Daily Anesthesiology Research Analysis
Analyzed 132 papers and selected 3 impactful papers.
Summary
Three impactful perioperative studies stood out today: a multicenter randomized trial showed intraoperative esketamine significantly increased short‑term remission of depressive symptoms after major surgery; a stepped‑wedge cluster‑randomized trial in pediatric gastrointestinal surgery found enhanced recovery benefits only when implementation fidelity was high; and a systematic review clarified genotype–phenotype relationships in butyrylcholinesterase deficiency, underscoring the value of genetic testing beyond traditional phenotyping.
Research Themes
- Perioperative mental health and anesthetic adjuncts
- Implementation fidelity in enhanced recovery protocols
- Pharmacogenetics of anesthesia-related complications
Selected Articles
1. Effect of intraoperative esketamine on moderate-to-severe depressive symptoms in major surgery patients: a randomized clinical trial.
In a multicenter, double‑blind RCT of 435 major surgery patients with moderate‑to‑severe depressive symptoms, intraoperative esketamine significantly increased 3‑day remission (28.3% vs 11.3%; OR 3.12) without changing acute pain. Monitoring for dissociative symptoms is advised, supporting cautious adoption of esketamine as a perioperative mental health adjunct.
Impact: This trial addresses a prevalent, under-treated perioperative outcome—depressive symptoms—using a pragmatic intraoperative intervention with rapid psychiatric benefit.
Clinical Implications: Consider intraoperative esketamine for patients with significant preoperative depressive symptoms, with structured screening and postoperative monitoring for dissociation; integrate into multimodal recovery pathways without expecting analgesic benefit.
Key Findings
- Esketamine increased 3-day remission of depressive symptoms vs placebo (28.3% vs 11.3%; OR 3.12, 95% CI 1.79–5.55).
- No difference in acute postoperative pain outcomes between groups.
- Dissociative/psychotomimetic symptoms necessitate careful monitoring after intraoperative esketamine.
Methodological Strengths
- Multicenter, randomized, double-blind, placebo-controlled design with adequate sample size (n=435).
- Predefined primary endpoint with clinically meaningful remission threshold (MADRS ≤10).
Limitations
- Short primary follow-up window (3 days) limits inference on durability of antidepressant effects.
- Adverse neuropsychiatric effects not quantified in detail; subgroup effects by surgery type not reported.
Future Directions: Assess durability and optimal dosing/timing across surgeries, define risk–benefit in high-risk psychiatric subgroups, and integrate perioperative mental health screening into ERAS pathways.
Perioperative depressive symptoms (PDSs) are common among patients who undergo major surgery and can lead to worse clinical outcomes. Esketamine has been reported to alleviate PDSs in patients undergoing certain types of surgery. However, there is a lack of evidence from large-scale, multisurgery studies to support its therapeutic effects in individuals with preexisting moderate-to-severe PDSs. Thus, we designed this multicenter, randomized, placebo-controlled and double-blinded trial to investigate whether esketamine is associated with greater improvements than the placebo among patients undergoing major surgery. Patients with moderate-to-severe PDSs who underwent major surgery were assessed for eligibility and randomly assigned to receive esketamine or placebo intraoperatively. The primary outcome was the remission rate 3 days after surgery, which was defined as a Montgomery-Åsberg Depression Rating Scale score less than or equal to 10. The secondary outcomes included pain, esketamine-related psychotic symptoms and safety outcomes after surgery. A total of 435 patients were randomized to receive either esketamine (n=218) or placebo (n=217). The remission rate was greater in the esketamine group than in the placebo group at 3 days post-surgery (28.3% vs. 11.3%; OR 3.12 [95% CI, 1.79-5.55]; P <0.001). The rates of acute pain were similar between the two groups. Intraoperative treatment with esketamine resulted in a greater proportion of participants whose depressive symptoms improved, but careful monitoring was necessary because of the possibility of developing dissociative symptoms. The clinical application of esketamine for depressive symptoms should consider its benefits and risks in the future. TRIAL REGISTRATION: Clinicaltrial.gov NCT04425473. LIST OF CHEMICAL COMPOUNDS: Esketamine (PubChem CID: 182137) and Ketamine (PubChem CID: 3821).
