BACKGROUND: General anaesthesia is usually associated with unconsciousness. 'Awareness' is when patients have postoperative recall of events or experiences during surgery. 'Wakefulness' is when patients become conscious during surgery, but have no postoperative recollection of the period of consciousness. OBJECTIVES: To evaluate the efficacy of two types of anaesthetic interventions in reducing clinically significant awareness: - anaesthetic drug regimens; and - intraoperative anaesthetic depth monitors. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, ISSUE 4 2016); PubMed from 1950 to April 2016; MEDLINE from 1950 to April 2016; and Embase from 1980 to April 2016. We contacted experts to identify additional studies. We performed a handsearch of the citations in the review. We did not search trial registries. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of either anaesthetic regimens or anaesthetic depth monitors. We excluded volunteer studies, studies of patients prior to skin incision, intensive care unit studies, and studies that only randomized different word presentations for memory tests (not anaesthetic interventions). Anaesthetic drug regimens included studies of induction or maintenance, or both. Anaesthetic depth monitors included the Bispectral Index monitor, M-Entropy, Narcotrend monitor, cerebral function monitor, cerebral state monitor, patient state index, and lower oesophageal contractility monitor. The use of anaesthetic depth monitors allows the titration of anaesthetic drugs to maintain unconsciousness. DATA COLLECTION AND ANALYSIS: At least two authors independently scanned abstracts, extracted data from the studies, and evaluated studies for risk of bias. We made attempts to contact all authors for additional clarification. We performed meta-analysis statistics in packages of the R language. MAIN RESULTS: We included 160 studies with 54,109 enrolled participants; 53,713 participants started the studies and 50,034 completed the studies or data analysis (or both). We could not use 115 RCTs in meta-analytic comparisons because they had zero awareness events. We did not merge 27 of the remaining 45 studies because they had excessive clinical and methodological heterogeneity. We pooled the remaining 18 eligible RCTs in meta-analysis. There are 10 studies awaiting classification which we will process when we update the review. The meta-analyses included 18 trials with 36,034 participants. In the analysis of anaesthetic depth monitoring (either Bispectral Index or M-entropy) versus standard clinical and electronic monitoring, there were nine trials with 34,744 participants. The overall event rate was 0.5%. The effect favoured neither anaesthetic depth monitoring nor standard clinical and electronic monitoring, with little precision in the odds ratio (OR) estimate (OR 0.98, 95% confidence interval (CI) 0.59 to 1.62). In a five-study subset of Bispectral Index monitoring versus standard clinical and electronic monitoring, with 34,181 participants, 503 participants gave awareness reports to a blinded, expert panel who adjudicated or judged the outcome for each patient after reviewing the questionnaires: no awareness, possible awareness, or definite awareness. Experts judged 351 patient awareness reports to have no awareness, 87 to have possible awareness, and 65 to have definite awareness. The effect size favoured neither Bispectral Index monitoring nor standard clinical and electronic monitoring, with little precision in the OR estimate for the combination of definite and possible awareness (OR 0.96, 95% CI 0.35 to 2.65). The effect size favoured Bispectral Index monitoring for definite awareness, but with little precision in the OR estimate (OR 0.60, 95% CI 0.13 to 2.75). We performed three smaller meta-analyses of anaesthetic drugs. There were nine studies with 1290 participants. Wakefulness was reduced by ketamine and etomidate compared to thiopental. Wakefulness was more frequent than awareness. Benzodiazepines reduces awareness compared to thiopental, ketamine, and placebo., Also, higher doses of inhaled anaesthetics versus lower doses reduced the risk of awareness. We graded the quality of the evidence as low or very low in the 'Summary of findings' tables for the five comparisons. Most of the secondary outcomes in this review were not reported in the included RCTs. AUTHORS' CONCLUSIONS: Anaesthetic depth monitors may have similar effects to standard clinical and electrical monitoring on the risk of awareness during surgery. In older studies comparing anaesthetics in a smaller portion of the patient sample, wakefulness occurred more frequently than awareness. Use of etomidate and ketamine lowered the risk of wakefulness compared to thiopental. Benzodiazepines compared to thiopental and ketamine, or higher doses of inhaled anaesthetics versus lower doses, reduced the risk of awareness. PLAIN LANGUAGE SUMMARY: Methods to prevent people waking during surgery and remembering surgical events KEY QUESTION: We reviewed the evidence about the use of devices to adjust the amount of drugs given during anaesthesia to prevent premature waking up. We also reviewed the evidence about the choice of drugs used during anaesthesia to prevent premature waking up. BACKGROUND: Anaesthesia is the use of drugs to render a patient unconscious for painful procedures and surgery. Being anaesthetized is not the same as being asleep. Someone sleeping may be easily awakened. Someone anaesthetized should only be allowed to awake when the surgery or procedure is completed. A very small percentage of patients may wake up during anaesthesia and surgery; this is called wakefulness. Patients usually do not remember being awake after emerging from anaesthesia. However, an even smaller percentage of patients do remember or recall events from surgery afterwards. This memory is called an awareness event. If that memory is distressing, it can impair the individual's quality of life. New devices known as anaesthetic depth monitors are being used to monitor the patient's brainwave response to anaesthetic drugs. Anaesthetic depth monitors have been compared to the usual clinical observations (e.g. fast heart rate, tearing, movement, etc.) during surgery to adjust the amount of drugs given and reduce the risk of wakefulness and awareness. Anaesthetic drugs have many different effects on brain function. Some drugs are used alone as the sole anaesthetic. Other drugs have insufficient effect to be used as a sole anaesthetic, but are used in combination with more powerful drugs. Drugs may have different risks of the patient waking up prematurely. SEARCH DATE: The evidence is current to April 2016. STUDY CHARACTERISTICS: We found 160 randomized controlled trials with 54,109 participants. Eighteen studies with 36,034 participants contributed evidence about devices and drugs to prevent premature waking up during surgery. Nine studies compared anaesthetic depth monitoring versus other methods to adjust drugs. Nine studies compared different drugs. There are 10 studies awaiting classification, which we will process when we update the review. KEY RESULTS: In the largest studies of anaesthetic depth monitors (five studies with 31,181 participants) there were 152 participants with possible or definite awareness (recall of surgery events after surgery). The use of anaesthetic depth monitors to adjust drugs during anaesthesia may have similar effects on the risk of awareness when compared with standard clinical and electrical monitoring. Wakefulness is reduced by ketamine and etomidate compared to thiopental. Benzodiazepines reduces awareness compared to thiopental, ketamine, and placebo. Also higher doses of inhaled anaesthetics versus lower doses reduced the risk of awareness. QUALITY OF EVIDENCE: The quality of the evidence was low or very low because the studies the results were not similar across studies, and there were not enough data.

