British Journal of Anaesthesia

Background: Perioperative observational studies are increasingly used to evaluate anesthesia practices that are difficult to test in randomized trials, but treatment selection is influenced by surgical procedure type. Scalable and robust methods are needed to adjust for procedure-level confounding across heterogeneous surgical cohorts. Methods: We developed and assessed the utility of a surgical-name embedding framework using free-text procedure names from 627,624 adult perioperative records. Procedure names were embedded using open-source sentence-embedding models, reduced with principal components analysis, and incorporated into entropy-balanced observational analyses. We compared unweighted, clinical covariate adjustment, and clinical covariate plus surgical-name embedding adjustment across three replications of recent perioperative randomized trials: GA-CARES for total intravenous versus volatile anesthesia on cancer mortality, PADDI for dexamethasone and surgical site infection, and GAP for perioperative gabapentin and postoperative length of stay. Results: In the GA-CARES replication, unweighted and clinical covariate adjustment suggested lower two-year mortality with total intravenous anesthesia, whereas adding surgical-name embeddings attenuated the estimate to a nonsignificant association consistent with the randomized trial (OR 0.84 [95% CI, 0.62-1.14]; p=0.274). In the PADDI replication, adding surgical-name adjustment reproduced the trial's overall non-harm finding for 30-day surgical site infection (OR 0.72 [95% CI 0.69-0.76], p<0.001) while preserving the expected protective association with postoperative nausea and/or vomiting. In the GAP replication, the full cohort was null across adjustment strategies, but surgical-name embeddings were required to recover trial-consistent null length-of-stay estimates across cardiac, thoracic, and abdominal subgroups. Department indicators and randomly generated covariates did not reproduce the effect of surgical-name embeddings, supporting the presence and importance of procedure-specific information. Conclusions: Free-text surgical-name embeddings provide a scalable method for representing surgical context in perioperative observational studies. Surgical-name adjustment improved concordance with randomized trial benchmarks while preserving expected treatment effects, supporting its use as an additional layer of confounding adjustment in large perioperative datasets.

Background: Postoperative delirium is a common syndrome of acute changes in attention, cognition, and consciousness that may result from inflammation and/or neuroinflammation, but few studies have distinguished the relationships of preoperative and 24-hour postoperative systemic inflammation (i.e. in blood) versus neuroinflammation (i.e. in cerebrospinal fluid, or CSF) in postoperative delirium. Methods: We measured CSF and plasma cytokine levels before and 24-hours after non-cardiac/non-neurologic surgery in 199 patients age [&ge;] 60 years who were enrolled in two prospective cohort studies. Delirium was assessed with the confusion assessment method (CAM), 3-minute diagnostic interview for CAM-defined delirium, or the CAM for the Intensive Care Unit (CAM-ICU) in patients who remained intubated postoperatively and validated chart review. Cytokines were measured with immunoassays for IL-6, IL-7, IL-8, IL-10, IL-16, TARC, MCP-1, and IP-10. Associations of CSF and plasma cytokine levels with postoperative delirium were assessed with univariable and multivariable logistic regression analyses with Holm correction for family-wise error. Results: Surgery was associated with significant changes in nearly all measured CSF and plasma cytokines (p < 0.05) except plasma IL-16 and MCP-1. In multivariable analyses adjusted for preoperative Mini-Mental Status Exam (MMSE) score and surgery duration, higher preoperative CSF IL-6 (OR 1.80, 95% CI 1.18-2.75, Holm p=0.049) and CSF IL-8 (OR 1.94, 95% CI 1.22-3.06, Holm p = 0.040) levels were independently associated with postoperative delirium. Higher 24-hour postoperative CSF IL-10 was nominally associated with delirium (OR 1.57, 95% CI 1.06-2.33, p = 0.026) in a multivariable regression controlling MMSE and surgery duration, but this association did not remain significant after multiple-comparison correction (Holm p = 0.21). No other preoperative or 24-hour postoperative CSF or plasma cytokine levels were associated with delirium (p > 0.05). Conclusions: Surgery elicited robust postoperative changes in CSF and plasma cytokines, but 24-hour postoperative cytokine elevations were not significantly associated with postoperative delirium after multiple-comparison correction. In contrast, elevated preoperative CSF IL-6 and IL-8 levels were associated with postoperative delirium independent of baseline cognitive status and surgery duration. Thus, our findings support an important role for preoperative neuroinflammation in postoperative delirium in older elective surgery patients.

