Late motor responses, such as F-waves and H-reflexes, may reflect excitability of specific spinal cord segments and motor pathway integrity, offering potential value during intraoperative neurophysiological monitoring (IONM). However, these responses are not routinely utilized. A better understanding of the effect of general anaesthesia on their characteristics, particularly across varying depths, is essential for integration into IONM. Participants received propofol/remifentanil-based anaesthesia, targeted at BIS values of 30, 40, and 50. F-waves, H-reflexes and Tc-mMEPs were recorded every 2-4min. Anaesthetic effect was evaluated using linear mixed-effects models. 23 of 25 patients exhibited consistent H-reflexes. F-waves were elicitable in all patients, though muscle-dependant variability was observed. H-reflex amplitude decreased by 10% per 10-point BIS increase (p=0.014), while F-wave amplitude increased by 6-9% per 10 points BIS increase in abductor hallucis and hand muscles (p<0.01), with no significant changes in the tibialis anterior and gastrocnemius muscles. F-wave persistence varied<5% per 10 BIS-points. Late responses can be reliably recorded during propofol/remifentanil anaesthesia. F-waves exhibit greater variability than H-reflexes, potentially limiting their utility in certain muscle groups. They were modestly influenced by deeper anaesthesia but were still elicitable and interpretable. Changing depth of anaesthesia has differential effects on late responses of different muscles.

Automated infrared pupillometry (AIP) provides a quantitative, non-invasive, and reproducible method for assessing the pupillary light reflex, which is mediated by brainstem pathways. Although AIP has been increasingly used in critical care settings, interpretation of pupillary parameters may be confounded by the administration of sedatives and analgesics. However, the influence of these medications on individual AIP parameters in postoperative intensive care unit patients remains insufficiently characterized. This proof-of-concept pilot study aimed to identify pupillometric parameters that remain relatively stable under routine sedative and analgesic exposure following elective cardiovascular surgery. This prospective observational study included 10 patients admitted to the coronary care unit (CCU) after elective open-heart surgery. AIP parameters and bispectral index (BIS) values were measured postoperatively at predefined time points from CCU admission to extubation. Temporal changes in each parameter were analyzed descriptively using within-patient comparisons over the postoperative course. The Neurological Pupil Index (NPi) and latency (LAT) showed minimal temporal variation throughout the observation period. In contrast, BIS values increased progressively after surgery, accompanied by gradual increases in constriction percentage (CH), mean contraction velocity (CV), and maximum contraction velocity, whereas mean dilation velocity remained relatively unchanged over time. When comparing predefined postoperative time points immediately after CCU admission and after extubation, only CH showed an increase (median [interquartile range]: 0.45 [0.38-0.52] vs. 0.68 [0.60-0.73]; p = 0.02). In this small postoperative cohort, NPi and LAT were relatively more stable than other pupillometric parameters under routine sedative and analgesic exposure. However, given the limited sample size and the absence of neurological complications, these findings should be interpreted as descriptive and hypothesis-generating, and no conclusions can be drawn regarding clinical utility for neurological monitoring or prognostication. In contrast, CH and CV require cautious interpretation, as they may be influenced by pharmacological agents rather than by the underlying neurological status.

Physiologic and anesthetic predictors of false-positive motor-evoked potential alerts during pediatric spine surgery.

Aberrantly Low BIS Values during Awake Paralysis.

BackgroundRemimazolam, an ultra-short-acting benzodiazepine, is characterised by rapid onset and recovery, metabolism independent of hepatic or renal function and haemostability. Despite the above pharmacokinetic (PK) advantages and potential benefits for renal- or hepatic-insufficient patients and the elderly patients, the effects and population pharmacokinetics–pharmacodynamics (popPK/PD) of remimazolam for general anaesthesia in elderly, hepatic or renal insufficient patients from large, randomised controlled trials remain unknown.Methods and analysisThis is a randomised controlled single-blind multicentre study. Patients undergoing selective surgeries (eg, abdominal, orthopaedic or urologic procedures) will be screened and randomised into the elderly (age ≥65 years), hepatic insufficiency (Child-Pugh class B or C) or renal insufficiency (estimated glomerular filtration rate <60 mL/min/1.73 m²) groups, with a target of 752 subjects per group. Patients in each group will randomly receive remimazolam or propofol for general anaesthesia induction and maintenance. The primary outcome is the quality of induction and maintenance of general anaesthesia (the time of maintaining bispectral index (BIS) 35–65 divided by the time for test-drug administration). Secondary outcomes are PK and PD characteristics of remimazolam in the target populations, which include: the incidence of hypotension; incidence and amount of vasoconstrictor agents; area under the curves of blood pressure over time; pain on injection; eye opening time; extubation time; time to reach modified Aldrete scores 9; nursing delirium screening scores and incidence of intraoperative awareness. Exploring outcomes are remimazolam besylate plasma concentrations; the ideal target remimazolam besylate plasma concentrations (plasma concentrations corresponding to a BIS value between 35 and 65) and the optimal dosage regimen based on the popPK/PD model.Ethics and disseminationThis study was approved by the Ethics Committee of West China Hospital, Sichuan University, on 30 August 2024, and registered at the Chinese Clinical Trial Registry. The findings of this study will be disseminated through presentations at relevant conferences and published in peer-reviewed journals.Trial registration numberChiCTR2400089033.

