Daily Anesthesiology Research Analysis
Three impactful studies span perioperative safety and analgesia. A mechanistic study identifies high-affinity anti-rocuronium antibodies capable of inducing anaphylaxis, offering the first structural epitopes and an in vivo model. Clinically, an RCT shows ketamine plus dexmedetomidine reduces opioid use and ICU stay after liver resection in cirrhotics, while a Bayesian analysis supports neuromuscular monitoring and pharmacologic reversal—favoring sugammadex—to lower postoperative pulmonary compl
Summary
Three impactful studies span perioperative safety and analgesia. A mechanistic study identifies high-affinity anti-rocuronium antibodies capable of inducing anaphylaxis, offering the first structural epitopes and an in vivo model. Clinically, an RCT shows ketamine plus dexmedetomidine reduces opioid use and ICU stay after liver resection in cirrhotics, while a Bayesian analysis supports neuromuscular monitoring and pharmacologic reversal—favoring sugammadex—to lower postoperative pulmonary complications.
Research Themes
- Perioperative drug hypersensitivity and immunology
- Opioid-sparing anesthesia in liver disease
- Neuromuscular block management and pulmonary complications
Selected Articles
1. Antibody-secreting cell repertoires hold high-affinity anti-rocuronium specificities that can induce anaphylaxis in vivo.
Using rocuronium-conjugates and single-cell antibody sequencing, the authors identified oligoclonal, high-affinity anti-rocuronium antibodies that, when expressed as human IgE, activated human mast cells/basophils and caused severe anaphylaxis in FcεRI-humanized mice. Cocrystal structures mapped distinct epitopes involving the ammonium group, establishing mechanistic foundations and the first murine model of NMBA anaphylaxis.
Impact: This is the first demonstration of anti-rocuronium IgE specificities with structural epitopes and in vivo anaphylactogenicity, addressing a critical unanswered question in perioperative anaphylaxis. It enables future diagnostics and preventive strategies for NMBA hypersensitivity.
Clinical Implications: Highlights the plausibility of pre-existing anti-rocuronium IgE driving perioperative anaphylaxis and suggests potential for epitope-guided diagnostics or risk stratification before NMBA exposure.
Key Findings
- Identified >500 VH–VL antibody pairs forming oligoclonal families specific to rocuronium.
- Human IgE versions activated human mast cells/basophils and induced severe anaphylaxis in FcεRI-humanized mice.
- Cocrystal structures revealed distinct binding modes with systematic involvement of the ammonium group.
- Defined monospecific and narrowly cross-reactive families toward closely related NMBAs.
Methodological Strengths
- Integrated droplet microfluidics single-cell VH/VL sequencing with structural biology and in vivo functional validation.
- Use of FcεRI-humanized mice to demonstrate anaphylactogenic potential of human IgE antibodies.
Limitations
- Preclinical study in mice; human clinical correlation and prevalence of such antibodies remain to be established.
- Rocuronium-conjugate immunization may not fully replicate natural sensitization pathways in humans.
Future Directions: Develop epitope-resolved diagnostic assays and prospective human studies to link preoperative anti-rocuronium IgE profiles with clinical anaphylaxis risk.
BACKGROUND: Neuromuscular blocking agents (NMBAs) are muscle relaxants used to assist mechanical ventilation but lead in 1 per 10,000 anesthesia cases to severe acute hypersensitivity reactions-that is, anaphylaxis. Incidences vary between types of NMBAs. Rocuronium, a widely used nondepolarizing aminosteroid NMBA, induces among the highest anaphylaxis rates. Rocuronium-induced anaphylaxis is proposed to rely on preexisting rocuronium-binding antibodies, but no such antibodies have ever been identified. OBJECTIVES: We sought to identify rocuronium-specific antibody repertoires from plasma cells or plasmablasts of rocuronium-immunized mice to determine the affinities, structures, and anaphylactogenic potential of these antibodies for rocuronium. METHODS: We engrafted rocuronium onto carrier proteins allowing immunization of mice against rocuronium, screening for rocuronium-specific antibody responses, and sorting of rocuronium-specific plasma cells using droplet microfluids coupled to single-cell antibody gene (variable heavy chain [VH] and variable light chain [VL]) sequencing. RESULTS: The 2 different repertoires of >500 VH-VL pairs were oligoclonal, comprised 3 major clonal families, and displayed convergence. Expressed as human IgG1, these antibodies demonstrated subnanomolar affinities for rocuronium with families either monospecific for rocuronium or cross-reactive only for closely related NMBAs. Expressed as human IgE, they triggered human mast cell and basophil activation, and severe passive systemic anaphylaxis in mice humanized for the IgE receptor FcεRI. Cocrystal structures between rocuronium and antibody representatives of 3 different VH-VL families revealed distinct interaction modes, with the ammonium group involved systematically in the binding interface. CONCLUSIONS: This work identifies the epitopes of antibody reactivity to rocuronium, demonstrates anaphylactogenic potential of anti-rocuronium IgE, and establishes the first mouse model of NMBA anaphylaxis.
