Benefit of general anesthesia monitored by bispectral index compared with monitoring guided only by clinical parameters. Systematic review and meta-analysis

Oliveira, Carlos Rogério Degrandi; Bernardo, Wanderley Marques; Nunes, Victor Moisés

doi:10.1016/j.bjane.2015.09.001

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Revista Brasileira de Anestesiologia

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Review Article • Rev. Bras. Anestesiol. 67 (1) • Jan-Feb 2017 • https://doi.org/10.1016/j.bjane.2015.09.001 copy

Benefit of general anesthesia monitored by bispectral index compared with monitoring guided only by clinical parameters. Systematic review and meta-analysis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background:

The bispectral index parameter is used to guide the titration of general anesthesia; however, many studies have shown conflicting results regarding the benefits of bispectral index monitoring. The objective of this systematic review with meta-analysis is to evaluate the clinical impact of monitoring with the bispectral index parameter.

Methods:

The search for evidence in scientific information sources was conducted during December 2013 to January 2015, the following primary databases: Medline/PubMed, LILACS, Cochrane, CINAHL, Ovid, SCOPUS and TESES. The criteria for inclusion in the study were randomized controlled trials, comparing general anesthesia monitored, with bispectral index parameter with anesthesia guided solely by clinical parameters, and patients aged over 18 years. The criteria for exclusion were studies involving anesthesia or sedation for diagnostic procedures, and intraoperative wake-up test for surgery of the spine.

Results:

The use of monitoring with the bispectral index has shown benefits reducing time to extubation, orientation in time and place, and discharge from both the operating room and post anesthetic care unit. The risk of nausea and vomiting after surgery was reduced by 12% in patients monitored with bispectral index. Occurred a reduction of 3% in the risk of cognitive impairment postoperatively at 3 months postoperatively and 6% reduction in the risk of postoperative delirium in patients monitored with bispectral index. Furthermore, the risk of intraoperative memory has been reduced by 1%.

Conclusion:

Clinically, anesthesia monitoring with the BIS can be justified because it allows advantages from reducing the recovery time after waking, mainly by reducing the administration of general anesthetics as well as the risk of adverse events.

KEYWORDS
General anesthesia; Anesthetics; Inhalation; Intravenous anesthesia; Bispectral index-monitoring

