Daily Anesthesiology Research Analysis
Across anesthesiology and perioperative medicine, three studies stand out: a pre-planned secondary analysis suggests a liberal transfusion threshold (Hb <9 g/dL) after subarachnoid hemorrhage may reduce cerebral ischemia; a multicenter prospective cohort shows gated respiratory control under general anesthesia improves stone-free rates and safety during RIRS; and a rapid review synthesizes strategies to manage severe heparin resistance during CPB after andexanet alfa exposure.
Summary
Across anesthesiology and perioperative medicine, three studies stand out: a pre-planned secondary analysis suggests a liberal transfusion threshold (Hb <9 g/dL) after subarachnoid hemorrhage may reduce cerebral ischemia; a multicenter prospective cohort shows gated respiratory control under general anesthesia improves stone-free rates and safety during RIRS; and a rapid review synthesizes strategies to manage severe heparin resistance during CPB after andexanet alfa exposure.
Research Themes
- Neurocritical care transfusion strategies after subarachnoid hemorrhage
- Respiratory control under general anesthesia to optimize endourologic outcomes
- Perioperative anticoagulation reversal and cardiopulmonary bypass heparinization
Selected Articles
1. Liberal versus restrictive transfusion strategies in subarachnoid hemorrhage: a secondary analysis of the TRAIN study.
In a pre-planned secondary analysis of SAH patients within the TRAIN RCT, a liberal transfusion threshold (Hb <9 g/dL) did not significantly reduce unfavorable outcomes at 180 days versus a restrictive threshold (Hb <7 g/dL) in unadjusted analyses. However, liberal strategy was associated with less cerebral ischemia and, after adjustment, with a lower risk of unfavorable outcome.
Impact: Transfusion thresholds in SAH are clinically controversial. This analysis provides randomized evidence suggesting potential benefits of a higher Hb target in reducing cerebral ischemia.
Clinical Implications: For neuroanesthesiology and neurocritical care, considering a more liberal transfusion threshold may reduce cerebral ischemia risk in SAH. Patient blood management protocols could individualize thresholds, especially in patients at high risk of delayed cerebral ischemia.
Key Findings
- Randomized comparison within TRAIN: liberal (Hb <9 g/dL) vs restrictive (Hb <7 g/dL) transfusion in 190 SAH patients.
- Unfavorable outcome at 180 days: RR 0.87 (95% CI 0.71–1.04) for liberal vs restrictive (not statistically significant).
- Cerebral ischemia significantly lower with liberal strategy: RR 0.63 (95% CI 0.41–0.97).
- Adjusted analysis associated liberal randomization with lower risk of unfavorable outcome: RR 0.83 (95% CI 0.70–0.99).
Methodological Strengths
- Pre-planned secondary analysis of a multicenter randomized trial (TRAIN).
- Clear, patient-centered primary outcome at 180 days and adjudicated cerebral ischemia.
- Intention to treat randomization maintained for transfusion thresholds.
Limitations
- Secondary analysis; potential for residual confounding despite adjustment.
- Liberal group was older; imbalances may influence outcomes.
- Trial not primarily powered for SAH subgroup alone.
Future Directions: A definitive SAH-specific RCT comparing transfusion thresholds with cerebral ischemia and functional outcomes as co-primary endpoints is warranted; mechanistic monitoring (e.g., brain tissue oxygenation) could guide individualized thresholds.
