Anovic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: The authors received no specific funding for this work. Competing Interests: The authors have declared that no competing interests exist.MethodsTwo authors performed independently a systematic search of English articles in PubMed and EMBASE database 1/2007-12/2015. Search order Entinostat included randomised controlled trials (RCTs), observational trials, and case reports (n>4 cases), which reported anaesthetic approach for AC and at least one of our pre-specified outcomes: intraoperative seizures, hypoxia, arterial hypertension, nausea and vomiting, neurological dysfunction, conversion into general anaesthesia and failure of AC. Random effects meta-analysis was used to estimate event rates for four outcomes. Relationship with anaesthesia technique was explored using logistic meta-regression, calculating the odds ratios (OR) and 95 confidence intervals [95 CI].ResultsWe have included forty-seven studies. Eighteen reported asleep-awake-asleep technique (SAS), twenty-seven monitored anaesthesia care (MAC), one reported both and one used the awake-awake-awake technique (AAA). Proportions of AC failures, intraoperative seizures, new neurological dysfunction and conversion into general anaesthesia (GA) were 2 [95 CI:1?], 8 [95 CI:6?1], 17 [95 CI:12?3] and 2 [95 CI:2?], respectively. Meta-regression of SAS and MAC technique did not reveal any relevant differences between outcomes explained by the technique, except for conversion into GA. EstimatedPLOS ONE | DOI:10.1371/journal.pone.0156448 May 26,1 /Anaesthesia Management for Awake CraniotomyOR comparing SAS to MAC for AC failures was 0.98 [95 CI:0.36?.69], 1.01 [95 CI:0.52?.88] for seizures, 1.66 [95 CI:1.35?.70] for new neurological dysfunction and 2.17 [95 CI:1.22?.85] for conversion into GA. The latter result has to be interpreted cautiously. It is based on one retrospective high-risk of bias study and significance was abolished in a sensitivity analysis of only prospectively conducted studies.ConclusionSAS and MAC techniques were feasible and safe, whereas data for AAA technique are limited. Large RCTs are required to prove superiority of one anaesthetic regime for AC.Introduction RationaleAwake craniotomy (AC) was initially used for removal of epileptic foci with simultaneous application of brain mapping and electrical current. Since the 1980s further developments brought this technique into use for Nutlin (3a) manufacturer resection of tumours involving functional cortex [1]. AC with live intraoperative brain mapping and monitoring of neurological function and neurocognitive performance, allows maximal resection of malignant gliomas with a favourable survival prognosis and without language deficits [2]. Tumour resection is adapted to the individual anatomy of the patient, which generally shows huge inter-individual variability [2,3]. The primary aim is to preserve or even improve the complex human brain function, while achieving maximal removal of tumours or epileptic foci [4]. Given the effectiveness of AC for resection of eloquent tumours, data suggest an expanded role for AC in brain tumour surgery regardless of tumour location [5]. In addition, ACs are establ.Anovic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: The authors received no specific funding for this work. Competing Interests: The authors have declared that no competing interests exist.MethodsTwo authors performed independently a systematic search of English articles in PubMed and EMBASE database 1/2007-12/2015. Search included randomised controlled trials (RCTs), observational trials, and case reports (n>4 cases), which reported anaesthetic approach for AC and at least one of our pre-specified outcomes: intraoperative seizures, hypoxia, arterial hypertension, nausea and vomiting, neurological dysfunction, conversion into general anaesthesia and failure of AC. Random effects meta-analysis was used to estimate event rates for four outcomes. Relationship with anaesthesia technique was explored using logistic meta-regression, calculating the odds ratios (OR) and 95 confidence intervals [95 CI].ResultsWe have included forty-seven studies. Eighteen reported asleep-awake-asleep technique (SAS), twenty-seven monitored anaesthesia care (MAC), one reported both and one used the awake-awake-awake technique (AAA). Proportions of AC failures, intraoperative seizures, new neurological dysfunction and conversion into general anaesthesia (GA) were 2 [95 CI:1?], 8 [95 CI:6?1], 17 [95 CI:12?3] and 2 [95 CI:2?], respectively. Meta-regression of SAS and MAC technique did not reveal any relevant differences between outcomes explained by the technique, except for conversion into GA. EstimatedPLOS ONE | DOI:10.1371/journal.pone.0156448 May 26,1 /Anaesthesia Management for Awake CraniotomyOR comparing SAS to MAC for AC failures was 0.98 [95 CI:0.36?.69], 1.01 [95 CI:0.52?.88] for seizures, 1.66 [95 CI:1.35?.70] for new neurological dysfunction and 2.17 [95 CI:1.22?.85] for conversion into GA. The latter result has to be interpreted cautiously. It is based on one retrospective high-risk of bias study and significance was abolished in a sensitivity analysis of only prospectively conducted studies.ConclusionSAS and MAC techniques were feasible and safe, whereas data for AAA technique are limited. Large RCTs are required to prove superiority of one anaesthetic regime for AC.Introduction RationaleAwake craniotomy (AC) was initially used for removal of epileptic foci with simultaneous application of brain mapping and electrical current. Since the 1980s further developments brought this technique into use for resection of tumours involving functional cortex [1]. AC with live intraoperative brain mapping and monitoring of neurological function and neurocognitive performance, allows maximal resection of malignant gliomas with a favourable survival prognosis and without language deficits [2]. Tumour resection is adapted to the individual anatomy of the patient, which generally shows huge inter-individual variability [2,3]. The primary aim is to preserve or even improve the complex human brain function, while achieving maximal removal of tumours or epileptic foci [4]. Given the effectiveness of AC for resection of eloquent tumours, data suggest an expanded role for AC in brain tumour surgery regardless of tumour location [5]. In addition, ACs are establ.