RCT	EL	J	R/A	I/C	P	I	C	O
Nelskylä et al. (2001)¹1 Nelskylä KA, Yli-Hankala AM, Puro PH, et al. Sevoflurane titration using bispectral index decreases postoperative vomiting in phase II recovery after ambulatory surgery. Anesth Analg. 2001;93:1165-9.	2B	0	62/62	32/30	ASA I or II, between 18 and 50 years, gynecological surgery.	BIS between 50 and 60 years	“Blinded” monitor. Anesthesia was adjusted according to clinical parameters.	Time for spontaneous eye opening, extubation, orientation in time and place, hospital discharge and PONV.
Wong et al. (2002)²2 Wong J, Song D, Blanshard H, et al. Titration of isoflurane using BIS index improves early recovery of elderly patients undergoing orthopedic surgeries. Can J Anaesth. 2002;49:13-8.	1B	3	68/60	29/31	>60 years, ASA I–III, orthopedic surgery.	BIS between 50 and 60.	“Blinded” monitor. Anesthesia was adjusted according to clinical parameters.	Time for spontaneous eye opening, orientation in time and place and PACU discharge.
Luginbühl et al. (2003)³3 Luginbühl M, Wüthrich S, Petersen-Felix S, et al. Different benefit of bispectal index (BIS) in desflurane and propofol anesthesia. Acta Anaesthesiol Scand. 2003;47:165-73.	2B	2	160/160	80/80	>18 years, gynecological surgery.	BIS between 45 and 55.	Anesthesia was adjusted according to clinical parameters.	Time to tracheal extubation.
Ahmad et al. (2003)⁴4 Ahmad S, Yilmaz M, Marcus RJ, et al. Impact of bispectral index monitoring on fast tracking of gynecologic patients undergoing laparoscopic surgery. Anesthesiology. 2003;98:849-52.	1B	3	99/97	49/48	>18 years, gynecological surgery.	BIS between 50 and 60.	Anesthesia was adjusted according to clinical parameters.	Time for hospital discharge.
Başar et al. (2003)⁵5 Başar H, Ozcan S, Buyukkocak U, et al. Effect of bispectral index monitoring on sevoflurane consumption. Eur J Anaesthesiol. 2003;20:396-400.	2B	0	60/60	30/30	>18 years, ASA I or II, abdominal surgery.	BIS between 40 and 60.	“Blinded” monitor. Anesthesia was adjusted according to clinical parameters.	Time of eye opening upon verbal command.
Puri and Murthy (2003)⁶6 Puri GD, Murthy SS. Bispectral index monitoring in patients undergoing cardiac surgery under cardiopulmonary bypass. Eur J Anaesthesiol. 2003;20:451-6.	2B	2	30/30	14/16	>18 years, myocardial revascularization or valve replacement with cardiopulmonary bypass, 18–70 years.	BIS between 45 and 55.	“Blinded” monitor. Anesthesia was adjusted according to clinical parameters.	Time of eye opening upon verbal command and extubation, intraoperative memory.
Kreuer et al. (2003)⁷7 Kreuer S, Biedler A, Larsen R, et al. Narcotrend monitoring allows faster emergence and a reduction of drug consumption in propofol-remifentanil anesthesia. Anesthesiology. 2003;99:34-41.	2B	2	120/120	40/40	>18 years, ASA I-III, orthopedic surgery.	BIS 50 and in the last 15 min of 60.	Anesthesia was adjusted according to clinical parameters.	Time for spontaneous eye opening and extubation.
Myles et al. (2004)⁸8 Myles PS, Leslie K, McNeil J, et al. Bispectral index monitoring to prevent awareness during anaesthesia: the B-Aware randomised controlled trial. Lancet. 2004;363:1757-63.	1B	5	2.503/2.463	1.225/1.238	>18 years with at least one high risk factor to intraoperative awakening.	BIS between 40 and 60.	Monitor turned off. Anesthesia was adjusted according to clinical parameters.	Time for spontaneous eye opening, time for discharge from PACU and intraoperative memory.
Bruhn et al. (2005)⁹9 Bruhn J, Kreuer S, Bischoff P, et al. Bispectral index and A-line AAI index as guidance for desflurane-remifentanil anaesthesia compared with a standard practice group: a multicentre study. Br J Anaesth. 2005;94:63-9.	2B	2	200/200	71/58	>18 years, ASA I-III.	BIS of 50. In the last 15 min BIS of 60.	Anesthesia was adjusted according to clinical parameters.	Time for spontaneous eye opening and extubation, PONV and intraoperative memory.
