Daily Anesthesiology Research Analysis
A single-center randomized trial found that tourniquet use during total knee arthroplasty in older adults increased postoperative delirium and was associated with biomarker changes suggesting hypoxia/oxidative stress. A simulation and applied re-analysis study identified multistate models as the optimal approach to analyze ventilator-free days in critical care trials. A meta-analysis of cesarean spinal anesthesia showed low-dose hypobaric local anesthetics reduce hypotension but may compromise a
Summary
A single-center randomized trial found that tourniquet use during total knee arthroplasty in older adults increased postoperative delirium and was associated with biomarker changes suggesting hypoxia/oxidative stress. A simulation and applied re-analysis study identified multistate models as the optimal approach to analyze ventilator-free days in critical care trials. A meta-analysis of cesarean spinal anesthesia showed low-dose hypobaric local anesthetics reduce hypotension but may compromise analgesic efficacy unless combined with intrathecal opioids.
Research Themes
- Perioperative neurocognitive disorders and modifiable surgical factors
- Methodological advances in ICU outcome analysis (ventilator-free days)
- Optimization of obstetric spinal anesthesia dosing and side-effect trade-offs
Selected Articles
1. Impact of tourniquet application on postoperative delirium in elderly patients undergoing total knee arthroplasty: a randomized clinical trial.
In 313 older adults undergoing TKA, tourniquet use nearly doubled postoperative delirium within 7 days (19.1% vs 9.6%). Biomarker changes (increased HIF-1α at 30 min and 24 h; decreased SOD at 24 h) suggest hypoxia/oxidative stress pathways. Postoperative complications and adverse events were similar between groups.
Impact: This randomized trial provides actionable evidence that a common intraoperative practice (tourniquet use) increases postoperative delirium in older adults and links it to plausible biological pathways.
Clinical Implications: Consider minimizing or avoiding tourniquet use in elderly TKA when feasible, intensifying delirium prevention, and monitoring oxidative stress-related biomarkers. Protocols targeting hypoxia/oxidative stress (e.g., optimizing oxygen delivery, antioxidant strategies) merit evaluation.
Key Findings
- Postoperative delirium incidence was higher with tourniquet (19.1%) vs no tourniquet (9.6%), RR 1.12 (95% CI 1.02–1.23), P=0.018.
- HIF-1α increased at 30 minutes and 24 hours postoperatively with tourniquet; SOD decreased at 24 hours.
- Postoperative complications and adverse events were comparable between groups.
Methodological Strengths
- Prospective randomized design with a sizable sample (n=313).
- Concurrent measurement of mechanistic biomarkers (HIF-1α, SOD, S100β) to support biological plausibility.
Limitations
- Single-center trial; generalizability may be limited.
- Blinding of clinicians/patients is unclear; potential performance/detection bias.
Future Directions: Multicenter RCTs comparing standardized tourniquet protocols (duration/pressure) and testing targeted interventions (e.g., HIF-1α modulation, antioxidant strategies) to prevent delirium.
BACKGROUND: Tourniquet is widely used in total knee arthroplasty (TKA), but its impact on postoperative delirium (POD) remains unclear. The purposes of this study were to investigate the impact of tourniquet application on POD in elderly patients TKA and to explore the possible mechanisms associated with POD. MATERIALS AND METHODS: In this prospective, single-center randomized clinical trial study, 313 patients scheduled for single TKA under general anesthesia were randomly assigned to groups with or without a limb tourniquet. The primary outcome was the incidence of POD within postoperative 7 days. Secondary outcomes were the levels of hypoxia-inducible factor-1α (HIF-1α), tumor necrosis factor-alpha, superoxide dismutase (SOD), and S100β protein (S100β) measured postoperative 30 minutes and 24 hours, blood loss, pain score, the time to first postoperative ambulation, postoperative hospitalization, postoperative complications, and adverse events. RESULTS: The incidence of POD in tourniquet group was significantly higher than that in no tourniquet group (19.1% vs. 9.6%, relative risk 1.12, 95% confidence interval: 1.02-1.23, P = 0.018). The serum level of HIF-1α was higher at postoperative 30 minutes and 24 hours and SOD was lower at postoperative 24 hours in tourniquet group compared with no tourniquet group. The incidence of postoperative complications and adverse events were comparable in both groups. CONCLUSION: We concluded that tourniquet application during TKA increased the incidence of POD within postoperative 7 days in older patients, and increased serum level of HIF-1α and decreased level of SOD, which indicated that they may be potential targets for preventing and treating POD.
2. What is the optimal approach to analyse ventilator-free days? A simulation study.
Across simulations and four applied RCT datasets, multistate models outperformed alternatives for analyzing ventilator-free days and offered interpretable effect sizes. Zero-inflated/hurdle count models and cause-specific Cox for death showed poor Type I error control, whereas time-to-event approaches, the Mann–Whitney test, proportional odds models, and the win ratio generally performed well.
Impact: This work provides a rigorous, comparative roadmap for analyzing a widely used ICU endpoint, enabling more robust and comparable evidence across trials.
Clinical Implications: Adopting multistate models for ventilator-free days can improve inference and comparability in critical care trials, informing regulatory and guideline-level analyses.
Key Findings
- Multistate models achieved superior performance and interpretability for VFD analysis in simulations and applied RCT datasets.
- Zero-inflated and hurdle Poisson/negative binomial models and cause-specific Cox for death exhibited poor Type I error control.