2. Impact of neuromuscular block monitoring and reversal on postoperative pulmonary complications in thoracic surgery: a Bayesian analysis of the iPROVE-OLV trial.
In a post hoc Bayesian analysis of 698 thoracic surgery patients, any neuromuscular monitoring and any reversal were associated with fewer PPCs (20% vs 34%), with a 77–94% posterior probability of benefit. Sugammadex showed a higher probability of benefit than neostigmine (97%), and both monitoring and reversal independently conferred benefit.
Impact: Addresses a modifiable perioperative factor with broad applicability in thoracic anesthesia and supports best practices using probabilistic evidence. Findings can influence monitoring and reversal strategies to reduce PPCs.
Clinical Implications: Implement routine quantitative neuromuscular monitoring and ensure full reversal, preferentially with sugammadex when appropriate, to potentially reduce postoperative pulmonary complications after thoracic surgery.
Key Findings
- PPCs occurred less frequently with any neuromuscular monitoring and any reversal (20%) vs neither (34%).
- Bayesian models indicated an odds ratio between 0.67 and 0.84 with 77–94% probability of benefit.
- Sugammadex had a 97% probability of benefit versus neostigmine in reducing PPCs.
- Monitoring and reversal each showed high probabilities of benefit when evaluated separately.
Methodological Strengths
- Large multicentre dataset with prespecified PPC composite outcome in the parent RCT.
- Bayesian random-effects logistic regression providing probability of benefit across priors.
Limitations
- Post hoc, nonrandomized comparison (657 vs 41) susceptible to confounding and selection bias.
- Findings are associative; causality and optimal monitoring/reversal protocols require prospective confirmation.
Future Directions: Prospective randomized evaluations of quantitative monitoring and reversal strategies (agent choice, dosing, timing) to causally reduce PPCs.
BACKGROUND: Postoperative pulmonary complications (PPCs) are a significant concern in thoracic surgery. A modifiable factor influencing PPCs is postoperative residual neuromuscular block (NMB), which impairs respiratory muscle function. METHODS: We performed a post hoc Bayesian analysis of data from the iPROVE-OLV study, a multicentre randomised controlled trial involving patients undergoing thoracic surgery with one-lung ventilation. We compared participants managed with any neuromuscular monitoring and any reversal vs those managed without either. The primary outcome was the occurrence of a composite of PPCs within the first 7 postoperative days. RESULTS: Of the 698 patients included, 657 received any neuromuscular monitoring and any reversal, while 41 did not. Patients managed with any neuromuscular monitoring and any reversal had a lower incidence of PPCs (20%) compared with those without either (34%). Bayesian random effect logistic regression indicated that the use of any neuromuscular monitoring and any reversal reduced PPCs with an odds ratio (OR) ranging from 0.67 (95% credibility interval, CrI, 0.39-1.11) to 0.84 (95% CrI 0.48-1.37), depending on the prior model used. The probability of benefit (OR <1) was between 77% and 94%. Subgroup analysis indicated that sugammadex was more effective than neostigmine in reducing PPCs, with a high probability of benefit (97%), and both neuromuscular monitoring and reversal reduced PCCs when evaluated separately with a high probability of benefit. CONCLUSION: Utilising neuromuscular monitoring and reversal agents significantly reduced the risk of PPCs in thoracic surgery. Sugammadex was more efficacious in reducing PPCs compared with neostigmine. These findings support the combined use of neuromuscular monitoring and reversal drugs. CLINICAL TRIAL REGISTRATION: NCT03182062.