Background: Low-flow anesthesia is increasingly used in modern anesthetic practice because it reduces consumption of volatile anesthetic agents, minimizes environmental pollution, and lowers anesthetic cost. However, accurate monitoring of anesthetic depth is essential to avoid excessive anesthetic administration and ensure adequate hypnosis during surgery. Conventional monitoring techniques rely on clinical parameters and end-tidal anesthetic concentration, which may not accurately reflect cerebral activity. The Bispectral Index (BIS) is an electroencephalography-based monitoring tool that provides objective assessment of anesthetic depth and may allow more precise titration of inhalational anesthetic agents. Aim: To evaluate the effect of BIS-guided monitoring on sevoflurane consumption per hour during low-flow anesthesia compared with conventional monitoring techniques. Methodology: This prospective randomized controlled trial was conducted in the Department of Anaesthesiology at ESIC Medical College and Hospital, Hyderabad, over a period of one year. A total of 150 patients aged 18–60 years with ASA physical status I–II scheduled for elective surgeries under general anesthesia were enrolled and randomly allocated into two groups of 75 each. In both groups, anesthesia was maintained using a low-flow technique with fresh gas flow of 1 L/min and sevoflurane as the inhalational agent. In the BIS group, anesthetic depth was monitored using BIS and sevoflurane concentration was titrated to maintain BIS values between 40 and 60. In the conventional monitoring group, anesthetic depth was guided by end-tidal anesthetic concentration and minimum alveolar concentration values. The primary outcome was mean sevoflurane consumption per hour (ml/h). Secondary outcomes included intraoperative haemodynamic parameters, recovery profile in terms of time to eye opening, extubation time, and Modified Aldrete Score, and incidence of intraoperative awareness. Statistical analysis was performed using SPSS software with a significance level of p &lt; 0.05. Results: The mean sevoflurane consumption per hour was significantly lower in the BIS group (12.4 ± 3.1 ml/h) compared with the conventional monitoring group (20.3 ± 4.2 ml/h; p &lt; 0.001). Recovery was significantly earlier in the BIS group, with shorter time to eye opening (7.8 ± 2.1 minutes vs 11.6 ± 3.2 minutes) and earlier extubation (8.2 ± 2.6 minutes vs 12.9 ± 3.8 minutes) compared with the conventional group. The Modified Aldrete Score at 10 minutes was also higher in the BIS group. Intraoperative haemodynamic parameters remained stable and comparable between the two groups. No patient in the BIS group experienced intraoperative awareness, whereas one patient (1.3%) in the conventional group reported possible awareness. Conclusion: BIS-guided monitoring during low-flow anesthesia significantly reduces sevoflurane consumption per hour and improves postoperative recovery profile without compromising haemodynamic stability or increasing the risk of intraoperative awareness. BIS monitoring therefore represents a valuable tool for optimizing anesthetic drug administration and enhancing perioperative patient outcomes.

Procedural sedation in patients with end-stage renal disease (ESRD) is challenging due to impaired renal function, which affects drug metabolism and increases the risk of adverse events. Remimazolam, a novel ultrashort-acting intravenous sedative, offers rapid onset and clearance independent of renal function, making it a potential alternative to dexmedetomidine for sedation in this patient population. This study aims to compare the efficacy and safety of remimazolam versus dexmedetomidine in ESRD patients undergoing procedural sedation. The primary hypothesis is that remimazolam will demonstrate superior sedation efficacy and a better safety profile, with reduced hemodynamic instability and faster recovery. This is a single-center, prospective, observer-blinded, randomized controlled trial (RCT). A total of 80 ESRD patients aged ≥ 18years scheduled for peritoneal dialysis catheter placement or removal will be randomly assigned to receive either remimazolam or dexmedetomidine. The primary outcome is the sedation success rate, defined as achieving a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score ≤ 1 within 10min of drug administration. Secondary outcomes include time to sedation, intraoperative movements, the duration of BIS values < 60 or > 80 during anesthesia maintenance, recovery time, the incidence of adverse events, incidence of postoperative nausea and vomiting (PONV), and postoperative pain scores. This is the first RCT to directly compare remimazolam and dexmedetomidine for sedation in ESRD patients undergoing procedural sedation. The results of this study will provide valuable insights into optimizing sedation strategies in this high-risk population, potentially improving clinical outcomes by minimizing complications associated with drug metabolism and recovery. Chinese Clinical Trial Registry. chictr.org.cn ChiCTR2300075278. Registered on August 31, 2023. https://www.chictr.org.cn/showproj.html?proj=205061.

