Weekly Anesthesiology Research Analysis
This week’s anesthesiology literature emphasizes pragmatic, practice-changing trials and mechanistic studies that inform perioperative and critical care management. Top papers include a multicentre phase 3 RCT showing inhaled isoflurane is non-inferior to IV midazolam for sedation in ventilated children, a randomized mechanistic trial identifying hyperoxia-induced impairment of endothelium‑independent vasodilation via sGC heme oxidation, and a large multicentre RCT demonstrating no benefit of pe
Summary
This week’s anesthesiology literature emphasizes pragmatic, practice-changing trials and mechanistic studies that inform perioperative and critical care management. Top papers include a multicentre phase 3 RCT showing inhaled isoflurane is non-inferior to IV midazolam for sedation in ventilated children, a randomized mechanistic trial identifying hyperoxia-induced impairment of endothelium‑independent vasodilation via sGC heme oxidation, and a large multicentre RCT demonstrating no benefit of perioperative gabapentin after major surgery. Together these reports favor broadened inhaled sedation options in PICU, tighter intraoperative oxygen titration and new mechanistic therapeutic targets, and de-implementation of low-value analgesic adjuncts.
Selected Articles
1. Inhaled isoflurane for sedation of mechanically ventilated children in intensive care (IsoCOMFORT): a multicentre, randomised, active-control, assessor-masked, non-inferiority phase 3 trial.
IsoCOMFORT is a multicentre, assessor-masked non-inferiority RCT (n=96) demonstrating inhaled isoflurane achieved a non-inferior percentage of time within target COMFORT‑B sedation range compared with intravenous midazolam in ventilated children, with comparable safety and no treatment-related deaths.
Impact: First multicentre phase 3 evidence supporting inhaled sedation as a viable PICU option, which may change sedation pharmacotherapy and device planning in pediatric ICUs.
Clinical Implications: Centers with vaporizer capability can consider adopting isoflurane for ventilated children to expand sedative options, potentially improving logistic flexibility without compromising sedation targets or safety.
Key Findings
- Non-inferiority met for COMFORT‑B target range time: 68.94% (isoflurane) vs 62.37% (midazolam); least-squares mean difference 6.57 percentage points within pre-specified margin.
- Serious adverse events were similar between groups and not attributed to study drugs; no treatment-related deaths.
- Randomization 2:1 across 19 PICUs with standardized COMFORT‑B titration up to 48±6 hours.
2. Effects of Oxygen on Perioperative Vascular Function: A Randomized Clinical Trial.
In 200 elective cardiac surgery patients randomized to intraoperative hyperoxia vs normoxia, hyperoxia did not alter endothelium-dependent flow‑mediated dilation but impaired endothelium‑independent vasodilation ex vivo, consistent with sGC heme oxidation; multimodal assays provided mechanistic evidence implicating sGC redox state as a target.
Impact: Provides mechanistic human trial data that challenge routine intraoperative hyperoxia and identify soluble guanylyl cyclase redox/heme state as a potentially druggable mechanism to preserve vascular responsiveness.
Clinical Implications: Clinicians should favor titration toward normoxia rather than routine hyperoxia in cardiac surgery; future trials of sGC‑targeted agents may be warranted to counteract hyperoxia-induced dysfunction.
Key Findings
- Randomized 200 patients; hyperoxia left FMD unchanged but impaired endothelium-independent vasodilation ex vivo.
- Impairment mechanistically linked to soluble guanylyl cyclase (sGC) heme oxidation.
- Multimodal endpoints (FMD, PAT, wire myography, plasma biomarkers) provided convergent mechanistic evidence.
3. Gabapentin for Pain Management after Major Surgery: A Placebo-controlled, Double-blinded, Randomized Clinical Trial (the GAP Study).
In a large multicentre, double‑blind RCT (n=1,196) across major cardiac, thoracic, and abdominal surgeries, perioperative gabapentin (600 mg preop, then 300 mg BID ×2 days) did not reduce length of hospital stay, serious adverse events, or produce meaningful analgesic benefits within a multimodal regimen compared with placebo.
Impact: A high-quality negative multicentre RCT assessing a widely used adjunct; supports de-implementation of routine perioperative gabapentin in major surgery and redirects focus to higher-yield analgesic strategies.
Clinical Implications: Reconsider routine inclusion of gabapentin in multimodal regimens for major surgery; prioritize evidence-backed nonopioid combinations (e.g., NSAIDs + dexamethasone, regional techniques) and limit polypharmacy.
Key Findings
- No reduction in median length of stay: gabapentin 5.94 days vs placebo 6.15 days (HR 1.07; 95% CI 0.95–1.20; P=0.26).
- Serious adverse event rates similar (31.7% gabapentin vs 32.6% placebo).
- Consistent lack of benefit across cardiac, thoracic, and abdominal surgery subgroups.