Psychological sequelae&Light anaesthesiaExplicit and implicit memory have been associated with patients who had been exposed to light levels of anesthesia during their surgical procedure. Expert views regarding the definition of these forms of memory as well as consciousness and post-traumatic stress syndrome (PTSD) are discussed.Cardiovascular Function & PathologiesTwo charts that describe the impact of anesthetic techniques on a normal and abnormal cardiovascular system.PTSD Diagnostic CriteriaVeterans administration hospital system summarizes the changes in the criteria used to diagnose post-traumatic stress syndrome (PTSD) between DSM IV and V.Wakefulness endnote 2014 annotateAnnotated endnote based literature review summary with each papers abstract that used the response to command (wakefulness) method from 1979 through 2014.Refinement of Sebel classification systemA brief description of the clinical context in which Dr Sebel and colleagues published their classification system in 2004.Sample size N=160A summation of each of the 160 RCT studies participants who were enrolled, recruited (started study) and completed each study and dropouts.Sample size NLanguageA list of the written language that each of the 160 included RCTs used.language.xlsxsurgical riskWe have based the classification of surgical risk in the document on a review of the current literature on risk and the number of base units in the chart in the document that is based on the perceived complexity of each procedure listed.primary.secondary.outcomeThis document lists the primary and secondary outcomes studied in each of the 160 included RCTs.NomenclatureThis paper describes the range of descriptors of anesthetic techniques.ROB.resultsThe grade for each of the seven risk of bias domain for the 160 included RCTs are listed.Excluded RCTs.315.xlsxReasons for excluding RCTs from the review.Continents.countriesA list of the countries associated with each included RCTs.Anesthesia Techniques.xlsxDifferent IV techniques were compared to IV techniques and volatile techniques and other techniques. Inadequate anesthesia protocol are summarized from some of the RCTs.MR.useThe use of muscle relaxants (MRs) or neuromuscular blockade (NMBs) within each of the 160 included RCTs.ADM all types A description of the types of anesthesia depth monitors (ADM) that were processed EEGs and auditory evoked potential (EVP) used in the included RCTs.Classification.Wang.Messina.Ward.gradeThe classification system that tracks patients level of consciousness during anesthesia and surgery. Grades 0 to 5 were assigned to each of the 160 included RCTs.patient awareness reports.xlsxPatient awareness reports submitted to the investigators in some of the RCTs studies and organized according to the classification of experts into possible and definite awareness.wakeful v wakeful.aware v wakefulAn analysis of the relationship between wakefulness and awareness.Thiopental studiesA literature review of recently published papers using thiopental as part of the anesthetic technique.RCTs not used in comparisons.xlsxA description of the RCTs not merged in the five comparisons.Quality of the evidence.docxExperts state that authors need to provide more specific information in order to properly grade the seven risk of bias domains.ACE130 reviewer#1.defense RCT merge criteria.summary.docxThe first of two documents of an edited version of peer reviewer #1's comments regarding the content of this review with our responses. These responses were revised since the original authors’ response. The focus of the first document is a summary of the more detailed second document which analyzes the strengths and weakness of the criteria used to merge the RCTs in the five comparisons of this review.ACE 130 reviewer#1. defense RCT merge criteria.summary.docxACE 130 reviewer#1.defense RCT merge criteria.details.docxA more detailed analysis of our response to peer reviewer #1 as described in the previous document.ACE 130 Peer reviewer.#2.docxOur responses to peer reviewer #2 discussed topics such as explicit and implicit memory, peri-operative dreams, PTSD, amongst other topics.ACE 130 reviewer #2.MWa response.classification table.docxAn analysis by the expert peer reviewer #2 and expert coauthor, MaW, of our classification system.ACE 130 reviewer #2.MWa response.classification table .docxACE 130 reviewer #3 peer review.docxA discussion of the definition of consciousness, wakefulness, implicit memory and awareness. There are discussions of IV techniques and IFT and the relevance the table in Cardiovascular Function & Pathologies called Effects of Anesthetic Drugs on Cardiovascular Function.Potential biases in the review processThe following concepts are discussed: impact of muscle relaxant use on the frequency of awareness, light anesthesia techniques, movement as spinal cord reflex, TEE and vasoactive drug use in the peri-operative period.