Daily Anesthesiology Research Analysis
A multicenter randomized trial (FARES-II) shows prothrombin complex concentrate achieves superior hemostasis and fewer adverse events than frozen plasma for coagulopathic bleeding in cardiac surgery. A large Medicare cohort links concurrent gabapentin and opioids to increased respiratory events in older adults. Post-hoc analyses indicate perioperative bleeding drives AKI indirectly through hypotension and positive fluid balance rather than as an independent risk factor.
Summary
A multicenter randomized trial (FARES-II) shows prothrombin complex concentrate achieves superior hemostasis and fewer adverse events than frozen plasma for coagulopathic bleeding in cardiac surgery. A large Medicare cohort links concurrent gabapentin and opioids to increased respiratory events in older adults. Post-hoc analyses indicate perioperative bleeding drives AKI indirectly through hypotension and positive fluid balance rather than as an independent risk factor.
Research Themes
- Perioperative transfusion and hemostasis optimization
- Opioid–gabapentinoid safety and respiratory risk
- Mechanisms of cardiac surgery–associated acute kidney injury
Selected Articles
1. Prothrombin Complex Concentrate vs Frozen Plasma for Coagulopathic Bleeding in Cardiac Surgery: The FARES-II Multicenter Randomized Clinical Trial.
In 528 randomized patients analyzed (primary analysis n=420), PCC achieved higher hemostatic effectiveness than frozen plasma (77.9% vs 60.4%; difference 17.6%; 95% CI 8.7%-26.4%; P<.001 for noninferiority and superiority), reduced allogeneic transfusion requirements, and lowered serious adverse events and AKI through day 30.
Impact: This pragmatic multicenter RCT demonstrates superiority of PCC over frozen plasma for coagulopathic bleeding, directly informing transfusion algorithms in cardiac surgery.
Clinical Implications: Consider PCC as first-line factor replacement for coagulopathic bleeding during cardiac surgery to improve hemostasis, reduce transfusion exposure, and decrease AKI risk; update perioperative blood management protocols accordingly.
Key Findings
- Hemostatic effectiveness was higher with PCC vs frozen plasma (77.9% vs 60.4%; difference 17.6%; 95% CI 8.7%-26.4%; P<.001).
- PCC reduced allogeneic transfusions (mean 6.6 vs 9.3 units; difference 2.7; 95% CI 1.0-4.4; P=.002).
- Serious adverse events were lower with PCC (RR 0.76; 95% CI 0.61-0.96; P=.02), including lower AKI (10.3% vs 18.8%; RR 0.55; 95% CI 0.34-0.89; P=.02).
- Trial registered at ClinicalTrials.gov (NCT05523297); conducted at 12 hospitals in Canada and the US.
Methodological Strengths
- Multicenter randomized controlled design with predefined noninferiority and superiority testing
- Clinically relevant composite hemostatic endpoint and 30-day follow-up with safety outcomes
Limitations
- Unblinded design may introduce performance or detection bias
- Second-dose and post-24h use of only frozen plasma could influence downstream transfusion metrics
Future Directions: Evaluate implementation of PCC-first algorithms across diverse cardiac procedures, cost-effectiveness, and thromboembolic safety in broader populations.
IMPORTANCE: Excessive bleeding is a common and prognostically important complication of cardiac surgery. For bleeding related to coagulation factor deficiency, frozen plasma is the most used therapy. Preliminary trials indicate that 4-factor prothrombin complex concentrate (PCC) may be a suitable alternative. OBJECTIVE: To compare the efficacy and safety of PCC with frozen plasma in patients undergoing cardiac surgery with coagulopathic bleeding. DESIGN, SETTING, AND PARTICIPANTS: Unblinded randomized noninfe
2. Adverse respiratory events during treatment with gabapentin and opioids among older adults with spine-related conditions: a propensity-matched cohort study in the US Medicare population.
