Wanek, Matthew

ImportanceDirect oral anticoagulant (DOAC)–associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH are limited.ObjectiveTo evaluate the safety and outcomes of DOAC reversal agents among patients with ICH.Data SourcesPubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022.Study SelectionThe eligibility criteria were (1) adult patients (age ≥18 years) with ICH receiving treatment with a DOAC, (2) reversal of DOAC, and (3) reported safety and anticoagulation reversal outcomes. All nonhuman studies and case reports, studies evaluating patients with ischemic stroke requiring anticoagulation reversal or different dosing regimens of DOAC reversal agents, and mixed study groups with DOAC and warfarin were excluded.Data Extraction and SynthesisPreferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for abstracting data and assessing data quality and validity. Two reviewers independently selected the studies and abstracted data. Data were pooled using the random-effects model.Main Outcomes and MeasuresThe primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent.ResultsA total of 36 studies met criteria for inclusion, with a total of 1832 patients (967 receiving 4-factor prothrombin complex concentrate [4F-PCC]; 525, andexanet alfa [AA]; 340, idarucizumab). The mean age was 76 (range, 68-83) years, and 57% were men. For 4F-PCC, anticoagulation reversal was 77% (95% CI, 72%-82%; I2 = 55%); all-cause mortality, 26% (95% CI, 20%-32%; I2 = 68%), and thromboembolic events, 8% (95% CI, 5%-12%; I2 = 41%). For AA, anticoagulation reversal was 75% (95% CI, 67%-81%; I2 = 48%); all-cause mortality, 24% (95% CI, 16%-34%; I2 = 73%), and thromboembolic events, 14% (95% CI, 10%-19%; I2 = 16%). Idarucizumab for reversal of dabigatran had an anticoagulation reversal rate of 82% (95% CI, 55%-95%; I2 = 41%), all-cause mortality, 11% (95% CI, 8%-15%, I2 = 0%), and thromboembolic events, 5% (95% CI, 3%-8%; I2 = 0%). A direct retrospective comparison of 4F-PCC and AA showed no differences in anticoagulation reversal, proportional mortality, or thromboembolic events.Conclusions and RelevanceIn the absence of randomized clinical comparison trials, the overall anticoagulation reversal, mortality, and thromboembolic event rates in this systematic review and meta-analysis appeared similar among available DOAC reversal agents for managing ICH. Cost, institutional formulary status, and availability may restrict reversal agent choice, particularly in small community hospitals.

Background: Vancomycin pharmacokinetics are altered in the critically ill and are further distorted by renal replacement therapy. Limited literature is available evaluating vancomycin dosing in continuous veno-venous hemodialysis (CVVHD). Objective: The goal of this analysis was to identify factors that affect vancomycin trough concentration in patients on CVVHD and to determine an appropriate dosing strategy. Methods: This was a single-center, retrospective cohort study of adult inpatients admitted to the Cleveland Clinic from May 2016-December 2017. Patients in the intensive care unit who received ≥ 2 doses of vancomycin during CVVHD were included. Patients with interruptions of CVVHD inappropriately timed troughs, a change in dialysate rate, and those who received different vancomycin dosages were excluded. Multivariable linear regression including age, sex, weight, Sequential Organ Failure Assessment score, albumin, 24-hour urine output (UOP), dialysate rate, filter type, and vancomycin dose was run to determine predictors of vancomycin concentration. Results: A total of 160 patients were included. The median vancomycin dose was 12.6 mg/kg with a trough of 24.6 mcg/mL. Weight, 24-hour UOP, vancomycin dose (mg/kg), and dialysate rate (mL/kg/h) were all determined to be independent predictors of vancomycin trough level. Patients who received <10 mg/kg doses of vancomycin (N=18) achieved a median trough of 21.5 mcg/mL, with 83% being therapuetic. In patients who received >10 mg/kg (N=142), the median trough was 25.5 mcg/mL, with 47% being therapeutic. Conclusion and Relevance: Vancomycin dose, dialysate rate, UOP, and weight are independently associated with vancomycin trough concentration. In CVVHD patients, vancomycin dosed at 10 mg/kg every 24 hours may be an appropriate recommendation.

Abstract Background The extracorporeal membrane oxygenation (ECMO) circuit causes pharmacokinetic alterations of medications which impact drug selection and dosing. Although hydromorphone has a favorable pharmacokinetic profile, it is unclear whether hydromorphone provides better patient‐centered benefits compared to fentanyl. The objective of this study is to compare opioid and sedative requirements in ECMO patients started on a fentanyl‐ versus hydromorphone‐based analgesia regimen. Methods This was a non‐interventional retrospective cohort study. It was conducted at a single center in the cardiovascular intensive care units and cardiac intensive care units. We included venovenous (VV) or venoarterial ECMO patients. Patients who were started on a fentanyl continuous infusion within 24 h of cannulation were compared to patients started on a hydromorphone continuous infusion. Results A linear mixed effects model was performed to compare doses of opioid, sedative, and propofol between groups over time. We included 28 hydromorphone patients and 53 fentanyl patients, with 85% on VV ECMO. There were no differences between hydromorphone and fentanyl groups in opioid or sedative (including propofol and benzodiazepine) doses for any ECMO day ( p value for interaction .63 and .83, respectively). Propofol doses alone, however, were significantly higher in the fentanyl group on ECMO days three, four, and five. Conclusions There appear to be no major differences in opioid or sedative requirements whether ECMO patients are initiated on a hydromorphone‐ or fentanyl‐based regimen.