Daily Anesthesiology Research Analysis
Three perioperative studies stand out today: donor-centric enzymatic conversion of ABO blood group antigens enabled an ABO-incompatible kidney transplant without hyperacute rejection in a human decedent model; machine learning analyses show cardiopulmonary exercise testing (CPET) adds no predictive value for complications after lung resection; and a triple-blinded pediatric RCT finds perineural dexamethasone or dexmedetomidine prolongs analgesia and reduces opioid use after foot/ankle surgery.
Summary
Three perioperative studies stand out today: donor-centric enzymatic conversion of ABO blood group antigens enabled an ABO-incompatible kidney transplant without hyperacute rejection in a human decedent model; machine learning analyses show cardiopulmonary exercise testing (CPET) adds no predictive value for complications after lung resection; and a triple-blinded pediatric RCT finds perineural dexamethasone or dexmedetomidine prolongs analgesia and reduces opioid use after foot/ankle surgery.
Research Themes
- Donor-centric organ engineering for ABO-incompatible transplantation
- Re-evaluating preoperative testing with machine learning
- Opioid-sparing pediatric regional anesthesia strategies
Selected Articles
1. Enzyme-converted O kidneys allow ABO-incompatible transplantation without hyperacute rejection in a human decedent model.
During hypothermic perfusion, enzymatic removal of A antigens converted type-A kidneys to enzyme-converted O and prevented hyperacute rejection ex vivo and for 2 days in a human decedent ABO-incompatible transplant. Antibody-mediated injury emerged after 3 days with antigen regeneration, while single-cell data suggested accommodation-related gene upregulation.
Impact: This is a first-in-human decedent demonstration of donor-centric antigen removal enabling ABO-incompatible transplantation without hyperacute rejection, representing a potentially paradigm-shifting strategy in transplant desensitization.
Clinical Implications: If validated in living donors/recipients, donor-centric enzymatic desensitization could reduce reliance on plasmapheresis, lowering infection and bleeding risks and expanding access to ABO-incompatible transplantation. Perioperative teams may need to adapt perfusion protocols and monitoring for antigen regeneration.
Key Findings
- Hypothermic perfusion with glycosidase enzymes removed A antigens, generating enzyme-converted O kidneys.
- Ex vivo models showed no antibody-mediated injury; a transplanted enzyme-converted O kidney in a type-O brain-dead recipient had no hyperacute rejection for 2 days.
- Antibody-mediated lesions and complement deposition appeared after day 3 with A-antigen regeneration; single-cell sequencing indicated upregulation of accommodation-related genes.
Methodological Strengths
- Integrated ex vivo perfusion engineering with in situ human decedent transplantation
- Multi-modal assessment including histopathology, complement deposition, and single-cell transcriptomics
Limitations
- Single human decedent transplant with very short follow-up
- Antigen regeneration and subsequent antibody-mediated injury occurred by day 3, limiting durability
Future Directions: Optimize enzyme cocktails and perfusion parameters to prevent antigen regeneration, extend to living donor/recipient clinical trials, and define perioperative immunosuppression strategies tailored to donor-centric desensitization.
2. Cardiopulmonary exercise testing before lung resection surgery: still indicated? Evaluating predictive utility using machine learning.
In 497 lung resection candidates from two prospective cohorts, adding CPET variables to preoperative PFTs and clinical data did not improve machine learning models predicting pulmonary or cardiovascular complications, including in subgroups meeting ACCP or ERS/ESTS criteria. Findings question routine CPET use for risk stratification.
Impact: Challenges a long-standing component of preoperative assessment using contemporary datasets and machine learning, with potential to streamline testing and resource use.
Clinical Implications: Preoperative pathways may de-emphasize CPET for unselected lung resection candidates, relying on PFTs and clinical variables without compromising risk prediction; targeted CPET could be reserved for specific scenarios pending further evidence.
Key Findings
- Across 497 patients, CPET parameters did not improve prediction of postoperative pulmonary complications (AUC-ROC 0.72–0.78; p=0.47) over PFTs and baseline data.
- CPET also failed to improve prediction of postoperative cardiovascular complications in overall and guideline-indicated subgroups (p≥0.82).
- Observed complication rates were PPCs 14% and PCCs 18%, supporting adequate model performance without CPET.
Methodological Strengths
- Use of two prospective multicentre cohorts with standardized preoperative data
- Nested cross-validation across multiple machine learning algorithms and metrics
Limitations
- Secondary analysis without randomized allocation to testing strategies
- Complications assessed during hospitalization only; external validation not reported
Future Directions: Conduct pragmatic trials or stepped-wedge implementations comparing pathways with versus without CPET, and develop parsimonious, externally validated prognostic models integrating PFTs and clinical data.
3. Effect of perineural dexamethasone versus dexmedetomidine as adjuvants to ropivacaine on analgesic duration in pediatric popliteal sciatic nerve blocks: a randomized, triple-blinded, placebo-controlled trial.
Both perineural dexamethasone and dexmedetomidine significantly prolonged analgesia after pediatric popliteal sciatic blocks versus placebo (≈19 vs 8.5 hours) and reduced opioid requirements; dexamethasone extended analgesia by about 1 hour beyond dexmedetomidine. No nerve injuries or hemodynamic instability occurred.
Impact: Provides high-quality, triple-blinded RCT evidence guiding adjuvant choice for pediatric regional anesthesia with clinically meaningful opioid-sparing benefits.
Clinical Implications: Perineural dexamethasone or dexmedetomidine can be considered to prolong pediatric block analgesia and reduce opioid exposure; the small advantage of dexamethasone over dexmedetomidine may be weighed against drug-specific safety profiles and institutional protocols.
Key Findings
- Time to first rescue opioid: DEX 19.4±2.0 h, DEM 18.4±1.7 h, placebo 8.5±1.2 h (p<0.0001); DEX vs DEM difference 1.0 h (95% CI 0.04–2.06; p=0.0400).
- Lower opioid use and pain scores with adjuvants: nalbuphine needed in 23.3% (DEX), 33.3% (DEM), vs 90% (placebo); FLACC scores reduced at 6–12 h.
- Reduced inflammatory response with dexamethasone: NLR at 48 h significantly lower (p=0.0136); no nerve injuries or hemodynamic complications.
Methodological Strengths
- Randomized, triple-blinded, placebo-controlled design with ultrasound-guided standardized blocks
- Clinically relevant endpoints including time to rescue opioid, opioid consumption, pain scores, and inflammatory markers
Limitations
- Single-center study with modest sample size
- Short follow-up limited to 48 hours; long-term safety and neurotoxicity not assessed
Future Directions: Larger multicentre trials to confirm safety, delineate optimal dosing, and compare systemic versus perineural administration in various pediatric blocks.