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Sugammadex, a specific reversal agent for steroidal neuromuscular blocking drugs, has on occasion been reported to be associated with clinical signs of awakening. We performed a study to systematically search for an increase in bispectral index values and signs of awakening in patients maintained under general anaesthesia following sugammadex administration. Patients, scheduled to receive general anaesthesia with neuromuscular blockade, were included in this double-blind randomised crossover study. After surgery was completed, and while the train-of-four ratio was zero, intravenous anaesthesia was continued with the aim of maintaining the bispectral index in the range of 40-60. Patients then received either sugammadex 4 mg.kg-1 or saline. In cases of incomplete reversal of neuromuscular blockade after 5 min, patients received the other drug. Bispectral index and train-of-four monitoring were recorded every minute and clinical signs of awakening noted. Fifty-one patients completed the study. Median (IQR [range]) bispectral index values increased after sugammadex administration from 49 (43-53 [38-64]) to 63 (53-80 [45-97]) (p < 0.01) with an increase of ≥ 20 in 22 patients; 14 (27%) patients had clinical signs of awakening. Saline had no effect on bispectral index values, clinical signs of awakening or degree of neuromuscular blockade. This study confirms that reversal of neuromuscular blockade with sugammadex may be associated with clinical signs of awakening despite maintenance of anaesthesia. Intravenous anaesthesia should be maintained until complete recovery of muscle function is achieved, especially when sugammadex is administered. [ABSTRACT FROM AUTHOR]

Background CNAP® provides continuous non-invasive arterial pressure ( AP) monitoring. We assessed its ability to detect minimal and maximal APs during induction of general anaesthesia and tracheal intubation. Methods Fifty-two patients undergoing surgery under general anaesthesia were enrolled. Invasive pressure monitoring was established at the radial artery, and CNAP monitoring using a finger sensor recording was begun before induction. Statistical analysis was conducted with the Bland- Altman method for comparison of repeated measures and intraclass correlation coefficient ( ICC). Results Patients' median age was 67 years [interquartile range (59-76)], median American Society of Anesthesiologists score was 3 [interquartile range (2-3)]. Bias was 5 and −7 mm Hg for peak and nadir systolic AP ( SAP), with upper and lower limits of agreement of (42:−32) and (27;−42), respectively. The corresponding ICC values were 0.74 [95% confidence interval ( CI) = 0.57-0.84] and 0.60 (95% CI = 0.44-0.73). Time lags to reach these values were 7.5 s (95% CI = −10.0 to 60.0) for the highest SAP and 10 s (95% CI = −12.5 to 72.5) for the lowest SAP. Bias, lower and upper limits of agreement for diastolic, and mean AP were −14 (−36 to 9) and −12 (−37 to 13) for the nadir value and −7 (−29 to 15) and −2 (−28 to 25) for the peak value. Conclusions The CNAP monitor could detect acute change in AP within a reasonable time lag. Precision of its measurements is not satisfactory, and therefore, it could only serve as a clue to the occurrence of changes in AP. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to investigate whether closed-loop compared to manual bispectral index (BIS)-guided target-controlled infusion of propofol and remifentanil could decrease the incidence of postoperative neurocognitive disorders after elective major noncardiac surgery., Methods: Patients aged >50 admitted for elective major noncardiac surgery were included in a single-blind randomized (ratio 2:1) trial. The anesthetic protocol was allocated by randomization into either closed-loop or manual BIS-guided propofol and remifentanil titration. The BIS target range was 40-60. All patients had cognitive assessment the day before surgery and within 72 hours after surgery using a battery of neuropsychological tests. The primary outcome was the rate of postoperative neurocognitive disorders. Postoperative neurocognitive disorders were defined as a decrease >20% from baseline on at least 3 scores. Intergroup comparison of the primary outcome was performed using the χ2 test., Results: A total of 143 and 61 patients were included in the closed-loop and manual groups, respectively (age: 66 [8] vs 66 [9] years). The primary outcome was observed in 18 (13%) and 10 (16%) patients of the closed-loop and manual groups, respectively (relative risk [95% confidence interval {CI}], 0.77 [0.38-1.57], P = .47). Intraoperative propofol consumption was lower (4.7 [1.4] vs 5.7 [1.4] mg·kg-1·h-1, mean difference [MD] [95% CI], -0.73 [-0.98 to -0.48], P < .0001) and the proportion of time within the BIS target range higher (84 [77-89] vs 74 [54-81]%, MD [95% CI], 0.94 [0.67-1.21], P < .0001) in the closed-loop group., Conclusions: Closed-loop compared to manual BIS-guided total intravenous anesthesia provided a significant reduction in episodes of an excessive depth of anesthesia while decreasing intraoperative propofol requirement but no evidence for a reduction of the incidence of postoperative neurocognitive disorders after elective major noncardiac surgery was observed., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2020 International Anesthesia Research Society.)