BACKGROUND: The optimal hemoglobin (Hb) threshold to trigger red blood cell transfusions (RBCT) in subarachnoid hemorrhage (SAH) patients is unclear. This study evaluated the impact of liberal versus restrictive transfusion strategies on neurological outcome in patients with SAH. METHODS: This is a pre-planned secondary analysis of the "TRansfusion Strategies in Acute brain INjured Patients" (TRAIN) study. We included all SAH patients from the original study that were randomized to receive RBCT when Hb levels dropped below 9 g/dL (liberal group) or 7 g/dL (restrictive group). The primary outcome was an unfavorable neurological outcome at 180 days, defined by a Glasgow Outcome Scale Extended score of 1-5. RESULTS: Of the 190 SAH patients in the trial, 188 (98.9%) had data available for the primary outcome, with 86 (45.3%) in the liberal group and 102 (53.6%) in the restrictive group. Patients in the liberal group were older than in the restrictive group, but otherwise had similar baseline characteristics. Patients in the liberal group received more RBCT and showed higher Hb levels over time. At 180 days, 57 (66.3%) patients in the liberal group and 78 (76.4%) in the restrictive group had unfavorable outcomes (risk ratio, RR 0.87; 95% confidence intervals, 95% CI 0.71-1.04). Patients in the liberal group had a significantly lower risk of cerebral ischemia (RR 0.63; 95% CI 0.41-0.97). In a multivariate analysis, randomization to the liberal group was associated with a lower risk of unfavorable outcome (RR 0.83, 95% CI 0.70-0.99). CONCLUSIONS: A liberal transfusion strategy was not associated with a lower incidence of unfavorable outcome after SAH when compared to a restrictive strategy. However, in a multivariable analysis adjusted for confounders randomization to the liberal group was associated with lower risk of unfavorable outcome. The occurrence of cerebral ischemia was significantly lower in the liberal transfusion strategy group. TRIAL REGISTRATION: ClinicalTrials.gov number-NCT02968654 registered on November 16th, 2016.
2. General anaesthesia with gated or controlled mechanical ventilation and its influence on peri and post operative outcomes of retrograde intra renal surgery when using flexible and navigable suction access sheath, an EAU-endourology and Global FANS collaborative study group: a prospective study.
In 562 adults undergoing RIRS with FANS under general anesthesia, gated respiration improved stone-free outcomes (Grade A+B 98.3% vs 91.3%), navigation and visibility, and reduced sheath-related bleeding. Gated respiration independently predicted stone-free status, underscoring anesthesiology–urology collaboration on respiratory control.
Impact: Demonstrates that intraoperative ventilatory strategy directly influences endourologic outcomes and safety, providing a practical lever for anesthesiologists to improve surgical efficacy.
Clinical Implications: Implementing gated/controlled ventilation protocols during RIRS may improve stone-free rates and reduce bleeding. Standardizing anesthetic-respiratory coordination with surgeons could be incorporated into RIRS pathways.
Key Findings
- Prospective multicenter cohort (n=562) comparing non-gated vs gated respiration during RIRS with FANS.
- Higher zero fragment (Grade A: 64.2% vs 59%) and overall stone-free (Grade A+B: 98.3% vs 91.3%; p=0.001) with gated respiration.
- Improved sheath navigation (91.2% vs 85.1%; p=0.038) and visibility (p=0.004) under gating.
- Reduced mild bleeding due to sheath movement (3.1% vs 11.2%; p<0.001).
- Gated respiration independently predicted stone-free status (OR 6.26; 95% CI 2.28–22.6; p<0.001).
Methodological Strengths
- Prospective multicenter design with standardized 30-day NCCT assessment of stone-free status.
- Multivariable logistic regression to identify independent predictors.
- Clinically relevant, surgeon-reported procedural metrics captured.
Limitations
- Non-randomized cohort; potential selection and performance bias.
- Surgeon- and center-level practices may confound results.
- Short-term (30-day) imaging follow-up; durability of results unknown.
Future Directions: Randomized trials comparing gated vs conventional ventilation during RIRS should assess long-term recurrence and cost-effectiveness; physiological studies to optimize ventilatory parameters for renal stabilization are warranted.
BACKGROUND: Retrograde intrarenal surgery (RIRS) is a preferred treatment for renal stones, yet challenges such as kidney movement due to respiration hinder surgical precision and outcomes. The introduction of flexible and navigable suction ureteral access sheaths (FANS) and novel techniques like gated respiration aim to improve stone-free rates (SFR) and reduce complications. This study evaluates the impact of gated respiration on perioperative outcomes in RIRS with FANS. METHODS: A prospective multicenter study enrolled 562 adult patients undergoing RIRS with FANS under general anesthesia. Patients were divided into two groups: non-gated respiration (Group 1) and gated respiration (Group 2). Stone-free status (SFS) was assessed at 30 days using NCCT scans. SFS was defined as follows: grade A, zero fragments; grade B, a single fragment ≤ 2 mm; grade C, a single fragment 2.1-4 mm; and grade D, single/multiple fragments > 4 mm. Procedural efficiency, perioperative complications, and surgeon-reported outcomes were compared. RESULTS: Patients in Group 2 had significantly higher zero residual fragment (Grade A) rates (64.2% vs. 59%) and overall SFR (Grade A + B: 98.3% vs. 91.3%, p = 0.001). Gated respiration improved sheath navigation (91.2% vs. 85.1%, p = 0.038) and visibility during lithotripsy (p = 0.004), while reducing complications like mild bleeding due to sheath movement (3.1% vs. 11.2%, p < 0.001). Logistic regression identified gated respiration as a significant predictor of SFS (OR 6.26, 95% CI 2.28-22.6, p < 0.001). CONCLUSION: Gated respiration synergistically enhances the efficacy of FANS in RIRS, improving SFR, procedural safety, and surgeon experience. This study highlights the importance of respiratory control as an adjunct to RIRS, emphasizing the need for interdisciplinary collaboration between surgical and anesthesiology teams.