A<sc>bstract</sc>Background and aimsThe COMFORT B score is a validated method for the assessment of the level of sedation in children, but it has its limitations. The bispectral index (BIS) is an electroencephalogram (EEG)-based tool used to assess the level of consciousness. The primary objective was to evaluate agreement between the BIS and the COMFORT B score for sedation in children on mechanical ventilation (MV).Patients and methodsThis prospective, noninterventional study was conducted on 138 patients, aged >6 months, receiving MV in the pediatric intensive care unit (PICU). COMFORT B score and BIS were taken 30 minutes after initiation or dosage change of sedatives and then once every 8 hours for a maximum of 96 hours.ResultsA total of 1,534 datasets were analyzed. Bispectral index values ranged from 11 to 89, while COMFORT B scores were between 6 and 28. The mean [± standard deviation (SD)] value for the BIS and COMFORT B scores was 54.4 ± 13.8 and 14 ± 4, respectively. Adequate sedation was recorded in 82.5 and 79.9% instances with BIS and COMFORT B scores, respectively. The correlation coefficient (r) of BIS and COMFORT B scores was 0.7. Overall agreement (kappa value) between the BIS and COMFORT B score was 0.642. A BIS score of 43 had 93% sensitivity and 70% specificity in differentiating oversedation from adequate sedation (AUROC 0.81). Similarly, a BIS value of 79 distinguished between adequate and undersedation (sensitivity 90%; specificity 98%; AUROC 0.966). The best AUROC (0.777) was observed in children with central nervous system (CNS) diseases, while the worst (0.54) occurred in patients with neuromuscular diseases.ConclusionThe BIS and COMFORT B scores have a good level of agreement in children, except in children with neuromuscular diseases.How to cite this articleJhunjhunwala M, Sachdev A, Gupta S, Gupta D, Gupta N. Bispectral Index and COMFORT B Score for Sedation in Mechanically Ventilated Children: A Prospective Observational Study. Indian J Crit Care Med 2026;30(4):305–310.

IntroductionDelta waves (0.1–4 Hz) are a hallmark of unconsciousness in both sleep and general anesthesia (GA). Closed-loop auditory stimulation (CLAS) delivers brief sounds phase-locked to ongoing slow oscillations and can modulate slow-wave activity (SWA) during sleep, but its efficacy and translational relevance under propofol anesthesia, particularly in the presence of nociceptive input, remain unknown.MethodsWe describe a prospective, within-subject protocol in 30 neurologically healthy adults undergoing elective surgery under propofol GA. Intraoperative high-density electroencephalography (hd-EEG; 128 channels) is recorded while a real-time CLAS algorithm detects δ-waves at the Fz electrode, and triggers pink-noise bursts in three conditions: in-phase (peak-locked), anti-phase (trough-locked), and sham. An extended in-phase block is then combined with a standardized tetanic nociceptive stimulus (100 Hz, 70 mA, 30 s) to test robustness under an arousal challenge. Depth of hypnosis is monitored with the Bispectral Index (BIS), and nociceptive/autonomic reactivity with the Nociception Level (NOL) index. Primary outcomes quantify δ-wave morphology and SWA (amplitude, slopes, duration/frequency, transition frequency, density, power spectral density), along with topography, source estimation, and propagation. Secondary outcomes include depth of anesthesia (BIS), nociceptive balance (NOL), functional connectivity (weighted and directed phase-lag indices), graph-theoretical organization (global efficiency, clustering, modularity, small-worldness), and EEG microstates (duration, coverage, transitions).Anticipated resultsWe hypothesize that in-phase CLAS will increase amplitude, slope, duration, and density of δ-waves, and decrease frequency and transition frequency relative to sham, whereas anti-phase CLAS will cause a disruption these parameters relative to sham. Under nociception, in-phase CLAS is expected to these parameters preserve δ-wave integrity, with effects attenuated relative to non-nociceptive conditions. We anticipate BIS values to remain within the surgical range but trend lower during in-phase CLAS, alongside reduced nociceptive/autonomic responses. At the network level, we expect CLAS-induced δ-wave reinforcement to be associated with more locally coherent δ-band activity and reduced frontoparietal integration, consistent with deeper unconsciousness.DiscussionIf confirmed, these findings would position CLAS as a candidate neuromodulation strategy to reinforce anesthetic δ-wave dynamics and help stabilize anesthesia without necessarily increasing pharmacological dose, while also providing a systems-level test of the role of slow oscillations in sustaining unconsciousness.