2. Implementation and Effectiveness of an Enhanced Recovery Protocol for Children Undergoing Surgery: The ENRICH-US Stepped-Wedge Cluster-Randomized Trial.
In a 18‑site stepped‑wedge cluster RCT (n=597), a pediatric GI surgery ERP did not reduce LOS by study phase overall, though it decreased inpatient opioid use and time to diet. Critically, high patient‑level fidelity (≥13 ERP elements) was associated with shorter LOS (-1.14 days) and fewer complications (aOR 0.48), highlighting fidelity as the key mediator of benefit.
Impact: Provides rigorous, multisite evidence that implementation fidelity determines ERP effectiveness in pediatrics, informing how to realize benefits rather than whether ERPs work.
Clinical Implications: ERP adoption should prioritize measurable fidelity (e.g., ≥13 core elements) via order set integration, culture change, and feedback loops to achieve reductions in LOS and complications.
Key Findings
- No overall phase-based reduction in LOS; decreased inpatient opioid use and faster time to regular diet across phases.
- Patients receiving ≥13 ERP elements had shorter LOS (-1.14 days) and fewer complications (aOR 0.48).
- Patient-level adherence increased over time; integration into order sets and culture correlated with fidelity.
Methodological Strengths
- Type 2 hybrid implementation‑effectiveness design with stepped‑wedge cluster randomization across 18 sites.
- Prospective measurement of fidelity and linkage to clinical outcomes with prespecified analyses.
Limitations
- Phase-level null results may reflect dilution from variable uptake and site heterogeneity.
- Generalizability limited to pediatric GI electives; patient-reported outcomes beyond hospitalization were limited.
Future Directions: Define minimal effective ERP bundles, develop fidelity dashboards, and test adaptive implementation strategies to sustain high adherence and scale benefits.
IMPORTANCE: Despite evidence that enhanced recovery protocols (ERPs) improve outcomes in adults undergoing surgery, adoption for pediatric populations has lagged. OBJECTIVE: To assess the implementation and clinical effectiveness of a consensus-based ERP for pediatric patients undergoing elective gastrointestinal (GI) surgery. DESIGN, SETTING, AND PARTICIPANTS: A prospective type 2 hybrid implementation-effectiveness, stepped-wedge, cluster-randomized by entry date into implementation phase, trial of pediatrics patients, 10 to 18 years of age, undergoing elective GI surgery at 18 US sites from September 2019 to June 2024. INTERVENTIONS: Sites were randomized into 3 groups, each spending at least 9 months in a control phase, with usual care, followed by an implementation phase at 6-month intervals that included a 21-element ERP supported by a structured Implementation Toolkit, based on 5 Active Implementation Frameworks (5AIFs), and a sustainment phase (12-24 months). Implementation was facilitated by a 1-year, group-based Learning Collaborative curriculum, a repository of tools, ERP adherence feedback, and implementation report cards. MAIN OUTCOMES AND MEASURES: Site-level scores were created based on 5AIFs domains. ERP adherence was assessed by ERP elements delivered at patient and site level. The primary effectiveness outcome, postoperative length of stay (LOS), and secondary effectiveness outcomes (including opioid use, time to regular diet, complications, readmission, and patient-reported health-related quality of life [HRQOL]) were evaluated across study phases (baseline, implementation, and sustainability). Correlations between site-level implementation scores and fidelity were estimated. RESULTS: Of the 597 enrolled pediatric patients (median [IQR] age, 15 [13-17] years; 274 [45.9%] female; 323 [54.1%] male), 433 (72.5%) had inflammatory bowel disease. No significant differences were found by study phase in LOS or secondary outcomes, except shorter time to regular diet and decreased opioid use during hospitalization. Patients who received at least 13 ERP elements had shorter median LOS (-1.14 days [95% CI -2.01 to -0.27]) and fewer complications (adjusted odds ratio, 0.48 [95% CI, 0.28-0.82]). Patient-level adherence increased by study phase (number of ERPs: 11 [10-13], 14 [12-15], and 14 [13-15], [P < .001]). ERP integration into order sets and site culture were moderately correlated with fidelity. CONCLUSIONS AND RELEVANCE: This stepped-wedge cluster-randomized trial found that despite multifaceted implementation strategies, a pediatric GI surgery ERP did not significantly reduce LOS. However, when accounting for implementation fidelity at the patient level, it resulted in significantly lower LOS and complications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04060303.
