Bispectral index dynamics during propofol hypnosis is similar in red-haired and dark-haired subjects.

BACKGROUND: We have previously shown that red hair is associated with increased desflurane requirement for immobility, compared with dark hair. The effect of red hair on IV anesthetic requirement remains unknown. We tested the hypothesis that the propofol concentration in the effect site associated with half maximal electroencephalogram response, Ce50, is at least 50% higher in subjects with red hair. METHODS: We modeled the propofol concentration versus electroencephalogram response relationship using a 2-step approach in 29 healthy dark- and red-haired volunteers receiving a propofol infusion to produce loss of consciousness. Bispectral Index (BIS) was the measure of drug effect. The parameters of a 3-compartment pharmacokinetic model were fit to measured arterial propofol concentrations. The relationship between effect-site propofol concentration (Ce) and BIS was characterized using a sigmoid Emax model. Model performance and accuracy of the estimated parameters were evaluated using accepted metrics and bootstrap resampling. The effect of hair color on the Ce50 for BIS response in the final model was assessed using a threshold of 6.63 (P<0.01) in reduction of -2 log likelihood. The influence of body weight on the model was also assessed. RESULTS: The inclusion of hair color as a model covariate did not improve either the pharmacokinetic or the pharmacodynamic model. A separate analysis for the dark- and red-haired subjects estimated a median (95% confidence interval) Ce50 BIS of 2.71 µg/mL (2.28-3.36 µg/mL) and 2.57 µg/mL (1.68-3.60 µg/mL), respectively. Body weight was a significant covariate for the CL1 and V1. CONCLUSIONS: Red hair phenotype does not affect the pharmacokinetics or pharmacodynamics of propofol.

Reinforcement learning versus proportional-integral-derivative control of hypnosis in a simulated intraoperative patient.

BACKGROUND: Research has demonstrated the efficacy of closed-loop control of anesthesia using bispectral index (BIS) as the controlled variable. Model-based and proportional-integral-derivative (PID) controllers outperform manual control. We investigated the application of reinforcement learning (RL), an intelligent systems control method, to closed-loop BIS-guided, propofol-induced hypnosis in simulated intraoperative patients. We also compared the performance of the RL agent against that of a conventional PID controller. METHODS: The RL and PID controllers were evaluated during propofol induction and maintenance of hypnosis. The patient-hypnotic episodes were designed to challenge both controllers with varying degrees of interindividual variation and noxious surgical stimulation. Each controller was tested in 1000 simulated patients, and control performance was assessed by calculating the median performance error (MDPE), median absolute performance error (MDAPE), Wobble, and Divergence for each controller group. A separate analysis was performed for the induction and maintenance phases of hypnosis. RESULTS: During maintenance, RL control demonstrated an MDPE of -1% and an MDAPE of 3.75%, with 80% of the time at BIS(target) ± 5. The PID controller yielded a MDPE of -8.5% and an MDAPE of 8.6%, with 57% of the time at BIS(target) ± 5. In comparison, the MDAPE in the worst-controlled patient of the RL group was observed to be almost half that of the worst-controlled patient in the PID group. CONCLUSIONS: When compared with the PID controller, RL control resulted in slower induction but less overshoot and faster attainment of steady state. No difference in interindividual patient variation and noxious destabilizing challenge on control performance was observed between the 2 patient groups.

Reinforcement learning: a novel method for optimal control of propofol-induced hypnosis.

Reinforcement learning (RL) is an intelligent systems technique with a history of success in difficult robotic control problems. Similar machine learning techniques, such as artificial neural networks and fuzzy logic, have been successfully applied to clinical control problems. Although RL presents a mathematically robust method of achieving optimal control in systems challenged with noise, nonlinearity, time delay, and uncertainty, no application of RL in clinical anesthesia has been reported.

Fuzzy control for closed-loop, patient-specific hypnosis in intraoperative patients: a simulation study.

Research has demonstrated the efficacy of closed-loop control of anesthesia using bispectral index (BIS) as the controlled variable, and the recent development of model-based, patient-adaptive systems has considerably improved anesthetic control. To further explore the use of model-based control in anesthesia, we investigated the application of fuzzy control in the delivery of patient-specific propofol-induced hypnosis. In simulated intraoperative patients, the fuzzy controller demonstrated clinically acceptable performance, suggesting that further study is warranted.

The timing of acupuncture stimulation does not influence anesthetic requirement.