Kreuer et al. (2005)¹⁰10 Kreuer S, Bruhn J, Stracke C, et al. Narcotrend or bispectral index monitoring during desflurane-remifentanil anesthesia: a comparison with a standard practice protocol. Anesth Analg. 2005;101:427-34.	1B	4	120/120	40/40	>18 years, ASA I-III, orthopedic surgery.	BIS 50 and in the last 15 min change to 60.	Anesthesia was adjusted according to clinical parameters.	Time for spontaneous eye opening, extubation and time for leaving operation room.
Vretzakis et al. (2005)¹¹11 Vretzakis G, Ferdi E, Argiriadou H, et al. Influence of bispectral index monitoring on decision making during cardiac anesthesia. J Clin Anesth. 2005;17:509-16.	1B	3	130/121	36/44	>18 years, myocardial revascularization or valve replacement with cardiopulmonary bypass, ejection fraction >45%.	BIS under 60.	Anesthesia was adjusted according to clinical parameters.	Intraoperative memory.
Aimé et al. (2006)¹²12 Aimé I, Verroust N, Masson-Lefoll C, et al. Does monitoring bispectral index or spectral entropy reduce sevoflurane use? Anesth Analg. 2006;103:1469-77.	2B	1	140/125	34/54	Age between 18 and 80 years, ASA I-III, urologic, orthopedic, abdominal and gynecological surgery.	BIS between 40 and 60.	“Blinded” monitor. Anesthesia was adjusted according to clinical parameters.	Time for spontaneous eye opening and traqueal extubation.
Ibraheim et al. (2008)¹³13 Ibraheim O, Alshaer A, Mazen K, et al. Effect of bispectral index (BIS) monitoring on postoperative recovery and sevoflurane consumption among morbidly obese patients undergoing laparoscopic gastric banding. Middle East J Anesthesiol. 2008;19:819-30.	2B	0	30/30	15/15	>18 years, morbid obese, gastric band surgery.	BIS between 40 and 60.	Anesthesia was adjusted according to clinical parameters	Time of eye opening upon verbal command, time for extubation and discharge from PACU.
Kamal et al. (2009)¹⁴14 Kamal NM, Omar SH, Radwan KG, et al. Bispectral index monitoring tailors clinical anesthetic delivery and reduces anesthetic drug consumption. J Med Sci. 2009;9:10-6.	2B	1	60/57	29/28	>18 years, ASA I-III, abdominal surgery	BIS between 50 and 60.	“Blinded” monitor. Anesthesia was adjusted according to clinical parameters.	Time for spontaneous eye opening, extubation, orientation in time and place, leaving operating room, discharge from PACU and intraoperative memory.
Zhang et al. (2011)¹⁵15 Zhang C, Xu L, Ma YQ, et al. Bispectral index monitoring prevent awareness during total intravenous anesthesia: a prospective, randomized, double-blinded, multi-center controlled trial. Chin Med J (Engl). 2011;124:3664-9.	1B	5	5.309/5.228	2.919/2.309	>18 years, total intravenous anesthesia	BIS between 40 and 60.	“Blinded” monitor. Anesthesia was adjusted according to clinical parameters.	Intraoperative memory.
Chan et al. (2013)¹⁶16 Chan MT, Cheng BC, Lee TM, et al. BIS-guided anesthesia decreases postoperative delirium and cognitive decline. J Neurosurg Anesthesiol. 2013;25:33-42.	1B	3	921/902	450/452	>60 years, elective non-cardiac surgery.	BIS between 40 and 60.	Anesthesia was adjusted according to clinical parameters.	Time for spontaneous eye opening, time for discharge from PACU, cognitive dysfunction in the postoperative period (one week and three months later) and delirium.
Radtke et al. (2013)¹⁷17 Radtke FM, Franck M, Lendner J, et al. Monitoring depth of anaesthesia in a randomized trial decreases the rate of postoperative delirium but not postoperative cognitive dysfunction. Br J Anaesth. 2013;110(Suppl. 1):i98-105.	1B	3	1.277/1.155	575/580	>60 years	BIS between 40 and 60.	“Blinded” monitor. Anesthesia was adjusted according to clinical parameters.	Cognitive dysfunction in the postoperative period (one week and three months later) and delirium.

