The Effect of Low-Dose Intraoperative Ketamine on Closed-Loop-Controlled General Anesthesia: A Randomized Controlled Equivalence Trial

Abstract

BACKGROUND: Closed-loop control of propofol-remifentanil anesthesia using the processed electroencephalography depth-of-hypnosis index provided by the NeuroSENSE monitor (WAVCNS) has been previously described. The purpose of this placebo-controlled study was to evaluate the performance (percentage time within ±10 units of the setpoint during the maintenance of anesthesia) of a closed-loop propofol-remifentanil controller during induction and maintenance of anesthesia in the presence of a low dose of ketamine. METHODS: Following ethical approval and informed consent, American Society of Anesthesiologist (ASA) physical status I–II patients aged 19–54 years, scheduled for elective orthopedic surgery requiring general anesthesia for >60 minutes duration, were enrolled in a double-blind randomized, placebo-controlled, 2-group equivalence trial. Immediately before induction of anesthesia, participants in the ketamine group received a 0.25 mg·kg−1 bolus of intravenous ketamine over 60 seconds followed by a continuous 5 µg·kg−1·min−1 infusion for up to 45 minutes. Participants in the control group received an equivalent volume of normal saline. After the initial study drug bolus, closed-loop induction of anesthesia was initiated; propofol and remifentanil remained under closed-loop control until the anesthetic was tapered and turned off at the anesthesiologist’s discretion. An equivalence range of ±8.99% was assumed for comparing controller performance. RESULTS: Sixty patients participated: 41 males, 54 ASA physical status I, with a median (interquartile range [IQR]) age of 29 [23, 38] years and weight of 82 [71, 93] kg. Complete data were available from 29 cases in the ketamine group and 27 in the control group. Percentage time within ±10 units of the WAVCNS setpoint was median [IQR] 86.6% [79.7, 90.2] in the ketamine group and 86.4% [76.5, 89.8] in the control group (median difference, 1.0%; 95% confidence interval [CI] −3.6 to 5.0). Mean propofol dose during maintenance of anesthesia for the ketamine group was higher than for the control group (median difference, 24.9 µg·kg−1·min−1; 95% CI, 6.5-43.1; P = .005). CONCLUSIONS: Because the 95% CI of the difference in controller performance lies entirely within the a priori equivalence range, we infer that this analgesic dose of ketamine did not alter controller performance. Further study is required to confirm the finding that mean propofol dosing was higher in the ketamine group, and to investigate the implication that this dose of ketamine may have affected the WAVCNS.

A utilização das técnicas opioid-free e opioid-sparing na prática Anestésica

“…Associada com o uso do propofol, a cetamina pode potencializar o efeito hipotensor do mesmo. Por isso, mais estudos devem ser realizados para o ajuste da profundidade da hipnose, em particular para doses mais altas de cetamina (bolus) em grupos de pacientes que poderão ter alguma sensibilidade diferente à mesma (NAPOLEONE et al, 2021).…”

Ready for a “breakthrough” with ketamine? A look at recent pharmacological insights!

“…PK/PD tools have also been suggested in combination with Bayesian model adaptation systems or closed-loop titration to improve accuracy and stability [35,49]. In a recent controlled equivalence trial, low-dose intraoperative ketamine was added to closed-loop control of propofol-remifentanil anesthesia using a processed EEG depth-of-hypnosis index (NeuroSENSE monitor [WAVCNS]) [53]. Ketamine did not alter controller performance, but propofol dosing was increased.…”

Uncertainty Minimization and Feasibility Study for Managing the Complex and Interacting Anesthesia-Hemodynamic System

“…There is evidence that computer-based control systems are feasible to be used with overall tighter control than manual guided total intravenous anesthesia (TIVA) by providing a significant reduction of excessive depth of anesthesia [5], [6]. Current solutions for computer-guided anesthesia management are based on feedback closed-loop control systems, either single loop, or dual-loop optimized, for part of the anesthesia states [5], [7], [8]. Nevertheless, core to the automation trend is the control of the full complex intravenous anesthetic states system.…”