesia monitors – Bispectral Index (BIS), E‐Entropy and Narcotrend‐Compact M [NICE diagnostics guidance 6]. www.nice.org.uk/nicemedia/live/13965/61547/61547.pdf (Accessed 13 January 2014).
Paech 2008
    1. Paech MJ, Scott KL, Clavisi O, Chua S, McDonnell N. A prospective study of awareness and recall associated with general anaesthesia for caesarean section. International Journal of Obstetric Anesthesia 2008;17(4):298‐303. [PUBMED: 18617387] - PubMed
Pandit 2013
    1. Pandit JJ, Cook TM, Jonker WR, O'Sullivan E, 5th National Audit Project of the Royal College of Anaesthetists and the Association of Anaesthetists of Great Britain and Ireland. A national survey of anaesthetists (NAP5 Baseline) to estimate an annual incidence of accidental awareness during general anaesthesia in the UK. Anaesthesia 2013; Vol. 68, issue 4:343‐53. [PUBMED: 23488832] - PubMed
Pandit 2014a
    1. Pandit JJ, Andrade J, Bogod DG, Hitchman JM, Jonker WR, Lucas N, et al. 5th National Audit Project (NAP5) on accidental awareness during general anaesthesia: protocol, methods, and analysis of data. British journal of anaesthesia 2014;113(4):540‐8. [PUBMED: 25204695] - PubMed
Pandit 2014b
    1. Pandit JJ, Andrade J, Bogod DG, Hitchman JM, Jonker WR, Lucas N, et al. 5th National Audit Project (NAP5) on accidental awareness during general anaesthesia: summary of main findings and risk factors. British Journal of Anaesthesia 2014;113(4):549‐59. [PUBMED: 25204697] - PubMed
Pollard 2007
    1. Pollard RJ, Coyle JP, Gilbert RL, Beck JE. Intraoperative awareness in a regional medical system: a review of 3 years' data. Anesthesiology 2007; Vol. 106, issue 2:269‐74. [PUBMED: 17264720] - PubMed
Punjasawadwong 2014
    1. Punjasawadwong Y, Phongchiewboon A, Bunchungmongkol N. Bispectral index for improving anaesthetic delivery and postoperative recovery. Cochrane Database of Systematic Reviews 2014, issue 6. [DOI: 10.1002/14651858.CD003843.pub3.] - DOI - PMC - PubMed
RevMan 5.3 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Rungreungvanich 2007
    1. Rungreungvanich M, Thienthong S, Charuluxananan S, Lekprasert V, Pulnitiporn A, Prakanrattana U. Predictors of intra‐operative recall of awareness: Thai Anesthesia Incidents Study (THAI Study): a case‐control study. Journal of the Medical Association of Thailand 2007;90(8):1551‐7. [PUBMED: 17926984] - PubMed
Samuelsson 2007
    1. Samuelsson P, Brudin L, Sandin RH. Late psychological symptoms after awareness among consecutively included surgical patients. Anesthesiology 2007;106(1):26‐32. [PUBMED: 17197842] - PubMed
Sanders 2010
    1. Sanders RD, Avidan MS. Evidence is lacking for interventions proposed to prevent unintended awareness during general anesthesia for cesarean delivery. Anesthesia and Analgesia 2010;110(3):972‐3; author reply 973‐4. [PUBMED: 20185675] - PubMed
Sandin 2000
    1. Sandin RH, Enlund G, Samuelsson P, Lennmarken C. Awareness during anaesthesia: a prospective case study. Lancet 2000;355(9205):707‐11. [PUBMED: 10703802] - PubMed
Schallner 2013
    1. Schallner N, Goebel U. The perioperative use of nitrous oxide: renaissance of an old gas or funeral of an ancient relict?. Current Opinion in Anaesthesiology 2013;26:354‐60. - PubMed
Sebel 2004
    1. Sebel PS, Bowdle TA, Ghoneim MM, Rampil IJ, Padilla RE, Gan TJ, et al. The incidence of awareness during anesthesia: a multicenter United States study. Anesthesia and Analgesia 2004;99(3):833‐9, table of contents. [PUBMED: 15333419] - PubMed
Sengupta 1988
    1. Sengupta P, Plantevin OM. Nitrous oxide and day‐case laparoscopy: effects on nausea, vomiting and return to normal activity. British Journal of Anaesthesia 1988;60(5):570‐3. [PUBMED: 2967712] - PubMed
Shepherd 2013
    1. Shepherd J, Jones J, Frampton G, Bryant J, Baxter L, Cooper K. Clinical effectiveness and cost‐effectiveness of depth of anaesthesia monitoring (E‐Entropy, Bispectral Index and Narcotrend): a systematic review and economic evaluation. Health Technology Assessment (Winchester, England) 2013;17(34):1‐264. [PUBMED: 23962378] - PMC - PubMed
Sun 2015
    1. Sun R, Jia WQ, Zhang P, Yang K, Tian JH, Ma B, et al. Nitrous oxide‐based techniques versus nitrous oxide‐free techniques for general anaesthesia. Cochrane Database of Systematic Reviews 2015, Issue 11. [DOI: 10.1002/14651858.CD008984.pub2; PUBMED: 26545294] - DOI - PMC - PubMed
Sury 2014
    1. Sury MJR, Palmer JH, Cook TM, Pandit JJ. The state of UK anaesthesia: a survey of National Health Service Activity in 2013. British Journal of Anaesthesia 2014;113:575‐84. [PUBMED: 26372493] - PubMed
Tramer 1996
    1. Tramer M, Moore A, McQuay H. Omitting nitrous oxide in general anaesthesia: meta‐analysis of intraoperative awareness and postoperative emesis in randomized controlled trials. British Journal of Anaesthesia 1996;76(2):186‐93. [PUBMED: 8777095] - PubMed
Turan 2013
    1. Turan A, Mascha EJ, You J, Kurz A, Shiba A, Saager L, et al. The association between nitrous oxide and postoperative mortality and morbidity after noncardiac surgery. Anesthesia and Analgesia 2013;116(5):1026‐33. [PUBMED: 22822187] - PubMed
Wennervirta 2002
    1. Wennervirta J, Ranta SO, Hynynen M. Awareness and recall in outpatient anesthesia. Anesthesia and Analgesia 2002;95(1):72‐7, table of contents. [PUBMED: 12088946] - PubMed
Wrigley 1991
    1. Wrigley SR, Fairfield JE, Jones RM, Black AE. Induction and recovery characteristics of desflurane in day case patients: a comparison with propofol. Anaesthesia 1991;46(8):615‐22. [PUBMED: 1887965] - PubMed
Zhang 2011
    1. Zhang C, Xu L, Ma YQ, Sun YX, Li YH, Zhang L, et al. Bispectral index monitoring prevent awareness during total intravenous anesthesia: a prospective, randomized, double‐blinded, multi‐center controlled trial. Chinese Medical Journal 2011;124(22):3664‐9. [PUBMED: 22340221] - PubMed

References to other published versions of this review

Nicholson 2014
    1. Nicholson A, Cook TM, Smith AF, Lewis SR. Nitrous oxide‐based versus nitrous oxide‐free general anaesthesia and accidental awareness during general anaesthesia in surgical patients. Cochrane Database of Systematic Reviews 2014, Issue 3. [DOI: 10.1002/14651858.CD011052] - DOI - PMC - PubMed

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