3. Andexanet-induced heparin resistance in cardiac surgery-a rapid review of case reports and series.
A rapid systematic review of 14 CPB cases exposed to andexanet demonstrated profound heparin resistance (mean initial ACT ~200 s despite large heparin doses), frequent circuit thrombosis, and potential benefit from pre-emptive antithrombin concentrate (≈50 IU/kg) to achieve target ACT. The report outlines mitigation strategies, including nafamostat use in select cases.
Impact: With increasing use of andexanet, recognizing and preemptively managing CPB heparin resistance is critical to prevent catastrophic thrombosis. This synthesis provides actionable strategies for cardiac anesthesiologists and perfusionists.
Clinical Implications: For patients recently receiving andexanet undergoing CPB, anticipate heparin resistance and consider pre-emptive high-dose antithrombin concentrate to reach ACT ≥400 s; prepare contingency strategies (e.g., nafamostat) and monitor for reservoir thrombosis.
Key Findings
- Fourteen CPB cases after andexanet showed severe heparin resistance: mean initial ACT 199.5 s despite mean total heparin 1123 U/kg.
- Circuit/reservoir thrombosis occurred in 35.7% of cases; two required circuit exchange.
- Prophylactic antithrombin concentrate (~49.9 IU/kg) often restored ACT >400 s; post-thrombosis low-dose AT had variable effects.
- Nafamostat mesylate was used as adjunct in some Japanese cases.
Methodological Strengths
- Systematic search across multiple databases and adverse event reporting systems.
- Quality appraisal using a validated tool for drug-induced adverse event case reports/series.
Limitations
- Evidence based on case reports/series; small sample size and publication bias likely.
- Heterogeneity in management protocols and reporting of outcomes.
- No controlled comparative data to define optimal dosing.
Future Directions: Prospective registries and mechanistic studies to define dosing strategies (AT concentrate timing/amount) and alternative anticoagulation pathways during CPB after andexanet; development of institutional protocols.
BACKGROUND: Andexanet alfa, a Food and Drug Administration (FDA)-approved antidote for apixaban and rivaroxaban, is used to manage life-threatening or uncontrolled bleeding. In patients undergoing cardiopulmonary bypass (CPB), preoperative exposure to andexanet can cause severe heparin resistance, necessitating effective mitigation strategies. A comprehensive review of such strategies remains lacking. OBJECTIVES: This study aimed to systematically review and characterize cases of andexanet-induced heparin resistance in patients undergoing CPB and to evaluate management strategies. METHODS: A systematic search was conducted across multiple databases via the Ovid interface, Cochrane Central Register of Controlled Trials, and the FDA Adverse Event Reporting System. Quality appraisal was performed using a validated instrument for case reports and series describing drug-induced adverse events. RESULTS: Fourteen discrete patient cases met inclusion criteria. After andexanet administration, the mean initial activated clotting time (ACT) was 199.5 seconds, falling short of a target of ≥400 seconds despite additional heparin dosing (mean total, 1123 U/kg). Moreover, 35.7% of all cases involved thrombus formation in the reservoir, 2 of which required a circuit replacement. Antithrombin (AT) concentrate was administered to 75% of those received an adjunct therapy. A prophylactic AT use (mean, 49.9 IU/kg) resulted in an ACT over 400 seconds, while its effects in low dose after the occurrence of thrombosis varied on ACT values. Nafamostat mesylate was used in some cases reported from Japan. CONCLUSION: Heparin resistance following andexanet exposure poses significant procoagulant risk during CPB. Pre-emptive high-dose AT therapy may improve ACT values. Further studies are needed to understand the mechanisms and optimize management of this condition.