Daily Anesthesiology Research Analysis
Three impactful anesthesiology-related studies stood out today: a large multicenter RCT found that Hypotension Prediction Index–guided hemodynamic therapy did not reduce postoperative acute kidney injury after major abdominal surgery; a meta-analysis of randomized trials showed no survival advantage of intraosseous over intravenous access in adult cardiac arrest and suggested lower sustained ROSC with intraosseous; and an innovative biobank study leveraged perioperative anesthetic exposures to r
Summary
Three impactful anesthesiology-related studies stood out today: a large multicenter RCT found that Hypotension Prediction Index–guided hemodynamic therapy did not reduce postoperative acute kidney injury after major abdominal surgery; a meta-analysis of randomized trials showed no survival advantage of intraosseous over intravenous access in adult cardiac arrest and suggested lower sustained ROSC with intraosseous; and an innovative biobank study leveraged perioperative anesthetic exposures to reclassify many RYR1/CACNA1S variants linked to malignant hyperthermia.
Research Themes
- Hemodynamic monitoring and kidney outcomes in abdominal surgery
- Vascular access strategy and outcomes in adult cardiac arrest
- Perioperative genomics and malignant hyperthermia risk refinement
Selected Articles
1. Hemodynamic Management Guided by the Hypotension Prediction Index in Abdominal Surgery: A Multicenter Randomized Clinical Trial.
In a 28-center RCT of 917 moderate-to-high-risk elective abdominal surgery patients, HPI-triggered hemodynamic interventions did not lower the 7-day incidence of moderate-to-severe AKI versus standard care. There were no differences in overall complications, RRT, length of stay, or 30-day mortality.
Impact: This large, pragmatic RCT provides high-level evidence challenging the clinical utility of HPI-guided therapy to prevent postoperative AKI, informing device adoption and intraoperative management strategies.
Clinical Implications: Routine intraoperative use of HPI-guided algorithms to reduce postoperative AKI is not supported; clinicians should prioritize established hemodynamic strategies and individualized care rather than relying on HPI thresholds.
Key Findings
- Moderate-to-severe AKI within 7 days: 6.1% (HPI) vs 7.0% (standard); RR 0.89 (95% CI 0.54–1.49), P=0.66.
- No differences in overall complications (31.9% vs 29.7%), renal replacement therapy, hospital length of stay (median 6 days in both), or 30-day mortality (1.1% vs 0.9%).
- Interventions were triggered at HPI >80 using fluids and vasoactive agents, yet outcomes were unchanged versus real-world standard care.
Methodological Strengths
- Multicenter, randomized, intention-to-treat design with a large sample (n=917).
- Clinically relevant endpoints including KDIGO-based AKI, complications, and 30-day mortality.
Limitations
- Open-label design with heterogeneous standard-care comparators across 28 hospitals.
- Potentially underpowered to detect small absolute differences in relatively low AKI rates.
Future Directions: Evaluate refined hemodynamic algorithms (e.g., individualized blood pressure targets, microcirculatory/end-organ perfusion markers) and assess cost-effectiveness and patient-centered outcomes.
