Comparison of Entropy vs. Bispectral Index Anesthetic Depth Monitoring during Isoflurane Anesthesia in Living Donor Liver Transplantation: Observational Study

Liver transplantation (LT) recipients are known to require less anesthetic agents. Providing minimally required anesthetics while avoiding awareness is especially important in LT recipients because it would help manage perioperative hemodynamic instability with less vasopressor and fast track recovery. This study aims to compare state entropy (SE) against bispectral index (BIS) during isoflurane anesthesia in LT. We adjusted anesthesia to BIS values 40 - 60, and compared it with concomitant SE values. BIS, SE values, and anesthetic requirements according to liver failure severity, etiology and LT stages were analyzed. For BIS-SE differences, SE value that is different from the concomitant BIS by more than 15 was defined as a significant disagreement. Mann Whitney, Kruskal Wallis test and a Poisson exact test were used for analysis. The BIS-SE pair sets of 2895 from 38 patients were analyzed. BIS, SE values and anesthetic requirements were significantly lower in MELD ≥ 20 (p < 0.001 in all) and in alcoholic etiology (p < 0.001 in all). For BIS-SE differences, 320 disagreement data pairs were seen at a rate of 1.33 times/hr (95% CI = [1.19, 1.48], p < 0.001). A significant disagreement was delineated in MELD score ≥ 20 (3.04 times/hr, CI = [2.64, 3.49], p < 0.001), alcoholic etiology (3.19 times/hr, [2.67, 3.78], p < 0.001) and postreperfusion stage (1.63 times/hr, [1.43, 1.85], p < 0.001). In these significant BIS-SE differences, 95.9% (307/320 disagreement data pairs) showed higher BIS than SE. In conclusion, in high MELD and alcoholic etiology, anesthetic requirements were significantly less, and BIS and SE showed great discrepancy with lower SE values. Therefore, when SE monitoring is used during LT, anesthesiologists may need to consider that in high MELD and alcoholic etiology, SE tends to show lower values than the concomitant BIS values that are within optimal anesthetic depth ranges.

Effects of anesthetic depth on postoperative pain and delirium:a meta-analysis of randomized controlled trials with trial sequential analysis

Background:Whether anesthetic depth affects postoperative outcomes remains controversial.This meta-analysis aimed to evaluate the effects of deepvs.light anesthesia on postoperative pain,cognitive function,recovery from anesthesia,complications,and mortality.Methods:PubMed,EMBASE,and Cochrane CENTRAL databases were searched until January 2022 for randomized controlled trials comparing deep and light anesthesia in adult surgical patients.The co-primary outcomes were postoperative pain and delirium(assessed using the confusion assessment method).We conducted a meta-analysis using a random-effects model.We assessed publication bias using the Begg’s rank correlation test and Egger’s linear regression.We evaluated the evidence using the trial sequential analysis and Grading of Recommendations Assessment,Development and Evaluation(GRADE)methodology.We conducted subgroup analyses for pain scores at different postoperative time points and delirium according to cardiac or non-cardiac surgery.Results:A total of 26 trials with 10,743 patients were included.Deep anesthesia compared with light anesthesia(a mean difference in bispectral index of-12 to-11)was associated with lower pain scores at rest at 0 to 1 h postoperatively(weighted mean difference=-0.72,95%confidence interval[CI]=-1.25 to-0.18,P=0.009;moderate-quality evidence)and an increased incidence of postoperative delirium(24.95%vs.15.92%;risk ratio=1.57,95%CI=1.28-1.91,P<0.0001;high-quality evidence).No publication bias was detected.For the exploratory secondary outcomes,deep anesthesia was associated with prolonged postoperative recovery,without affecting neurocognitive outcomes,major complications,or mortality.In the subgroup analyses,the deep anesthesia group had lower pain scores at rest and on movement during 24 h postoperatively,without statistically significant subgroup differences,and deep anesthesia was associated with an increased incidence of delirium after non-cardiac and cardiac surgeries,without statistically significant subgroup differences.Conclusions:Deep anesthesia reduced early postoperative pain but increased postoperative delirium.The current evidence does not support the use of deep anesthesia in clinical practice.

Propofol Target-Controlled Infusion Modeling in Rabbits:Pharmacokinetic and Pharmacodynamic Analysis

This study aimed to establish a new propofol target-controlled infusion（TCI） model in animals so as to study the general anesthetic mechanism at multi-levels in vivo. Twenty Japanese white rabbits were enrolled and propofol（10 mg/kg） was administrated intravenously. Artery blood samples were collected at various time points after injection, and plasma concentrations of propofol were measured. Pharmacokinetic modeling was performed using Win Nonlin software. Propofol TCI within the acquired parameters integrated was conducted to achieve different anesthetic depths in rabbits, monitored by narcotrend. The pharmacodynamics was analyzed using a sigmoidal inhibitory maximal effect model for narcotrend index（NI） versus effect-site concentration. The results showed the pharmacokinetics of propofol in Japanese white rabbits was best described by a two-compartment model. The target plasma concentrations of propofol required at light anesthetic depth was 9.77±0.23 μg/m L, while 12.52±0.69 μg/m L at deep anesthetic depth. NI was 76.17±4.25 at light anesthetic depth, while 27.41±5.77 at deep anesthetic depth. The effect-site elimination rate constant（ke0） was 0.263/min, and the propofol dose required to achieve a 50% decrease in the NI value from baseline was 11.19 μg/m L（95% CI, 10.25–13.67）. Our results established a new propofol TCI animal model and proved the model controlled the anesthetic depth accurately and stably in rabbits. The study provides a powerful method for exploring general anesthetic mechanisms at different anesthetic depths in vivo.