In a 1:1 propensity-matched Medicare cohort (n=133,720), concurrent gabapentin plus opioids was associated with a higher risk of composite respiratory events than TCA/duloxetine plus opioids (adjusted HR 1.19; 95% CI 1.13–1.25). Pneumonia and respiratory failure were the most frequent events, and findings were robust in sensitivity analyses.
Impact: Addresses a common perioperative/pain management prescribing pattern with large-scale, active-comparator evidence linking gabapentin–opioid co-use to respiratory harm.
Clinical Implications: Use caution when co-prescribing gabapentin with opioids in older adults; consider alternatives (e.g., TCAs or duloxetine), start low-dose with close respiratory monitoring, and reassess necessity.
Key Findings
- Gabapentin+opioids increased composite respiratory events vs TCA/duloxetine+opioids (aHR 1.19; 95% CI 1.13–1.25; p<.0001).
- Event rates: pneumonia 3.7% vs 3.0%, respiratory failure 2.3% vs 1.8% in gabapentin vs comparator groups.
- Results consistent in sensitivity analyses restricted to ≤30 days and requiring ≥2 prescription fills.
- Incident-user, active-comparator, propensity-matched design reduced confounding by indication.
Methodological Strengths
- Incident-user, active-comparator, propensity score-matched cohort design
- Large national dataset with prespecified composite respiratory outcomes and sensitivity analyses
Limitations
- Residual confounding and misclassification inherent to administrative claims data
- Medication adherence, in-hospital sedation, and physiologic parameters not captured
Future Directions: Prospective studies to validate causality, dose–response, and identify high-risk subgroups; trials testing deprescribing or alternative regimens in older adults.
BACKGROUND CONTEXT: Recent work indicates no increased mortality risk with concurrent gabapentin and opioid use when using an active comparator control design. However, concurrent gabapentin and opioid prescriptions have been associated with greater risk of respiratory depression in some studies. PURPOSE: To compare the risk of respiratory events among Medicare enrollees with histories of spine-related diagnoses treated with gabapentin+opioids versus those treated with tricyclic antidepressants (TCA) or duloxetine+opioids. We hypothesized that enrollees treated with gabapentin+opioids would have increased risk of adverse respiratory events compared to those treated with an active control+opioids. STUDY DESIGN/SETTING: Propensity score-matched cohort study with an incident user, active comparator (TCA/duloxetine) control design. The primary analysis included those who concurrently (within 30 days) filled ≥1 incident gabapentin+≥1 opioid or ≥1 incident TCA/duloxetine+≥1 opioid prescription. PATIENT SAMPLE: US Medicare beneficiaries with histories of spine-related diagnoses 2017 to 2019. People treated with gabapentin+opioids (n=66,860) were matched on demographic and clinical factors to people treated with TCAs/duloxetine+opioids (n=66,860). OUTCOME MEASURES: Time to a composite respiratory outcome consisting of mechanical ventilation, intubation, respiratory failure, pneumonia, or acute respiratory distress syndrome. METHODS: Cox proportional hazard regression was used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs). RESULTS: Among 133,720 Medicare enrollees (median age 73.3 years; 66.9% female), 6277 (4.7%) experienced respiratory events before the end of follow-up. A total of 3,469 (5.2%) of people who were treated with gabapentin+opioids (median initial dose/day of gabapentin was 300 mg) had respiratory events compared to 2808 (4.2%) of those treated with an active control+opioids. The increased risk in those treated with gabapentin+opioids was statistically significant after adjustment (HR 1.19; 95% CI 1.13, 1.25; p<.0001). The most common respiratory events were pneumonia (3.7% of people in the gabapentin+opioids group versus 3.0% of people in the TCA/duloxetine+opioids group) and respiratory failure (2.3% in the gabapentin+opioids group versus 1.8% in the TCA/duloxetine+opioids group). Results were similar in analyses (a) restricted to ≤30-day follow-up and (b) that required ≥2 fills of each prescription. CONCLUSIONS: While recent work indicates no increased mortality risk with concurrent gabapentin and opioid use in this population, the current findings suggest clinicians should exercise caution in prescribing gabapentin to older adults with spine conditions who are using opioids, due to possible impacts on respiratory events. However, we cannot be certain that unmeasured confounding may explain these results and replication is needed.