A dual-loop controller permits the automated titration of propofol and remifentanil during anesthesia; it has never been used in intensive care after cardiac surgery. The goal of this preliminary study was to determine the efficacy of this controller to provide postoperative sedation in 19 adult cardiac surgery patients with a Bispectral Index target of 50. Results are presented as numbers (percentages) or medians [25th-75th percentiles]. The sedation period lasted 139 min [89-205] during which the Richmond Agitation Sedation Scale was at - 5 and the Behavioral Pain Scale score at three points for all patients and observation times but one (82 out of 83 assessments). Sedation time in the range 40-60 for the Bispectral Index was 87% [57-95]; one patient had a period of electrical silence defined as Suppression Ratio at least > 10% for more than 60 s. The time between the end of infusions and tracheal extubation was 84 min [63-129]. The Richmond Agitation Sedation Scale was 0 [0-0], 0 [- 1 to 0], and 0 [0-0] respectively during the 3 h following extubation while the verbal numerical pain scores were 6 [4.5-7], 5 [4-6], and 2 [0-5]. Mean arterial pressure decreased during sedation requiring therapeutic interventions, mainly vascular filling in 15 (79%) patients. Automated sedation device was discontinued in two patients for hemodynamic instability. No patient had awareness of the postoperative sedation period. Dual closed-loop can provide postoperative sedation after cardiac surgery but the choice of the depth of sedation should take into account the risk of hypotension.

Little is known about respecting the recommended range of bispectral index (BIS) in practice. This exploratory retrospective analysis of 138 robotic surgical patients having received total intravenous anesthesia shows that BIS was between 40 and 60 during 61.3% ± 25.2% (mean ± standard deviation [SD]) of maintenance, >60 during 3.1% ± 5.5%, and <40 during 35.7% ± 26.9%. Burst suppression was present during 17.8% ± 22.2%. Female sex is associated with increased periods of BIS <40 (P = .002) as is body mass index (BMI) <26 (P = .012). Increased age is associated with increase in burst suppression (P = .005). A larger study is required to confirm the role of patients' factors on the number of periods of low BIS.

Automated titration of intravenous anesthesia and analgesia using processed electroencephalography monitoring is no longer a novel concept. Closed-loop control of fluid administration to provide goal-directed fluid therapy has also been increasingly described. However, simultaneously combining 2 independent closed-loop systems together in patients undergoing major vascular surgery has not been previously detailed. The aim of this pilot study was to evaluate the clinical performance of fully automated hypnosis, analgesia, and fluid management using 2 independent closed-loop controllers in patients undergoing major vascular surgery before implementation within a larger study evaluating true patient outcomes.

Introduction: Post-operative cognitive dysfunction (POCD) is frequent in patients older than 60 years undergoing major non-cardiac surgery, and increases both morbidity and mortality. Anesthetic drugs may exert neurotoxic effects and contribute to the genesis of POCD. The hypothesis of the POCD-ELA trial was that closed-loop target-controlled infusion of propofol and remifentanil could reduce the occurrence of POCD by decreasing the risk of excessive depth of anesthesia and the dose of anesthetic drugs., Methods and Analysis: We designed a single-center, single-blind, randomized, controlled, parallel trial and aim to include 204 patients aged >60 years undergoing elective major non-cardiac surgery. Patients will be randomized to receive closed-loop versus manual target-controlled infusion of propofol and remifentanil guided by bispectral index monitoring. Cognitive assessment will be performed the day before surgery (baseline) and within 72 hours after surgery, using a battery of validated neuropsychological tests. The primary outcome is the incidence of POCD within 72 hours after surgery. POCD is defined as a Z-score value > 1.96 for at least 2 different tests or a Z-score composite value >1.96. The calculation of the Z-score is based on data from an age-matched control population who did not undergo surgery or general anesthesia., Ethics and Dissemination: This study was approved by the Ethics Committee (Comité de Protection des Personnes Est-II) and authorized by the French Health Products Agency (Agence Nationale de Sécurité des Médicaments, Saint-Denis, France). The University Hospital of Besancon is the trial sponsor and the holder of all data and publication rights. Results of the study will be submitted for publication in a peer-review international medical journal and for presentation in abstract (oral or poster) in international peer-reviewed congresses., Registration: The trial is registered with ClinicalTrials.gov (Identifier: NCT02841423, principal investigator: Prof Emmanuel Samain, date of registration: July 22, 2016). Last amendment of protocol: version 8.0 April 2018.

Background: Hypnosis has a positive effect on peri-operative anxiety and pain., Objective: The objective of this study was to assess the impact of a formal deep hypnosis session on the consumption of propofol for anaesthetic induction using automated administration of propofol guided by the bispectral index (BIS) in a closed loop., Design: A 1 : 1 randomised, usual-care-controlled, single-centre trial., Setting: Tertiary care centre in France from April 2014 to December 2015., Patients: Female adult patients scheduled for outpatient gynaecological surgery under general anaesthesia., Intervention: Before surgery, patients were randomised to receive either a deep hypnosis session or routine care. Anaesthetic induction was performed automatically by propofol without opioids and was assisted by the BIS in a closed loop., Main Outcome Measures: The primary endpoint was the propofol dose required for anaesthesia induction, defined as a BIS less than 60 for at least 30 s., Results: Data for 31 patients in the hypnosis group and 35 in the control group were analysed. There was no evidence of a difference in the mean required propofol dose for anaesthetic induction between the hypnosis and the control groups (2.06 mg kg (95% confidence interval [1.68 to 2.43]) versus 1.79 mg kg (95% CI [1.54 to 2.03]), P = 0.25, respectively)., Conclusion: The current study, which was designed to determine the effect of a deep hypnosis session on anaesthesia induction using an automated tool for propofol administration, failed to detect a difference in the required dose of propofol., Trial Registration: ClinicalTrials.gov, NCT02249364.

