Daily Anesthesiology Research Analysis
Three studies stand out today in anesthesiology and perioperative care: a large multicenter RCT found that maintaining very low tidal volume ventilation with PEEP during cardiopulmonary bypass did not reduce postoperative infections; a phase IV randomized trial showed sugammadex rapidly and safely reverses neuromuscular block in infants under 2 years; and a triple-blind RCT demonstrated intraoperative esketamine infusion reduced postoperative delirium and inflammation after off-pump CABG.
Summary
Three studies stand out today in anesthesiology and perioperative care: a large multicenter RCT found that maintaining very low tidal volume ventilation with PEEP during cardiopulmonary bypass did not reduce postoperative infections; a phase IV randomized trial showed sugammadex rapidly and safely reverses neuromuscular block in infants under 2 years; and a triple-blind RCT demonstrated intraoperative esketamine infusion reduced postoperative delirium and inflammation after off-pump CABG.
Research Themes
- Intraoperative ventilation strategies during cardiopulmonary bypass
- Pediatric reversal of neuromuscular blockade
- Anesthetic modulation of postoperative delirium and inflammation
Selected Articles
1. Sugammadex for Reversal of Neuromuscular Blockade in Neonates and Infants Less than 2 Years Old: Results from a Phase IV Randomized Clinical Trial.
In a multicenter phase IV randomized trial including 138 neonates and infants (1–720 days), 2 mg/kg sugammadex reversed moderate neuromuscular block faster than neostigmine (median 1.4 vs 4.4 min; HR 2.40; P=0.0002) and 4 mg/kg provided rapid recovery from deep block (median 1.1 min). Tolerability was similar to neostigmine with no drug-related serious adverse events or hypersensitivity.
Impact: This is the first rigorous randomized evidence establishing dosing and performance of sugammadex in children under 2 years, addressing a key gap in pediatric anesthesia.
Clinical Implications: For neonates and infants, 2 mg/kg sugammadex can be used to reverse moderate NMB and 4 mg/kg for deep NMB, with rapid recovery and acceptable safety, providing an alternative to neostigmine.
Key Findings
- 2 mg/kg sugammadex reversed moderate NMB faster than neostigmine (median 1.4 vs 4.4 minutes; HR 2.40; 95% CI 1.37–4.18; P=0.0002).
- 4 mg/kg sugammadex achieved rapid reversal of deep NMB (median TTNMR 1.1 minutes).
- Safety profiles were similar between sugammadex and neostigmine; no deaths, drug-related serious adverse events, hypersensitivity, or anaphylaxis were reported.
- Pharmacokinetic assessments indicated no need for age-based dose adjustment within 0–<2 years.
Methodological Strengths
- Randomized, multicenter, double-blind design in efficacy part
- Predefined primary endpoint (TTNMR) with appropriate statistical analysis
Limitations
- Moderate sample size may not detect rare adverse events such as anaphylaxis
- Part A was open-label for pharmacokinetics and the trial did not assess longer-term outcomes
Future Directions: Postmarketing surveillance and larger registries in neonates are needed to quantify rare hypersensitivity risks and to assess outcomes across different anesthetic regimens and comorbidities.
BACKGROUND: Sugammadex is well tolerated and effective for reversing neuromuscular blockade (NMB) in adults and children as young as 2 yr old. There is little information on its use in younger children. The aim of this study was to evaluate the efficacy and tolerability of sugammadex in children under 2 yr of age. METHODS: This was a phase IV, randomized, parallel-group, multicenter clinical trial of sugammadex in participants aged birth to less than 2 yr (NCT03909165). Part A was open label and included pharmacokinetic assessments to determine whether sugammadex dose adjustment for part B was necessary based on age. Part B was double-blind and evaluated doses of 2 and 4 mg/kg sugammadex. Participants were randomized to (1) moderate NMB and reversal with 2 mg/kg sugammadex; (2) moderate NMB and reversal with neostigmine + glycopyrrolate or atropine (hereafter, called neostigmine); or (3) deep NMB and reversal with 4 mg/kg sugammadex. The primary efficacy endpoint was time to neuromuscular recovery (TTNMR). The primary efficacy hypothesis was that 2 mg/kg sugammadex would be superior to neostigmine for the reversal of moderate NMB as measured by TTNMR in part B. RESULTS: A total of 138 participants aged 1 to
2. Maintaining ventilation with very low tidal volume and positive-end expiratory pressure versus no ventilation during cardiopulmonary bypass for cardiac surgery in adults: a randomized clinical trial.
In a multicenter randomized trial of 1,362 adults undergoing CPB, maintaining ventilation with tidal volumes of 2.5 mL/kg PBW and 5–7 cmH2O PEEP did not reduce 28-day postoperative infections versus stopping ventilation. Antibiotic exposure was higher when ventilation was maintained; other outcomes and adverse events were similar.
Impact: This large RCT directly tests a common recommendation and shows no infection benefit from maintaining ventilation during CPB, potentially informing guideline revisions and standardizing practice.
Clinical Implications: During CPB, routinely maintaining very low tidal volume ventilation with PEEP should not be expected to reduce postoperative infections; practices can prioritize simplicity and reduce unnecessary antibiotic exposure.
Key Findings
- No reduction in 28-day postoperative infections with ventilation maintained during CPB (10.0% vs 10.9%; RR 0.92; 95% CI 0.67–1.25; p=0.58).