Introduction: The BIS monitor is an FDA approved multiprocessed EEG that can be used to guide general anesthesia, sedation procedures and ICU sedation. Over and under sedation can be avoided, allowing for a more efficient sedation process and reducing the risks of awareness. During sedation procedures the correct timing of titration is important to reduce the risk of over-sedation. If the sedatives are repeated before their peak effect has occurred this may result in respiratory depression. The aim of this study was to use the BIS monitor to determine the time to IV bolus peak effect for 3 sedative agents; Midazolam (MID), Fentanyl (FENT) and Propofol (PROP). The second aim was to determine the BIS value at which no movement to stimulus occurs, i.e. the ideal target depth. Methods: After IRB approval and informed consent meeting the inclusion criteria were patients of ages 10-17 undergoing a surgical dental extraction under deep intravenous sedation. All patients received the same sedative based regimen: Midazolam, Propofol and Fentanyl. Sedation doses were age and weight based. The only difference was the sequence of sedative administration prior to procedure start. On initial local anesthetic placement (a “sharp” stimulus of palatal LA), the BIS monitor to computer data stream was real-time highlighted. Patient movement in response to stimulation was assessed by two observers. Results: We have recruited 70 patients so far, ages ranged from 10 to 17 years, average procedure time of 16.6 minutes and recovery time of 34.3 minutes. The peak effect onset time for MID, PROP and FENT were ~ 95 seconds, ~ 55 seconds, Unable (FENT had a minimal BIS effect), these take into account a BIS recording delay of about 25 seconds for our model. About 25% patients moved with stimulus. The risk of movement was 4 x greater if the BIS was 50 or higher. Conclusions: The peak onset time for MID and PROP were identified which suggests that repeat dosing should be about 2 minutes apart for MID and 1 minute for PROP. Due to minimal FENT BIS effect no peak onset could be established. Movement was minimized with lower BIS, c/w deeper sedation, in GA territory. Deep sedation even with A BIS in the 50’s may not prevent patient movement to surgical stimulation.

Introduction Awake fiberoptic intubation (AFOI) is commonly employed in neurosurgical patients with anticipated difficult airways to minimize spinal cord compression and intracranial pressure fluctuations, although procedural discomfort remains a major limitation. This prospective observational study evaluated the AFOI with two commonly used conscious sedation regimens-dexmedetomidine and a propofol-fentanyl combination-guided by Bispectral Index (BIS) and the Observer's Assessment of Alertness/Sedation (OAA/S) scale, along with spray-as-you-go (SAYGO) topical anesthesia. Outcomes assessed included AFOI conditions - cough severity and intubation conditions; time to achieve target sedation (BIS value of 70); hemodynamic changes; total intubating attempts; intubation time; correlation between BIS and OAA/S; perioperative complications; and postoperative recall. Methods Forty consecutive adult patients undergoing AFOI for elective neurosurgical procedures received conscious sedation with either dexmedetomidine (Group D) or propofol-fentanyl (Group PF) as part of routine clinical practice. Conscious sedation was titrated using BIS, and the corresponding OAA/S scores were assessed. Airway topicalization was achieved using the SAYGO technique. Results Patients receiving propofol-fentanyl demonstrated superior intubation conditions compared with dexmedetomidine, as evidenced by higher total intubation scores (7.80 ± 0.62 vs. 7.11 ± 1.24; p = 0.039) and shorter intubation times (16.10 ± 10.95 vs. 27.79 ± 21.18 seconds; p = 0.036). Additionally, the propofol-fentanyl group also exhibited less coughing, better endotracheal tube tolerance, lower lignocaine requirements, and improved postoperative recovery profile with fewer complaints of sore throat during the first 48 hours after surgery. Procedure recall was absent in both groups. Conclusion In routine clinical practice, BIS-guided conscious sedation with a propofol-fentanyl combination was associated with better intubating conditions and procedural tolerance than dexmedetomidine during AFOI in high-risk neurosurgical patients. The SAYGO technique further enhanced patient comfort and safety, providing a practical alternative to conventional airway nerve blocks.