3. Opioid sparing anesthesia in patients with liver cirrhosis undergoing liver resection: a controlled randomized double-blind study.
In a double-blind RCT of 92 Child-Pugh A cirrhotics undergoing liver resection, intraoperative ketamine plus dexmedetomidine reduced intraoperative fentanyl by ~40% and 48-hour postoperative fentanyl by ~55% versus opioid-based anesthesia. Early postoperative pain scores improved, opioid-related adverse events were fewer, and ICU stay was shorter in the opioid-sparing group.
Impact: Demonstrates a practical opioid-sparing anesthetic strategy tailored to cirrhosis, a population with altered opioid handling, with benefits across analgesia, adverse events, and ICU stay.
Clinical Implications: Consider ketamine and dexmedetomidine infusions as part of intraoperative multimodal anesthesia for Child-Pugh A cirrhotics undergoing liver resection to reduce perioperative opioid exposure and ICU utilization.
Key Findings
- Intraoperative fentanyl use was lower with ketamine+dexmedetomidine (183.2±35.6 µg) vs control (313.5±75.1 µg), P<0.001.
- 48-hour postoperative fentanyl was lower in the opioid-sparing group (354.5±112.6 µg) vs control (779.1±295.0 µg), P<0.001.
- Early postoperative pain scores improved; opioid-related adverse events were fewer, and ICU stay was shorter in the opioid-sparing group.
Methodological Strengths
- Randomized, double-blind, controlled design with clearly defined primary analgesic outcomes.
- Homogeneous population (Child-Pugh A cirrhosis) relevant to altered opioid pharmacology.
Limitations
- Single-condition and likely single-centre context with modest sample size (n=92), limiting generalizability.
- Short follow-up focused on 48-hour analgesic consumption; long-term outcomes and safety not assessed.
Future Directions: Validate in multicentre trials across broader cirrhosis severities and surgical types, and assess patient-centred outcomes (functional recovery, quality of life) and safety.
OBJECTIVE: Opioid metabolism and pharmacodynamics may be affected in hepatic patients. Ketamine and dexmedetomidine are conventional anesthetics used in our daily practice. The opioid-sparing effects of this combination have not been evaluated in patients with liver cirrhosis undergoing liver resection. We aimed to investigate the potential peri-operative opioid-sparing effects of intra-operative dexmedetomidine and ketamine infusions in patients with Child A liver cirrhosis undergoing liver resection. METHODS: This study was a randomized controlled double-blind trial. 92 adult patients of both sex with Child class (A) liver cirrhosis aged 18 to 65 years entering and completing the study. We excluded patients with renal or cardiac dysfunction or contraindications from study medications.46 patients in the opioid-sparing group (OS) receiving ketamine and dexmedetomidine infusions and 46 patients in the opioid-based (OB) group as controls. The main outcome measures: were intra-operative fentanyl requirements, postoperative fentanyl requirements, visual analogue pain scores, postoperative nausea, vomiting, ileus, desaturation, intra-operative hemodynamic events, and ICU stay were recorded. RESULTS: The total intra-operative fentanyl consumption was significantly lower in the OS group compared with the OB group, 183.2 ± 35.61 µg and 313.5 ± 75.06 µg, respectively, P < 0.001. The postoperative 1st 48 h fentanyl consumption was significantly lower in the OS group compared with the OB group, 354.5 ± 112.62 µg and 779.1 ± 294.97 ± µg, respectively, P < 0.001. Visual analogue scores were significantly better in the OS group at the early 2-hour assessment point postoperatively. The postoperative adverse events were significantly more frequent in the opioid-based group. ICU stay was significantly shorter in the OS group. CONCLUSIONS: Administering dexmedetomidine and ketamine infusions intra-operatively to patients with Child A liver cirrhosis undergoing liver resection resulted in notable opioid-sparing effects, with reductions of approximately 40% intra-operatively and 55% postoperatively. The opioid-sparing group exhibited improved postoperative outcomes, including reduced pain, decreased incidence of opioid-related side effects and shorter ICU stays.