Reversal of neuromuscular blockade with sugammadex during continuous administration of anaesthetic agents: a double-blind randomised crossover study using the bispectral index.

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.

Feasibility of closed-loop co-administration of propofol and remifentanil guided by the bispectral index in obese patients: a prospective cohort comparison.

BACKGROUND: We used an automated bispectral index (BIS)-guided dual-loop controller to determine propofol and remifentanil requirements during general anaesthesia in obese and lean surgical patients. METHODS: Obese patients, BMI>35 kg m(-2), and lean patients (<25 kg m(-2)) having laparoscopic procedures were prospectively evaluated in this multicentre single-blind study. The automated controller targeted BIS between 40 and 60 by adjusting propofol and remifentanil administration. Propofol and remifentanil consumptions were calculated using both total body weight (TBW) and ideal body weight (IBW). Results are expressed as medians (inter-quartile range). RESULTS: Thirty obese [BMI=43 (40-49) kg m(-2)] and 29 lean [BMI=23 (21-25) kg m(-2)] patients completed the study. BIS was between 40 and 60 during 84 (69-91)% vs 85 (78-92)% of the anaesthetic time, P=0.46. The amount of propofol given during induction [1.2 (1.1-1.6) vs 1.3 (1.0-1.7) mg kg(-1), P=0.47] and maintenance [5.2 (4.1-6) vs 5.3 (4.7-6.4) mg kg(-1) h(-1), P=0.39] calculated using TBW was similar between the two groups. The dual-loop controller delivered half as much remifentanil to the obese patients during induction [1.0 (0.8-1.6) vs 2.2 (1.5-2.7) µg kg(-1), P<0.001] and maintenance [0.12 (0.07-0.16) vs 0.25 (0.17-0.29) µg kg(-1) min(-1), P<0.001] calculated using TBW. But when remifentanil consumption was calculated using IBW, the amounts were similar during induction at 2.2 (1.6-3.5) vs 2.0 (1.6-3.0) µg kg(-1) IBW, P=0.48, and during maintenance at 0.26 (0.16-0.34) vs 0.27 (0.18-0.33 ) µg kg(-1) min(-1), P=0.50. CONCLUSIONS: The amount of propofol-remifentanil administered by the controller is consistent with current knowledge, propofol is best dosed using TBW whereas remifentanil is best dosed using IBW. CLINICAL TRIAL REGISTRATION: NCT00779844.

Nitrous oxide does not produce a clinically important sparing effect during closed-loop delivered propofol-remifentanil anaesthesia guided by the bispectral index: a randomized multicentre study.

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.

CNAP(®) does not reliably detect minimal or maximal arterial blood pressures during induction of anaesthesia and tracheal intubation.

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 mmHg 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.

The Analgesia Nociception Index: a pilot study to evaluation of a new pain parameter during labor.

BACKGROUND: Objective pain assessment that is not subject to influences from either cultural or comprehension issues is desirable. Analysis of heart rate variability has been proposed as a potential method. This pilot study aimed to assess the performance of the PhysioDoloris™ analgesia monitor which calculates an Analgesia Nociception Index derived from heart rate variability. It was compared with visual analogical pain scores. METHODS: Forty-five parturients who requested epidural analgesia were recruited. Simultaneous couplets of pain scores and Analgesia Nociception Index values were recorded every 5 min regardless of the presence or absence of uterine contractions. The relationship between indices was characterized, and a cut-off value of Analgesia Nociception Index corresponding to a visual analogical score >30 (range 0-100) was used to determine the positive and negative predictive value of the Analgesia Nociception Index. RESULTS: There was a negative linear relationship between visual analogical pain scores and Analgesia Nociception Index values regardless of the presence of uterine contractions (regression coefficient ± SEM=-0.18 ± 0.032 for entire dataset). Uterine contraction significantly reduced the Analgesia Nociception Index (P<0.0001). Using a visual analogical pain score >30 to define a painful sensation, the lower 95% confidence limit for the Analgesia Nociception Index score was 49. CONCLUSION: The Analgesia Nociception Index has an inverse linear relationship with visual analogical pain scores. Further studies are necessary to confirm the results of this pilot study and to look at the influence of epidural analgesia on the Analgesia Nociception Index.

Occurrence of and risk factors for electroencephalogram burst suppression during propofol-remifentanil anaesthesia.