Article	Reason of exclusion
Sebel et al. (1997)¹⁸18 Sebel PS, Lang E, Rampil IJ, et al. A multicenter study of bispectral electroencephalogram analysis for monitoring anesthetic effect. Anesth Analg. 1997;84:891-9.	Before incision tetanus stimulation was applied to the ulnar nerve. Any presence of movement, anesthesia was deepened. In the absence of movement, anesthesia was maintained. After incision any movement was considered for the deepening of anesthesia. The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Yli-Hankala et al. (1999)¹⁹19 Yli-Hankala A, Vakkuri A, Annila P, et al. EEG bispectral index monitoring in sevoflurane or propofol anaesthesia: analysis of direct costs and immediate recovery. Acta Anaesthesiol Scand. 1999;43:545-9.	The data expression of the outcomes was made in medians.
Mi et al. (1999)²⁰20 Mi WD, Sakai T, Singh H, et al. Hypnotic endpoints vs. the bispectral index, 95% spectral edge frequency and median frequency during propofol infusion with or without fentanyl. Eur J Anaesthesiol. 1999;16:47-52.	Patients were monitored with BIS and outcomes were analyzed due to different anesthetic regimens. The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Nakayama et al. (2002)²¹21 Nakayama M, Ichinose H, Yamamoto S, et al. The effect of fentanyl on hemodynamic and Bispectral Index changes during anesthesia induction with propofol. J Clin Anesth. 2002;14:146-9.	All patients were monitored with BIS and outcomes were analyzed due to different anesthetic regimens (only propofol or propofol and fentanyl). The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Lehmann et al. (2002)²²22 Lehmann A, Boldt J, Thaler E, et al. Bispectral Index in patients with target-controlled or manually-controlled infusion of propofol. Anesth Analg. 2002;95:639-44.	All patients were monitored with BIS and analyzed outcomes resulting from different anesthetic techniques (with manual propofol infusion vs. propofol in Target Controlled Infusion – TCI). The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Paventi et al. (2002)²³23 Paventi S, Santevecchi A, Perilli V, et al. Effects of remifentanil infusion BIS-titrated on early recovery for obese outpatients undergoing laparoscopic cholecystectomy. Minerva Anestesiol. 2002;68:651-7.	All patients were monitored with BIS and analyzed outcomes resulting from different anesthetic techniques (manual propofol infusion vs. propofol in TCI). The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Lehmann et al. (2003)²⁴24 Lehmann A, Karzau J, Boldt J, et al. Bispectral Index-guided anesthesia in patients undergoing aortocoronary bypass grafting. Anesth Analg. 2003;96:336-43.	All patients were monitored with BIS (group BIS 50 and group BIS 40). The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Yamaguchi et al. (2003)²⁵25 Yamaguchi S, Egawa H, Mishio M, et al. Bispectral monitoring during vital capacity rapid inhalation induction with sevoflurane. J Clin Anesth. 2003;15:24-8.	All patients were monitored with BIS and analyzed outcomes resulting from different anesthetic drugs and techniques (propofol group/iv induction and sevoflurane group with inhalational induction in adult by the vital capacity technique). The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Buyukkocak et al. (2003)²⁶26 Buyukkocak U, Ozcan S, Daphan C, et al. A comparison of four intravenous sedation techniques and Bispectral Index monitoring in sinonasal surgery. Anaesth Intensive Care. 2003;31:164-71.	All patients were monitored with BIS and outcomes were analyzed due to different anesthetic drugs, four different methods of sedation associated with topical anesthesia. The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Forestier et al. (2003)²⁷27 Forestier F, Hirschi M, Rouget P, et al. Propofol and sufentanil titration with the Bispectral Index to provide anesthesia for coronary artery surgery. Anesthesiology. 2003;99:334-46.	All patients were monitored with BIS and analyzed five groups with different concentrations of sufentanil. The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Schneider et al. (2003)²⁸28 Schneider G, Gelb AW, Schmeller B, et al. Detection of awareness in surgical patients with EEG-based indices-bispectral index and patient state index. Br J Anaesth. 2003;91:329-35.	All patients were monitored with BIS and analyzed four different anesthetic regimens. The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Schneider et al. (2003)²⁹29 Schneider G, Elidrissi C, Sebel PS. Bispectral index-guided administration of anaesthesia: comparison between remifentanil/propofol and remifentanil/isoflurane. Eur J Anaesthesiol. 2003;20:624-30.	All patients were monitored with BIS and analyzed two different anesthetic regimens. The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Liu (2004)³⁰30 Liu SS. Effects of Bispectral Index monitoring on ambulatory anesthesia. Anesthesiology. 2004;101:311-315.	Meta-analysis. The criteria for inclusion in the systematic review were randomized controlled trials.