Background: Emergence delirium (ED) is an acute change in cognition after general anesthesia (GA) occurring in operative room, recovery room or in postanesthesia care. The automated propofol-remifentanil titration by Bispectral Index (BIS) (AutoTIVA) avoids period of deep (BIS<40) anesthesia and could potentially decrease the ED. The aim of this study was to evaluate ED in surgical patients under AutoTIVA, manual titration of propofol-remifentanil (ManualTIVA) or volatile BIS-guided GA. Moreover, we aimed to evaluate age-related postoperative Mini-Mental State Examination (MMSE) changes., Methods: One hundred and thirty-two adult patients scheduled for elective urologic surgery were randomized in: AutoTIVA, desflurane (DES), sevoflurane (SEVO), ManualTIVA anesthesia. The MMSE was performed before GA and 15 minutes after tracheal extubation., Results: The percentage of BIS 40-60 was significantly higher in the AutoTIVA compared to DES, SEVO and ManualTIVA (87% vs. 78 %, 58%, 39%, respectively; P≤0.001). The percentage of BIS<40 was significantly lower in AutoTIVA than in the other groups (P<0.001). No difference in hemodynamics was found among groups. Postoperative MMSE scores were similar to baseline in the AutoTIVA (26 [24-28] vs. 26 [23-28]) while they markedly decreased in all other groups (P<0.001). Postoperative MMSE decreased at any age. None experienced awareness was recorded., Conclusions: Our results suggest that patients treated with AutoTIVA performed better in the cognitive test compared to the other groups receiving manual target-controlled GA due to a higher adequate level of anesthesia measured by BIS. Cognitive tests should be performed to test ED in all patients undergoing GA.

Background: Decrease of the nociceptive stimulation induced by laryngoscopy could be an advantage for patients without risk of difficult intubation. The present study aimed to compare the difference in nociceptive stimulation between the use of a conventional laryngoscope or of a videolaryngoscope. Amount of nociception was assessed indirectly using the peak remifentanil concentration determined by a closed-loop administration of propofol and remifentanil with bispectral index (BIS) as the input signal (target 50)., Methods: A prospective single-center randomized study was performed including surgical patients without predictable risk of difficult mask ventilation or of difficult tracheal intubation. Forty consecutive surgery patients were randomly assigned to CL group (conventional laryngoscope) or VL group (McGrath Mac videolaryngoscope). Induction of anesthesia was performed automatically using the closed-loop system and myorelaxation with atracurium. The allocation was revealed just before tracheal intubation. The primary outcome was the peak plasma remifentanil concentration observed during the 5-minute period which followed intubation., Results: Sixteen patients in the CL group and 11 in the VL group were analyzed. Plasmatic remifentanil and propofol concentrations were similar in both groups either before tracheal intubation or during the 5 minutes following intubation. There was a nonsignificant between-group difference (P = .09) for the peak concentration of remifentanil. A comparable result was observed for other outcomes except for the heart rate which increased in the CL group., Conclusion: Use of the videolaryngoscope McGrath Mac did not reduce the nociceptive stimulation induced during intubation as evaluated by the automatically administered remifentanil concentration., Trial Registration: ClinicalTrials.gov, NCT02245789.

Background: Thoracic epidural analgesia (TEA) combined with general anesthesia decreases anesthetic requirements by half when hemodynamic criteria are used for the titration of analgesia. We therefore determined the impact of TEA on anesthetic requirements, when a closed-loop controller was used allowing the automated coadministration of propofol-remifentanil guided solely by the Bispectral index., Methods: This single-center double-blind study enrolled patients scheduled for elective posterolateral thoracotomy using TEA. Patients were randomly assigned to receive a bolus followed by a continuous infusion of levobupivacaine 0.5% (levo group) or saline 0.9% solution (saline group). General anesthesia was performed by the same automated controller. Stroke volume optimization guided by an esophageal Doppler probe was performed before randomization. The primary outcome variable was the amount of remifentanil delivered by the automated controller between skin incision and closure. Major arterial hypotension was recorded. Data are presented as medians [interquartile range] or number (%) RESULTS:: Nineteen adult patients per group completed the study. At similar depth of anesthesia evaluated by the percentage of time with the Bispectral index in the range 40-60 (85 [77-88] vs 83 [72-87]; P = .39), patients with neuraxial block required less remifentanil (0.15 [0.10-0.20] vs 0.23 [0.14-0.25], µg·kg·min; P = .03) and propofol (4.3 [3.7-4.9] vs 5.7 [4.6-7.3] mg·kg·h; P = .005). Major arterial hypotension was similar in both groups (6 [32%] vs 5 [25%]; P = .46; levo versus saline group, respectively)., Conclusions: Epidurally administered levobupivacaine allowed a decrease by one-third of remifentanil requirement. After stroke volume optimization, major arterial hypotension was similar between groups.