3. Perioperative Bleeding Is Not an Independent Risk Factor for Acute Kidney Injury in On-pump Cardiac Surgery-A Post-hoc Analysis of a Randomized Clinical Trial.
Among 1,386 on-pump cardiac surgery patients, severe/massive bleeding correlated with AKI in conventional models, but mediation analysis showed no direct effect; AKI risk was mediated by lower mean arterial pressure and positive fluid balance. Fresh frozen plasma transfusion was also associated with AKI.
Impact: Clarifies mechanistic pathways to cardiac surgery–associated AKI, redirecting focus from bleeding per se to hemodynamic and fluid management targets.
Clinical Implications: Prioritize maintaining adequate mean arterial pressure and avoiding fluid overload while preventing bleeding; reassess transfusion strategies, particularly fresh frozen plasma, to mitigate AKI risk.
Key Findings
- AKI incidence was 10% (139/1,386) using KDIGO creatinine criteria.
- Severe/massive bleeding associated with AKI in logistic model (OR severe 2.16; massive 6.78), but no direct effect in mediation analysis (beta 0.32; 95% CI -0.26 to 0.91).
- Lower mean arterial pressure and positive fluid balance showed indirect effects mediating AKI risk; fresh frozen plasma transfusion associated with AKI (OR 1.29; 95% CI 1.06–1.58).
Methodological Strengths
- Use of standardized definitions (KDIGO, UDPB) and multivariable logistic plus mediation analyses
- Large single-center cohort derived from an RCT framework with detailed perioperative data
Limitations
- Post-hoc, single-center analysis limits generalizability and causal inference
- Potential residual confounding and limited granularity on intraoperative management beyond modeled variables
Future Directions: Prospective, multicenter studies testing hemodynamic and fluid management protocols to prevent AKI; evaluate differential impacts of specific blood products.
OBJECTIVES: To study the association between bleeding and acute kidney injury (AKI). DESIGN: Post-hoc study of a randomized trial of 4% albumin versus Ringer's acetate for cardiopulmonary bypass priming and perioperative volume replacement. SETTING: Single-center study. PATIENTS: 1,386 on-pump cardiac surgical patients. MEASUREMENTS AND RESULTS: AKI was defined by the Kidney Disease: Improving Global Outcomes creatinine criteria, and bleeding by the Universal Definition of Perioperative Bleeding (UDPB) classification. With univariably independent factors, two logistic regression analyses (Model 1: AKI Risk Score, EuroSCORE II, and UDPB class; Model 2: risk scores, components of the UDPB classification, and factor VIII/von Willebrand factor concentrate) and a mediation analysis (Model 3: risk scores, UDPB class, and perioperative factors) were performed. A total of 139 (10%) patients developed AKI. In Model 1, UDPB class "severe" (odds ratio: 2.16, 95% confidence interval: 1.19-3.89), "massive" bleeding (6.78, 1.8-25.33), and AKI Risk Score (1.51, 1.29-1.78) were associated with AKI. In Model 2, AKI Risk Score (1.55, 1.33-1.82) and fresh frozen plasma transfusion (1.29, 1.06-1.58) were associated with AKI. In Model 3, the combined UDPB classes "severe" and "massive" bleeding did not have a direct effect (regression coefficient: 0.32, 95% confidence interval: -0.26 to 0.91), while mean arterial pressure (0.08, 0.003-0.21) and fluid balance (0.12, 0.17-0.27) had indirect effects on AKI. CONCLUSIONS: In on-pump cardiac surgery, perioperative bleeding was not an independent risk factor for AKI but manifested as AKI via hypotension and higher fluid balance. Prevention of bleeding may reduce AKI in cardiac surgery.