BACKGROUND: Postoperative acute kidney injury (AKI) after major abdominal surgery leads to poor outcomes. The Hypotension Prediction Index (HPI; Edwards Lifesciences, USA) may aid in managing intraoperative hemodynamic instability. This study assessed whether HPI-guided therapy reduces moderate-to-severe AKI incidence in moderate- to high-risk elective abdominal surgery patients. METHODS: This multicenter randomized trial was conducted from October 2022 to February 2024 across 28 hospitals evaluating HPI-guided management compared to a wide range of real-world hemodynamic approaches. A total of 917 patients (65 yr or older or older than 18 yr with American Society of Anesthesiologists Physical Status greater than II) undergoing moderate- to high-risk elective abdominal surgery were included in the intention-to-treat analysis. HPI-guided management triggered interventions when the HPI exceeded 80, using fluids and/or vasopressors/inotropes based on hemodynamic data. The primary outcome was the incidence of moderate-to-severe AKI within the first 7 days after surgery. Secondary outcomes included overall complications, the need for renal replacement therapy, duration of hospital stay, and 30-day mortality. RESULTS: Median age was 71 yr (interquartile range, 65 to 77) in the HPI group and 70 yr (interquartile range, 63 to 76) in standard care group. American Society of Anesthesiologists Physical Status III/IV was 58.3% (268 of 459) in the HPI group and 57.9% (263 of 458) in standard care group. The incidence of moderate-to-severe AKI was 6.1% (28 of 459) in the HPI group and 7.0% (32 of 458) in the standard care group (risk ratio, 0.89; 95% CI, 0.54 to 1.49; P = 0.66). Overall complications occurred in 31.9% (146 of 459) of the HPI group and 29.7% (136 of 458) of the standard care group (risk ratio, 1.08; 95% CI, 0.85 to 1.37; P = 0.52). The incidence of renal replacement therapy did not differ between groups. Median length of hospital stay was 6 days (interquartile range, 4 to 10) in both groups. The 30-day mortality was 1.1% (5 of 459) in the HPI group versus 0.9% (4 of 458) in standard care group (risk ratio, 1.35; 95% CI, 0.36 to 5.10; P = 0.66). CONCLUSIONS: HPI-guided hemodynamic therapy did not reduce the incidence of postoperative AKI or overall complications compared to standard care.
2. Intraosseous and intravenous vascular access during adult cardiac arrest: A systematic review and meta-analysis.
Across three randomized trials (n=9,332) in out-of-hospital cardiac arrest, initial intraosseous access did not improve 30-day survival or favorable neurological outcome compared with intravenous access and was associated with lower odds of sustained ROSC.
Impact: This meta-analysis of randomized trials provides high-level evidence to guide first-line vascular access choices during cardiac arrest, a frequent responsibility for anesthesiologists and resuscitation teams.
Clinical Implications: When feasible, prioritize rapid intravenous access for initial drug delivery during adult cardiac arrest; intraosseous remains an important backup but may be less likely to achieve sustained ROSC.
Key Findings
- 30-day survival: no difference IO vs IV (OR 0.99, 95% CI 0.84–1.17; moderate-certainty).
- Favorable neurological outcome: no difference (OR 1.07, 95% CI 0.88–1.30; low-certainty).
- Sustained ROSC was lower with IO (OR 0.89, 95% CI 0.80–0.99; moderate-certainty).
Methodological Strengths
- Randomized evidence synthesis with prespecified outcomes and GRADE assessment.
- Large cumulative sample size (n>9,000) enhancing precision for key outcomes.
Limitations
- Limited to out-of-hospital cardiac arrest; applicability to in-hospital settings uncertain.
- Heterogeneity in IO sites, timing, and concomitant interventions across trials.
Future Directions: Research should clarify optimal access sequences integrating ultrasound-guided IV, IO placement speed/quality, and pharmacokinetic consequences, and evaluate training/algorithm adherence in real-world resuscitation systems.
OBJECTIVE: To summarise evidence on the clinical effectiveness of initial vascular attempts via the intraosseous route compared to the intravenous route in adult cardiac arrest. METHODS: We searched MEDLINE and Embase (OVID platform), the Cochrane library, and the International Clinical Trials Registry Platform from inception to September 4th 2024 for randomised clinical trials comparing the intraosseous route with the intravenous route in adult cardiac arrest. Our primary outcome was 30-day survival. Secondary outcomes included favourable neurological outcome at 30-days/ hospital discharge and return of spontaneous circulation (both any ROSC and sustained ROSC). We performed meta-analyses using a fixed-effect model. We assessed risk of bias using the Cochrane Risk of Bias-2 tool and evidence certainty using the GRADE approach. RESULTS: We included three randomised clinical trials encompassing 9,332 participants with out-of-hospital cardiac arrest. Initial attempts via the intraosseous, compared with intravenous, route did not increase the odds of 30-day survival (odds ratio 0.99, 95% confidence interval 0.84-1.17; 9,272 participants; three trials; moderate-certainty evidence) or favourable neurological outcome at 30-days/ hospital discharge (odds ratio 1.07, 95% confidence interval 0.88-1.30; 9,186 participants; three trials; low-certainty evidence). The odds of achieving sustained return of spontaneous circulation were lower in the intraosseous group (odds ratio 0.89, 95% confidence interval 0.80-0.99; 7,518 participants; two trials; moderate-certainty evidence). CONCLUSION: Initial vascular access attempts via the intraosseous, compared with intravenous, route in adult cardiac arrest did not improve 30-day survival and may reduce the odds of a sustained return of spontaneous circulation.
