Daily Anesthesiology Research Analysis
Analyzed 80 papers and selected 3 impactful papers.
Summary
Three impactful studies span translational organ support, perioperative sustainability, and transplant economics. A Nature Medicine decedent-model study demonstrates feasible xenogeneic extracorporeal liver cross-circulation with gene-edited pig livers. A BMJ Quality & Safety quality-improvement pathway reduces perioperative warming’s carbon footprint and costs without increasing hypothermia, while a cost-utility analysis shows ex-vivo lung perfusion (EVLP) shortens wait time, lowers mortality, and is cost-effective.
Research Themes
- Xenogeneic organ support and translational perfusion platforms
- Low-carbon perioperative pathways and quality improvement
- Transplant access and economics of ex-vivo organ perfusion
Selected Articles
1. Extracorporeal liver cross-circulation using transgenic xenogeneic pig livers with brain-dead human decedents.
Using extensively gene-edited pig livers, the team established extracorporeal liver cross-circulation support in four brain-dead human decedents, including one who received exclusive xenogeneic liver support after hepatectomy for 48 hours with maintained hemodynamics and metabolic homeostasis. Histology showed preserved architecture with mild immune infiltration under minimal immunosuppression, and xenogeneic livers produced bile and augmented hepatocellular function.
Impact: This work provides a translational bridge for temporary liver support using xenogeneic organs, demonstrating feasibility, physiologic efficacy, and manageable immunologic signals in a realistic human model.
Clinical Implications: If validated in clinical trials, xenogeneic ELC could serve as a bridge to transplant or recovery in acute liver failure, expanding access to organ support when human grafts are unavailable.
Key Findings
- Feasible xenogeneic extracorporeal liver cross-circulation was achieved in 4 human decedents using pig livers with triple glycan KO, 7 human transgenes, and PERV inactivation.
- In 3 decedents with native livers in situ, ELC was sustained for 72–84 hours; in 1 decedent after hepatectomy, 48 hours of xenogeneic liver-only support maintained hemodynamics, pH, lactate, ammonia, and INR.
- Xenogeneic livers produced bile and showed preserved parenchymal architecture with mild immune infiltration and IgM deposition under minimal methylprednisolone immunosuppression.
Methodological Strengths
- Use of extensively gene-edited pig livers (triple glycan KO, 7 human transgenes, PERV inactivation) with a realistic human decedent model.
- Multimodal assessment including continuous physiologic monitoring and histopathology across prolonged ELC runs.
Limitations
- Small sample size (n=4) and decedent model limit generalizability to living patients.
- Short-to-moderate support durations and lack of a control group; immunosuppression strategy not systematically varied.
Future Directions: Early-phase clinical trials in acute liver failure, optimization of anticoagulation and immunomodulation for longer ELC, and comparative studies versus MARS/albumin dialysis.
Extracorporeal liver cross-circulation (ELC) using genetically modified pig livers may address an unmet need for temporary liver support in patients with acute or acute-on-chronic liver failure. This study used the ELC platform to evaluate early immune responses and assess xenogeneic liver physiological support in a human decedent model. Four human decedents underwent ELC using pig livers with a triple glycan knockout; insertion of seven human transgenes and inactivation of pig endogenous retroviruses. Intravenous methylprednisolone was administered for immunosuppression. In the case of decedents 1-3, ELC was performed for 72-84 h with the native livers of the decedents remaining in situ. In the case of decedent 4, hepatectomy was performed, followed by 48 h of xenogeneic liver support exclusively using ELC. Biopsies of xenogeneic livers demonstrated preserved parenchymal architecture, mild immune infiltration and IgM deposition. Xenogeneic livers produced bile and supplemented native hepatocellular function. In decedent 4, xenogeneic liver-only support after hepatectomy maintained hemodynamic stability, normal pH, lactate, ammonia, international normalized ratio and sustained metabolic function. This study shows that ELC is feasible using xenogeneic livers with minimal immunosuppression and can provide effective liver support.
2. Economic evaluation of ex-vivo lung perfusion for lung transplantation: a cost-utility analysis from a large Canadian centre.
In an individual-level lifetime simulation informed by a large lung transplant program, EVLP availability reduced waitlist time (101 vs 258 days) and mortality (9.1% vs 19.3%), lowered lifetime hospital costs, and increased QALYs. EVLP was cost-effective across willingness-to-pay thresholds, with an incremental net monetary benefit of $70,987 at $50,000/QALY.
Impact: Provides robust economic evidence that EVLP improves access and outcomes while reducing costs, directly informing programmatic investment and policy in lung transplantation.
Clinical Implications: Centers can justify EVLP implementation to expand the donor pool, shorten waitlists, reduce waitlist deaths, and achieve cost-effective care with higher QALYs.
Key Findings
- EVLP availability reduced median waitlist duration to 101 days (95% CI 79–125) versus 258 days (95% CI 222–294).
- Waitlist mortality decreased from 19.3% to 9.1% with EVLP (both p<0.001).
- Lifetime hospital costs were lower with EVLP ($273,827 vs $308,790), with higher QALYs (4.72 vs 4.00) and iNMB of $70,987 at $50,000/QALY; EVLP was cost-effective across $0–$100,000/QALY.
Methodological Strengths
- Individual-level lifetime simulation with credible intervals and hospital-perspective costing.
- Direct comparison of EVLP-available versus No-EVLP scenarios using real-world program data over 2005–2019.
Limitations
- Single-center data may limit generalizability; model assumptions (costs, utilities) may vary across systems.
- Economic modeling is not a randomized comparison; potential unmeasured confounding in source data.
Future Directions: Multi-center validations, societal-perspective analyses, and integration of evolving EVLP outcomes and costs to refine decision models.