Objective: The automated administration of propofol in a closed loop could be used to objectively evaluate the nonpharmacological anesthetic action of hypnotherapy. The objective of this study was to evaluate the impact of a conversational hypnosis session on the consumption of propofol for anesthetic induction., Design: A randomized, usual care-controlled, single-center, patient-blind trial., Setting: Tertiary care center in France from November 2012 to December 2013., Participants: Adult patients scheduled for a surgical procedure under general anesthesia., Interventions: Before surgery, patients were randomized with a computer-generated random list for a preoperative conversational hypnosis session or for usual care. The conversational hypnosis session was conducted and individualized by the therapist with an academic degree in hypnosis in a quiet environment. Anesthetic induction was automatically performed by propofol without opioids and was assisted by the bispectral index in a closed loop., Outcome: Primary endpoint was the propofol dose required for anesthesia induction, defined as a Bispectral index less than 60 for at least 30 seconds., Results: The study included 48 patients in the hypnosis group and 49 patients in the control group. No difference in propofol consumption to obtain anesthesia induction was observed between the groups (total dose: 138.6 [67.5] and 130 [47.9] mg, P = .47; adjusted dose: 2.15 [1.09] and 1.95 [0.66] mg/kg, P = .28, for the hypnosis and control groups, respectively). Hetero-evaluation of arm movement during propofol injection (no reaction: 98% and 74%; P = .004, in the hypnosis and control groups, respectively) and face reaction at venous access placement (no reaction 59% and 30%; P = .017, in the hypnosis and control groups, respectively) were lower in the hypnosis group. No adverse event was reported., Conclusions: No difference in propofol consumption was observed in this study designed to evaluate the effect of a hypnotic conversational session on anesthesia induction using an automated tool for propofol administration.

Background: Currently, patients older than 60 years of age represent 25% of the population and are at an increased risk during surgery. Therefore, reducing postoperative morbidity and mortality is a major concern in medical research and practice. Dependence on caregivers and cognitive impairment represent two major risk factors in the elderly, especially in frail patients after surgery under general anesthesia. In this context, continuous monitoring of the depth of anesthesia using a bispectral index (BIS) sensor may reduce the occurrence of impairments by gaining better control of the anesthetic depth. The first aim of this study is to compare manual versus automated administration of intravenous anesthetics with regard to 6-month functional decline in persons aged 70 years and older. The secondary objective includes an evaluation of the influence of the frail phenotype on self-sufficiency in elderly patients after general anesthesia., Methods/design: After receiving ethical committee approval and written consent, a complete preoperative assessment of physiological reserve and self-sufficiency will be performed on patients more than 70 years old who are scheduled for surgery under general anesthesia. This evaluation will determine the patient's frailty status in three categories: robust, pre-frail, and frail. Then, patients will be randomized into two groups: manual administration of anesthetics guided by BIS sensor (manual group) or automated administration (automated group) with recording of the anesthesia. A second examination will be scheduled after 6 months to assess changes in functional abilities, cognitive functions, and frailty status. A priori calculation of sample size gives a population of 430 patients to be included in this multicenter trial., Discussion: This clinical study is designed to detect any postoperative complications and deaths related to the performance of the general anesthesia guided by the BIS sensor and the preoperative functional status of the elderly: robust, pre-frail, or frail., Trial Registration: ClinicalTrials.gov, NCT02524327 . Registered on 10 August 2015.

Background: In obese patients, the incidence of postoperative nausea and vomiting (PONV) following sleeve gastrectomy under titration of total intravenous anaesthesia (TIVA) and the relevance of risk factors to indicate prophylaxis is unknown., Objectives: The hypothesis was that after automated TIVA, prophylaxis reduces PONV following laparoscopic sleeve gastrectomy. Our objective was to determine the incidence of PONV and evaluate the efficacy of dexamethasone and ondansetron as prophylaxis when automated intravenous anaesthesia is employed., Design: A randomised, placebo-controlled, single-centre, double-blinded study., Setting: Secondary care centre in New Caledonia from June 2013 to January 2014., Patients: A total of 122 patients were randomised and 117 (92 women) were included in the analysis (58 in the prophylaxis group and 59 in the placebo group). Eligibility criteria included at least two of the known risk factors for PONV: female sex, nonsmoking status, prior history of PONV or motion sickness and expected postoperative opioid analgesia. Exclusion criteria included disorders limiting the use of the bispectral index., Interventions: All patients received propofol and remifentanil controlled by the same automated system during induction and maintenance of general anaesthesia. The controller modifies the calculated effect-site concentrations according to bispectral index values. Patients received either intravenous dexamethasone 4 mg after tracheal intubation and ondansetron 4 mg during skin closure, or placebo., Main Outcome Measures: The primary endpoint was the cumulative incidences of 24-h PONV and severe PONV (vomiting or nausea with a score of ≥4 on an 11-point verbal rating scale). Data are presented as percentage (95% confidence interval)., Results: PONV in the first 24 h occurred in 45 (34 to 60)% of patients who received prophylaxis and 54 (41 to 67)% in the placebo group (P = 0.35). The numbers of patients who suffered severe PONV [19 (10 to 32)% in the prophylaxis group vs. 20 (11 to 33)%, P = 1, in the placebo group] and who required rescue antiemetic drugs [55 (41 to 68) vs. 63 (49 to 75)%, P = 0.46] were similar between the groups., Conclusion: The combination of dexamethasone and ondansetron was not effective in preventing PONV or severe PONV in obese patients undergoing laparoscopic sleeve gastrectomy after TIVA., Trial Registration: Clinicaltrials.gov identifier: NCT01876290.