Background: Post-induction hypotension is a predictable haemodynamic hazard in older adults undergoing general anaesthesia. Prevention remains divided among volume optimisation, anaesthetic dose reduction, rescue treatment after hypotension occurs and proactive vasoactive support. Methods: We searched PubMed, Embase, Web of Science, CENTRAL, CNKI, Wanfang and VIP from inception to 30 March 2026. Eligible studies were randomised trials of prophylactic vasoactive drugs given before, during or immediately after induction in older adults. The primary outcome was post-induction hypotension. Secondary outcomes were post-induction mean arterial pressure (MAP), systolic arterial pressure (SBP), heart rate (HR) and reported haemodynamic adverse events. Random-effects network meta-analysis was used, and confidence in network estimates was assessed using CINeMA principles. Results: Thirty-one trials including 2,821 participants were included in the revised network. Compared with placebo/control, all active agents favoured lower post-induction hypotension. The most favourable point estimates were observed for phenylephrine (odds ratio [OR] 0.17, 95% confidence interval [CI] 0.01 to 2.16) and metaraminol (OR 0.19, 95% CI 0.02 to 1.53), although both were imprecise. More precise reductions were observed for methoxamine (OR 0.23, 95% CI 0.13 to 0.43), norepinephrine (OR 0.25, 95% CI 0.13 to 0.47) and ephedrine (OR 0.34, 95% CI 0.19 to 0.63). Phenylephrine ranked highest for MAP support, norepinephrine ranked highest for SBP support, and ephedrine ranked highest for HR preservation. Global inconsistency was detected for SBP but not for hypotension incidence, MAP or HR, supporting cautious profile-based interpretation. Conclusions: Prophylactic vasopressor choice during induction should be guided by haemodynamic phenotype rather than ranking alone. In the revised network, active prophylaxis consistently favoured lower hypotension, but sparse nodes produced uncertainty. Norepinephrine retained a comparatively balanced profile when vasodilatory post-induction hypotension is anticipated, phenylephrine and related alpha-agonists provided stronger pressure support when HR and cardiac-output reserve are preserved, and ephedrine was most relevant when chronotropic support is desired. Keywords: general anaesthesia; induction; hypotension; norepinephrine; phenylephrine; ephedrine; network meta-analysis; older adults.

Introduction Postoperative analgesic management after minimally invasive cardiac surgery (MICS) should facilitate early recovery while providing adequate pain control. However, direct evidence comparing postoperative remifentanil- and fentanyl-based analgesic strategies after MICS remains limited. We compared these strategies and explored their associations with postoperative recovery, postoperative nausea and vomiting (PONV), and pain management. Methods This retrospective single-center observational cohort study included patients who underwent MICS via a right mini-thoracotomy between January 2023 and June 2026. Patients were categorized according to postoperative remifentanil- or fentanyl-based analgesia in the intensive care unit. Outcomes included time to extubation, PONV, postoperative pain assessed using the numerical rating scale (NRS), additional analgesic use, and intensive care unit length of stay. Multivariable logistic regression examined the association between postoperative opioid strategy and PONV, adjusting for age, sex, and smoking history. Results PONV occurred less frequently in the remifentanil group than in the fentanyl group (20.6% vs 45.0%, P = 0.004), and this association remained significant after adjustment (adjusted odds ratio, 0.23; 95% confidence interval, 0.10-0.56; P = 0.001). Time to extubation was shorter with remifentanil (median, 179 [interquartile range, 134-240.5] vs 247 [190.2-276.5] min; P < 0.001). In contrast, NRS pain scores on postoperative day 0 were higher with remifentanil (3 [1-6] vs 1 [0-2]; P < 0.001), and additional analgesics were used more frequently (80.6% vs 33.3%; P < 0.001). Pain scores on postoperative day 1 did not differ significantly between groups. Conclusion Postoperative remifentanil-based analgesia after MICS was associated with less PONV and earlier extubation but also with greater early postoperative pain and more frequent additional analgesic use than fentanyl-based analgesia. Appropriate transition to longer-acting analgesics with multimodal analgesia may help preserve the potential benefits of remifentanil while maintaining adequate postoperative pain control.

Background: DNA methylation is an epigenetic modification that regulates gene expression in response to environmental exposures. We measured differential DNA methylation levels in blood before after general anesthesia and surgery in participants with and without postoperative delirium (POD) and postoperative neurocognitive disorder (PNCD). Methods: Blood sampling, delirium assessment and cognitive testing were prospectively performed at baseline before non-cardiac, non-neurologic surgery, and at 24 hours (24h) and 6 weeks (6wk) thereafter in 94 participants comprising 13 with POD and 81 without POD, and 40 with PNCD and 54 without PNCD 6wk after surgery who were matched for age and sex in the INTUIT and MADCO cohorts. DNA methylation was assessed using the Illumina Infinium MethylationEPIC Beadchip. Results: 132 differentially methylated positions (DMPs) annotated to 198 differentially methylated genes (DMGs) were identified in 94 participants 24h after surgery compared to baseline with a local false discovery rate (LFDR) <0.05 including CHRNB1, LGALS1, SMAD4, RYR2, CHST11, CDC25B, OBSCN, ABHD16A. No DMPs were identified between samples collected at baseline compared to 6wk after surgery. In baseline samples, 8 DMPs annotated to 12 DMGs were identified between participants who did and did not develop POD including MBTD1, BID, PPAN, ANGPTL6, PHF21B, and RBM5. In 24h samples, 87 DMPs annotated to 91 DMGs were identified between participants with and without POD including CLEC19A, FILIP1, ERICH1, PSENEN, SLC6A3, and TMEM196. In 6wk samples, 1 DMP annotated to FILIP1 and LOC124901509 in participants with and without POD. No DMPs in baseline, 24h or 6wk blood samples were identified between patients with and without PNCD at 6k after surgery. Conclusions: Differential DNA methylation levels are present throughout the genome 24h after anesthesia and surgery. Differential DNA methylation levels before surgery and at 24h after surgery distinguishes patients with and without POD. Differential DNA methylation levels were not identified between baseline and 6wk after surgery in the entire cohort, or between patients with and without PNCD at 6 weeks.

