Daily Anesthesiology Research Analysis
Three impactful perioperative studies stand out today: a meta-analysis of 26 RCTs shows NSAIDs do not increase postoperative bleeding after pediatric tonsillectomy and reduce PONV; a population PK analysis across four trials in pregnant individuals supports fixed tranexamic acid dosing and validates intramuscular administration for postpartum hemorrhage; and an RCT demonstrates that combining esketamine with sufentanil improves pain control and depressive symptoms after cardiac surgery.
Summary
Three impactful perioperative studies stand out today: a meta-analysis of 26 RCTs shows NSAIDs do not increase postoperative bleeding after pediatric tonsillectomy and reduce PONV; a population PK analysis across four trials in pregnant individuals supports fixed tranexamic acid dosing and validates intramuscular administration for postpartum hemorrhage; and an RCT demonstrates that combining esketamine with sufentanil improves pain control and depressive symptoms after cardiac surgery.
Research Themes
- Perioperative analgesia safety and optimization
- Dose and route optimization for obstetric hemorrhage management
- Integrating mental health outcomes into postoperative pain strategies
Selected Articles
1. The impact of non-steroidal anti-inflammatory drugs on postoperative bleeding in children undergoing tonsillectomy: a meta-analysis of randomized controlled trials.
In 26 RCTs including 2,717 children, perioperative NSAIDs did not significantly increase total, primary, or secondary postoperative bleeding after tonsillectomy. NSAIDs significantly reduced postoperative nausea and vomiting. These findings support NSAIDs as opioid-sparing analgesics in pediatric tonsillectomy without elevating bleeding risk.
Impact: This meta-analysis addresses a longstanding safety concern and synthesizes RCT evidence showing NSAIDs do not increase bleeding in pediatric tonsillectomy while improving PONV.
Clinical Implications: NSAIDs can be incorporated into multimodal analgesia after pediatric tonsillectomy to reduce opioid use and PONV without increasing bleeding risk. Clinicians can consider routine NSAID use while continuing to monitor for standard bleeding risks.
Key Findings
- Across 26 RCTs (n=2,717), NSAIDs did not significantly increase total postoperative bleeding (RR 1.19, 95% CI 0.90–1.58).
- No significant effect on primary (RR 1.13, 95% CI 0.77–1.65) or secondary bleeding (RR 1.36, 95% CI 0.86–2.14).
- NSAIDs significantly reduced postoperative nausea and vomiting (RR 0.78, 95% CI 0.67–0.92).
- Subgroup analyses by NSAID type and administration method showed no bleeding risk increase.
Methodological Strengths
- PRISMA-compliant systematic search across multiple databases with 26 RCTs included
- Prespecified subgroup analyses and pooled risk estimates (RR with 95% CI)
Limitations
- Potential heterogeneity in bleeding definitions and follow-up periods across trials
- Trial quality and reporting variability; publication bias cannot be fully excluded
Future Directions: High-quality, adequately powered RCTs with standardized bleeding endpoints and follow-up are needed to refine guidelines and explore specific NSAID regimens.
2. Evaluating Tranexamic Acid Dosing Strategies for Postpartum Hemorrhage: A Population Pharmacokinetic Approach in Pregnant Individuals.
Population PK modeling of 211 pregnant participants across four trials found that a two-compartment model best described TXA disposition. Fixed dosing achieved similar exposure to weight-based dosing, and intramuscular administration produced target exposures comparable to intravenous dosing. These findings support fixed dosing and intramuscular TXA as practical options for postpartum hemorrhage care.
Impact: The study informs real-world dosing and route decisions for TXA in PPH, a global maternal health priority, by showing fixed dosing suffices and intramuscular delivery is viable.
Clinical Implications: Fixed-dose TXA regimens can be used without weight-based adjustments, simplifying protocols, and intramuscular TXA is a practical alternative when IV access is delayed or limited. Implementation may expand timely TXA use in low-resource or emergent settings.
Key Findings
- A two-compartment model with first-order processes best fit TXA PK across IV, IM, and oral routes.
- Actual body weight was a significant covariate but explained little variability, supporting fixed dosing.
- Simulations showed minimal exposure differences between fixed and weight-based regimens.
- Intramuscular TXA achieved exposure targets comparable to intravenous administration.
Methodological Strengths
- Population PK using nonlinear mixed-effects modeling aggregating data from four clinical trials
- Systematic covariate assessment with simulations to compare dosing strategies and routes
Limitations
- PK-focused analysis without direct clinical outcome (efficacy/safety) comparisons
- Potential heterogeneity across trials and limited generalizability beyond studied regimens
Future Directions: Prospective PK–PD and outcome trials comparing IV vs IM TXA, validating fixed-dose protocols against clinical endpoints (bleeding control, mortality), especially in low-resource settings.
3. Effectiveness of intravenous administration of a combination of sufentanil and esketamine on post-cardiac surgery pain management and depression: a randomized controlled trial.
In a randomized trial of 104 cardiac surgery patients, adding esketamine to sufentanil significantly reduced PCIA demand and pain scores and improved mood, with lower HAMD and HAMA scores compared with control. These data support multimodal analgesia leveraging esketamine’s analgesic and antidepressant properties early after cardiac surgery.
Impact: This RCT integrates mental health outcomes into postoperative analgesia strategy, showing concurrent pain and mood benefits after high-risk cardiac surgery.
Clinical Implications: Consider esketamine as an adjunct to opioid-based PCIA after cardiac surgery to reduce opioid demand and improve early depressive/anxiety symptoms, with careful monitoring protocols.
Key Findings
- PCIA button presses were significantly fewer with esketamine+sufentanil (2.41±0.72) vs control (6.20±1.31), P<0.001.
- Pain scores (VAS) were lower at multiple postoperative time points in the experimental group (P<0.05).
- HAMD scores were reduced (7.52±4.24 vs 13.84±2.76), and HAMA scores were also lower in the esketamine group.
- Trial registered (ChiCTR2400092428), supporting methodological transparency.
Methodological Strengths
- Randomized controlled design with clear clinical endpoints (PCIA use, VAS, HAMD/HAMA)
- Prospective data collection with trial registration
Limitations
- Single-center study with modest sample size; blinding not specified
- Short-term outcomes; limited safety detail beyond early postoperative period
Future Directions: Multicenter, blinded RCTs powered for safety and longer-term neuropsychiatric outcomes, dose-finding for esketamine, and comparisons against other adjuncts.