Daily Anesthesiology Research Analysis
Three impactful studies in anesthesiology and perioperative care stand out today: a phase III randomized trial shows adamgammadex is noninferior to sugammadex for rapid reversal of deep rocuronium block; a Cochrane network meta-analysis finds commonly used regional blocks for breast surgery offer broadly comparable analgesia and safety; and a randomized trial demonstrates propofol-based anesthesia improves first-night postoperative sleep in older adults, potentially via reduced orexin-A.
Summary
Three impactful studies in anesthesiology and perioperative care stand out today: a phase III randomized trial shows adamgammadex is noninferior to sugammadex for rapid reversal of deep rocuronium block; a Cochrane network meta-analysis finds commonly used regional blocks for breast surgery offer broadly comparable analgesia and safety; and a randomized trial demonstrates propofol-based anesthesia improves first-night postoperative sleep in older adults, potentially via reduced orexin-A.
Research Themes
- Neuromuscular blockade reversal and perioperative safety
- Regional anesthesia optimization for breast cancer surgery
- Anesthetic choice and postoperative sleep physiology in older adults
Selected Articles
1. Efficacy and safety of adamgammadex for reversing rocuronium-induced deep neuromuscular block: a multicentre, randomised, double-blind, positive-controlled phase III trial.
In a multicentre, double-blind phase III noninferiority RCT (n=321), adamgammadex 8 mg/kg rapidly reversed deep rocuronium-induced neuromuscular block with a 98.7% success rate to TOFR 0.9, noninferior to sugammadex (100%). Median time to TOFR 0.9 was 2.5 vs 2.2 minutes, and safety profiles were comparable.
Impact: Introduces a potential alternative to sugammadex for rapid reversal of deep neuromuscular block, with rigorous RCT evidence supporting efficacy and safety.
Clinical Implications: Adamgammadex could expand options for reliable reversal of deep rocuronium block, aiding throughput and safety in the OR/PACU. Adoption will depend on availability, cost, and postmarketing safety data.
Key Findings
- Noninferiority achieved for TOFR 0.9 recovery success: 98.7% (adamgammadex) vs 100% (sugammadex); difference -1.3% (95% CI -4.6 to 1.2).
- Median time to TOFR 0.9: 2.5 minutes (adamgammadex) vs 2.2 minutes (sugammadex); between-group difference 0.5 minutes (95% CI 0.3 to 0.7), within noninferiority margin.
- No significant differences in safety profile between groups.
Methodological Strengths
- Multicentre, randomized, double-blind, positive-controlled noninferiority design
- Prespecified noninferiority margins and adequate sample size with trial registration
Limitations
- Details of dosing strata and subgroup analyses are limited in the abstract
- Long-term safety and rare adverse events require postmarketing surveillance
Future Directions: Head-to-head cost-effectiveness studies versus sugammadex; evaluation in special populations (renal impairment, pediatrics) and across varying depths of block.
BACKGROUND: Adamgammadex, a newly developed modified γ-cyclodextrin derivative, has demonstrated efficacy in reversing deep rocuronium-induced neuromuscular block in early clinical trials. METHODS: This multicentre, randomised, double-blind, positive-controlled, noninferiority phase III clinical trial aimed to investigate the efficacy and safety of adamagammadex compared with sugammadex in reversing deep rocuronium-induced neuromuscular block. In total, 321 patients were randomly assigned to either the adamgammadex 8 mg kg RESULTS: For the primary efficacy outcome, the success rate for recovery of TOFR to 0.9 was 98.7% in the adamgammadex group and 100% in the sugammadex group, with an observed difference of -1.3% (95% confidence interval [CI] -4.6%, 1.2%). The lower limit of -4.6% was higher than the noninferiority margin of -10%. For the key secondary efficacy outcomes, the median (interquartile range) time from administration of adamgammadex or sugammadex to recovery of TOFR to 0.9 was 2.5 (2.0, 3.2) min and 2.2 (1.7, 2.7) min, respectively. The difference was 0.5 min (95% CI 0.3, 0.7), and the upper limit of 0.7 min was lower than the noninferiority margin of 5 min. We observed no inferiority in secondary efficacy outcomes. There was no significant difference in the safety profile between adamgammadex and sugammadex. CONCLUSIONS: Adamgammadex was noninferior to sugammadex in reversing deep neuromuscular block from rocuronium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200056471, registered February 6, 2022; https://www.chictr.org.cn/showproj.html?proj=141077).