Background: Postoperative nausea and vomiting (PONV) is a common consequence of anaesthesia, affecting up to 30% of postoperative patients. Female sex is one of the strongest risk factors for PONV, yet no dedicated analysis has examined how this association varies across surgical settings and timepoints. This systematic review and meta-analysis aimed to quantify sex differences in PONV incidence across different surgical contexts. Methods: A systematic search was conducted using PRISMA guidelines across Medline and Embase from inception to September 1, 2025. Eligible studies were observational cohort studies (n[&ge;]500) of adult patients that conducted multivariate regression analyses including sex as a variable. Two reviewers independently screened, extracted data, and assessed risk of bias using ROBINS-E. A random-effects meta-analysis was performed. Subgroup analyses and multiple sensitivity analyses were completed. Results: From 4620 identified studies, 23 met the inclusion criteria, including 462,828 patients across various surgical settings and specialties (52% female). The pooled incidence of PONV was 21% (95% CI[16-27%]), with high heterogeneity (I2=99.9%). Meta-analysis confirmed females had a higher risk of developing PONV compared to males (pooled OR=2.40, 95% CI[2.06-2.79], I2=93.1%, p<0.0001). Sensitivity analyses confirmed robustness of pooled estimates. Subgroup analyses demonstrated consistently elevated risk of PONV for females at all three timepoints (PACU, 24-hour, 48-hour post-operative) and across studies including and excluding female-only surgeries. Studies were generally at high risk of bias. Discussion: Female sex is a strong risk factor for PONV across surgical settings. Further research into precise subgroups, underlying mechanisms of sex-differences, and the use of prophylaxis may help improve this inequity.

Background. Videolaryngoscopy still requires adjuncts or hyperangulated rescue in a clinically important minority, and bedside screening discriminates modestly. Point-of-care ultrasound (POCUS) of the anterior airway is a promising alternative, but existing prediction models are opaque or assume a pre-specified functional form. We developed and internally validated a parsimonious, fully disclosed POCUS risk equation whose form is recovered from data and whose structural properties are machine-checked by formal proof - to our knowledge the first formally verified clinical risk predictor - following TRIPOD+AI 2024. Methods. In a prospective single-centre, single-operator cohort of 259 adults undergoing elective videolaryngoscopy (no-Easy airway 68/259, 26.3%), Sequentially Thresholded Least Squares with bootstrap stability selection (B=300) screened a 71-term library of nine POCUS features and retained a seven-term logistic equation; a two-term bootstrap-stable model was pre-specified as robustness analysis. Internal validation used 5x10 repeated cross-validation plus temporal and device hold-outs, with pre-specified overfitting and optimism assessments. Five behavioural properties of the deployed equation were machine-checked in Lean 4. Results. Two interactions met the |c|/sigma_c>2 stability criterion: skin-to-epiglottis x skin-to-hyoid-bone distance and tongue volume x sagittal tongue area. The seven-term equation reached a 5x10 cross-validated C-statistic of 0.966 (optimism-corrected 0.968) and held across temporal and device hold-outs (0.94-0.97). Calibration-in-the-large matched prevalence, with cross-validated slope 0.90 attenuating to 0.625 out-of-time; standard recalibration restored 0.92 without loss of discrimination. The pre-specified two-term robustness model reproduced this performance (C-statistic 0.964-0.968; events-per-parameter 34; shrinkage 0.99), confirming the result is not an artefact of the screening stage. Net benefit over a clinical baseline was positive across 10-50% thresholds. All five Lean 4 theorems compiled without sorry. Conclusions. A sparse, formally verified POCUS equation predicts difficult videolaryngoscopy with high internally validated discrimination and quantified, modest overfitting. Because the equation was developed in a single-operator cohort and its inputs are operator-dependent, external validation requires prior harmonisation of the measurement protocol and operator credentialing.