Background/Objectives: Pupillometry offers a non-invasive method for assessing nociceptive responses during anesthesia. This study aimed to evaluate the effects of intravenous lidocaine on pupillary reflex dilation (PDR) and the Pupillary Pain Index (PPI) during general anesthesia with orotracheal intubation. Methods: In this prospective, randomized, single-blind trial, 90 ASA I-II patients aged 18-65 years, scheduled for elective surgery under general anesthesia, were enrolled. Participants were randomized into three groups: control, study (lidocaine 1.5 mg/kg), and placebo. Standardized anesthesia induction was performed using propofol, fentanyl, and rocuronium. Pupil diameter was measured using the Algiscan pupillometer. PDR was assessed during intubation, while PPI was measured five minutes post-intubation through controlled electrical stimulation. Hemodynamic parameters and BIS values were recorded throughout. Eighty-six patients completed the study. No significant differences in demographics, anesthetic drug doses, or hemodynamic parameters were noted between groups. Results: PDR during intubation showed no significant difference between the control and study groups (median dilation: 0.34 mm vs. 0.33 mm; p = 0.76), but was significantly lower in the lidocaine group compared to placebo (median dilation: 0.33 mm vs. 0.50 mm; p = 0.02). PPI scores did not differ significantly between groups (p > 0.05). A positive correlation was observed between PDR and BIS values, indicating that lighter anesthesia depth increased PDR response. No such correlation was found with PPI. Conclusions: Intravenous lidocaine attenuates the pupillary response to nociceptive stimuli during orotracheal intubation but does not influence PPI scores. Pupillometry remains a valuable adjunct for intraoperative nociceptive monitoring.

WHAT IS KNOWN : •Low-concentration nitrous oxide (LCNO) has been used in dentistry and some ophthalmic procedures and is believed to reduce anxiety and discomfort. •Evidence for its sedative effect in cataract microsurgery has largely relied on subjective patient reports rather than objective monitoring. • This study provides objective evidence, using bispectral index (BIS) monitoring, that LCNO induces mild sedation during routine cataract microsurgery. •LCNO significantly reduced the BIS values during surgery without causing clinically relevant changes in the vital signs or adverse events, supporting its safety and practicality for outpatient cataract surgery.

Background: Achieving a rapid and high-quality recovery is a cornerstone of modern procedural sedation, particularly in high-turnover ambulatory bronchoscopy suites. Patients presenting for bronchoscopy often exhibit significant pulmonary pathology, including ventilation-perfusion mismatch, which may theoretically impede the alveolar washout of volatile anesthetics. This study aimed to compare the recovery kinetics, hemodynamic stability, and adverse event profiles of Propofol Target-Controlled Infusion (TCI) utilizing the Schnider model versus standard Sevoflurane inhalational anesthesia. Methods: In this single-blind, prospective, randomized controlled trial, 36 adult patients (ASA I–III) undergoing elective flexible bronchoscopy were recruited. Participants were randomly allocated to receive either Propofol TCI (Group P; Schnider model, target effect-site concentration 4–6 micrograms/mL) or Sevoflurane (Group S; 2 volume percent). The depth of anesthesia was strictly titrated using Bispectral Index (BIS) monitoring to maintain a range between 40 and 60. The primary outcome was recovery time, defined as the duration from anesthetic discontinuation to eye-opening upon verbal command. Secondary outcomes included intraoperative hemodynamic stability (Mean Arterial Pressure and Heart Rate), BIS values at the moment of emergence, and the incidence of postoperative nausea and vomiting (PONV). Results: The Propofol TCI group demonstrated a statistically significant reduction in recovery time (9.72 ± 1.52 minutes) compared to the Sevoflurane group (12.11 ± 1.49 minutes; p &lt; 0.001). Procedural duration was comparable between groups (p = 0.412), eliminating surgical time as a confounding variable. Group P exhibited superior hemodynamic stability, with significantly less deviation from baseline Mean Arterial Pressure at 10 and 15 minutes into the procedure (p &lt; 0.05). Furthermore, BIS values at the moment of eye-opening were significantly higher in Group P (88.4 ± 4.2) compared to Group S (82.1 ± 5.1; p = 0.021), suggesting a distinct emergence neurophysiology. The incidence of PONV was notably lower in the Propofol group (5.5 percent) compared to the Sevoflurane group (22.2 percent). Conclusion: Propofol target-controlled infusion facilitates significantly faster emergence and greater hemodynamic stability than Sevoflurane in patients undergoing flexible bronchoscopy. The pharmacokinetic independence of Propofol from pulmonary gas exchange offers a distinct physiological advantage in this specific patient population. These findings support the adoption of TIVA-TCI as the standard of care for optimizing throughput in interventional pulmonology.

