Comparative Analysis of the Performance of Electroencephalogram Parameters for Monitoring the Depth of Sedation During Remimazolam Target-Controlled Infusion.

BACKGROUND: The changes in hypnotic indicators in remimazolam sedation remain unclear. We investigated the correlation of the electroencephalogram (EEG) parameters with the effect-site remimazolam concentration and the depth of sedation in patients receiving a target-controlled infusion of remimazolam. METHODS: This prospective observational study enrolled 35 patients (32 analyzed) who underwent lower extremity varicose vein surgery or lower extremity orthopedic surgery under spinal anesthesia. We administered remimazolam by target-controlled infusion using the pharmacokinetic model introduced by Schüttler et al. The EEG data were continuously recorded, including the bispectral index (BIS), patient state index (PSI), spectral edge frequency (SEF), and raw EEG signals. The relative beta ratio (RBR), defined as log (spectral power [30-47 Hz]/spectral power [11-20 Hz]), was obtained by analyzing raw EEG. The level of sedation corresponding to each effect-site remimazolam concentration was assessed using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S). The prediction probability (Pk) and Spearman's correlation coefficients (R) were calculated between effect-site remimazolam concentration, MOAA/S, and EEG parameters. RESULTS: BIS and PSI showed significantly higher Pk for effect-site remimazolam concentration (Pk = 0.76 [0.72-0.79], P < .001 for BIS; Pk = 0.76 [0.73-0.79], P < .001 for PSI) compared to RBR (Pk = 0.71 [0.68-0.74], P < .001) and SEF (Pk = 0.58 [0.53-0.63], P = .002). BIS, PSI, and RBR showed significantly higher correlation coefficients for effect-site remimazolam concentration (R = -0.70 [-0.78 to -0.63], P < .001 for BIS; R = -0.72 [-0.79 to -0.66], P < .001 for PSI; R = -0.61 [-0.69 to -0.54], P < .001 for RBR) compared to SEF (R = -0.22 [-0.36 to -0.08], P = .002). BIS and PSI also had significantly higher Pk and correlation coefficients for MOAA/S (Pk = 0.81 [0.79-0.83], P < .001; R = 0.84 [0.81-0.88], P < .001 for BIS) (Pk = 0.80 [0.78-0.83], P < .001; R = 0.82 [0.78-0.87], P < .001 for PSI) compared to RBR (Pk = 0.74 [0.72-0.77], P < .001; R = 0.72 [0.65-0.78], P < .001) and SEF (Pk = 0.55 [0.50-0.59], P = .041; R = 0.13 [-0.01 to 0.27], P = .067). CONCLUSIONS: BIS, PSI, and RBR showed an acceptable correlation with the effect-site remimazolam concentration and depth of sedation in this study, suggesting that these EEG-derived parameters are potentially reliable hypnotic indicators during remimazolam sedation. BIS and PSI showed superior performance as hypnotic indicators to RBR and SEF in patients receiving target-controlled infusion of remimazolam.

Association between preoperative frontal electroencephalogram alpha asymmetry and postoperative quality of recovery: an observational study.

BACKGROUND: Left-sided frontal alpha asymmetry on electroencephalograms, which indicates decreased relative left-hemispheric activity, has been associated with depression, anxiety, and stress responsivity. We aimed to evaluate the association between perioperative measures of frontal alpha asymmetry and quality of recovery (QoR) after surgery. METHODS: We enrolled 110 female patients undergoing thyroidectomy and recorded perioperative electroencephalograms. The power of the prefrontal alpha band (8-13 Hz) was measured in the Fp1 and Fp2 leads. Left-sided frontal alpha asymmetry was defined as a higher alpha band power in Fp1 than in Fp2 and vice versa. QoR was assessed using the QoR-15 score on the day before surgery and postoperative days 1 and 2. The primary study endpoint was a difference in postoperative global QoR-15 score between preoperative left-sided and right-sided alpha asymmetry groups. The predictability of frontal alpha asymmetry for poor QoR-15 score was also evaluated. RESULTS: The global QoR-15 score showed a significant group-by-time interaction, and post-hoc analysis revealed significantly lower scores on postoperative days 1 (P=0.006) and 2 (P<0.001) in the left-sided frontal alpha asymmetry group. In the multivariate logistic regression analysis, preoperative left-sided frontal alpha asymmetry was associated with a 3.3-fold increased risk of the lowest tertile for the postoperative day 1 QoR-15 score (95% CI: 1.31-8.24; P=0.011). CONCLUSIONS: Preoperative left-sided frontal alpha asymmetry was independently associated with a lower postoperative QoR-15 score in female patients undergoing thyroidectomy, highlighting the potential role of preoperative frontal electroencephalography in predicting patient-centred outcomes after surgery. CLINICAL TRIAL REGISTRATION: KCT0006586 (http://cris.nih.go.kr/).

