Daily Anesthesiology Research Analysis
Across anesthesiology and perioperative medicine, three studies advance precision risk assessment and therapy selection: a double-blind RCT shows inhaled nitric oxide does not prevent AKI after prolonged cardiopulmonary bypass in patients with endothelial dysfunction; a Medicare analysis links advanced CKM syndrome stages to higher postoperative MACE and mortality; and large dual-cohort data identify creatinine–cystatin C eGFR discordance as a novel predictor of postoperative complications.
Summary
Across anesthesiology and perioperative medicine, three studies advance precision risk assessment and therapy selection: a double-blind RCT shows inhaled nitric oxide does not prevent AKI after prolonged cardiopulmonary bypass in patients with endothelial dysfunction; a Medicare analysis links advanced CKM syndrome stages to higher postoperative MACE and mortality; and large dual-cohort data identify creatinine–cystatin C eGFR discordance as a novel predictor of postoperative complications.
Research Themes
- Perioperative risk stratification and phenotyping
- Organ protection and negative trials informing practice
- Biomarker-driven precision perioperative medicine
Selected Articles
1. Nitric Oxide to Reduce Acute Kidney Injury in Patients with Pre-existing Endothelial Dysfunction Requiring Prolonged Cardiopulmonary Bypass: A Randomized Clinical Trial.
In a double-blind RCT of 250 cardiac surgery patients with endothelial dysfunction undergoing prolonged CPB, perioperative inhaled NO (80 ppm for 24 h) did not reduce AKI by KDIGO criteria or RRT use at any follow-up time point. The results argue against routine NO use for AKI prevention in this high-risk subgroup.
Impact: A well-controlled, registered RCT providing definitive negative evidence in a biologically plausible subgroup helps de-implement low-value therapy and refocus organ-protection strategies.
Clinical Implications: Do not routinely administer 80 ppm inhaled NO for 24 h to prevent AKI in cardiac surgery patients with endothelial dysfunction undergoing prolonged CPB; emphasize multimodal AKI prevention bundles (hemodynamics, nephrotoxin avoidance, perfusion strategies) and target alternative trials.
Key Findings
- AKI incidence: 44.0% (NO) vs 43.2% (control); adjusted OR 1.00 (95% CI 0.59–1.69).
- No differences in AKI severity (KDIGO stages 1–3) between groups.
- No reduction in renal replacement therapy during hospitalization or at 6 weeks, 90 days, or 1 year.
Methodological Strengths
- Double-blind, placebo-controlled, randomized design with trial registration (NCT02836899).
- Clinically meaningful outcomes using KDIGO criteria and longitudinal RRT assessments.
Limitations
- Single-center design may limit generalizability.
- Trial may be underpowered to detect smaller effects on less frequent endpoints (e.g., long-term RRT).
Future Directions: Explore alternative perioperative nephroprotection strategies (e.g., perfusion pressure targets, hemolysis mitigation, nitric oxide bioavailability via different routes) and phenotype-enriched trials beyond endothelial dysfunction alone.
BACKGROUND: Prolonged cardiopulmonary bypass (CPB) causes hemolysis, reducing nitric oxide (NO) availability and increasing the risk of acute kidney injury (AKI) after cardiac surgery. While prior studies suggest inhaled NO may reduce AKI in certain populations, its effect in patients with pre-existing endothelial dysfunction, a condition marked by impaired NO production is unknown. This trial investigates whether perioperative NO administration reduces AKI in patients with pre-existing endothelial dysfunction undergoing prolonged CPB. METHODS: We conducted a double-blind, single-center, placebo-controlled, randomized clinical trial involved 250 adult cardiac surgery patients with pre-existing endothelial dysfunction undergoing cardiopulmonary bypass lasting more than 90 minutes. Participants were randomized to either receive NO at 80 ppm via the oxygenator during cardiopulmonary bypass, continuing post-operatively via ventilator and facemask, or a placebo of nitrogen-oxygen gas mixture for 24 hours. The primary outcome was the incidence of post-operative AKI, defined by KDIGO criteria. Secondary outcomes included AKI severity, and the need for renal replacement therapy (RRT) during hospitalization and at 6 weeks, 90 days, and 1 year. RESULTS: Of the 250 patients [median age: 66 (59, 73) years; 56 (22.4%) females], 125 were assigned to each group. AKI occurred in 55 (44.0%) patients in the NO group and 54 (43.2%) patients in the control group [OR adj : 1.00 (95%CI: 0.59-1.69)]. Secondary outcomes, including stage 1, 2, or 3 AKI and RRT at all time points, were also similar between groups. CONCLUSIONS: In cardiac surgery patients with pre-existing endothelial dysfunction undergoing prolonged cardiopulmonary bypass, peri-operative administration of 80 ppm NO for 24 hours did not significantly reduce post-operative AKI. These findings do not support the routine use of NO in this patient population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02836899.
2. Association of the cardiovascular-kidney-metabolic syndrome and adverse outcomes after noncardiac surgery.
In a Medicare cohort of over 2.1 million surgeries, advanced CKM stages (≥3) independently increased risks of MACE (AOR 1.70–3.42), mortality (1.52–3.61), and non-home discharge (1.98–4.25). These associations were consistent across race/ethnicity and sex within CKM stages.
Impact: Provides scalable, phenotype-based perioperative risk stratification using CKM staging across a national dataset, informing preoperative evaluation and resource planning.
Clinical Implications: Incorporate CKM staging into preoperative assessment to identify patients at high risk for MACE and mortality, guide optimization (cardiac, renal, metabolic), and plan postoperative disposition and monitoring.