Background: Perioperative hypotension is associated with postoperative organ injury. However, trials of hypotension avoidance have not found meaningful improvements in postoperative cardiovascular, renal, neurological or functional outcomes. One possible explanation is that organ perfusion depends on patients individual autoregulatory ranges. Hence, technology enabling monitoring of the autoregulatory status of vital organs, e.g. the brain, could provide a physiologic basis for personalising of blood pressure targets. However, current established methodologies for monitoring cerebral autoregulation in noncardiac surgery, e.g. the cerebral oximetry index (COx), are limited by performance and usability. The Medtronic Cotrending algorithm has been developed to provide automated, near real-time assessment of cerebral autoregulation. While feasibility was demonstrated in cardiac surgery, its applicability in major noncardiac surgery remains unknown. This study aims to evaluate the technical feasibility and clinical implications of Cotrending-based cerebral autoregulation monitoring in major noncardiac surgery. Objectives: Primary objective: To evaluate the technical feasibility of using the Medtronic Cotrending algorithm to monitor intraoperative cerebral autoregulation in real-time during major noncardiac surgery, drawing comparisons to the COx algorithm. Secondary objectives: to investigate the potential clinical implications of Cotrending-based cerebral autoregulation monitoring. Design: Single-centre, prospective cohort study. Setting: Swiss tertiary care centre Patients: Patients enrolled in AUTOREGULATE-NONCARDIAC who were monitored intraoperatively with the Medtronic INVOS(TM) 5100 near-infrared spectroscopy (NIRS) system. Outcomes: Technical feasibility outcomes include success rate of determination of the lower limit of cerebral autoregulation, intraoperative uptime, time to first estimate of the lower limit of cerebral autoregulation, sensitivity to external factors and to data artefacts; agreement of Cotrending-derived lower limit of cerebral autoregulation with COx-derived lower limit of cerebral autoregulation. Conclusions: N/A Trial registration: Clinicaltrials.gov NCT07630129

Background: In Denmark, perioperative high-dose glucocorticoid treatment were step-wisely implemented for total hip arthroplasty (THA), total knee arthroplasty (TKA), and unicompartmental knee arthroplasty (UKA). We aimed to estimate the effect of a single high dose of glucocorticoids on opioid consumption following primary THA, TKA, and UKA. Methods: This was a prespecified analysis of a multicenter natural experiment using electronic health record data. We included elective THA, TKA, or UKA surgeries performed in Eastern Denmark from 2017-2025. At each center, surgeries before implementation of high-dose glucocorticoids served as controls, whereas surgeries after implementation comprised the intervention group. The primary outcome was the between-group difference in cumulative 0-24h opioid consumption, which included preemptive end-of-surgery doses. The predefined minimal important difference was set at 5 mg IV morphine equivalents. Secondary outcomes were maximum 0-10 numerical rating scale (NRS) pain score and incidence of opioid-related adverse events within 24 hours, hospital length of stay, and days alive and out of hospital at 30 days. Results: A total of 47,317 surgeries performed at nine centers were analyzed: 13,010 controls and 34,307 in the intervention group. During the study period, five centers implemented high-dose glucocorticoids for THA patients, two for TKA/UKA patients. High-dose glucocorticoids were administered to 6% of patients before implementation versus 92% after. High-dose glucocorticoids resulted in a mean reduction of 3.8 mg intravenous (IV) morphine equivalents (95% CI 3.3;4.3). The intervention also reduced the maximum 0-24h NRS pain score by 0.8 points (99% CI 0.7;0.9), but there was no difference in adverse events, length of stay, or days alive and out of hospital. Conclusions: Implementation of high-dose glucocorticoids reduced 0-24-hour opioid consumption by 3.8 mg IV morphine equivalents after elective hip and knee arthroplasty. This difference was below the prespecified minimal important difference threshold. Online registration: https://doi.org/10.1101/2025.11.11.25339982

ABSTRACT Background: Post-traumatic elbow stiffness is a recognised complication following orthopaedic trauma surgery, occurring in 10-15% of trauma patients sustaining injuries. Pain remains the primary barrier to physiotherapy compliance, with surgical arthrolysis carrying recurrence rates of up to 34%. The supraclavicular brachial plexus block, referred to as the 'spinal of the arm', provides anaesthesia and analgesia to the entire upper limb below the shoulder. A structured non-surgical approach combining continuous catheter analgesia with timed rehabilitation was identified as an unmet need in this patient group. Methods: A single-centre retrospective observational study was conducted on data of patients treated for post-surgical upper limb stiffness between January 2022 and April 2026. Of 30 patients identified, 28 with elbow involvement formed the primary analysis group following exclusion of 2 patients with isolated wrist stiffness and complex regional pain syndrome. Ultrasound- guided supraclavicular brachial plexus catheters were inserted using the Contiplex system. Patients received 0.5% Bupivacaine (10-15ml) for initial blockade, followed by daily top-up doses of 0.2% Ropivacaine(20ml) given 30 minutes prior to structured physiotherapy and CPM sessions for up to 5 days. The primary outcome was change in arc of elbow motion in degrees, measured by the attending orthopaedic consultant using standard goniometry. Results: Complete pre- and post- intervention data were available for all 28 patients. Mean pre-intervention arc of elbow motion was 39.1{degrees}(SD+/-23.2{degrees}), improving to 104.2{degrees}(SD+/- 30.0{degrees}) post-intervention. Mean improvement was 65.1{degrees}(SD+/- 30.6{degrees} ); 95% CI 53.8{degrees} to 76.4{degrees} ; range 10{degrees}-140{degrees} ; paired t-test t=-11.27, p<0.0001). Mean catheter duration was 5.2 days (SD+/- 1.3). Five patients (17.9%) experienced mechanical catheter complications- 3 dislodgements, 1 kinking and 1 block failure- with no episodes of Local Anaesthetic Systemic toxicity, infection or neurological deficit. Conclusion: Continuous supraclavicular brachial plexus catheter analgesia represents a promising, minimally invasive rehabilitation tool for post-surgical elbow stiffness - achieving statistically and clinically meaningful Range of Motion (ROM) improvement through targeted regional analgesia, without the need for surgical intervention. These findings support prospective evaluation of this protocol as a primary non-surgical rehabilitation strategy.

