Wieruszewski, Patrick M.

Abstract Background Management of acute cardiogenic shock for post-cardiotomy and post-transplant patients remains challenging. The use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for circulatory support is a key intervention, yet the optimal cannulation strategy—central vs. peripheral—remains debated. This study evaluates outcomes associated with each approach to inform clinical decision-making. Methods A retrospective analysis was conducted on 319 patients who received VA-ECMO for CS intraoperatively or within 24 hours postoperatively at Mayo Clinic (2010–2023). Patients were categorized into central (n=241) and peripheral (n=78) ECMO groups. Propensity score (PS) weighting using stabilized inverse probability of treatment weighting was applied to minimize baseline imbalances. Outcomes included in-hospital mortality, bleeding requiring reoperation, limb ischemia, prolonged ventilation (>7 days), and sepsis. Results The median age at ECMO initiation was 68.5 years, with 37.3% female patients. Right ventricular (RV) dysfunction was the predominant indication for ECMO initiation (p<0.001). After PS weighting, no significant difference was observed in in-hospital mortality (49.8% vs. 44.5%, p=0.416) or other major complications between central and peripheral ECMO (see Table 1). Stroke was more frequent in central ECMO (P = 0.159), though not statistically significant. Reoperation for bleeding occurred significantly more often in central ECMO in the unweighted analysis (P = 0.047), but the difference lost statistical significance after weighting (P = 0.071). Renal failure was comparable between groups (P = 0.888). Notably, sternal infection rates were comparable between groups (P=0.921). Acute limb ischemia was more common in the peripheral group (P = 0.209). Limb ischemia associated with central ECMO was not caused by the ECMO cannulas but was instead related to concomitant use of femoral intra-aortic balloon pump. Conclusions After propensity score weighting, analysis showed no significant differences in mortality or complications between central ECMO and peripheral ECMO for post-cardiotomy and post-transplant cardiogenic shock.

OBJECTIVE: Volatile anesthetics (VAs) are gaining renewed interest as a sedation strategy in the intensive care, offering an alternative to traditional IV agents. VAs provide several pharmacologic advantages, including rapid onset and offset, minimal systemic metabolism, and favorable recovery profiles. Advances in delivery systems enabled the safe and practical administration of volatile agents in the ICU. Thus, we aimed to describe the pharmacology and safety aspects of inhaled agents as well as the systems designed to deliver VAs in the ICU. DATA SOURCES: Relevant literature was identified through PubMed and MEDLINE databases. STUDY SELECTION: Original research, review articles, commentaries, and guidelines addressing safety, efficacy, and use of VAs in adult ICU patients were included. DATA EXTRACTION: Studies were reviewed by the authors, with key findings summarized and organized by pharmacologic properties, delivery systems, and safety domains. DATA SYNTHESIS: VAs are halogenated hydrocarbons whose mechanism of action is not fully understood. Although the CNS is the primary site of action, the end-tidal concentration of exhaled anesthetic is used to monitor clinical effects such as immobility to a noxious stimulus. Inhaled agents have unique pharmacokinetics, minimal metabolisms, and distinct recovery. The side effect profile is also unique, with malignant hyperthermia being the most feared, yet rare complication. Two systems for inhalational sedation delivery are available internationally, with one currently under evaluation in the United States. The systems are composed of a miniature vaporizer, delivery controller, and a monitor. The systems have distinct safety considerations, such as tidal volume limits. CONCLUSIONS: VAs can be used as sedative agents in the ICU. This article comprehensively reviews the pharmacology of VAs along with their safety profile and describes the structure and function of miniature vaporizers currently available on the world market.