2. Propofol versus sevoflurane anesthesia on postoperative sleep quality in older patients after major abdominal surgery: A randomized clinical trial.
In older adults undergoing major abdominal surgery (n=144), propofol-based anesthesia increased first-night total sleep time by a median of 29 minutes versus sevoflurane and was associated with lower perioperative plasma orexin-A levels. Findings point to anesthetic-specific effects on postoperative sleep physiology.
Impact: Links anesthetic choice to objectively measured postoperative sleep outcomes and neuropeptide biology in an at-risk population, informing ERAS and geriatric anesthesia strategies.
Clinical Implications: Propofol may be preferred when postoperative sleep restoration is prioritized in older patients, while monitoring for other trade-offs. Integration with multimodal sleep-promoting strategies is warranted.
Key Findings
- First postoperative night total sleep time was longer with propofol: median 150 vs 111 minutes; median difference 29 minutes (95% CI 4 to 53), P=0.025.
- Propofol group had lower plasma orexin-A at 1 hour after induction and at 06:00 on postoperative day 1 (both P<0.05).
- Randomized design in 144 patients aged 65–90 supports internal validity for sleep outcome differences.
Methodological Strengths
- Randomized allocation between anesthetic strategies with objective actigraphy monitoring
- Biomarker assessment (orexin-A) supports mechanistic inference
Limitations
- Single-center setting may limit generalizability
- Effect size modest; blinding of clinicians/patients to anesthetic type is inherently difficult
Future Directions: Multicenter trials integrating sleep, delirium, and functional recovery endpoints; exploration of dosing and adjuncts that modulate orexin signaling.
STUDY OBJECTIVE: Sleep disturbances are common in older patients following major surgery. Both propofol and sevoflurane are frequently used anesthetics. In this study, we compared the effect of propofol- versus sevoflurane-based anesthesia on postoperative sleep quality in this patient population. DESIGN: A randomized clinical trial. SETTING: A university hospital. PATIENTS: Patients aged 65 to 90 years who were scheduled for elective major abdominal surgery. INTERVENTIONS: Enrolled patients were randomized to receive either propofol-based intravenous anesthesia or sevoflurane-based inhalational anesthesia. MEASUREMENTS: Primary endpoint was total sleep time monitored by actigraphy on the first postoperative night. Secondary endpoints included plasma orexin-A concentrations at various timepoints from baseline (before anesthesia) until the second postoperative morning. MAIN RESULTS: From May 23, 2022 to April 3, 2023, 144 patients (mean age 72.9 years; 58.3 % male) were enrolled and randomly assigned. Total sleep time on the first postoperative night was longer with propofol anesthesia (median 150 min [interquartile range 99 to 200]) than with sevoflurane anesthesia (111 min [80 to 160]; median difference 29 min [95 % CI 4 to 53]; P = 0.025). Plasma orexin-A concentration was lower in the propofol group at 1 h after anesthesia induction (median difference - 31.3 pg/mL [95 % CI -58.1 to -2.2]; P = 0.033) and 6:00 on the first postoperative morning (median difference - 29.8 pg/mL [95 % CI -58.3 to -2.3]; P = 0.036). CONCLUSIONS: Among older patients undergoing major abdominal surgery, propofol anesthesia, compared with sevoflurane anesthesia, was associated with a longer total sleep time on the first postoperative night. This difference may be partially attributable to lowered plasma orexin-A level. TRIAL REGISTRATION: This randomized trial was approved by Biomedical Research Ethical Committee of Peking University First Hospital (No.2022-155) on April 26, 2022. Chinese Clinical Trial Registry (No. ChiCTR2200060120) URL: https://www.chictr.org.cn/showproj.html?proj=169584, May 19, 2022.