Background Thoracoscopic esophagectomy with intrathoracic carbon dioxide insufflation and lung collapse, usually performed in the prone position, can markedly alter respiratory physiology and acid-base balance. Serum potassium elevation is often observed during acute respiratory acidosis in these procedures, despite the conventional view that respiratory acidosis has little effect on potassium. We quantified the intraoperative potassium change and explored associated factors. Methods This multicenter retrospective study included adults undergoing thoracoscopic esophagectomy with carbon dioxide insufflation in the prone or lateral decubitus position during 2022-2024. Arterial blood gas variables were evaluated after anesthesia induction and at the time of the lowest arterial pH during carbon dioxide insufflation. The primary outcome was the paired difference in serum potassium. Sensitivity, subgroup, and regression analyses were performed. Results All 131 patients were included: 117 in the prone position and 14 in the lateral decubitus position. Serum potassium increased from 3.96 {+/-} 0.38 to 4.59 {+/-} 0.63 mEq/L (mean increase, 0.64 mEq/L; 95% confidence interval, 0.55-0.73; p < 0.001). During the same period, pH decreased from 7.387 to 7.247 and arterial carbon dioxide tension increased from 41.48 to 58.60 mmHg. After excluding marked metabolic acidosis, the increase remained significant and similar in magnitude (0.618 mEq/L). In the centered multivariable model, lactate change was independently associated with potassium change ({beta} = 0.303; p = 0.004), whereas arterial carbon dioxide change and preoperative renal function were not. The intercept remained significantly positive. Conclusions A clinically meaningful potassium increase was observed during thoracoscopic esophagectomy with carbon dioxide insufflation, while acute respiratory acidosis developed during the same period. The increase persisted after excluding marked metabolic acidosis and may not be explained solely by metabolic stress. Arterial blood gas assessment, including potassium measurement, is warranted during significant hypercapnia, and potential electrolyte consequences should be considered when permissive hypercapnia is accepted.

Objectives: Incisional hernia (IH) affects 13-30% of people after abdominal surgery, resulting in substantial morbidity and costs. While clinical risk factors have been studied extensively, genomic risk for IH is incompletely understood. We aimed to evaluate the impact of polygenic risk scores (PRS) on IH risk prediction. Methods] We created and evaluated three PRS for abdominal hernia, ventral hernia and latent hernia susceptibility for prediction of IH in an institutional biobank. The primary outcome was defined as the diagnosis or repair of an IH based on ICD-9/10-CM/PCS and CPT codes. Clinical covariates included age, sex, body mass index (BMI), smoking status, index procedure type, and perioperative surgical site infection. A phenome-wide association study (PheWAS) was performed to assess clinical associations with increased PRS. We then tested the ability of the PRS to improve prediction for IH by modeling clinical covariates with and without PRS in patients who underwent abdominal surgery. Model performance was assessed using 10 iterations of 5-fold cross-validation to estimate Brier scores and area under the receiver operating characteristic curve (AUROC), which were compared using cross-model Bayesian analysis of variance. Results: In 55,809 subjects, assessed PRS was significantly associated with incisional, umbilical, and ventral hernia on PheWAS, with 1.19 greater odds of developing IH per 1-SD increase in PRS (95% CI: 1.13-1.25, P \< 0.001). Of 9,909 subjects who underwent qualifying abdominal surgery, 706 developed IH. In this cohort, the latent hernia susceptibility PRS was associated with a 16% increased hazard of developing IH per 1-SD increase (HR 1.16; 95% CI: 1.07-1.26; P \< 0.001). Compared to a predictive model using clinical covariates (Brier score = 0.047, 95% CI: 0.046-0.048; AUROC = 0.660, 95% CI: 0.653-0.666), addition of the PRS showed similar Brier score and AUROC estimates (Brier score = 0.047, 95% CI: 0.046-0.048; AUROC: 0.667, 95% CI: 0.661-0.673) at five years. Cross-model Bayesian analysis demonstrated \>99% probability of practical equivalence when trying to detect a difference of [&ge;] 0.02. Conclusion: All three PRS for hernia were independently associated with IH, suggesting that genomic factors contribute significantly to IH development. However, none of the three PRS meaningfully improved clinical IH risk prediction in patients who underwent abdominal surgery. This suggests that clinical comorbidities and surgical techniques may be equally as important as genomic architecture.