Abstract Background Posaconazole immediate release (IR) suspension is the standard product for enteral feeding tube (EFT) administration but has erratic pharmacokinetic behavior and results in sub satisfactory concentrations. Limited evidence suggests that the posaconazole oral delayed-release (DR) tablets may be crushed. Methods This was a retrospective cohort study of hospitalized adults who received EFT administration of posaconazole IR suspension or crushed DR tablets between 2018 and 2024. Patients were eligible if they had at least one serum concentration drawn ≥5 days after posaconazole initiation. The primary outcome was the attainment of therapeutic (≥700ng/mL for prophylaxis, ≥1,000ng/mL for treatment) serum concentration within 30 days. Secondary outcomes included time to therapeutic serum concentration, adverse drug effects, and frequency of clogged EFT. Multivariable cox proportional hazards regression was used to assess the relationship between posaconazole formulation and attainment of therapeutic concentrations while adjusting for confounding variables. Results Of the included patients, 100 received DR tablets and 48 received IR suspension. There were no significant differences in baseline characteristics or severity of illness. Among DR tablet and IR suspension recipients, 59% and 23% achieved therapeutic concentrations, respectively (p < 0.001). After adjusting for age, sex, BMI, drug interactions, posaconazole indication, malabsorptive gastrointestinal conditions, IR suspension was significantly less likely than crushed DR tablets to achieve therapeutic posaconazole concentrations within 30-days (HR 0.37, 95% CI 0.20-0.71; p < 0.003). The crushed DR tablet group required less total daily posaconazole to achieve therapeutic concentrations (400 vs 600 mg/day, p = 0.003). Clogged EFTs were more frequent in the crushed DR tablet group (27% vs 10%, p = 0.022), while no differences were observed in the occurrence of hepatotoxicity or hypokalemia. Conclusion Administration of crushed posaconazole DR tablets via EFT is more likely to attain therapeutic concentrations compared to IR suspension. The optimal technique for administering crushed DR tablets to prevent EFT complications warrants investigation. Disclosures Patrick M. Wieruszewski, PharmD, FCCM, Wolters Kluwer/UpToDate: Advisor/Consultant

OBJECTIVES: Vasoplegia is a common complication of cardiac surgery that uses cardiopulmonary bypass and contributes to morbidity and mortality, yet a consensus definition does not exist. The objective of this study was to evaluate the diagnostic criteria and definitions used to characterize vasoplegia and how different criteria influence incidence estimates. DATA SOURCES: Ovid Embase, Ovid MEDLINE, Scopus, Web of Science Core Collection, ClinicalTrials.gov, Ovid Cochrane Central Register of Controlled Trials, and the World Health Organization’s International Clinical Trials Registry Platform clinical trials registry. STUDY SELECTION: Randomized clinical trials and observational studies reporting on vasoplegia in adults undergoing any type of cardiac surgery that used cardiopulmonary bypass. DATA EXTRACTION: Proportional meta-analysis using a random-effects model and the inverse variance method was used to calculate the pooled incidence of vasoplegia and its clinical outcomes. DATA SYNTHESIS: A total of 68 studies encompassing 56,580 patients were identified, from which 63 unique vasoplegia definitions were used. Blood pressure ( n = 57 studies, 84%) and cardiac output ( n = 50 studies, 74%) were among the most common criteria used in vasoplegia definitions; however, there was a vast variety of threshold values applied within these criteria and all other criteria comprising the definitions. The pooled incidence of vasoplegia was 21% (95% CI, 17–25%), acute kidney injury was 32% (95% CI, 21–45%), and mortality was 12% (95% CI, 9–16%). Subgroup analysis revealed that transplantation and left ventricular assist device implantation surgeries, and those with baseline left ventricular ejection fraction less than 40% had a significantly greater incidence of vasoplegia. CONCLUSIONS: The published literature varies greatly in the criteria used to define vasoplegia associated with on-pump cardiac surgery. Generation and adoption of a unified definition for vasoplegia must be an international priority.

ABSTRACT Background The Extracorporeal Life Support Organization recommends daily antithrombin monitoring and supplementation to achieve > 50%–80% activity during extracorporeal membrane oxygenation (ECMO). Evidence supporting this practice is uncertain, and whether it confers clinical benefit or harm is unclear. Methods This was a systematic review with meta‐analysis to evaluate the safety and efficacy of antithrombin supplementation during ECMO. We systematically searched databases and registers for studies comparing patients on ECMO who received antithrombin supplementation to those who did not. Random effects meta‐analysis was performed. Risk of bias was independently assessed by two investigators. A priori subgroup and sensitivity analyses were performed to explore reasons for heterogeneity. Results A total of 11 studies were identified. In the pooled meta‐analysis, antithrombin supplementation resulted in no difference in bleeding events (OR 1.38, 95% CI, 0.88–2.17, p = 0.16), thrombotic events (OR 1.57, 95% CI, 0.84–2.90, p = 0.15), or mortality (OR 1.21, 95% CI, 0.81–1.81, p = 0.35) when compared to those who did not receive antithrombin. Subgroup analysis revealed no difference in bleeding events or mortality in pediatric or adult patients; however, pediatric patients that received antithrombin were more likely to experience a thrombotic event (OR 1.70, 95% CI, 1.51–1.91). Sensitivity analysis in only low risk of bias studies confirmed these findings. Conclusions Antithrombin supplementation was not associated with differences in mortality or hemostatic outcomes during ECMO support and may be associated with harm in pediatric patients on ECMO.