BACKGROUNDPreoperative sleep disorders are common in elderly gastric cancer patients and may increase the risk of postoperative anxiety and depression. Traditional anesthesia depth monitoring relies on clinical signs, which may not accurately reflect the true anesthetic state in elderly patients. This study evaluates the effect of individualized anesthesia guided by electroencephalogram (EEG) monitoring on postoperative anxiety and depression symptoms in elderly gastric cancer patients with preoperative sleep disorders.AIMTo determine whether EEG-guided anesthesia improves psychological recovery by stabilizing anesthesia depth in elderly gastric cancer patients with preoperative sleep disorders.METHODSThis retrospective study included 240 patients aged ≥ 65 years with preoperative sleep disorders (Pittsburgh Sleep Quality Index ≥ 5) who underwent elective radical gastrectomy between January 2022 and December 2023. Patients were divided into an EEG monitoring group (n = 118) and a conventional monitoring group (control, n = 122). The EEG group used Bispectral Index (BIS) monitoring to adjust anesthetic dosage, maintaining BIS values between 40 and 60, while the control group relied on conventional clinical indicators for anesthesia depth adjustment. The primary outcomes were Hospital Anxiety and Depression Scale (HADS) scores at 3 days and 1 month postoperatively; secondary outcomes included postoperative delirium incidence, length of stay, and quality of life scores.RESULTSA total of 240 elderly gastric cancer patients with preoperative sleep disorders were included (118 EEG group, 122 control group) with well-matched baseline characteristics. EEG-guided anesthesia significantly reduced anesthetic drug consumption (propofol: 5.8 ± 1.2 mg/kg/hour vs 7.3 ± 1.4 mg/kg/hour, P < 0.001; remifentanil: 0.18 ± 0.04 μg/kg/minute vs 0.24 ± 0.05 μg/kg/minute, P < 0.001) and achieved 18.6% cost reduction. Primary outcomes showed the EEG group had significantly lower postoperative anxiety and depression scores at 3 days (HADS total: 11.8 ± 3.7 vs 15.9 ± 4.9, P < 0.001) and 1 month (8.7 ± 3.2 vs 13.2 ± 4.1, P < 0.001). The proportion of patients with clinically significant symptoms was reduced from 62.3% to 39.0% at 3 days and from 45.9% to 21.2% at 1 month (both P < 0.001). Multivariate analysis identified EEG-guided anesthesia as the strongest protective factor [odds ratio (OR) = 0.56, 95%CI: 0.41-0.78, P = 0.003], while poor sleep efficiency (OR = 2.24, P < 0.001) and frequent sleep disturbances (OR = 1.95, P = 0.001) were the most significant risk factors. Subgroup analysis revealed a dose-response relationship, with greatest benefits in patients with severe sleep disorders. BIS stability metrics strongly correlated with psychological outcomes (r = -0.462 for target range maintenance, P < 0.001). Secondary outcomes demonstrated significant improvements in the EEG group: (1) Lower complication rates (32.2% vs 48.4%, P = 0.010); (2) Reduced postoperative delirium (8.5% vs 17.2%, P = 0.038); and (3) Superior pain control, faster recovery, and shorter hospital stay (10.8 ± 2.7 days vs 12.5 ± 3.0 days, P < 0.001).CONCLUSIONFor elderly gastric cancer patients with preoperative sleep disorders, individualized anesthesia guided by EEG monitoring significantly reduces postoperative anxiety and depression symptoms, lowers postoperative delirium risk, shortens hospital stay, and improves postoperative quality of life. The stability of anesthesia depth is closely associated with postoperative mental health outcomes, providing new clinical evidence and individualized strategies for perioperative management of high-risk elderly patients.