Automated anesthesia which may offer to the physician time to control hemodynamic and to supervise neurological outcome and which may offer to the patient safety and quality was until recently consider as a holy grail. But this field of research is now increasing in every component of general anesthesia (hypnosis, nociception, neuromuscular blockade) and literature describes some successful algorithms - single or multi closed-loop controller. The aim of these devices is to control a predefined target and to continuously titrate anesthetics whatever the patients' co morbidities and surgical events to reach this target. Literature contains many randomized trials comparing manual and automated anesthesia and shows feasibility and safety of this system. Automation could quickly concern other aspects of anesthesia as fluid management and this review proposes an overview of closed-loop systems in anesthesia.

Background: NeuroSENSE is a depth of anesthesia monitor that uses automated electroencephalogram quantification. The Wavelet-based Anesthetic Value for Central Nervous System (WAVCNS) index calculated by this monitor is based on wavelet analysis of a normalized electroencephalogram signal in the γ-frequency band. The aim of this study was to determine the extent of disagreement between the Bispectral Index (BIS) and the WAVCNS index during propofol-based and sevoflurane-based maintenance of general anesthesia in a routine surgical population., Methods: Patients undergoing elective surgery were enrolled in the study and randomly assigned to receive either propofol or sevoflurane for the maintenance of anesthesia and remifentanil in both groups. Anesthesiologists were blinded to monitors in both groups. Discordance between the 2 monitors was assessed by the count of discrepancy in recommendation (DR) (type 1 defined as one parameter <40 and the other >60, or type 2 defined as BIS and WAVCNS values on different sides of a threshold [40 or 60]) and also by the proportion of agreement (P0) between WAVCNS and BIS, obtained every 5 seconds, in 3 categories of index (<40, 40-60, and >60)., Results: The analyzed data set consisted of 22 patients (36,872 data pairs) in the propofol group and 24 patients (32,826 data pairs) in the sevoflurane group. The type 1 DR rarely occurred in both the groups (<1%); however, the median (interquartile range) type 2 DR was significantly more frequent in the propofol group (20.6% [7.0-36.9] vs 4.5% [2.3-12.4]; P = 0.0005). The median difference in P0 was 11.53% (95% confidence interval, 0.57-21.32). Major disagreement between WAVCNS index and BIS was related to the weight of burst suppression pattern for the index calculation., Conclusions: Disagreement between BIS and NeuroSENSE during the maintenance of general anesthesia was worse in the propofol group than that in the sevoflurane groups. The disagreement increases during deep anesthesia or in the occurrence of burst suppression.

Background: This study was designed to assess the feasibility of dual closed-loop titration of propofol and remifentanil guided solely by the Bispectral Index (BIS) monitor in pediatric and adolescent patients during anesthesia., Methods: Children undergoing elective surgery in this single-blind randomized study were allocated into the closed-loop (auto) or manual (manual) group. Primary outcome was the percentage of time with the BIS in the range 40 to 60 (BIS40-60). Secondary outcomes were the percentage of deep (BIS<40) anesthesia and drug consumption. Data are presented as median (interquartile range) or number (%)., Results: Twenty-three patients (12 [10 to 14] yr) were assigned to the auto group and 19 (14 [7 to 14] yr) to the manual group. The closed-loop controller was able to provide induction and maintenance for all patients. The percentage of time with BIS40-60 was greater in the auto group (87% [75 to 96] vs. 72% [48 to 79]; P = 0.002), with a decrease in the percentage of BIS<40 (7% [2 to 17] vs. 21% [11 to 38]; P = 0.002). Propofol (2.4 [1.9 to 3.3] vs. 1.7 [1.2 to 2.8] mg/kg) and remifentanil (2.3 [2.0 to 3.0] vs. 2.5 [1.2 to 4.3] μg/kg) consumptions were similar in auto versus manual groups during induction, respectively. During maintenance, propofol consumption (8.2 [6.0 to 10.2] vs. 7.9 [7.2 to 9.1] mg kg h; P = 0.89) was similar between the two groups, but remifentanil consumption was greater in the auto group (0.39 [0.22 to 0.60] vs. 0.22 [0.17 to 0.32] μg kg min; P = 0.003). Perioperative adverse events and length of stay in the postanesthesia care unit were similar., Conclusion: Intraoperative automated control of hypnosis and analgesia guided by the BIS is clinically feasible in pediatric and adolescent patients and outperformed skilled manual control.

