Fludrocortisone Plus Hydrocortisone Versus Hydrocortisone Alone as Adjunctive Therapy in Septic Shock: A Retrospective Cohort Study.

BACKGROUND: Trials evaluating hydrocortisone (HC) for septic shock are conflicting with all finding decreased time to shock reversal but few with mortality difference. Those with improved mortality included fludrocortisone (FC), but it is unknown if FC affected the outcome or is coincidental as there are no comparative data. OBJECTIVE: The objective of this study was to determine the effectiveness and safety of FC + HC versus HC alone as adjunctive therapy in septic shock. METHODS: A single-center, retrospective cohort study was conducted of medical intensive care unit (ICU) patients with septic shock refractory to fluids and vasopressors. Patients receiving FC + HC were compared with those receiving HC. Primary outcome was time to shock reversal. Secondary outcomes included in-hospital, 28-, and 90-day mortality; ICU and hospital length of stay (LOS); and safety. RESULTS: There were 251 patients included (FC + HC, n = 114 vs HC, n = 137). There was no difference in time to shock reversal (65.2 vs 71 hours; P = 0.24). Cox proportional hazards model showed time to first corticosteroid dose, full-dose HC duration, and use of FC + HC were associated with shorter shock duration, while time to vasopressor therapy was not. However, in 2 multivariable models controlling for covariates, use of FC + HC was not an independent predictor of shock reversal at greater than 72 hours and in-hospital mortality. No differences were seen in hospital LOS or mortality. Hyperglycemia occurred more frequently with FC + HC (62.3% vs 45.6%; P = 0.01). CONCLUSION AND RELEVANCE: FC + HC was not associated with shock reversal at greater than 72 hours or decreased in-hospital mortality. These data may be useful for determining corticosteroid regimen in patients with septic shock refractory to fluids and vasopressors. Future prospective, randomized studies are needed to further evaluate the role of FC in this patient population.

Comparison of Droperidol and Midazolam Versus Haloperidol and Lorazepam for Acute Agitation Management in the Emergency Department.

BACKGROUND: Acute agitation accounts for up to 2.6% of visits to the emergency department (ED). To date, a standard of care for the management of acute agitation has not been established. Few studies have evaluated antipsychotic and benzodiazepine combinations. OBJECTIVE: The purpose of this study was to evaluate effectiveness and safety of combination therapy for acute agitation with intramuscular (IM) droperidol and midazolam (D+M) compared with IM haloperidol and lorazepam (H+L) in patients in the ED. METHODS: This was a single-center, retrospective medical record review of patients presenting to a large, academic ED with acute agitation from July 2020 through October 2021. The primary outcome was percentage of patients requiring additional agitation medication within 60 minutes of combination administration. Secondary outcomes included average time to repeat dose administration and average number of repeat doses required before ED discharge. RESULTS: A total of 306 patients were included for analysis: 102 in the D+M group and 204 in the H+L group. Repeat dose within 60 minutes occurred in 7 (6.9%) and 28 (13.8%) patients in the D+M and H+L groups, respectively (P = 0.065). A total of 28.4% of D+M patients and 30.9% of H+L patients required any repeat dose during their ED visit. Time to repeat dose was 12 and 24 minutes in the D+M and H+L, respectively (P = 0.22). The adverse event rate was 2.9% in each group. CONCLUSION AND RELEVANCE: IM D+M resulted in a lower rate of repeat doses of acute agitation medication compared with IM H+L, though this was not statistically significant. Both therapies were safe, and the adverse event rate was low.

Hemostatic Efficacy and Safety of 4-Factor Prothrombin Complex Concentrate in Doac-Associated Intracranial Hemorrhage.

Background: Factor Xa (FXa) inhibitor use has increased over the last decade and though associated rates of major bleeding are lower compared to warfarin, outcomes from intracranial hemorrhage (ICH) are still significant. Targeted FXa inhibitor reversal agent became available in 2018, however use of 4-factor prothrombin complex concentrate (4F-PCC) for FXa inhibitor-associated ICH continues at many institutions. Objective: Evaluate the safety and hemostatic efficacy of 4F-PCC for FXa inhibitor-associated ICH. Methods: Single-center, retrospective study of patients who received 4F-PCC for FXa inhibitor-associated ICH. The primary efficacy endpoint was hemostasis and thrombosis was the main safety endpoint. Secondary endpoints included in-hospital mortality and discharge disposition. Results: 76 patients on apixaban or rivaroxaban were included. Good or excellent hemostasis was achieved in 80.3% of patients. Five patients experienced a thrombotic event. Favorable discharge disposition and lower in-hospital mortality was more likely in patients who achieved excellent hemostasis. Conclusion: 4F-PCC is safe and effective for FXa inhibitor associated ICH.