Ning of surgery (n = 1). Fentanyl 25?0g was additionally applied in 3 patients. SAS (n = 2): cessation of propofol, removal of LMA and start of dexmedetomidine 0.1?0.3 g kg-1 h-1, MAC (n = 4) continuous dexmedetomidine. NK NK No No NK SAS (n = 2) reinduction of propofol and reinsertion of LMA. Combination of midazolam, dehydrobenzperidol and piritramide TIVA-TCI with propofol (Marsh’s Model), and sufentanil (Bovill’s model) or remifentanil (Minto’s model) NK NK No BISWrede 2011 [61]NANAZhang 2008 [62]NANANasopharyngeal airway (spontaneous breathing)PLOS ONE | DOI:10.1371/journal.pone.AZD-8055 dose 0156448 May 26, 2016 Anaesthesia Management for Awake Craniotomy?SD, and standard deviation; Cp, target plasma concentration; n =, specified number of patients; NA, not applicable; NK, not known as not reported; OAA/S, observer Assessmentof alertness/ sedation score; RE, response entropy index; SD, standard deviation; TCI, target-controlled infusion.doi:10.1371/journal.pone.0156448.t21 /Table 4. Intraoperative characteristics and adverse events.Duration awake phase in min., mean [range]/ ?SD AC failure Intraoperative hypoxia Nausea and/or vomiting intraoperative hypertension (>20 AnlotinibMedChemExpress Anlotinib deviation from baseline) 2 NK NK 1 2 (postoperative), 1 (intraoperative) 1 (postoperative), 0 (intraoperative) NK 4/2 Conversion into GA Intraoperative seizures /history of seizures in these patients 2/NK 2/NK 2 (dex group)/2 12/NK 1 0 5 1 NK NK NK 166 [75?20] 3 (LMA leakage n = 1, respiratory insufficiency n = 1, intraoperative bleeding n = 1) 0 14/12 NK, but no anaesthesiological complication reported 0 NK 0 0 0 NK 0 0 28/NK NK 0 1 (brain bulge) 1 (seizure) 0 20 (18 young and 2 elderly)/NK 1/NK 8/NK 20/19 0 NK NK NK NK 3 NK NK, but no anaesthesiological complication reported NK NK NK NK 0 1 0 0 NK 5 NK NK 22 (>10 deviation) NK 3 (LMA leakage n = 1, respiratory insufficiency n = 1, intraoperative bleeding n = 1) 0 0 0 0 0 NKStudyDuration surgery in min., mean ?SD [range]Abdou 2010 [17]168.8 ?19.4; [150?215]Ali 2009 [18]173 ?Amorim 2008 [19]NKAndersen 2010 [20]NKBeez 2013 [21]NK76 [20?37]NKBilotta 2014 [10] NK NK NK 96 ?45 1 (pain) 0 0 0 0 NK NK 1 (brain bulge) 1 (seizure) 3 (seizures) NK 0 0 0 0 4/NK 0/NK 1 (pain) 0 NK 98 ?27 NK NK NK NK NK NK NK 1 (restlessness) 0 3/NK 0 0 0 0 0 13/NKNKNK NK NK NK NK NK 3 (intraoperative) NK NK 0 NK NK 1 (postoperative) NKPLOS ONE | DOI:10.1371/journal.pone.0156448 May 26,NK 0 0 7/69 NK NK NKBoetto 2015 [22]NKCai 2013 [23][450?80]Chacko 2013 [24]NKChaki 2014 [25]NKConte 2013 [26]median 403 [259?562]Deras 2012 [27]NKGaravaglia 2014 [28]median 210 [180?540]Gonen 2014 [29]NKGrossman 2007 [30]202 ?Grossman 2013 [31]NKGupta 2007 [32]Hansen 2013 [33]217?5 [105?95]HerveyJumper 2015 [34]NKIlmberger 2008 [35]NK(Continued)Anaesthesia Management for Awake Craniotomy22 /Table 4. (Continued)Duration awake phase in min., mean [range]/ ?SD AC failure Intraoperative hypoxia Nausea and/or vomiting intraoperative hypertension (>20 deviation from baseline) NK 2 (intraoperative) Conversion into GA Intraoperative seizures /history of seizures in these patients 2/NK 1 NK 0StudyDuration surgery in min., mean ?SD [range]JadavjiMithani 2015 [36] NK NK NK NK NK NK 9 (seizures n = 5, severe restlessness n = 3, acute brain oedema n = 1). 49 /NK NK 27 (seizures n = 5, severe restlessness n = 8, acute brain oedema n = 1, severe dysphasia n = 11, somnolence n = 2). 37 (intractable seizures n = 11), dysphasia, restlessness, and somnolence n = 26). 