BACKGROUND: Suppression ratio (SR) derived from bispectral index (BIS) monitoring is correlated to EEG burst suppression. It may occur during deep anaesthesia, but also in the case of metabolic or haemodynamic brain injury. The goal of the study was to describe the occurrence of SR and to determine factors associated with SR during propofol-remifentanil general anaesthesia maintenance. METHODS: We conducted a post hoc analysis of BIS recordings in consecutive patients included in two multi-centre trials, undergoing non-cardiac surgery using a dual closed-loop BIS controller allowing automated propofol-remifentanil administration. The percentage of time spent with a BIS value between 40 and 60 (T(BIS 40-60)) was measured. Two groups of patients were defined: the SR group, including patients with at least one episode of SR value >10% lasting more than 1 min, and the control group. Factors associated with SR were analysed using a stepwise multivariate analysis. RESULTS: A total of 1494 patients [age=57 (17) yr; T(BIS 40-60)=76 (17%)] were analysed and 131 (8.7%) patients constituted the SR group. The main independent factors associated with SR were advanced age [odds ratio (95% confidence interval)=4.80 (1.85-12.43) (P=0.027), 10.59 (3.76-29.81) (P<0.0001), for categories of age 60-80 and >80 yr, respectively], history of coronary artery disease (CAD) [2.53 (1.47-4.37) (P=0.001)] and male gender [1.57 (1.03-2.40) (P=0.03)]. CONCLUSIONS: The occurrence of SR during BIS-controlled propofol and remifentanil anaesthesia is mainly observed in elderly male patients or in patients with a history of CAD. The mechanisms underlying SR and the potential consequences for the patient's postoperative outcome remain unsolved.

BIS response to tamponade and dobutamine in swine varies with hypnotic/opiate ratio.

OBJECTIVES: This study in swine assessed BIS stability in response to decreases and increases in cardiac output under two propofol/remifentanil dosage combinations, both producing the same depth of surgical anaesthesia. METHODS: Eight anaesthetized-paralyzed ventilated adult swine were studied using a random-order cross-over design. Four received a P low/R high combination (P, 8.4+/-0.9 mg/kg/h; and R, 0.54+/-0.02 microg/kg/min) and then a P high/R low combination (P, 26.7+/-2.1mg/kg/h; and R, 0.34+/-0.01 microg/kg/min). The other four had these two combinations in the reverse order. Under each P/R combination, and after a 60-minutes steady state, a 15-minute stable cardiac tamponade was induced by intrapericardial gelatine infusion. Then, after returning to pre tamponade condition, a 15 minutes period with dobutamine was allowed. RESULTS: Tamponade induced falls in average mean arterial pressure (MAP) (from 79+/-18 to 47+/-9 mm Hg; p<0.05) and cardiac output (Qc) (from 1.90+/-0.46 l/min to 1.20+/-0.38 l/min, p<0.05). Conversely, dobutamine increased both MAP and Qc (p<0.05). During each type of hemodynamic challenges, changes in anaesthesia depth as assessed by BIS differed dramatically between the two drug combinations, despite observing the same percent change in P and R effect-site concentration. With P high/R low and tamponade, BIS fell from 65+/-5 to 29+/-10 (p<0.05); dobutamine produced opposite effects. With P low/R high, in contrast, BIS was not influenced by either of the hemodynamic challenges. CONCLUSION: Conversely to a high propofol/low remifentanil combination, a low propofol/high remifentanil combination allows constant anaesthetic depth in the face of haemodynamic challenges.

[Closed-loop titration of propofol guided by the bispectral index]. / Titration automatisée du propofol guidée par l'index bispectral.

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.

Feasibility of closed-loop titration of propofol guided by the Bispectral Index for general anaesthesia induction: a prospective randomized study.

BACKGROUND: This study was designed to evaluate the feasibility of propofol infusion by a closed-loop system for the titration of anaesthetic induction guided by Bispectral Index. METHODS: Forty patients were prospectively and randomly allocated into two groups: the target control infusion (TCI) group, where propofol titration was performed manually guided by the Bispectral Index using a commercial pharmacokinetic model (Diprifusor device) and the closed-loop group where titration was performed using a proportional differential algorithm. For both groups, the objective was to achieve a Bispectral Index of 50. Remifentanil TCI was infused at a target of 2 ng mL-1 and was maintained constant throughout the study. Feasibility of automatic induction was evaluated with performance error and haemodynamic data. RESULTS: Bispectral Index overshoot (-9 +/- 13% vs. -16 +/- 20%, P = 0.035) and mean duration of induction (381 +/- 106 s vs. 490 +/- 131 s, P = 0.004) were lower in the closed-loop group than in the TCI group. Haemodynamic data were similar between groups with a similar use of ephedrine bolus. CONCLUSION: The system was able to allow induction clinically for all patients. Automated titration guided by Bispectral Index for propofol infusion was feasible without increase in haemodynamic adverse effects.