Studies suggest that acupuncture is more effective when induced before the induction of general anesthesia than afterwards. We tested the hypothesis that electro-acupuncture initiated 30 min before the induction reduces anesthetic requirement more than acupuncture initiated after the induction. Seven volunteers were each anesthetized with desflurane on 3 study days. Needles were inserted percutaneously at four acupuncture points thought to produce analgesia in the upper abdominal area and provide generalized sedative and analgesic effects: Zusanli (St36), Sanyinjiao (Sp6), Liangqiu (Sp34), and Hegu (LI4). Needles were stimulated at 2 Hz and 10 Hz, with frequencies alternating at 2-s intervals. On Preinduction day, electro-acupuncture was started 30 min before the induction of anesthesia and maintained throughout the study. On At-induction day, needles were positioned before the induction of anesthesia, but electro-acupuncture stimulation was not initiated until after the induction. On Control day, electrodes were positioned near the acupoints, but needles were not inserted. Noxious electrical stimulation was administered via 25-gauge needles on the upper abdomen (70 mA; 100 Hz; 10 s). The desflurane concentration was increased 0.5% when movement occurred and decreased 0.5% when it did not. These up-and-down sequences continued until volunteers crossed from movement to no movement four times. The P(50) of logistic regression identified desflurane requirement. Desflurane requirement was similar on the Control (mean +/- sd; 5.2% +/- 0.6%), Preinduction (5.0% +/- 0.8%), and At-induction (4.7% +/- 0.3%; P = 0.125) days. This type of acupuncture is thus unlikely to facilitate general anesthesia or decrease the requirement for anesthetic drugs.

Electro-acupuncture at the Zusanli, Yanglingquan, and Kunlun points does not reduce anesthetic requirement.

UNLABELLED: We tested the hypothesis that electro-acupuncture at the Zusanli, Yanglingquan, and Kunlun acupuncture points on the legs decreases anesthetic requirement. Fourteen young, healthy volunteers were anesthetized with desflurane on two separate days. Needle electrodes were positioned at the three acupuncture points thought to produce a generalized sedative and analgesic effect. Needles were percutaneously placed on treatment days; on control days, they were insulated and taped near the insertion points. The electrodes were stimulated on the treatment day. Stimulation consisted of 2-Hz and 100-Hz currents alternated at 2-s intervals. When the end-tidal desflurane concentration of 5.5% was stable for 15 min, noxious electrical stimuli were administered via 25-gauge needles on both thighs (70 mA at 100 Hz for 10 s). Desflurane concentration was increased 0.5% when movement occurred and decreased 0.5% when it did not. An investigator, blinded to treatment, determined movement. These up-and-down sequences were continued until volunteers crossed from movement to no movement four times. A logistic regression determined the partial pressure of desflurane that produced a 50% likelihood of movement in response to noxious stimulation and consequently identified the minimum alveolar anesthetic concentration equivalent for desflurane. There was no significant difference in minimum alveolar anesthetic concentration equivalents between the electro-acupuncture (4.6% +/- 0.6%, mean +/- SD) and control (4.6% +/- 0.8%) days (P = 0.8). These data provided an 80% power for detecting a difference of 0.35 volume-percent between the groups. IMPLICATIONS: Electro-stimulation of three general acupuncture points on the leg did not reduce desflurane requirements. This type of acupuncture is thus unlikely to facilitate general anesthesia or decrease the need for anesthetic drugs.

Transcutaneous electrical stimulation of an auricular acupuncture point decreases anesthetic requirement.

BACKGROUND: German anesthesiologists have long used transcutaneous electrical stimulation of an acupuncture point near the tragus to reduce anesthetic requirement in unblinded and uncontrolled trials. This is known as auricular electrically stimulated analgesia. The authors therefore tested the hypothesis that auricular electrically stimulated analgesia reduces anesthetic requirement. METHODS: In a randomized, double-blind, crossover trial, volunteers were anesthetized twice with desflurane. Electrical stimulation of an auricular acupuncture point in the vicinity of the tragus was used on 1 randomly assigned day, and no electrical stimulation of the same point was used on the other study day. Treatment consisted of bilateral electrical stimulation of the lateralization control point, 3 cm anterior to the tragus. The 10-mA current was set to 299 Hz on the dominant side of the face and to 149 Hz on the contralateral side. Anesthetic requirement was determined by the Dixon up-and-down method and was defined by the average desflurane concentration required to prevent purposeful movement of the extremities in response to noxious electrical stimulation. RESULTS: Ten men and 10 women completed the protocol. Electrical stimulation of the lateralization control point reduced anesthetic requirement by 11 +/- 7% (P < 0.001), with the reduction being similar in women and men. Women required more desflurane to prevent movement on the control day than the men (5.5 +/- 1.0 vs. 4.6 +/- 0.6 vol%; P = 0.028). CONCLUSION: This double-blinded trial with an objective outcome demonstrates that electrical stimulation of the lateralization control point significantly reduces anesthetic requirement.