Background: The α2-adrenergic agonist dexmedetomidine is a sedative and can be used as an adjunct to anesthetics. Our primary goal was thus to determine the extent to which dexmedetomidine reduces the requirement for propofol and remifentanil., Methods: This double-blinded, randomized study (NCT00921284) used an automated dual closed-loop administration to maintain the Bispectral Index between 40 and 60. Sixty-6 ASA physical status I and II patients were given either dexmedetomidine (1 μg/kg over 10 minutes followed by a continuous infusion of 0.5 μg/kg/h throughout surgery) or comparable volumes of saline as a placebo. Propofol and remifentanil requirements were compared using nonparametric tests and expressed as medians (interquartile ranges)., Results: Twenty-eight patients in each group completed the study. Patients given dexmedetomidine required less propofol (1.0 [0.7-1.3] vs 1.3 [1.0-1.7] mg/kg, P = 0.002) and remifentanil (1.2 [1.0-1.4] vs 1.6 [1.1-2.8] μg/kg, P = 0.02) for anesthetic induction. The propofol dosage required for anesthetic maintenance was 29% (with a 95% confidence interval, 18-40) lower in patients given dexmedetomidine (2.2 [1.5-3.0] vs 3.1 [2.4-4.5] mg/kg/h, P = 0.005), whereas the remifentanil dosage was not significantly different (0.16 [0.09-0.17] vs 0.14 [0.13-0.21] μg/kg/h with P = 0.3). The incidence of adverse events, including hemodynamic instability and delayed recovery, was comparable with and without dexmedetomidine. The first postoperative request for morphine analgesia was delayed in patients given dexmedetomidine (median fourth hour vs first hour, P = 0.008)., Conclusions: Dexmedetomidine administration significantly reduced the requirement for both propofol and remifentanil during anesthetic induction and reduced propofol use during maintenance of anesthesia. Dexmedetomidine also delayed postoperative analgesic use. Dexmedetomidine is a useful adjuvant that reduces anesthetic requirement and provides postoperative analgesia.

Background: Nitrous oxide (N2O) offers both hypnotic and analgesic characteristics. We therefore tested the hypothesis that N2O administration decreases the amount of propofol and remifentanil given by a closed-loop automated controller to maintain a similar bispectral index (BIS)., Methods: In a randomized multicentre double-blind study, patients undergoing elective surgery were randomly assigned to breathe 60% inspired N2O (N2O group) or 40% oxygen (AIR group). Anaesthesia depth was evaluated by the proportion of time where BIS was within the range of 40-60 (BIS40-60). The primary outcomes were propofol and remifentanil consumption, with reductions of 20% in either being considered clinically important., Results: A total of 302 patients were randomized to the N2O group and 299 to the AIR group. At similar BIS40-60 [79 (67-86)% vs 76 (65-85)%], N2O slightly decreased propofol consumption [4.5 (3.7-5.5) vs 4.8 (4.0-5.9) mg kg(-1) h(-1), P=0.032], but not remifentanil consumption [0.17 (0.12-0.23) vs 0.18 (0.14-0.24) µg kg(-1) min(-1)]. For the subgroups of men, at similar BIS40-60 [80 (72-88)% vs 80 (70-87)%], propofol [4.2 (3.4-5.3) vs 4.4 (3.6-5.4) mg kg(-1) h(-1)] and remifentanil [0.19 (0.13-0.25) vs 0.18 (0.15-0.23) µg kg(-1) min(-1)] consumptions were similar in the N2O vs AIR group, respectively. For the subgroups of women, at similar BIS40-60 [76 (64-84)% vs 72 (62-82)%], propofol [4.7 (4.0-5.8) vs 5.3 (4.5-6.6) mg kg(-1) h(-1), P=0.004] and remifentanil [0.18 (0.13-0.25) vs 0.20 (0.15-0.27) µg kg(-1) min(-1), P=0.029] consumptions decreased with the co-administration of N2O., Conclusions: With automated drug administration titrated to comparable BIS, N2O only slightly reduced propofol consumption and did not reduce remifentanil consumption. There was a minor gender dependence, but not by a clinically important amount. Clinical trial registration This study was registered at ClinicalTrials.gov, number NCT00547209.

Background: Several commercial formulations of propofol are available. The primary outcome of this study was the required dose of propofol alone or combined with lidocaine to achieve induction of general anesthesia., Methods: This multicenter, double-blinded trial randomized patients (American Society of Anesthesiologists physical status I-III) just before elective surgery with the use of a computer-generated list. Three different propofol 1% formulations-Diprivan (Astra-Zeneca, Cheshire, United Kingdom), Propoven (Fresenius-Kabi AG, Bad Homburg, Germany), and Lipuro (B-Braun, Melshungen AG, Germany)-were compared with either placebo (saline solution) or lidocaine 1% mixed to the propofol solution. Depth of anesthesia was automatically guided by bispectral index and by a computerized closed-loop system for induction, thus avoiding dosing bias. The authors recorded the total dose of propofol and duration of induction and the patient's discomfort through a behavioral scale (facial expression, verbal response, and arm withdrawal) ranging from 0 to 6. The authors further evaluated postoperative recall of pain using a Visual Analog Scale., Results: Of the 227 patients enrolled, 217 were available for analysis. Demographic characteristics were similar in each group. Propoven required a higher dose for induction (2.2 ± 0.1 mg/kg) than Diprivan (1.8 ± 0.1 mg/kg) or Lipuro (1.7 ± 0.1 mg/kg; P = 0.02). However, induction doses were similar when propofol formulations were mixed with lidocaine. Patient discomfort during injection was significantly reduced with lidocaine for every formulation: Diprivan (0.5 ± 0.3 vs. 2.3 ± 0.3), Propoven (0.4 ± 0.3 vs. 2.4 ± 0.3), and Lipuro (1.1 ± 0.3 vs. 1.4 ± 0.3), all differences significant, with P < 0.0001. No adverse effect was reported., Conclusion: Plain propofol formulations are not equipotent, but comparable doses were required when lidocaine was concomitantly administered.