7 (seizures) 60/37 2 (LMA l.Ning of surgery (n = 1). Fentanyl 25?0g was additionally applied in 3 patients. SAS (n = 2): cessation of propofol, removal of LMA and start of dexmedetomidine 0.1?0.3 g kg-1 h-1, MAC (n = 4) continuous dexmedetomidine. NK NK No No NK SAS (n = 2) reinduction of propofol and reinsertion of LMA. Combination of midazolam, dehydrobenzperidol and piritramide TIVA-TCI with propofol (Marsh’s Model), and sufentanil (Bovill’s model) or remifentanil (Minto’s model) NK NK No BISWrede 2011 [61]NANAZhang 2008 [62]NANANasopharyngeal airway (spontaneous breathing)PLOS ONE | DOI:10.1371/journal.pone.0156448 May 26, 2016 Anaesthesia Management for Awake Craniotomy?SD, and standard deviation; Cp, target plasma concentration; n =, specified number of patients; NA, not applicable; NK, not known as not reported; OAA/S, observer Assessmentof alertness/ sedation score; RE, response entropy index; SD, standard deviation; TCI, target-controlled infusion.doi:10.1371/journal.pone.0156448.t21 /Table 4. Intraoperative characteristics and adverse events.Duration awake phase in min., mean [range]/ ?SD AC failure Intraoperative hypoxia Nausea and/or vomiting intraoperative hypertension (>20 deviation from baseline) 2 NK NK 1 2 (postoperative), 1 (intraoperative) 1 (postoperative), 0 (intraoperative) NK 4/2 Conversion into GA Intraoperative seizures /history of seizures in these patients 2/NK 2/NK 2 (dex group)/2 12/NK 1 0 5 1 NK NK NK 166 [75?20] 3 (LMA leakage n = 1, respiratory insufficiency n = 1, intraoperative bleeding n = 1) 0 14/12 NK, but no anaesthesiological complication reported 0 NK 0 0 0 NK 0 0 28/NK NK 0 1 (brain bulge) 1 (seizure) 0 20 (18 young and 2 elderly)/NK 1/NK 8/NK 20/19 0 NK NK NK NK 3 NK NK, but no anaesthesiological complication reported NK NK NK NK 0 1 0 0 NK 5 NK NK 22 (>10 deviation) NK 3 (LMA leakage n = 1, respiratory insufficiency n = 1, intraoperative bleeding n = 1) 0 0 0 0 0 NKStudyDuration surgery in min., mean ?SD [range]Abdou 2010 [17]168.8 ?19.4; [150?215]Ali 2009 [18]173 ?Amorim 2008 [19]NKAndersen 2010 [20]NKBeez 2013 [21]NK76 [20?37]NKBilotta 2014 [10] NK NK NK 96 ?45 1 (pain) 0 0 0 0 NK NK 1 (brain bulge) 1 (seizure) 3 (seizures) NK 0 0 0 0 4/NK 0/NK 1 (pain) 0 NK 98 ?27 NK NK NK NK NK NK NK 1 (restlessness) 0 3/NK 0 0 0 0 0 13/NKNKNK NK NK NK NK NK 3 (intraoperative) NK NK 0 NK NK 1 (postoperative) NKPLOS ONE | DOI:10.1371/journal.pone.0156448 May 26,NK 0 0 7/69 NK NK NKBoetto 2015 [22]NKCai 2013 [23][450?80]Chacko 2013 [24]NKChaki 2014 [25]NKConte 2013 [26]median 403 [259?562]Deras 2012 [27]NKGaravaglia 2014 [28]median 210 [180?540]Gonen 2014 [29]NKGrossman 2007 [30]202 ?Grossman 2013 [31]NKGupta 2007 [32]Hansen 2013 [33]217?5 [105?95]HerveyJumper 2015 [34]NKIlmberger 2008 [35]NK(Continued)Anaesthesia Management for Awake Craniotomy22 /Table 4. (Continued)Duration awake phase in min., mean [range]/ ?SD AC failure Intraoperative hypoxia Nausea and/or vomiting intraoperative hypertension (>20 deviation from baseline) NK 2 (intraoperative) Conversion into GA Intraoperative seizures /history of seizures in these patients 2/NK 1 NK 0StudyDuration surgery in min., mean ?SD [range]JadavjiMithani 2015 [36] NK NK NK NK NK NK 9 (seizures n = 5, severe restlessness n = 3, acute brain oedema n = 1). 49 /NK NK 27 (seizures n = 5, severe restlessness n = 8, acute brain oedema n = 1, severe dysphasia n = 11, somnolence n = 2). 37 (intractable seizures n = 11), dysphasia, restlessness, and somnolence n = 26). 7 (seizures) 60/37 2 (LMA l.