- Higher antibiotic use in the ventilation-maintained group (incidence risk ratio 1.08; 95% CI 1.02–1.15; p=0.02).
- No significant differences in other secondary outcomes or adverse events between groups.
Methodological Strengths
- Large sample size across six centers with randomized allocation
- Pre-registered trial with clinically meaningful primary endpoint and intention-to-treat analysis
Limitations
- Single-blind design may introduce performance bias
- Antibiotic stewardship practices could confound infection detection and treatment patterns
Future Directions: Evaluate patient-centered pulmonary outcomes (e.g., ventilator-associated complications, lung mechanics) and explore whether specific subgroups benefit from tailored intra-CPB ventilation strategies.
PURPOSE: Cardiopulmonary bypass (CPB) during cardiac surgery mechanically circulates and oxygenates the blood, bypassing the heart and lungs. Despite limited evidence, maintaining mechanical ventilation (MV) during CPB is recommended, as ventilator strategies during surgery may reduce the occurrence of postoperative infections. We aimed to determine whether maintaining MV for cardiac surgery would decrease postoperative infections compared with stopping MV during CPB. METHODS: We conducted a multicenter, single-blind, randomized trial among adult patients undergoing scheduled cardiac surgery with CPB in six hospitals in France. During CPB, the tracheal tube was disconnected from the ventilator in the control group (MV- group). In the MV + group, ventilation was maintained during CPB with very low tidal volume ventilation, using a tidal volume of 2.5 mL/kg of predicted body weight, with 5-7 cmH RESULTS: A total of 1362 patients were enrolled in the study. Postoperative infection occurred in 74 out of 680 patients (10.9%) in the MV- group, compared to 68 out of 682 patients (10.0%) in the MV + group (relative risk, 0.92; 95% confidence interval [CI] 0.67-1.25; p = 0.58). Antibiotic use was higher in the MV + group than in the MV- group (incidence risk ratio, 1.08; 95% CI 1.02-1.15; p = 0.02). There were no significant differences between the groups for all other secondary outcomes or for the incidence of adverse events. CONCLUSIONS: Maintaining very low tidal volume ventilation with positive end-expiratory pressure during CPB did not reduce postoperative infections at 28 days compared to when mechanical ventilation was stopped during CPB. An unexpectedly higher use of antibiotics was observed when ventilation was maintained. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03372174).
3. Effect of Esketamine on Postoperative Delirium and Inflammatory Response in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting: A Randomized Controlled Study.
In a triple-blind RCT of 140 OPCAB patients, intraoperative esketamine infusion (0.25 mg/kg/h) reduced 7-day postoperative delirium (RR 0.474) and lowered IL-6 at 12 and 72 hours and CRP at 72 hours compared with placebo. Findings support anti-inflammatory and neuroprotective properties of esketamine in cardiac surgery.
Impact: Demonstrates a pragmatic, modifiable intraoperative strategy to reduce POD—a common and morbid complication after cardiac surgery—while elucidating inflammatory biomarkers.
Clinical Implications: Esketamine infusion may be considered as part of multimodal anesthesia to prevent POD (術後せん妄) in OPCAB, particularly in patients at high delirium risk, with attention to hemodynamic monitoring.
Key Findings
- Esketamine reduced 7-day POD incidence vs placebo (RR 0.474; 95% CI 0.231–0.970; p=0.034).
- Lower postoperative IL-6 at 12 and 72 hours with esketamine (Z = -2.697, p=0.007; Z = -2.022, p=0.043).
- Lower CRP at 72 hours with esketamine (Z = -2.134, p=0.003).
Methodological Strengths
- Triple-blind randomized controlled design with biomarker assessment
- Clinically relevant primary endpoint (POD) with standardized assessment window (7 days)
Limitations
- Single-center design limits generalizability
- Dose regimen evaluated was a single infusion rate; dose-response and safety across broader populations require confirmation
Future Directions: Multicenter trials should assess efficacy across cardiac procedures, evaluate cognitive outcomes beyond 7 days, and compare esketamine to alternative POD prevention strategies.
OBJECTIVES: To investigate whether continuous intravenous infusion of esketamine during surgery can improve postoperative delirium (POD) and inflammatory response in patients undergoing off-pump coronary artery bypass grafting (OPCAB). DESIGN: Prospective, triple-blind, randomized controlled trial. SETTING: A single tertiary center. PARTICIPANTS: 140 adult patients undergoing elective OPCAB. INTERVENTIONS: Patients in Group S (esketamine group) received an infusion of esketamine at a dose of 0.25 mg/kg/h, while those in Group P (placebo group) received an equal volume of saline. MEASUREMENTS AND MAIN RESULTS: The main outcome was the incidence of POD within the first 7 days after surgery. The incidence of POD within 7 days after surgery was significantly lower in Group S compared with Group P (relative risk: 0.474, 95% confidence interval: 0.231-0.970, p = 0.034). Furthermore, the levels of interleukin-6 (IL-6) at 12th and 72nd postoperative hours were significantly lower in Group S than in Group P (Z = -2.697, p = 0.007; Z = -2.022, p = 0.043). The C-reactive protein level at 72nd postoperative hour was also significantly lower in Group S (Z = -2.134, p = 0.003). CONCLUSIONS: Esketamine can decrease the incidence of POD, reduce postoperative inflammatory levels, and alleviate short-term inflammatory responses in OPCAB patients.