Bauer et al. (2004)³¹31 Bauer M, Wilhelm W, Kraemer T, et al. Impact of Bispectral Index monitoring on stress response and propofol consumption in patients undergoing coronary artery bypass surgery. Anesthesiology. 2004;101:1096-104.	All patients were monitored with BIS and analyzed two different anesthetic regimens (TCI vs. manual propofol infusion). The BIS was used but is not described whether it was blinded. The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Bestas et al. (2004)³²32 Bestas A, Yasar MA, Bayar MK, et al. The effects of two different anaesthesia techniques on bispectral index values and awareness during off-pump coronary artery bypass grafting. J Clin Monit Comput. 2004;18:347-51.	All 50 patients (two groups of 25) were monitored with BIS and were blinded, with analysis of two different anesthetic regimes. The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Boztug et al. (2006)³³33 Boztug N, Bigat Z, Akyüz M, et al. Does using the Bispectral Index (BIS) during craniotomy affect the quality of recovery? J Neurosurg Anesthesiol. 2006;18:1-4.	Article not found.
Puri et al. (2007)³⁴34 Puri GD, Kumar B, Aveek J. Closed-loop anaesthesia delivery system (CLADS) using bispectral index: a performance assessment study. Anaesth Intensive Care. 2007;35:357-62.	All patients were monitored with BIS, with analysis of two different types of propofol infusion. The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Lindholm et al. (2008)³⁵35 Lindholm ML, Brudin L, Sandin RH. Bispectral index monitoring: appreciated but does not affect drug dosing and hypnotic levels. Acta Anaesthesiol Scand. 2008;52:88-94.	The paper analyzes the degree of proficiency in handling the BIS by nurses’ anesthetists. The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Avidan et al. (2008)³⁶36 Avidan MS, Zhang L, Burnside BA, et al. Anesthesia awareness and the Bispectral Index. N Engl J Med. 2008;358:1097-108.	In the control group, anesthesia was maintained with BIS “blinded” but with an expired fraction of 0.7–1.3 minimum alveolar concentration of inhaled anesthetic.
Bejjani et al. (2009)³⁷37 Bejjani G, Lequeux PY, Schmartz D, et al. No evidence of memory processing during propofol-remifentanil target-controlled infusion anesthesia with Bispectral Index monitoring in cardiac surgery. J Cardiothorac Vasc Anesth. 2009;23:175-81.	All patients were monitored with BIS with memory processing analysis. The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Delfino et al. (2009)³⁸38 Delfino AE, Cortinez LI, Fierro CV, et al. Propofol consumption and recovery times after bispectral index or cerebral state index guidance of anaesthesia. Br J Anaesth. 2009;103:255-9.	All patients were monitored with BIS or cerebral state index, with analysis of propofol infusion with these two types of monitoring. The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Kerssens et al. (2009)³⁹39 Kerssens C, Gaither JR, Sebel PS. Preserved memory function during Bispectral Index-guided anesthesia with sevoflurane for major orthopedic surgery. Anesthesiology. 2009;111:518-24.	Study of intraoperative memory and retrieval of words heard during the trans-operative, through memory tests postoperatively.
Mashour et al. (2009)⁴⁰40 Mashour GA, Tremper KK, Avidan MS. Protocol for the "Michigan Awareness Control Study": a prospective, randomized, controlled trial comparing electronic alerts based on bispectral index monitoring or minimum alveolar concentration for the prevention of intraoperative awareness. BMC Anesthesiol. 2009;9:7.	Cohort study. The criteria for inclusion in the systematic review were randomized controlled trials.
Satisha et al. (2010)⁴¹41 Satisha M, Sanders GM, Badrinath MR, et al. Introduction of bispectral index monitoring in a district general hospital operating suite: a prospective audit of clinical and economic effects. Eur J Anaesthesiol. 2010;27:196-220.	Cohort study. The criteria for inclusion in the systematic review were randomized controlled trials.