An allometric pharmacokinetic model and minimum effective analgesic concentration of fentanyl in patients undergoing major abdominal surgery.

BACKGROUND: We aimed to characterise the population pharmacokinetics of fentanyl in adults and to determine the minimum effective concentration (MEC) and minimum effective analgesic concentration (MEAC) of i.v. fentanyl in patients after major abdominal open surgery. METHODS: In the pharmacokinetic study, subjects received an intravenous bolus of fentanyl 100 µg during operation, and arterial blood was sampled at pre-set intervals. In addition, data from previously published fentanyl pharmacokinetic studies were incorporated to build a pharmacokinetic model. In the MEAC study, subjects were asked to rate their pain every 10 min using a VAS (0=no pain, 10=most severe pain) in the PACU. The first blood sample was obtained when wound pain was rated as ≥3 at rest or ≥5 during compression. Then, fentanyl 50 µg was administered every 10 min until the pain intensity had decreased to <3 at rest and <5 during compression, at which point the second blood was sampled and the first MEAC of fentanyl was measured. The same procedure was repeated to obtain a third sample (MEC) and a fourth sample (second MEAC). RESULTS: In the population pharmacokinetic study (n=95), the plasma concentration of fentanyl over time was well-described by the three-compartment mammillary model using an allometric expression. The V1, V2, V3, Cl, Q1, and Q2 of a 70 kg subject were 10.1, 26.5, 206 L, 0.704, 2.38, and 1.49 L min-1, respectively. In the MEAC study (n=30), the median (inter-quartile range) MEC and MEAC were 0.72 (0.58-1.05) ng ml-1, and 0.99 (0.76-1.28) ng ml-1, respectively. CONCLUSION: These results provide a scientific basis for the use of fentanyl for acute postoperative pain management in surgical patients. CLINICAL TRIAL REGISTRATION: KCT0003273 (http://cris.nih.go.kr).

The changes of cerebral hemodynamics during ketamine induced anesthesia in a rat model.

Current electroencephalogram (EEG) based-consciousness monitoring technique is vulnerable to specific clinical conditions (eg, epilepsy and dementia). However, hemodynamics is the most fundamental and well-preserved parameter to evaluate, even under severe clinical situations. In this study, we applied near-infrared spectroscopy (NIRS) system to monitor hemodynamic change during ketamine-induced anesthesia to find its correlation with the level of consciousness. Oxy-hemoglobin (OHb) and deoxy-hemoglobin concentration levels were continuously acquired throughout the experiment, and the reflectance ratio between 730 and 850 nm was calculated to quantify the hemodynamic changes. The results showed double peaks of OHb concentration change during ketamine anesthesia, which seems to be closely related to the consciousness state of the rat. This finding suggests the possibility of NIRS based-hemodynamic monitoring as a supplementary parameter for consciousness monitoring, compensating drawbacks of EEG signal based monitoring.

Monitoring cerebral oxygenation and local field potential with a variation of isoflurane concentration in a rat model.

We aimed to investigate experimentally how anesthetic levels affect cerebral metabolism measured by near-infrared spectroscopy (NIRS) and to identify a robust marker among NIRS parameters to discriminate various stages of anesthetic depth in rats under isoflurane anesthesia. In order to record the hemodynamic changes and local field potential (LFP) in the brain, fiber-optic cannulae and custom-made microelectrodes were implanted in the frontal cortex of the skull. The NIRS and LFP signals were continuously monitored before, during and after isoflurane anesthesia. As isoflurane concentration is reduced, the level of oxyhemoglobin and total hemoglobin concentrations of the frontal cortex decreased gradually, while deoxyhemoglobin increased. The reflectance ratio between 730nm and 850nm and burst suppression ratio (BSR) correspond similarly with the change of oxyhemoglobin during the variation of isoflurane concentration. These results suggest that NIRS signals in addition to EEG may provide a possibility of developing a new anesthetic depth index.