3. Genotype-phenotype relationships in butyrylcholinesterase deficiency: a systematic review.
Across 30 studies (n=290), 72% of individuals with normal inhibition phenotypes carried at least one BCHE variant, while absent activity aligned with truncating variants. Findings demonstrate that enzyme inhibition assays miss carriers and that combined genotyping–phenotyping improves diagnosis and risk stratification for prolonged paralysis after suxamethonium/mivacurium.
Impact: Clarifies actionable genotype–phenotype links for a classic anesthesia safety issue and supports modernizing preoperative screening beyond dibucaine/fluoride numbers.
Clinical Implications: In patients with suspected BChE deficiency or personal/family history of prolonged paralysis, combine BCHE genotyping with phenotyping to guide neuromuscular blocker choice, avoid suxamethonium/mivacurium when indicated, and counsel relatives.
Key Findings
- Among 290 cases, 32% normal, 38% atypical, 23% intermediate phenotypes; 7% had no measurable activity.
- 72% of individuals with a normal phenotype harbored at least one BCHE variant, indicating phenotyping alone misses carriers.
- Absent activity associated with truncating variants; common variants included A-variant (p.Asp98Gly) and K-variant (p.Ala567Thr).
Methodological Strengths
- PROSPERO-registered systematic review with comprehensive database search and JBI quality appraisal.
- Extraction of paired genotype–phenotype data enabling translational risk assessment.
Limitations
- Heterogeneity and variable reporting precluded a standardized diagnostic algorithm or meta-analysis.
- Selection and publication bias cannot be excluded across decades of literature.
Future Directions: Develop and validate integrated genotype–phenotype risk algorithms and decision aids for preoperative screening and family counseling.
BACKGROUND: Butyrylcholinesterase (BChE) deficiency is a recessive condition that can cause prolonged paralysis after suxamethonium or mivacurium. Conventional phenotyping using dibucaine and fluoride inhibition can overlook heterozygous carriers. The aim of this systematic review was to identify studies reporting paired BCHE genotype and biochemical phenotype data to propose a risk-assessment protocol. METHODS: We searched PubMed, EMBASE, and the Cochrane Library (1946-2024; PROSPERO CRD420250627891) for human studies reporting both BCHE genotype and biochemical phenotype. Extracted data included enzyme activity, dibucaine and fluoride numbers, and the genotyping method used. Study quality was assessed using the JBI Critical Appraisal Tools. RESULTS: A total of 30 studies met the inclusion criteria. Among 290 patients included, 92 (32%) had a normal, 110 (38%) an atypical, 66 (23%) an intermediate phenotype, and 22 (7%) had no measurable enzyme activity. Of those with a normal phenotype, 66 (72%) carried at least one BCHE variant. Atypical phenotypes were associated with reduced enzyme activity and with carriage of multiple variants. Patients with absent activity harboured frameshift or nonsense variants. The A-variant (p.Asp98Gly) and K-variant (p.Ala567Thr) were the most frequent. CONCLUSIONS: Genetic testing in suspected BChE deficiency provides valuable information beyond biochemical phenotyping, particularly in multi-allelic cases. Inhibition studies are insensitive to detecting variants with null or modest biological effects. Heterogeneity across studies precludes delivering a standardised diagnostic algorithm. An assessment framework integrating genotyping and phenotyping may facilitate variant annotation and improve diagnostic accuracy, risk stratification, and genetic counselling. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD420250627891).