Daily Anesthesiology Research Analysis
Three perioperative pain studies stand out today. A large multicenter RCT found no benefit of adding gabapentin to multimodal analgesia after major surgery. An instrumental-variable analysis across 23,238 VA procedures identified NSAIDs plus dexamethasone or regional anesthesia as optimal non-opioid combinations to reduce postoperative opioids. An RCT of intraoperative ketamine showed no overall benefit after breast surgery, but patients with higher baseline temporal summation appeared to benefi
Summary
Three perioperative pain studies stand out today. A large multicenter RCT found no benefit of adding gabapentin to multimodal analgesia after major surgery. An instrumental-variable analysis across 23,238 VA procedures identified NSAIDs plus dexamethasone or regional anesthesia as optimal non-opioid combinations to reduce postoperative opioids. An RCT of intraoperative ketamine showed no overall benefit after breast surgery, but patients with higher baseline temporal summation appeared to benefit, supporting precision analgesia.
Research Themes
- Optimization of multimodal analgesia combinations
- De-implementation of low-value perioperative adjuncts
- Mechanism-informed precision analgesia
Selected Articles
1. Gabapentin for Pain Management after Major Surgery: A Placebo-controlled, Double-blinded, Randomized Clinical Trial (the GAP Study).
In a multicenter, double-blind RCT of 1,196 patients undergoing major cardiac, thoracic, or abdominal surgery, perioperative gabapentin did not reduce length of stay or serious adverse events versus placebo. The dosing regimen (600 mg preop; 300 mg BID for 2 days) produced no clinically meaningful benefit within a multimodal analgesia program.
Impact: This high-quality RCT directly tests a widely used but weakly evidenced adjunct and shows no benefit, supporting de-implementation of routine perioperative gabapentin for major surgery.
Clinical Implications: Routine addition of gabapentin to multimodal analgesia after major surgery should be reconsidered, focusing instead on interventions with proven benefit and minimizing polypharmacy.
Key Findings
- No reduction in length of stay: median 5.94 days (gabapentin) vs 6.15 days (placebo); HR 1.07 (95% CI 0.95–1.20), P=0.26.
- Serious adverse events were similar: 31.7% (gabapentin) vs 32.6% (placebo).
- Effect consistency across cardiac (n=500), thoracic (n=346), and abdominal (n=350) surgery subgroups.
Methodological Strengths
- Multicenter, double-blind, placebo-controlled RCT with large sample (n=1,196).
- Clear primary endpoint and prespecified follow-up at 4 weeks and 4 months.
Limitations
- Primary outcome (length of stay) may be influenced by non-analgesic factors, potentially diluting analgesic effects.
- Gabapentin dosing limited to 2 postoperative days; different regimens might produce different effects.
Future Directions: Focus on analgesic components with proven outcome benefits; evaluate patient-phenotyping strategies to target adjuncts to subgroups most likely to benefit.
2. Optimal multimodal analgesia combinations to reduce pain and opioid use following non-cardiac surgery: an instrumental variable analysis.
Using anesthesiologist assignment as an instrument across 23,238 non-cardiac surgeries, multimodal analgesia reduced opioids and pain. The most effective non-opioid combinations were NSAIDs plus dexamethasone or regional anesthesia, each cutting postoperative opioid consumption by roughly 28–30 oral morphine equivalents.
Impact: This quasi-experimental analysis identifies concrete, high-yield non-opioid combinations within MMA, offering actionable guidance to optimize perioperative protocols.
Clinical Implications: Incorporate NSAIDs plus dexamethasone and consider regional anesthesia to maximize opioid-sparing after non-cardiac surgery; reevaluate the marginal role of IV acetaminophen in MMA.
Key Findings
- Among 23,238 cases, MMA reduced inpatient postoperative opioid use by 6.8 OMEs (95% CI -10.2 to -3.4) and outpatient pain by 1.0 unit (95% CI -1.6 to -0.4).
- NSAIDs plus dexamethasone reduced opioids by -29.5 OMEs (95% CI -36.9 to -19.5).
- Regional anesthesia combinations reduced opioids by -28.4 OMEs (95% CI -40.1 to -16.8).
Methodological Strengths
- Instrumental variable design emulating randomization across multiple hospitals.
- Large, real-world cohort enabling robust estimates of treatment effects.
Limitations
- Observational design relies on instrument validity (exclusion restriction) and may be affected by residual confounding.
- Veterans Health Administration cohort may limit generalizability (older, predominantly male population).
Future Directions: Prospective trials to validate NSAID–dexamethasone synergies, quantify risks (e.g., bleeding, glycemic effects), and clarify the independent value of IV acetaminophen.
3. A Randomized Controlled Trial of Intraoperative Ketamine for Acute Postsurgical Pain after Breast Cancer Surgery: The Moderating Effect of Baseline Temporal Summation of Pain.
In 225 breast surgery patients, intraoperative ketamine did not improve 2-week postoperative pain outcomes overall versus saline. Exploratory moderation indicated potential benefit among patients with higher baseline temporal summation of pain, suggesting a phenotype-driven, mechanism-based approach to ketamine use.
Impact: This trial advances precision analgesia by linking ketamine efficacy to a mechanistic pain phenotype (temporal summation), moving beyond one-size-fits-all perioperative analgesia.
Clinical Implications: Routine intraoperative ketamine for breast surgery is not supported; consider targeting ketamine to patients with high temporal summation (central sensitization tendency) when quantified preoperatively.
Key Findings
- No overall difference in pain severity or pain impact at 2 weeks between ketamine (n=113) and saline (n=112).
- Moderation analysis: higher baseline temporal summation predicted greater ketamine-associated reductions in pain.
- Surgical mix included lumpectomy (53%), mastectomy (16%), and mastectomy with reconstruction (30%).
Methodological Strengths
- Prospective randomized controlled design with adjustment for relevant covariates.
- Integration of quantitative sensory testing to probe mechanistic moderation.
Limitations
- Moderation findings were exploratory and sensory testing was limited to a subset.
- Two-week follow-up may miss longer-term effects on persistent postsurgical pain.
Future Directions: Validate phenotype-guided ketamine use in pre-specified trials; assess feasibility of perioperative temporal summation screening and long-term pain outcomes.