3. Updating probability of pathogenicity for RYR1 and CACNA1S exon variants in individuals without malignant hyperthermia after exposure to triggering anesthetics.
Linking biobank genotypes with real-world exposures to triggering anesthetics in 253 patients allowed Bayesian reclassification of many RYR1/CACNA1S variants, downgrading 45% overall and 72% of VUS to benign/likely benign when unique exposures were considered.
Impact: Introduces a pragmatic, data-driven approach to variant classification in malignant hyperthermia by incorporating anesthetic exposure outcomes, reducing uncertainty and improving perioperative risk assessment.
Clinical Implications: Genetic counseling and perioperative planning for suspected MH can be refined by incorporating anesthetic exposure history with biobank-linked evidence, potentially reducing unnecessary alerts and guiding testing.
Key Findings
- Among 107 variants assessed with exposure data, 48 (45%) were downgraded (9 to benign, 37 to likely benign, 2 to VUS).
- Of 57 variants of uncertain significance (VUS), 41 (72%) were downgraded to benign or likely benign with unique exposure evidence.
- Counting repeat anesthetics per individual as one exposure still led to 39% downgrading overall and 65% of VUS to likely benign.
Methodological Strengths
- Bayesian application of ACMG/AMP framework integrating real-world anesthetic exposure data.
- Use of biobank-scale genotyping enabling systematic variant reassessment.
Limitations
- Retrospective design with potential selection and exposure misclassification biases.
- Lack of functional validation for reclassified variants and limited generalizability beyond the biobank cohort.
Future Directions: Prospective validation combining in vitro functional assays, contracture testing, and multi-institutional anesthetic exposure registries to formalize evidence weighting in MH variant classification.
OBJECTIVES: We aimed to classify genetic variants in RYR1 and CACNA1S associated with malignant hyperthermia using biobank genotyping data in patients exposed to triggering anesthetics without malignant hyperthermia phenotype. METHODS: We identified individuals who underwent surgery and were exposed to triggering anesthetics without malignant hyperthermia phenotype and who had RYR1 or CACNA1S genotyping data available in our biobank. We classified all variants in the cohort using a Bayesian framework of the American College of Medical Genetics and Genomics and the Association of Molecular Pathologists guidelines for variant classification and updated the posterior probabilities from this model with the new information from our biobank cohort. RESULTS: We identified 253 patients with 95 RYR1 variants and 12 CACNA1S variants. After applying a Bayesian framework, we classified 17 variants as benign (B), 31 as likely benign (LB), 57 as uncertain (VUS), and 2 as likely pathogenic (LP). When we incorporated evidence about unique exposures to malignant hyperthermia triggering anesthetic agents, 48 of 107 (45%) variants were downgraded (9 to B, 37 to LB, and 2 to VUS). Notably, 41 (72%) of 57 VUSs were downgraded to B or LB. When repeat anesthetics in the same individual were counted as one exposure, 42 of 107 (39%) of variants were downgraded (5 to B, 35 to LB, and 2 to VUS). Specifically, 37 (65%) of 57 VUSs were downgraded to LB. CONCLUSION: Deidentified biorepositories linked with anesthetic data offer a new method of integrating clinical evidence into the assessment of variant probability of pathogenicity.