S et al. [27]. Only four studies used a sleep-awake (SA) protocol for some patients [21] respective all patients [20,26,44]. Almost all patients undergoing SA(S) management underwent successful AC and the failure rate was minimal with 13 out of 1313 procedures (where failure rate was reported, and excluding the duplicate studies [27,44]). The meta-analysis showed a proportion of 2 [95 CI: 1?] (Fig 2). MAC–monitored anaesthesia care. Defined by the “American Society of Anesthesiologists” (ASA) this technique enables purposeful patient response to tactile or verbal stimulation, while preserving spontaneous ventilation without any airway instrumentation [8]. Twentyeight included studies reported the successful use of MAC in AC [10,17?9,24,28?2,34?PLOS ONE | DOI:10.1371/journal.pone.0156448 May 26,27 /Anaesthesia Management for Awake CraniotomyFig 2. Forrest plot of awake craniotomy failure. 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 Ixazomib citrate cancer grouping by technique. Of note, Souter et al. [60] have used both anaesthesia techniques. doi:10.1371/journal.pone.0156448.gPLOS ONE | DOI:10.1371/journal.pone.0156448 May 26,28 /Anaesthesia Management for Awake Craniotomy36,40?3,47?9,52,54,55,58?2]. Except of three studies, which only used local infiltration anaesthesia [36,48,61] respectively one, which did not mention the use of infiltration anaesthesia [17], all others applied an additional RSNB at the beginning of the surgery. The airway was secured with an oxygen mask, a nasal cannula or an additional nasal trumpet under maintained spontaneous breathing. Except in two studies [17,61], the used anaesthetics consisted of all possible combinations of fentanyl, remifentanil, propofol, midazolam and dexmedetomidine. Abdou et al. applied in the same syringe a mixture of ketamine and propofol 1:1 “ketofol” [17], and Wrede et al. used piritramide and midazolam for their conscious sedation [61]. Propofol and remifentanil were mostly discontinued 15 minutes before brain mapping and the patients did not receive any sedation and analgesia during the “awake” phase in thirteen studies [10,17,24,28?1,36,41?3,49,54], respectively three studies which applied only opioids if needed [34,47,52]. Three studies continued conscious sedation with propofol in a reduced dosage also during the awake phase [18,32], and the awake anaesthesia management is unknown for six studies [19,35,55,58,61,62]. Dexmedetomidine (around 0.1?.7 g kg-1 h-1) was continued in totally 36 procedures during the “awake” phase [48,59,60]. It could be shown, that dexmedetomidine has a minimal interference with electrocorticography (ECoG) during AC in a dosage of 0.2?.5 g kg-1 h-1 [60]. Anaesthesia for the end of surgery was not described in detail in the identified MAC studies, but it may be assumed that the initial regime was resumed until skin closure. Interestingly, Peruzzi et al. used additional sevoflurane until the opening of dura mater, to decrease the amount of propofol [48]. Grossman et al. included in their study 90 elderly patients, with a mean age of 71.7?.1 years, of totally 424 patients [31]. Preservation of the neurological status has a strong impact on the quality of life in especially this population. They showed that a maximum gross total resection (GTR) of high-grade Vesatolimod dose glioma under AC is feasible, without increased mortality or postoperative morbidi.S et al. [27]. Only four studies used a sleep-awake (SA) protocol for some patients [21] respective all patients [20,26,44]. Almost all patients undergoing SA(S) management underwent successful AC and the failure rate was minimal with 13 out of 1313 procedures (where failure rate was reported, and excluding the duplicate studies [27,44]). The meta-analysis showed a proportion of 2 [95 CI: 1?] (Fig 2). MAC–monitored anaesthesia care. Defined by the “American Society of Anesthesiologists” (ASA) this technique enables purposeful patient response to tactile or verbal stimulation, while preserving spontaneous ventilation without any airway instrumentation [8]. Twentyeight included studies reported the successful use of MAC in AC [10,17?9,24,28?2,34?PLOS ONE | DOI:10.1371/journal.pone.0156448 May 26,27 /Anaesthesia Management for Awake CraniotomyFig 2. Forrest plot of awake craniotomy failure. 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. [60] have used both anaesthesia techniques. doi:10.1371/journal.pone.0156448.gPLOS ONE | DOI:10.1371/journal.pone.0156448 May 26,28 /Anaesthesia Management for Awake Craniotomy36,40?3,47?9,52,54,55,58?2]. Except of three studies, which only used local infiltration anaesthesia [36,48,61] respectively one, which did not mention the use of infiltration anaesthesia [17], all others applied an additional RSNB at the beginning of the surgery. The airway was secured with an oxygen mask, a nasal cannula or an additional nasal trumpet under maintained spontaneous breathing. Except in two studies [17,61], the used anaesthetics consisted of all possible combinations of fentanyl, remifentanil, propofol, midazolam and dexmedetomidine. Abdou et al. applied in the same syringe a mixture of ketamine and propofol 1:1 “ketofol” [17], and Wrede et al. used piritramide and midazolam for their conscious sedation [61]. Propofol and remifentanil were mostly discontinued 15 minutes before brain mapping and the patients did not receive any sedation and analgesia during the “awake” phase in thirteen studies [10,17,24,28?1,36,41?3,49,54], respectively three studies which applied only opioids if needed [34,47,52]. Three studies continued conscious sedation with propofol in a reduced dosage also during the awake phase [18,32], and the awake anaesthesia management is unknown for six studies [19,35,55,58,61,62]. Dexmedetomidine (around 0.1?.7 g kg-1 h-1) was continued in totally 36 procedures during the “awake” phase [48,59,60]. It could be shown, that dexmedetomidine has a minimal interference with electrocorticography (ECoG) during AC in a dosage of 0.2?.5 g kg-1 h-1 [60]. Anaesthesia for the end of surgery was not described in detail in the identified MAC studies, but it may be assumed that the initial regime was resumed until skin closure. Interestingly, Peruzzi et al. used additional sevoflurane until the opening of dura mater, to decrease the amount of propofol [48]. Grossman et al. included in their study 90 elderly patients, with a mean age of 71.7?.1 years, of totally 424 patients [31]. Preservation of the neurological status has a strong impact on the quality of life in especially this population. They showed that a maximum gross total resection (GTR) of high-grade glioma under AC is feasible, without increased mortality or postoperative morbidi.