BACKGROUND: Ex-vivo lung perfusion (EVLP) enables evaluation and rehabilitation of potentially-useable donor lungs outside the body prior to transplantation. However, its health economic implications are unclear. We sought to determine the cost-utility of adding EVLP to the Toronto Lung Transplant Program. METHODS: We performed a cost-utility analysis, from the hospital perspective, using an individual-level simulation with a lifetime time horizon. We considered adults with end-stage lung disease waitlisted for first lung transplantation in Ontario, Canada from 2005-2019. We compared a situation in which all donor lungs were conventionally preserved (No-EVLP) versus a situation with conventionally-preserved lungs plus EVLP-treated qualifying donor lungs (EVLP available). We estimated lifetime costs (2019 CAD), health outcomes, and quality-adjusted life years (QALYs), discounted at 1.5% annually; results were summarized as incremental net monetary benefit (iNMB). RESULTS: EVLP-availability yielded shorter waitlist duration (101 [95% credible interval CI 79-125] days versus 258 [95% CI 222-294] days; p<0.001) and reduced waitlist mortality (9.1% [95%CI 7.3%-11%] versus 19.3% [95%CI 17.1%-21.8%]; p<0.001). Having EVLP available resulted in lower cumulative costs ($273,827 [95%CI $248,190-$299,654] versus $308,790 [95%CI $271,836-$342,431]; p<0.001), with higher QALY (4.72 [95%CI 3.75-5.26] QALY versus 4 [95%CI 3.07-4.59] QALY; p<0.001). At a cost-effectiveness threshold of $50,000 per QALY, we estimated an iNMB of $70,987 (95%CI $57,721-$76,414); EVLP was considered cost-effective at all thresholds evaluated between $0 and $100,000 per QALY. CONCLUSIONS: The benefits of having EVLP available at our centre outweighed its costs; investment in EVLP is economically justifiable. TWITTER / X POST: In economic evaluation, the benefits of having ex-vivo lung perfusion for lung transplantation outweighed its costs. EVLP was cost-effective at all thresholds, with higher QALYs and lower cumulative costs.
3. Implementing and evaluating a low-carbon, high-quality perioperative patient warming pathway.
A multifaceted, evidence-based perioperative warming pathway reduced flannel blanket use (6 to 3 per patient), increased active warming preoperatively (55% to 80%) and postoperatively (0% to 55%), maintained hypothermia rates, and projected annual savings of 940,339 kg CO2e and C$117,978.
Impact: Demonstrates a scalable, low-carbon warming strategy that preserves clinical quality, offering immediate pathways for anesthesia departments to cut emissions and costs.
Clinical Implications: Adopting resistive blankets, preserving FAW gowns across the perioperative journey, and minimizing flannel blankets can reduce environmental impact and costs without increasing hypothermia.
Key Findings
- Flannel blanket use decreased from an average of 6 to 3 per patient (p<0.01) after pathway implementation.
- Active warming increased from 55% to 80% preoperatively (p=0.04) and from 0% to 55% postoperatively (p<0.01).
- No significant change in hypothermia incidence (18% to 15%, p=0.77); projected annual savings: 940,339 kg CO2e and C$117,978.
Methodological Strengths
- Integration of scoping review, environmental LCA insights, and root cause analysis into a multi-PDSA implementation.
- Concurrent evaluation of environmental, financial, and clinical outcomes with pre/post audits.
Limitations
- Single tertiary hospital and before-after design without a control group may introduce confounding.
- Lifecycle and cost projections depend on local usage patterns and may vary by setting.
Future Directions: Multi-center controlled studies comparing resistive versus FAW strategies, longer-term monitoring of hypothermia and infection outcomes, and updated LCAs.
BACKGROUND: Intraoperative hypothermia can lead to adverse clinical outcomes and avoidable financial and environmental costs. Environmentally preferable warming practices have been identified, including using reusable resistive blankets, extending the life cycle of forced air warming (FAW) garments and minimising flannel blanket use. This study integrates existing environmental data with best practices and quality improvement methodology to develop an optimised patient warming pathway (OPWP). This pathway was adapted to our local context, implemented and evaluated. METHODS: The OPWP was developed using a scoping review, prior environmental impact assessment and root cause analysis. It was tailored to the workflows, patient population and warming practices at a tertiary care hospital and implemented using a multifaceted approach encompassing nine PDSA (Plan-Do-Study-Act) cycles. Major interventions included expanding pre-warming criteria to meet best practice guidelines, preserving the FAW Flex Gown, staff education and training, behaviourally informed strategies, gamification and policy development. Pre-intervention and post-intervention audits assessed environmental and financial savings, incidence of hypothermia and patient-reported outcomes (PROs). RESULTS: The OPWP recommends preferential use of the resistive blanket for intraoperative warming, preservation of the Flex Gown for postoperative use when warming with FAW and minimising flannel blanket use. A modified pathway was implemented using FAW with preservation of a single Flex Gown throughout the perioperative journey. From pre-intervention (N=51) to post-intervention (N=64), flannel blanket use decreased from an average of 6 to 3 per patient (p<0.01). Active warming increased from 55% to 80% (p=0.04) preoperatively and from 0% to 55% (p<0.01) postoperatively. There was no significant change in the incidence of hypothermia (18% to 15%, p=0.77) and PROs remained favourable. Implementation of this pathway could lead to annual environmental savings of 940 339 kg of carbon dioxide equivalents and cost savings of $C117 978. CONCLUSIONS: This study demonstrates the successful implementation of an evidence-based and environmentally sustainable perioperative warming pathway to achieve low-carbon, high-quality patient care.