Closed loop target-control infusion systems using a Bispectral (BIS) signal as an input (TCI Loop) can automatically maintain intravenous anesthesia in a BIS range of 40-60 %. Our purpose was to assess to what extent such a system could decrease anesthesia workload in comparison to the use of a stand alone TCI system manually adjusted to fit the same BIS range of 40-60 % (TCI Manual). Patients scheduled for elective vascular or thoracic surgery were randomized to the TCI Loop or TCI Manual method for administering propofol and remifentanil during both induction and maintenance of general anesthesia. Assessment of workload was performed by an independent observer who quoted each time the physician looked at the BIS monitor. The number of propofol and remifentanil target modifications, the percentage of time of adequate anesthesia i.e. BIS in the range 40-60 and hemodynamic data were recorded. Eighteen patients per group were enrolled. Characteristics, duration of surgery and propofol-remifentanil consumption were similar between groups. However, the percentage of time in the BIS range 40-60 % was higher in the TCI Loop versus TCI Manual groups (94 % ± 12 vs. 74 % ± 19, p < 0.001). Mean arterial pressure was lower with TCI Manual (78 ± 6 vs. 88 ± 13 mmHg, p < 0.001). The number of times the anesthesiologist watched the controller or BIS monitor (p < 0.05) and the number of manual adjustments (p < 0.001) performed in each group was lower with TCI Loop group during induction and maintenance of anesthesia. An automated controller strikingly frees the anesthesiologist from manual intervention to adjust drug delivery.

Background: Anesthesia for rigid bronchoscopic procedures is a demanding procedure. Automatic titration of propofol and remifentanil to maintain the bispectral index (BIS) within the recommended range (40-60) has been reported during routine surgical procedures. The aim of the present study was to evaluate its use during rigid bronchoscopy., Methods: Patients were enrolled in a randomized study comparing manual target-controlled infusion of propofol and remifentanil (manual TCI group) with automatic titration guided by the BIS (dual-loop group). Categorical variables were compared by the Fisher's exact test, and continuous variables (median [interquartile range 25-75]) were compared by the Mann-Whitney test., Results: Thirty-four patients were included in the manual TCI group and 33 were included in the dual-loop group. Baseline characteristics were well balanced between the groups. Intervention by the anesthesiologist in charge to modify propofol and/or remifentanil targets in the dual-loop group was not necessary. Percentage of time spent in the BIS interval (40-60) was similar in the manual TCI and dual-loop groups (69% [48-79] vs 70% [58-80], respectively). Durations of induction and of maintenance and propofol and remifentanil doses were also similar between groups, except for the amount of propofol needed for induction (P = 0.002). Time to tracheal extubation was also similar. No case of intraoperational awareness was detected., Conclusion: The present study could not establish the superiority of automatic system over manual adjustment for bronchoscopy. Further studies with a different design and a larger number of patients are required to establish the place of automatic delivery of anesthetic agents. This study was registered at ClinicalTrials.gov number, NCT00571181.

Background: Emergency physicians and anesthesiologists need accurate estimates of stroke volume when massive unexpected hemorrhage occurs. Using an animal model of hemorrhagic shock under general anesthesia, we hypothesized that the pulse pressure-heart rate ratio (PP/HR) would be an accurate marker of stroke volume changes during hemorrhage and resuscitation., Methods: In 16 swine under bispectral index-controlled, intravenous propofol-remifentanil anesthesia, pressure-controlled hemorrhagic shock was induced to achieve 30 mm Hg of mean arterial pressure, after which treatment was randomized to fluid (HES, n = 4), norepinephrine (NE, n = 4), both (HES + NE, n = 4), or neither (control, n = 4). Pulmonary artery thermodilution continuous cardiac output, stroke volume, and central arterial pressures were recorded at baseline (T0), after 30 minutes (T30) and 60 (T60) minutes of hemorrhage, during treatment (T90 and T120) and after blood retransfusion (T180)., Results: At T60, blood withdrawal was 995 (301) mL (38 [8] mL/kg), resulting in a 70% decrease in stroke volume and a 3.3-fold decrease in PP/HR (each p < 0.01). When stroke volume data pointed at T0, T30 and T60 were plotted against the various hemodynamic variables under study, the PP/HR ratio exhibited the strongest relationship to stroke volume (r = 0.72). The area under the receiver operating characteristic curve set to detect a 15% stroke volume decrease was larger for PP/HR (0.95 [0.94-0.97]) than for mean arterial pressure (0.91 [0.89-0.93]) (p < 0.013). During resuscitation in the HES and NE groups, correlation coefficients were significantly higher between stroke volume and PP/HR (0.75 [0.63-0.84] and 0.79 [0.67-0.86]) than between stroke volume and mean arterial pressure (0.52 [0.32-0.67], p = 0.042, and 0.49 [0.28-0.65], p = 0.0018, respectively)., Conclusion: The PP/HR ratio was strongly related to stroke volume during hemorrhagic shock and resuscitation in anesthetized swine.