Introduction: The incidence of postoperative delirium (POD) is high in frail elderly patients who have undergone gastrointestinal surgery, and POD significantly increases the risk of complications and medical burden. Opioid-free anaesthesia (OFA) involves a multimodal analgesic strategy, which may help to reduce the risk of POD. However, relevant studies focusing on frail elderly patients are still limited. This study aims to investigate the effect of OFA on the occurrence of POD in frail elderly patients after gastrointestinal surgery. Methods: This single-centre, prospective, randomized controlled trial (RCT) will be conducted at the First Affiliated Hospital of Shandong First Medical University, China. A total of 44 frail elderly patients aged 65 years or older who plan to undergo elective gastrointestinal surgery (modified frailty index (mFI > 0.27) will be randomly assigned to either the OFA group (receiving dexmedetomidine, esmolol, and ketamine) or the opioid-based anaesthesia (OBA) group. The primary outcome is the incidence of POD within 7 days after surgery or at discharge. Secondary outcome measures include the perioperative stress response, inflammation, intraoperative haemodynamics, postoperative 30-day all-cause mortality, intraoperative haemodynamic changes, 15-item quality of recovery (QoR-15), and postoperative complications during hospitalization. This study focuses on frail elderly individuals (a high-risk population) and aims to investigate the potential benefits of the OFA strategy in reducing the incidence of POD by reducing exposure to opioids through multimodal analgesia. If positive results are obtained in this study, they may provide new evidence for optimizing the perioperative management of such patients. This study is a single-centre, prospective RCT, and the results can provide preliminary evidence for subsequent studies to be performed on a larger scale. Discussion: This study focuses on frail elderly individuals (a high-risk population) and aims to investigate the potential benefits of the OFA strategy in reducing the incidence of POD by reducing exposure to opioids through multimodal analgesia. If positive results are obtained in this study, they may provide new evidence for optimizing the perioperative management of such patients. This study is a single-centre, prospective RCT, and the results can provide preliminary evidence for subsequent studies to be performed on a larger scale. Trial registration: NCT07603596.

Background High-risk preoperative triage remains fragmented: existing tools often estimate risk without identifying modifiable mechanisms or linking classification to postoperative monitoring, destination planning, and rescue resources. This protocol describes implementation and evaluation of a Reserve-Stress-Rescue (RSR Framework), pathway that operationalizes perioperative high risk as a mismatch among patient physiologic reserve, procedural stress, and system rescue capacity. Approach RSR is a proposed clinician-facing, modular scoring framework for adults undergoing major surgery, especially patients with frailty, multimorbidity, poor functional capacity, anemia or malnutrition, cardiopulmonary disease, or limited postoperative support. Each domain, Reserve, Stress, and Rescue, is scored from 0 to 4 and recorded as both a three-part profile and a total score from 0 to 12. Scores map to Green, Amber, Red, and Crimson triage bands that trigger escalating actions, including targeted optimization, multidisciplinary review, anesthesia and surgical planning, postoperative destination selection, monitoring intensity, and predefined escalation criteria. Validation Plan The initial phase of this study received an exemption determination from the Yale University Institutional Review Board on June 3, 2026, under IRB Protocol ID 2000042729, with exempt categories 2(ii) and 4(iii), including a waiver of HIPAA authorization for access to and use of protected health information as described in the approved protocol. Evaluation will proceed in stages, assessing feasibility, interrater reliability, completeness, acceptability, discrimination, calibration, and clinical utility. Key outcomes include postoperative complications, unplanned escalation of care, intensive care utilization, failure to rescue, mortality, length of stay, triage burden, low-yield testing cascades, and management-changing pathway activation. Conclusion The RSR pathway reframes high-risk status as a modifiable interaction between vulnerability, operative insult, and rescue capacity rather than a fixed patient label. If feasible and valid, RSR may standardize high-risk identification, align perioperative resources with anticipated physiology, improve communication, and support safer, actionable shared decision-making.