Key Findings
- Advanced CKM stages (≥3) associated with higher MACE risk (AOR 1.70–3.42).
- Mortality and non-home discharge risks increased with CKM stage (AOR 1.52–3.61 and 1.98–4.25).
- No excess MACE risk differences by race/ethnicity or sex within the same CKM stage.
Methodological Strengths
- Very large national cohort with detailed administrative data.
- Multivariable modeling across CKM stages with assessment of disparities.
Limitations
- Retrospective administrative data subject to residual confounding and misclassification.
- Limited generalizability to patients under 65 years or outside Medicare.
Future Directions: Prospective validation of CKM-integrated perioperative risk tools and interventional studies targeting modifiable CKM components to reduce postoperative events.
BACKGROUND: Fifteen percent of US adults have advanced stages of the cardiovascular-kidney-metabolic (CKM) syndrome. The association between advanced stages of CKM and adverse surgical outcomes is not well established. METHODS: This retrospective cohort study used US Medicare data between 2017 and 2020 for patients ≥65 yr old who underwent major noncardiac surgery. Multivariable logistic regression was used to examine the association between CKM stages and the primary outcome, major adverse cardiovascular events (MACE). Secondary outcomes were mortality and non-home discharges. Disparities by race, ethnicity, and sex were also examined. RESULTS: Among 2 129 997 surgeries (mean age: 75 yr [65-112]; 52% female), 274 574 (12.9%) were undertaken in patients with CKM Stage 0 (no risk factors). CKM Stage 3 (subclinical cardiovascular disease) was recorded in surgeries involving 37 031 individuals (1.74%); 537 894 (25.3%) surgeries were undertaken in individuals with Stage 4 CKM (established cardiovascular disease, with metabolic risk factors, chronic kidney disease, or both). Advanced stages of CKM ≥3 were independently associated with increased risk of MACE (adjusted odds ratio [AOR] range: 1.70-3.42), mortality (AOR range: 1.52-3.61), and non-home discharge (AOR range: 1.98-4.25), compared with patients without CKM (all P<0.001). Black, Hispanic, and female individuals did not have a higher risk of MACE compared with White or male individuals with the same CKM stage. CONCLUSIONS: Advanced stages of CKM were associated with a higher risk of major adverse cardiovascular events, mortality, and non-home discharge, but this was unrelated to race, ethnicity, or sex.
3. Discordances Between Preoperative Creatinine- and Cystatin C-Based Estimated Glomerular Filtration Rate and Outcomes After Noncardiac Surgery: An Observational Study.
Across two large Chinese surgical cohorts (n=35,488 and 23,417), a more negative preoperative eGFRdiff (cystatin C minus creatinine) independently predicted higher risks of a composite of postoperative complications and death, with similar effect sizes per 10 mL/min/1.73 m² decrease.
Impact: Introduces a simple, physiologically grounded biomarker (eGFRdiff) for perioperative risk stratification with consistent performance across independent cohorts.
Clinical Implications: Consider measuring both cystatin C and creatinine to compute eGFRdiff in preoperative evaluation; a negative eGFRdiff may flag higher risk for cardiovascular events, AKI, infections, and pulmonary complications to guide monitoring and optimization.
Key Findings
- Per 10 mL/min/1.73 m² decrease in eGFRdiff, adjusted ORs for the composite outcome were 1.12 (95% CI 1.09–1.15) and 1.11 (95% CI 1.09–1.14) in two cohorts (P<0.001).
- Associations were consistent across component outcomes: cardiovascular events, AKI, infections, pulmonary complications, and death.
- Findings replicated across two geographically distinct, ethnically different hospital cohorts.
Methodological Strengths
- Large, dual-cohort design with multivariable adjustment for demographics, comorbidities, and labs.
- Consistent effect sizes across independent populations and outcomes.
Limitations
- Retrospective design with potential residual confounding and assay variability.
- Generalizability beyond Asian populations and two-center settings requires validation.
Future Directions: Prospective, multicenter validation and integration of eGFRdiff into perioperative risk calculators; exploration of mechanisms underlying discordance and targeted optimization strategies.
BACKGROUND: Differences between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFR) have been associated with adverse outcomes in both chronic disease and general population cohorts, but their significance in surgical patients is unknown. We hypothesized that lower cystatin C-based relative to creatinine-based eGFR would be associated with higher risks of postoperative complications. METHODS: We conducted a retrospective cohort study of patients who had major noncardiac surgery at two large hospitals in China, located in geographically distant regions and with differing ethnic compositions. The exposure was difference in preoperative eGFR based on cystatin C and creatinine (eGFRdiff = eGFRcys - eGFRcr). The primary outcome was a composite of postoperative complications and death. Associations were assessed using logistic regression models adjusting for demographics, comorbidities, surgery characteristics, and laboratory results. RESULTS: A total of 35,488 patients from the Nanfang cohort and 23,417 from the Xinjiang cohort were included. The primary outcome occurred in 8.4% and 14.4% of patients, respectively. More negative eGFRdiff values were consistently associated with higher risk of the primary outcome (adjusted odds ratio per 10 mL/min/1.73 m² decrease, 1.12 [95% CI 1.09-1.15] in Nanfang cohort and 1.11 [95% CI 1.09-1.14] in Xinjiang cohort; both P <0.001). Associations were also observed across categories of component outcomes (cardiovascular events, acute kidney injury, infections, pulmonary complications, and death). CONCLUSIONS: More negative preoperative eGFRdiff was independently associated with higher risk of postoperative complications in Asian patients undergoing noncardiac surgery. eGFRdiff may represent a novel risk marker with potential utility for perioperative risk stratification.