Purpose: To compare automated administration of propofol and remifentanil guided by the Bispectral index (BIS) versus manual administration of short-acting drugs in critical care patients requiring deep sedation. The primary outcome was the percentage of BIS values between 40 and 60 (BIS(40-60))., Methods: This randomized controlled phase II trial in the intensive care unit (ICU) was conducted in adults with multiorgan failure. Thirty-one patients were assigned to receive sedation with propofol or remifentanil either by an automated or a manual system, both targeting BIS(40-60). Performance and feasibility of an automated administration were assessed., Results: The study groups were well balanced in terms of demographic characteristics. Study duration averaged 18 [8-24] h in the automated group and 14 [9-21] h in the manual group (p = 0.81). Adequate sedation (BIS(40-60)) was significantly more frequent in the automated group 77 [59-82] % than in the manual group 36 [22-56] %, with p = 0.001. Propofol consumption was reduced by a factor of 2 in the automated group with a median change of infusion rates of 39 ± 9 times per hour. In contrast, there were only 2 ± 1 propofol and 1 ± 1 remifentanil dose changes per hour in the manual group compared to 40 ± 9 for remifentanil in the automated group (p < 0.001). Vasopressors were more often discontinued or reduced in the automated group than in the manual control group (36 [6-40] vs. 12 [4-20] modifications, p = 0.03)., Conclusions: Continuous titration of propofol and remifentanil sedation with an automatic controller maintains deep sedation better than manual control in severely ill patients. It is associated with reduced sedative and vasopressor use.

Background: We have developed a proportional-integral-derivative controller allowing the closed-loop coadministration of propofol and remifentanil, guided by a Bispectral Index (BIS) monitor, during induction and maintenance of general anesthesia. The controller was compared with manual target-controlled infusion., Methods: In a multicenter study, 196 surgical patients were randomly assigned to dual closed-loop or manual administration of propofol and remifentanil. Comparison between groups was evaluated by calculating a global score that characterized the overall performance of the controller including the percentage of adequate anesthesia, defined as BIS between 40 and 60, the median absolute performance error, and wobble. Secondary outcomes included occurrence of burst suppression ratio, time to tracheal extubation, and drug consumption., Results: Eighty-three patients assigned to dual-loop control and 84 patients assigned to manual control completed the study. The global score and the percentage of time with BIS between 40 and 60 were better in the dual-loop group (26 ± 11 vs 43 ± 40, P < 0.0001; 82% ± 12% vs 71% ± 19%, P < 0.0001). Overshoot (BIS <40), undershoot (BIS >60), and burst suppression ratio were all significantly less common in the dual-loop group. Modifications to the propofol and remifentanil infusions were more frequent, and adjustments smaller in the dual-loop group. Remifentanil consumption was greater (0.22 ± 0.07 vs 0.16 ± 0.07 μg · kg(-1) · min(-1); P < 0.0001) and the speed to tracheal extubation was shorter (10 ± 4 vs 11 ± 5 minutes; P = 0.02) in the dual-loop group., Conclusion: The controller allows the automated delivery of propofol and remifentanil and maintains BIS values in predetermined boundaries during general anesthesia better than manual administration.

We report a case during which it was simultaneously recorded usual Bispectral Index (BIS) values and elevated suppression ratio (SR) during resuscitation maneuvers. A 52-year-old woman, scheduled for a suspension laryngoscopy, required cardio-pulmonary resuscitation due to an anaphylactic shock secondary to the administration of succinylcholine. Post-crisis analysis of the BIS trace showed both BIS numbers consistent with an adequate level hypnosis and an increase in SR. Simultaneous hypnotic BIS values and an elevated SR is striking as SR quantifies electroenceph- alographic suppression. Clinicians must remember that SR is one of the parameters incorporated into BIS and must take SR into account even when the BIS is within the target range.

Objective: To determine if propofol infusion can be steered automatically by using bispectral index (BIS) as a controller during lung transplantation., Design: A prospective study of patients undergoing lung transplantation., Setting: University hospital., Participants: Twenty consecutive patients scheduled for bilateral (n = 14) or single (n = 6) lung transplantation., Interventions: The goal of the closed-loop administration of propofol was to maintain the BIS value between 40 and 60 during the maintenance phase. The remifentanil infusion was adjusted according to standard clinical practice., Measurements and Main Results: The closed-loop system was able to provide anesthesia maintenance for all patients. Cardiopulmonary bypass was used in 5 patients, and 14 patients received a thoracic epidural catheter. The BIS value was maintained between 40 and 60 during 84% +/- 16% of the maintenance phase. Eleven patients were extubated in the operating room, and 1 patient needed reintubation., Conclusion: Closed-loop control of consciousness by a computer during lung transplantation is clinically feasible.

This review analyzes the clinical studies concerning the automated perfusion, or closed-loop, of propofol guided by the bispectral index (BIS). To carry out the maintenance of general anaesthesia by a closed loop propofol-BIS is feasible as shown by studies comprising few low risk patients. We showed that induction of anaesthesia is feasible with a closed loop, haemodynamic stability being similar to a manual titration. A second study, bearing on the whole of the anaesthesia of patients ASA I to III undergoing very diverse surgical acts, showed that the closed loop propofol-BIS was more precise than a manual perfusion. This confirms that the closed loop propofol-BIS is not an esoteric research and that it represents a tool with a future for the clinician.