Molly Droege

Effect of a dalteparin prophylaxis protocol using anti-factor Xa concentrations on venous thromboembolism in high-risk trauma patients

BACKGROUND Low anti-factor Xa (anti-Xa) concentrations with twice-daily enoxaparin are associated with venous thromboembolism (VTE) in high-risk trauma patients. Concerns have been raised with once-daily dalteparin regarding effectiveness and achievable anti-Xa concentrations. The purpose of this before-and-after study was to evaluate the effectiveness of a VTE prophylaxis protocol using anti-Xa concentrations and associated dalteparin dose adjustment in high-risk trauma patients. METHODS Adult trauma patients receiving VTE chemoprophylaxis and hospitalized for at least 3 days were prospectively followed during two 6-month epochs before (PRE) and after (POST) implementation of anti-Xa monitoring. In both groups, high-risk patients received dalteparin 5,000 U subcutaneously once daily; low-risk patients received subcutaneous unfractionated heparin. High-risk POST patients with anti-Xa less than 0.1 IU/mL 12 hours after initial dalteparin dose received dalteparin every 12 hours. All patients underwent routine VTE ultrasound surveillance of the lower extremities. The primary outcome was incidence of VTE. RESULTS A total of 785 patients (PRE, n = 428; POST, n = 357) were included. Demographics, injury patterns, Injury Severity Score (ISS), red blood cell transfusions, intensive care unit and hospital stays, and mortality did not differ between groups. Overall, POST patients had lower VTE (7.0% vs. 13%, p = 0.009) including acute VTE (6.4% vs. 12%, p = 0.01) and proximal deep vein thromboembolism (2.2% vs. 5.7%, p = 0.019). Between high-risk patients, VTE occurred in 53 (16.3%) PRE compared with 24 (9.0%) POST patients (p = 0.01); there was no difference in VTE between low-risk patients (PRE, 2.0% vs. POST, 1.1%; p = 0.86). Among 190 high-risk POST patients with anti-Xa, 97 (51%) were less than 0.1 IU/mL. Patients with low anti-Xa had higher rates of VTE (14.0% vs. 5.4%, p = 0.05) and deep vein thromboembolism (14.4% vs. 3.2%, p = 0.01). Younger age (odds ratio, 0.97; 95% confidence interval, 0.95–0.99) and greater weight (odds ratio, 1.02; 95% confidence interval, 1.00–1.03) predicted low anti-Xa on multivariate regression. CONCLUSION A VTE prophylaxis protocol using anti-Xa–based dalteparin dosage adjustment in high-risk trauma patients was associated with decreased VTE. Once-daily dalteparin 12-hour anti-Xa concentrations are suboptimal in a majority of patients and associated with VTE. LEVEL OF EVIDENCE Therapeutic study, level IV.

995: METHADONE VERSUS SCHEDULED OPIOID THERAPY IN TIME TO CONTINUOUS INFUSION ANALGESIA DISCONTINUATION

Critical Care Medicine • Volume 46 • Number 1 (Supplement) www.ccmjournal.org Learning Objectives: Patients in the intensive care unit (ICU) routinely experience pain. Scheduled opioids may be employed to facilitate weaning of continuous infusion (CI) analgesia in mechanically ventilated (MV) patients to avoid withdrawal. However, an optimum strategy has not been identified. Methadone may be an optimal choice as it possesses a long duration of action and has the ability to be administered intravenously and enterally. Methods: This single center, retrospective, cohort study included adult ICU patients on MV for 48 hours that received CI analgesia plus concomitant methadone or scheduled, enteral immediate release opioids (IRO). The primary outcome was comparison of time to CI analgesia discontinuation. Secondary outcomes included comparison of initial, 96-hour, and final methadone or IRO dose in oral morphine equivalents (OME) at CI analgesia discontinuation and prolonged QTc interval incidence at 96 hours. Logistic regression analyses were performed to determine independent predictors of methadone response. Results: Seventy-four patients were included in the analysis. Time to CI analgesia discontinuation was similar between the two treatment groups (methadone, 69 hours vs IRO, 57.5 hours; p = 0.527). CI analgesia dose at study drug initiation and maximum dose were similar between the two groups. The methadone group received statistically more daily OME at all time points analyzed (initiation, 90 vs 60 mg, p = 0.009; 96 hours, 90 vs 45 mg, p < 0.001; CI analgesia discontinuation, 90 vs 30 mg, p < 0.001). No difference in prolonged QTc interval at 96 hours was observed (methadone, 445 vs IRO, 460 ms; p = 0.110). Patients that received methadone were significantly more likely to discharged with a long-acting opioid prescription (51.4 vs 2.7%, p < 0.001). No independent predictors for methadone response were identified. Conclusions: Methadone was not associated with a quicker time to CI analgesia discontinuation when compared to scheduled IRO. Patients that received methadone were more likely to be discharged with a prescription for a long-acting opioid and received significantly more opioid analgesia until CI analgesia was discontinued.

970: Continuous Renal Replacement Therapy and Flow Rate Influence on Cefepime Pharmacokinetics

performed, and if an adverse drug event (ADE) had been averted. Averted ADEs were further categorized by severity level of the potential error. The intervening bedside pharmacist reviewed and classified the interventions recorded during the study. A second pharmacist not involved in data collection reviewed all of the interventions. Results: A total of 148 interventions were included in the study from the before-group pharmacists and a total of 238 interventions were included from the after-group (p <0.001). More bedside activities were performed by pharmacists in the after-group (51%) than the before-group (29%), p <0.001. There were more averted ADEs during the after-study (82%) than the before-study (63%), p <0.001. There was not a difference in the severity level of the averted ADEs between the 2 groups. Conclusions: More interventions were performed by the bedside pharmacists than the satellite-based pharmacists. More ADEs were averted with the presence of a bedside pharmacist, however there was not a difference in the severity levels of the averted ADEs.