Background: Sleep, pain, affect, cognition and energy (SPACE) has been described as a latent symptom-severity construct in chronic overlapping pain conditions. Its population-level structure and associations with chronic pain interference and functional disability remain uncertain. Methods: We conducted a cross-sectional analysis of UK Biobank participants. Prespecified standardised symptom domains were examined using correlation analysis, principal component analysis, exploratory factor analysis and k-means clustering. Associations with chronic pain interference, current work disability, poor self-rated health and longstanding illness or disability were assessed using covariate-adjusted logistic regression. A four-domain score excluding pain tested whether associations extended beyond the pain domain. Secondary analyses examined convergence with actigraphy, biomarkers, polygenic risk scores and brain magnetic resonance imaging phenotypes. Results: Of 501,935 eligible participants, 475,134 had complete domain data. Domains were modestly intercorrelated (r=0.04-0.46). Clustering identified lower- and higher-burden phenotypes comprising 70.5% and 29.5% of participants; current work disability occurred in 1.3% and 10.3%, respectively. Adding the four non-pain domains increased the area under the curve for chronic pain interference from 0.593 to 0.672 and for work disability from 0.748 to 0.850. Inclusion of pain increased the work-disability area under the curve to 0.863. Multimodal measures added smaller increments. Conclusions: A multidimensional symptom profile was identifiable at population scale and was concurrently associated with chronic pain interference and work disability, with non-pain domains contributing information beyond pain burden alone.

The Acute to Chronic Pain Signatures (A2CPS) project is a large, multisite, longitudinal observational study designed to identify biomarkers that predict the transition from acute to chronic pain following surgery in more than 2200 patients. Two participant cohorts were recruited before undergoing either knee arthroplasty or thoracic surgery. A unique feature of this study is its comprehensive evaluation of pain, including evoked and recall pain measures collected at baseline, 6-weeks, and 3-months following surgery, in addition to the primary pain outcome assessed remotely at 6 months. This paper describes the acquisition, quality control procedures, and available pain and pain sensitivity variables included in the A2CPS study. Self-report pain assessments include surgical site (i.e., index) pain intensity, pain interference and quality, spatial distribution of pain using body maps, and pain-related dysfunction specific to each cohort. Quantitative sensory testing yielded evoked pain sensitivity data including pressure pain thresholds, temporal summation of pain, dynamic mechanical allodynia, and conditioned pain modulation at both index and common sites across cohorts. Movement-evoked pain was assessed for each cohort using relevant functional tasks (knee: 10m walk and five-time-sit-to-stand tests, thoracic: deep breathing and coughing). Using baseline data from release v2.1.0, comprising approximately 1,400 participants, we evaluated interrelationships among pain variables. Overall, the A2CPS pain and pain sensitivity data provide a robust, comprehensive set of variables that supports the study goal of uncovering predictive biomarkers of post-operative chronic pain and enables broader exploration relative to other study outcomes, including imaging, psychosocial, and omics data.

Background. Whether predictors of intraoperative hypotension (IOH) add information beyond the mean arterial pressure (MAP) already displayed on the monitor is contested: selection bias in common evaluation designs inflates apparent performance, and the field has called for comparisons against simple MAP-based references under bias-resistant protocols. Existing predictors also depend on proprietary waveform analysis or pulse-contour monitors, restricting both deployment and external validation. Methods. Using 807 non-cardiac surgery patients from the open VitalDB database, we derived an additive gradient boosting model (one split per tree: a learned shape function per variable, no interactions) from three variables computable from an arterial line alone: current MAP, its drift from the patient's own 20-minute baseline, and the growth of its rolling variance (critical slowing down). Evaluation used patient-level 5-fold cross-validation under a strict protocol - exclusion of the 65-75 mmHg grey zone and of all samples already hypotensive at prediction time - with MAP alone (same learner class) as comparator. The frozen model was then validated, without any refitting, on an independent cohort from another continent (MOVER, University of California Irvine) following a pre-registered plan sealed before external data access. Results. In development the pressure-only model reached AUROC 0.907 vs. 0.884 for MAP alone (Delta AUROC +0.023, 95% CI +0.017 to +0.029) at 5 min, with +0.031 and +0.032 at 10 and 15 min, and good calibration (Brier skill +0.418 vs. prevalence). In external validation on 3,069 patients (442,194 samples, 1-minute charting, event prevalence 5.8%), the advantage not only transferred but was larger than in development: AUROC 0.696 vs. 0.638, Delta AUROC +0.058 (95% CI +0.051 to +0.064), meeting both pre-registered gates. Discrimination transferred; calibration did not (external Brier skill -0.014), requiring local recalibration. In the unrestricted scenario, where samples already at threshold are retained, the advantage collapsed (+0.007), reproducing the selection effect this paper documents. A secondary model adding pulse-contour cardiac output and stroke volume variation improved development discrimination further (Delta AUROC +0.035) but could be externally validated in only 39 patients, because those signals are rarely recorded. Conclusions. The dynamics of arterial pressure itself - drift from a patient-specific baseline and variance growth - carry predictive information beyond its current value, in a fully interpretable additive model that requires only an arterial line, no waveform access and no proprietary hardware. The advantage is confirmed in a pre-registered frozen-model external validation of over three thousand patients, and is largest at coarse recording cadence, where instantaneous pressure is least informative.