- Time-to-event approaches, Mann–Whitney test, proportional odds model, and win ratio generally showed good performance.
Methodological Strengths
- Comprehensive simulations with varied scenarios (16 datasets) and evaluation of 12 statistical methods.
- External application to four landmark RCT datasets with sensitivity analyses.
Limitations
- Simulated scenarios cannot encompass all clinical complexities and endpoint definitions.
- Recommendations are methodological; no direct patient-level intervention tested.
Future Directions: Develop consensus guidelines and provide user-friendly tools for multistate modeling of VFDs; extend evaluations to other composite ICU endpoints.
BACKGROUND: Ventilator-free days (VFDs) are a composite outcome in critical care research, reflecting both survival and mechanical ventilation duration. However, analysis methods for VFDs are inconsistent, with some focusing on counts and others on time-to-event outcomes, while other approaches such as the multistate model and the win ratio have emerged. We aimed to evaluate various statistical models through simulations to identify the optimal approach for analysing VFDs. METHODS: First, 16 datasets of 300 individuals were simulated, comparing a control group to an intervention with varying survival rates and ventilation durations. Various statistical models were evaluated for statistical power and Type I error rate. Four clinical trial datasets (LIVE study, NCT02149589; ARMA study, NCT00000579; ACURASYS study, NCT00299650; COVIDICUS study, NCT04344730) were then used to apply the same statistical models to analyse VFDs. Twelve statistical methods were evaluated, including count-based, time-to-event approaches, and the win-ratio. Additionally, sensitivity analyses were conducted.
3. Efficacy of low-dose hypobaric anesthetics in spinal anesthesia for cesarean delivery: systematic review and meta-analysis.
Across 17 RCTs (n=1,280), low-dose hypobaric spinal local anesthetics reduced maternal hypotension (RR 0.56) but increased the need for analgesic supplementation (RR 3.13). When low-dose anesthetic was combined with intrathecal opioids, analgesic efficacy was comparable to conventional-dose local anesthetic without opioid.
Impact: This synthesis clarifies dose–side effect trade-offs in obstetric spinal anesthesia and supports opioid adjuvants to maintain efficacy while minimizing hypotension.
Clinical Implications: For cesarean spinal anesthesia, consider low-dose hypobaric local anesthetic with intrathecal opioid to reduce hypotension without sacrificing analgesic efficacy, while individualizing dosing and monitoring.
Key Findings
- Low-dose hypobaric local anesthetics reduced maternal hypotension (RR 0.56; 95% CI 0.43–0.73).
- Analgesic supplementation was more frequent with low-dose regimens (RR 3.13; 95% CI 2.14–5.59).
- With intrathecal opioid adjuvants, low-dose anesthetic achieved similar efficacy to conventional-dose without opioid (RR 1.32; 95% CI 0.58–3.00).
Methodological Strengths
- Systematic review and meta-analysis of 17 RCTs with protocol registered on PROSPERO.
- Subgroup analyses addressing the role of intrathecal opioid adjuvants and multiple secondary outcomes.
Limitations
- Evidence grades for key outcomes were low to moderate; heterogeneity in dosing and anesthetic agents.
- Potential variability in definitions and reporting of hypotension and analgesic supplementation across trials.
Future Directions: Head-to-head, standardized RCTs comparing low-dose plus opioid vs conventional-dose regimens, with patient-centered outcomes and neonatal safety.
OBJECTIVE: Many studies have compared the anesthetic effects of different doses of hypobaric local anesthetics (without glucose) in spinal anesthesia for cesarean sections. Therefore, a meta-analysis of these trials is warranted. METHODS: Systematic review and meta-analysis of eligible randomized controlled trials comparing the efficacy of low-dose spinal hypobaric anesthetics (Bupivacaine < 10 mg, levobupivacaine < 10 mg, ropivacaine < 15 mg) with conventional dose (Bupivacaine/Levobupivacaine ≥ 10 mg, ropivacaine ≥ 15 mg) in elective and subemergency Cesarean sections in data sources RESULTS: We obtained data from 1,280 patients from 17 published trials. Low-dose hypobaric local anesthetics reduce hypotension occurrence (risk ratio [RR], 0.56; 95% confidence interval [CI], 0.43 to 0.73; low evidence grade) but comprise anesthesia effect (analgesic-supplementation risk: RR 3.13, 95%CI 2.14 to 5.59, moderate evidence grade). In the subgroup analysis (based on whether opioid adjuvants mixed with local anesthetics were equal), there were no differences in anesthetic effects between low-dose local anesthetics mixed with opioid adjuvants and conventional-dose local anesthetics without opioid adjuvants between the two groups (analgesic-supplementation risk: RR 1.32, 95%CI 0.58 to 3.00, moderate evidence grade). Other secondary outcomes, including hypotensive side effects (nausea/vomiting and bradycardia), ephedrine consumption, and highest block plane, were observed less or lower in the low-dose group. No significant differences were found in trembling, pruritus, time to maximum block, or neonatal outcomes between the two groups. CONCLUSION: Low-dose hypobaric local anesthetics in spinal anesthesia may reduce maternal side effects (hypotension, nausea/vomiting, and bradycardia) but comprise anesthetic efficacy (analgesic-supplementation risk). Furthermore, intrathecal opioid adjuvants improve anesthetic efficacy. DETAILS OF REGISTRATION: The protocol for this systematic review was registered on PROSPERO (CRD42024533150).