This study evaluated the optimal depth of anesthesia guided by closed-loop target-controlled infusion (TCI) in preschool-aged children undergoing dental surgery. Dental procedures in this population are frequently associated with heightened anxiety and procedural distress, often necessitating general anesthesia; however, the appropriate depth of anesthesia remains insufficiently defined. A randomized, double-blind, controlled trial was conducted involving 60 children aged 3 to 6 years scheduled for dental surgery. Participants were allocated to 3 groups (A, B, and C), with bispectral index (BIS) values maintained at 50, 55, and 60, respectively, using a closed-loop TCI system. The primary outcomes were heart rate (HR) and mean arterial pressure (MAP), recorded at 7 intraoperative time points. Secondary outcomes included surgical duration, time to first eye opening (defined as eyelid movement in response to verbal command without implying full orientation), extubation time, discharge time, and total propofol dose. No statistically significant differences were observed among groups in HR or MAP at any intraoperative time point (between-subject effect: HR, F=2.73, P=0.074; MAP, F=1.54, P=0.222). Surgical duration (F=0.521, P=0.596) and total propofol dosage (P=0.165) also did not differ significantly. Recovery parameters demonstrated significant group differences. Time to first eye opening was 37.75±8.81 minutes in group A, 28.35±2.45 minutes in group B, and 20.70±5.21 minutes in group C (P<0.001). Extubation time was 39.40±8.08 minutes, 29.60±2.58 minutes, and 22.70±5.63 minutes in groups A, B, and C, respectively (P<0.001). Discharge time was shortest in group C (135.6±30.9min), followed by group B (160.5±25.3min), and longest in group A (202.5±26.5min) (F=29.77, P<0.001). The incidence of adverse events was comparable across groups, and no serious adverse events occurred. Maintaining a BIS value of 60 (±5) with a closed-loop infusion system provided adequate anesthetic depth for dental procedures in preschool-aged children, while significantly reducing recovery and discharge times. This anesthetic strategy may support enhanced recovery and improve perioperative efficiency in pediatric populations.

ObjectiveTo develop and validate a population pharmacokinetic/pharmacodynamic (PK/PD) model for ciprofol in elderly surgical patients, delineating its pharmacokinetic profile and concentration-effect relationship to inform precision dosing.MethodsTwenty patients (aged ≥65 years) undergoing elective surgery were enrolled. We performed population PK/PD analysis using nonlinear mixed-effects modeling on 386 arterial blood samples and synchronized Bispectral Index (BIS) data. A linear three-compartment model and a sigmoid Emax model described the PK and PD (BIS), respectively. Covariates (age, weight, gender, and laboratory parameters) were tested via stepwise selection. Model performance was evaluated using goodness-of-fit plots, bootstrap (n = 1,000), and prediction-corrected visual predictive checks. Dosing regimens were optimized via Monte Carlo simulation.ResultsA three-compartment model best described the PK. The center volume (V1) was generally approximated at 2.95 L, but the peripheral volumes (V2 and V3) were 45.15 L and 76.79 L, respectively. The clearance (CL) was assessed at 1.01 L min-1. Body weight and age significantly influenced CL. PD analysis showed rapid effect-site equilibration (Ke0: 1.09 min-1), with an EC50 of 233.91 ng mL-1 and a Hill coefficient of 3.00. No covariates significantly affected PD parameters. The model exhibited sufficient fit and strong predictive efficacy. The simulation results confirmed that administering an intravenous loading dose of 0.4 mg kg-1 over 1 min, followed by an initial continuous infusion at a rate of 0.6 mg kg-1·h-1 for 2 h, could stably maintain the patients’ BIS values within the target range of 40–60.ConclusionA population PK/PD model for ciprofol in elderly patients was successfully established and validated. The model supports optimized, individualized dosing to achieve target anesthesia depth in this population.

ABSTRACTObjective:To investigate prospectively the effect of testosterone treatment applied to patients with micropenis for hypospadias surgery on the depth of general anesthesia during surgery.Another objective was to make recommendations for the awareness of patients who have testosterone treatment used for sex reassignment surgery under anesthesia in the early period.Methodology:The study was a prospective cohort study conducted by the Department of Anesthesiology, Intensive Care and Pain Management of Tekirdağ Namık Kemal University Hospital between September 2024 and December 2024 (four months). We recorded the effect of intramuscular testosterone treatment administered to patients with micropenis hypospadias two weeks prior to surgery on the depth of anesthesia (1.1-1.2 MAC), as well as intraoperative changes in bispectral index (BIS), heart rate (HR), and peak airway pressure (PIP) at 5, 15, 30, 45, and 60 minutes.Results:Statistical differences were found between Group-C (Control) (n=30) and Group-T (Testosterone) (n=11). Although the depth of anesthesia was found to be between normal values for general anesthesia (BIS 40-60) in both groups, statistical differences were found between BIS, HR, and PIP values. (p< 0.05).Conclusion:For surgeries requiring testosterone treatment (such as micropenis, after gender reassignment) in the acute phase or chronic phase under general anesthesia, monitoring of anesthesia depth is recommended.Clinical Trial Number: This trial was prospectively registered on September 13, 2024 in clinicaltrials.gov with trial number “NCT06606496”.