Background: Intraoperative hypotension is associated with cardiovascular complications and mortality, making accurate blood pressure monitoring essential. However, the accuracy of noninvasive oscillometric cuff blood pressure (Cuff BP) during hypotension is uncertain. We examined the association between intraoperative hypotension and Cuff BP inaccuracy. Methods: A single-center retrospective cohort included 22,812 adults undergoing noncardiac surgery from April 2013 through November 2023, with 159,782 simultaneous Cuff BP and invasive arterial blood pressure (Arterial BP) pairs. Pairs with arterial systolic BP >120 mmHg or diastolic BP >80 mm Hg were excluded to focus on hypotensive range. Hypotension was defined as arterial mean arterial pressure (MAP) <65 mmHg and categorized as mild (55 to <65), moderate (45 to <55), or severe (35 to <45 mmHg). Cuff BP inaccuracy was defined as an absolute MAP difference >10 mmHg from Arterial BP. Multivariable logistic regression estimated adjusted odds ratios (ORs) and 95% CIs. Results: Compared with normal MAP (?65 mmHg), hypotension was associated with greater odds of Cuff BP inaccuracy (adjusted OR, 1.45 [95% CI, 1.41?1.49]). Adjusted ORs increased with severity (P for trend <0.001): 1.23 (95% CI, 1.19?1.27) for mild, 2.36 (95% CI, 2.24?2.50) for moderate, and 7.39 (95% CI, 6.34?8.62) for severe hypotension. Sensitivity for correct MAP classification decreased from 87.1% for normal MAP to 32.0%, 19.6%, and 10.2% for mild, moderate, and severe hypotension. Conclusions: We found a significantly higher risk of Cuff BP inaccuracy in patients with intraoperative hypotension, supporting cautious interpretation of Cuff BP during intraoperative hypotension.

BACKGROUND: Caudal block is widely employed in pediatric lower abdominal surgeries and adult anorectal surgical by its simplicity of operation, reliable efficacy, and high safety. Previous studies have found that the dose of ropivacaine for Caudal block in adults exhibits gender differences. However, it remains unclear whether such differences in the median effective concentration (EC50) of ropivacaine also exist in the elderly population . METHODS: This is a double-blind, prospective study, We enrolled patients aged 60-80 years with ASA physical status I-? who were scheduled for anorectal surgery under caudal anesthesia, and allocated them to 2 study groups according to their gender. Each participant received a single injection of 20mL ropivacaine. Using Dixons up-and-down sequential allocation, the initial concentration of ropivacaine was set at 0.35% and the subsequent concentrations were determined by the analgesic response of the previous patients to the pinprick testing. The concentration change was 0.025%. The EC50 of ropivacaine in each group was determined using the the up-and-down method and probit regression. The primary outcome was the EC50 (95% confidence interval [CI]) of the 2 groups. Data on the surgical time, analgesic duration, and adverse events during surgery were also recorded. RESULTS: This study included a total of 40 elderly patients (20 male and 20 female). The EC50 of ropivacaine for caudal block in elderly male patients was 0.263% (95% CI: 0.179%-0.311%), while that in elderly female patients was 0.281% (95% CI: 0.161%-0.353%). The EC50 of ropivacaine for caudal block in elderly female patients was approximately 6.4% higher than that in elderly male patients. CONCLUSIONS: There is a significant gender difference in the EC50 of ropivacaine for caudal block among the elderly, with elderly female requiring a higher EC50 than male.

Background: Hemoglobin (Hb) elevation is the hallmark of high-altitude adaptation, yet its effect on surgical outcomes may depend on arterial oxygen saturation (SpO2)--previously uninvestigated. Objectives: To explore whether preoperative Hb effect on postoperative length of stay (LOS) after laparoscopic cholecystectomy (LC) reverses across SpO2 strata. Methods: Retrospective single-center cohort of 612 adults undergoing elective LC (2018-2023) at Qinghai Red Cross Hospital, Xining, China (2260 m). Exposure: preoperative Hb (82-233 g/L) and SpO2 (86%-99%), stratified as low (<93%), mid (93%-95%), high (>=96%). Primary analysis: multivariable linear regression with Hb x SpO2 interaction, adjusted for BMI, age, sex, season. Results: Among 612 patients (65.8% female; mean age 43.5 [11.9] years; mean Hb 151.4 [20.7] g/L; mean SpO2 94.6% [2.3%]), the Hb x SpO2 interaction was significant (beta = -0.0095; P = .009). Hb effect reversed: in SpO2 >=93%, each 1 g/L Hb prolonged LOS by 0.003 days (P = .079); in SpO2 <93%, each 1 g/L reduced LOS by 0.006 days. In mid-SpO2 stratum (n = 251), Hb >=180 g/L had longer LOS (1.88 vs 1.62 days; P = .001; d = 0.54). Five computational robustness analyses confirmed the interaction (leave-one-out: 100% P < .05 across 612 iterations). Conclusions: In this exploratory cohort, we observed an SpO2-dependent reversal of the Hb effect on postoperative LOS, designated the "Plateau Hemoglobin Paradox." Given single-center design and achieved power of 0.754, findings require replication. If replicated, this pattern may inform future perioperative risk stratification at high altitude.