Utcome analysis together with AC failure and intraoperative seizure. AC failure. Our primary ASP015K supplement outcome of interest was the failure rate of AC, depending on the used anaesthesia technique. The meta-analysis for the proportion of awake craniotomy failures, depending on the used anaesthetic approach (MAC vs. SAS) included thirty-eight studies (Fig 2) [10,18?6,28,29,32,34?1,43,47?2]. It included the largest of the duplicate studies and excluded the smaller ones [27,42,44], which have also reported this outcome, according to Tramer et al. [14] and van Elm et al. [15]. The particular reasons for AC failures are shown in Table 4 and included all cases where a complete intraoperative awake monitoring of the brain function during the tumour resection could not be achieved. Of note, an AC failure was not only restricted to the cases, where conversion to GA was required. The proportion of AC failures was 2 [95 CI 1?], and the studies showed a substantial heterogeneity (I2 = 61 ) (Fig 2). The relationship of the used technique (SAS/ MAC) as a possible source of the heterogeneity was explored using logistic meta-regression. The OR comparing SAS to MAC was 0.98 [CI95 : 0.36?.69]. The employed anaesthesia technique did not FPS-ZM1 custom synthesis explain a substantial portion of the heterogeneity between studies (QM = 0.001, df = 1, p = 0.972), and the test for residual heterogeneity was significant (QE = 93.70, df = 37, p < 0.001). Conversion into general anaesthesia. The discrepancy between the numbers of required conversion to GA and AC failure rates may be explained as follows: Not every AC failure required conversion into GA and not every conversion into GA was performed during the awake tumour resection phase, but also at the end of surgery, where it did not compromise the success of AC, like in the study of Sinha et al. [58]. Forty-two studies reported 47 unplanned conversions into GA during totally 4971 AC procedures [10,17?9,31?7,39,40,42?4,47?2]. The particular reasons for unplanned conversion into GA are shown in Table 4. After exclusion of the duplicate studies [27,31,42,44] and the AAA study of Hansen et al. [33], our meta-analysis showed a total proportion of conversion into GA of 2 [95 CI 1?] (Fig 3). Logistic metaregression was also performed for this outcome, to analyse if the used technique (SAS/ MAC) may explain the differences between the studies. The OR comparing SAS to MAC was 2.17 [95 CI: 1.22?.85] and the likelihood ratio test (LR test) showed a significant p-value of 0.03. However, the predicted proportion of conversions in the MAC and SAS group were not substantially different (MAC: 2 [95 CI: 1?], SAS: 3 [95 CI: 2?]). Seizures. Threatening adverse events during AC are seizures. The most seizures in the included studies were triggered by electrical cortical stimulation and were self-limited after cessation of cortical stimulation. The other could be treated with cold saline solution, or finally with anticonvulsive medication, or low doses of propofol, thiopental or benzodiazepines. Discontinuation of AC was rarely necessary. Thirty-nine studies reported the incidence ofPLOS ONE | DOI:10.1371/journal.pone.0156448 May 26,30 /Anaesthesia Management for Awake CraniotomyFig 3. Forrest plot of conversion into general anaesthesia. The summary value is an overall estimate from a random-effect model. The vertical dotted line shows an overall estimate of outcome proportion (based on the meta-analysis) disregarding grouping by technique. Of note, Souter et al.Utcome analysis together with AC failure and intraoperative seizure. AC failure. Our primary outcome of interest was the failure rate of AC, depending on the used anaesthesia technique. The meta-analysis for the proportion of awake craniotomy failures, depending on the used anaesthetic approach (MAC vs. SAS) included thirty-eight studies (Fig 2) [10,18?6,28,29,32,34?1,43,47?2]. It included the largest of the duplicate studies and excluded the smaller ones [27,42,44], which have also reported this outcome, according to Tramer et al. [14] and van Elm et al. [15]. The particular reasons for AC failures are shown in Table 4 and included all cases where a complete intraoperative awake monitoring of the brain function during the tumour resection could not be achieved. Of note, an AC failure was not only restricted to the cases, where conversion to GA was required. The proportion of AC failures was 2 [95 CI 1?], and the studies showed a substantial heterogeneity (I2 = 61 ) (Fig 2). The relationship of the used technique (SAS/ MAC) as a possible source of the heterogeneity was explored using logistic meta-regression. The OR comparing SAS to MAC was 0.98 [CI95 : 0.36?.69]. The employed anaesthesia technique did not explain a substantial portion of the heterogeneity between studies (QM = 0.001, df = 1, p = 0.972), and the test for residual heterogeneity was significant (QE = 93.70, df = 37, p < 0.001). Conversion into general anaesthesia. The discrepancy between the numbers of required conversion to GA and AC failure rates may be explained as follows: Not every AC failure required conversion into GA and not every conversion into GA was performed during the awake tumour resection phase, but also at the end of surgery, where it did not compromise the success of AC, like in the study of Sinha et al. [58]. Forty-two studies reported 47 unplanned conversions into GA during totally 4971 AC procedures [10,17?9,31?7,39,40,42?4,47?2]. The particular reasons for unplanned conversion into GA are shown in Table 4. After exclusion of the duplicate studies [27,31,42,44] and the AAA study of Hansen et al. [33], our meta-analysis showed a total proportion of conversion into GA of 2 [95 CI 1?] (Fig 3). Logistic metaregression was also performed for this outcome, to analyse if the used technique (SAS/ MAC) may explain the differences between the studies. The OR comparing SAS to MAC was 2.17 [95 CI: 1.22?.85] and the likelihood ratio test (LR test) showed a significant p-value of 0.03. However, the predicted proportion of conversions in the MAC and SAS group were not substantially different (MAC: 2 [95 CI: 1?], SAS: 3 [95 CI: 2?]). Seizures. Threatening adverse events during AC are seizures. The most seizures in the included studies were triggered by electrical cortical stimulation and were self-limited after cessation of cortical stimulation. The other could be treated with cold saline solution, or finally with anticonvulsive medication, or low doses of propofol, thiopental or benzodiazepines. Discontinuation of AC was rarely necessary. Thirty-nine studies reported the incidence ofPLOS ONE | DOI:10.1371/journal.pone.0156448 May 26,30 /Anaesthesia Management for Awake CraniotomyFig 3. Forrest plot of conversion into general anaesthesia. The summary value is an overall estimate from a random-effect model. The vertical dotted line shows an overall estimate of outcome proportion (based on the meta-analysis) disregarding grouping by technique. Of note, Souter et al.