3. Regional analgesia techniques for postoperative pain after breast cancer surgery: a network meta-analysis.
Across 39 RCTs (n=2348), network meta-analysis found broadly comparable postoperative pain relief and complication rates among paravertebral, erector spinae plane, pectoral, and serratus anterior plane blocks for breast surgery. PEC block showed a small advantage over PVB at 2 hours (MD -0.47 on a 0–10 scale), below the 1-point MCID.
Impact: Provides high-level comparative effectiveness evidence to guide selection among commonly used regional blocks in breast surgery, emphasizing flexibility and clinician expertise.
Clinical Implications: Block choice can prioritize provider expertise, patient-specific anatomy, and resource availability, as analgesic efficacy and safety are largely similar. Training and ultrasound guidance remain key.
Key Findings
- Included 39 RCTs (n=2348); primary NMA for pain included low risk-of-bias studies.
- At 2 hours post-op (rest), PEC slightly reduced pain versus PVB (MD -0.47; 95% CI -0.73 to -0.22), below the 1-point MCID.
- Overall, regional techniques (PVB, ESPB, PEC, SAPB) showed comparable analgesic efficacy and complication rates.
Methodological Strengths
- Cochrane-compliant systematic review with network meta-analysis and CINeMA certainty assessment
- Restriction to low risk-of-bias trials in primary analysis; comprehensive, multilingual search
Limitations
- Heterogeneity in block techniques, anesthetic dosing, and surgical procedures; some analyses truncated by available data
- Clinical significance of small MDs questionable; long-term outcomes variably reported
Future Directions: Head-to-head pragmatic RCTs incorporating patient-centered outcomes (quality of recovery, chronic pain) and cost; standardized protocols to reduce heterogeneity.
RATIONALE: Postoperative pain is an important outcome for individuals undergoing breast cancer surgery. Regional analgesia techniques are considered integral to postoperative pain management, but are not without risks. OBJECTIVES: To assess the analgesic benefits and harms of different regional analgesia techniques in women undergoing breast cancer surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Scopus, and Web of Science from inception to 6 June 2023 without restrictions on language, publication year, or publication status. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) comparing two or three of the following regional analgesia techniques in women undergoing breast cancer surgery: paravertebral block (PVB), erector spinae plane block (ESPB), pectoral nerve block (PEC), and serratus anterior plane block (SAPB). OUTCOMES: Our critical outcomes were postoperative pain (rated on a visual analogue scale (VAS) or numeric rating scale (NRS) of 0-10) and rates of regional analgesia-related complications. Our important outcomes were quality of recovery, time to first analgesic request, postoperative opioid and nonsteroidal anti-inflammatory drug (NSAID) use, and postoperative nausea and vomiting (PONV). RISK OF BIAS: We used the Cochrane risk of bias tool (RoB 2) to assess risk of bias. SYNTHESIS METHODS: We conducted network meta-analyses (NMAs) using multivariate frequentist random-effects models to calculate mean differences (MDs), standardised mean differences (SMDs), or risk ratios (RRs), each with its 95% confidence interval (CI). We used CINeMA to rate the certainty of evidence. We only included studies with an overall low risk of bias in the primary analysis. For postoperative pain, we considered one point difference as the minimal clinically important difference (MCID). INCLUDED STUDIES: We included 39 RCTs with a total of 2348 participants. The studies were conducted between 2013 and 2023 in Egypt, India, Turkey, China, Japan, USA, and Thailand. Most used single-shot long-acting anaesthetics administered with ultrasound guidance. In 35 studies, the surgery was modified radical mastectomy. All studies performed surgery under general anaesthesia in the hospital. Our primary analysis for postoperative pain included 16 studies. SYNTHESIS OF RESULTS: Critical outcomes Postoperative pain at rest at two hours This NMA included seven studies (384 participants). PEC is slightly more effective than PVB in reducing postoperative pain at rest at two hours (MD -0.47, 95% CI -0.73 to -0.22; P < 0.001, I AUTHORS' CONCLUSIONS: Overall, the regional analgesia techniques included in our NMAs seem comparable in reducing postoperative pain and rates of complications. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol (2022): doi.org/10.1002/14651858.CD014818.