Vicadrostat, an aldosterone synthase inhibitor in development in combination with empagliflozin for chronic kidney disease, heart failure, and cardiovascular risk reduction, undergoes extensive hepatic glucuronidation primarily by UDP-glucuronosyltransferase (UGT)2B7 to form BI 689875, an ether glucuronide metabolite. Despite its hepatic formation, BI 689875 is predominantly excreted in urine, as determined in a human ADME study of vicadrostat. This study elucidated mechanisms underlying BI 689875 disposition in humans. BI 689875 was evaluated as a substrate of various drug transporters using transporter-expressing membrane vesicles and HEK293 cells. BI 689875 was identified as a substrate of MRP2, MRP3, MRP4, BCRP, OAT3, OATP1B1, and OATP1B3, but not of P-gp, OAT1, OAT2, OAT4, MATE1, or MATE2-K. The affinity of BI 689875 for MRP3 (Km = 39 μM) and OAT3 (Km = 46 μM) was substantially greater than that for other uptake/efflux transporters (not saturable up to 300 μM). In vitro-in vivo extrapolation using a proteomics-informed approach correcting for in vitro versus in vivo transporter expressions revealed that MRP3- and OAT3-mediated intrinsic clearance values for BI 689875 were substantially higher than those of other transporters. These findings suggest that basolateral efflux via MRP3 is the dominant hepatic elimination pathway for BI 689875, explaining its minimal fecal excretion observed in the human ADME study. They also indicate that OAT3-mediated uptake is the primary renal elimination route, with renal basolateral uptake substantially higher than hepatic uptake, consistent with the preferential urinary elimination of BI 689875. Transporter interplay between hepatic MRP3 and renal OAT3 determines the primary route of BI 689875 disposition. SIGNIFICANCE STATEMENT: BI 689875, a glucuronide metabolite, is formed in the liver but eliminated in urine. Through proteomics-informed in vitro-in vivo extrapolation, hepatic MRP3 and renal OAT3 were identified as key contributors to its predominant urinary elimination, highlighting interorgan transporter interplay.

Introduction: Dexmedetomidine, a selective alpha-2 adrenergic receptor agonist, is gaining momentum in neurosurgical anaesthesia for its sedative, analgesic, and sympatholytic effects. Propofol, although widely used, has its risks, like hypotension and respiratory depression at high doses. When these two drugs are given together during neurosurgical procedures, evaluating those changes may provide their potential as an anaesthetic adjunct while reducing risks associated with excessive propofol use when used alone. Aim: To evaluate the efficacy of Dexmedetomidine infusion in reducing intraoperative Propofol requirement and maintaining depth of anaesthesia during elective neurosurgical procedures. Materials and Methods: This was a randomised controlled study conducted at the Department of Anaesthesiology, Krishna Institute of Medical Sciences, Krishna Vishwa Vidyapeeth (Deemed to be University), Karad, Maharashtra, India, from February 2023 to October 2024. It comprised 50 the American Society of Anesthesiologists Physical Status (ASA-PS) I–II patients aged 18-60 years undergoing elective neurosurgery. Patients were randomised into two groups: Group P (standard anaesthesia with Propofol infusion) and Group PD (same regimen plus Dexmedetomidine infusion: 1 µg/kg bolus over 10 minutes followed by 0.5 µg/kg/hr). Propofol was titrated to maintain the Bispectral Index (BIS) between 40-60. Haemodynamic parameters, total Propofol consumption (mg/kg/hr), and intraoperative complications were recorded and analysed using Repeated-measures One way-Analysis of Variance (ANOVA) or Student’s t-test. Results: The two study groups were comparable in age (group P: 42.3±10.5 years; group PD: 41.8±9.8 years; p-value=0.82), Body Mass Index (BMI) (group P: 24.9±2.5 kg/m2; group PD: 25.1±2.4 kg/m2; p-value=0.85). Group PD showed significantly reduced intraoperative Propofol consumption compared to group P (3.00±0.8 mg/kg/hr vs. 4.50±1.0 mg/kg/hr, p-value &lt;0.001). Haemodynamic parameters {Heart rate (HR), Mean Arterial Pressure (MAP)} remained more stable in the Dexmedetomidine group across all intraoperative time points. In the group PD, the incidence of hypotension was slightly lower than in group P {3(12%) vs. 6 (24%)}. Target BIS range (40- 60) was maintained in both the study groups. However, group PD consistently demonstrated lower BIS values (e.g., 52.0±3.8 vs. 55.2±4.5 at 5 min, p-value=0.02), with reduced variability (5.8±0.9% vs. 7.2±1.1%, p-value &lt;0.001). Conclusion: Dexmedetomidine infusion significantly reduces the intraoperative Propofol requirement while maintaining adequate depth of anaesthesia and providing superior haemodynamic stability in elective neurosurgical procedures. Its use as an adjuvant can enhance anaesthetic efficiency and patient safety when carefully monitored.