Meybohm et al. (2010)⁴²42 Meybohm P, Gruenewald M, Höcker J, et al. Correlation and agreement between the bispectral index vs. state entropy during hypothermic cardio-pulmonary bypass. Acta Anaesthesiol Scand. 2010;54:169-75.	Protocol study. The criteria for inclusion in the systematic review were randomized controlled trials.
Leslie et al. (2010)⁴³43 Leslie K, Myles PS, Forbes A, et al. The effect of Bispectral Index monitoring on long-term survival in the B-Aware trial. Anesth Analg. 2010;110:816-22.	Retrospective cohort study. The criteria for inclusion in the systematic review were randomized controlled trials.
Avidan et al. (2009)⁴⁴44 Avidan MS, Palanca BJ, Glick D, et al. Protocol for the BAG-RECALL clinical trial: a prospective, multi-center, randomized, controlled trial to determine whether a bispectral index-guided protocol is superior to an anesthesia gas-guided protocol in reducing intraoperative awareness with explicit recall in high risk surgical patients. BMC Anesthesiol. 2009;9:8.	Protocol study. The criteria for inclusion in the systematic review were randomized controlled trials.
Ellerkmann et al. (2010)⁴⁵45 Ellerkmann RK, Soehle M, Riese G, et al. The Entropy Module and Bispectral Index as guidance for propofol-remifentanil anaesthesia in combination with regional anaesthesia compared with a standard clinical practice group. Anaesth Intensive Care. 2010;38:159-66.	Inhalation or intravenous anesthesia, complemented by regional anesthesia (combined anesthesia). The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Yufune et al. (2011)⁴⁶46 Yufune S, Takamatsu I, Masui K, et al. Effect of remifentanil on plasma propofol concentration and bispectral index during propofol anaesthesia. Br J Anaesth. 2011;106:208-14.	The 38 patients were monitored with BIS and outcomes were analyzed due to different anesthetic regimens, as well as different concentrations of remifentanil. The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Liu et al. (2011)⁴⁷47 Liu N, Chazot T, Hamada S, et al. Closed-loop coadministration of propofol and remifentanil guided by Bispectral Index: a randomized multicenter study. Anesth Analg. 2011;112:546-57.	All patients were monitored with BIS and outcomes were analyzed due to different anesthetic regimens, target controlled infusion of propofol vs. closed-loop management. The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Avidan et al. (2011)⁴⁸48 Avidan MS, Jacobsohn E, Glick D, et al. Prevention of intraoperative awareness in a high-risk surgical population. N Engl J Med. 2011;365:591-600.	The control group was adjusted for maintaining an expired fraction of 0.7–1.3 minimum alveolar concentration of inhaled anesthetic.
Aimé et al. (2012)⁴⁹49 Aimé I, Gayat E, Fermanian C, et al. Effect of age on the comparability of bispectral and state entropy indices during the maintenance of propofol-sufentanil anaesthesia. Br J Anaesth. 2012;108:638-43.	The 102 patients were monitored with BIS or Entropy, in both groups, the values were blinded, and anesthesia was conducted by clinical parameters. The study goes out of focus – BIS intervention compared to the control group (consciousness guided by clinical parameters only).
Mashour et al. (2012)⁵⁰50 Mashour GA, Shanks A, Tremper KK, et al. Prevention of intraoperative awareness with explicit recall in an unselected surgical population. Anesthesiology. 2012;117:717-25.	The control group was blinded, but adjusted to a minimum alveolar concentration of inhaled anesthetic by age.
Persec et al. (2012)⁵¹51 Persec J, Persec Z, Kopljar M, et al. Effect of bispectral index monitoring on extubation time and analgesic consumption in abdominal surgery: a randomised clinical trial. Swiss Med Wkly. 2012;142:w13689.	The results of this study cannot be meta-analyzed as they provide no standard deviation.
Fritz et al. (2013)⁵²52 Fritz BA, Rao P, Mashour GA, et al. Postoperative recovery with Bispectral Index versus anesthetic concentration-guided protocols. Anesthesiology. 2013;118:1113-22.	Retrospective cohort study. The criteria for inclusion in the systematic review were randomized controlled trials.
Villafranca et al. (2013)⁵³53 Villafranca A, Thomson IA, Grocott HP, et al. The impact of Bispectral Index versus end-tidal anesthetic concentration-guided anesthesia on time to tracheal extubation in fast-track cardiac surgery. Anesth Analg. 2013;116:541-8.	Retrospective cohort study. The criteria for inclusion in the systematic review were randomized controlled trials.

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[1] * Corresponding author. E-mail:degrandi@gmail.com (C.R. Oliveira).