Vasopressin Initiation as a Second-Line VasoPressor in Early Septic Shock (VISPSS).

BACKGROUND: Vasopressin is recommended as a second-line vasoactive agent for the management of septic shock; however, a paucity of data to guide its optimal use remains. The aim was to evaluate the effect of time-to vasopressin initiation and norepinephrine (NE) dose at vasopressin initiation on clinical outcomes in patients presenting with septic shock. METHODS: This was a multi-centered, retrospective, observational study conducted in patients with septic shock. Patients were divided into 2 groups: patients initiated on vasopressin when NE-equivalent dose (NEE) < 0.25 mcg/kg/min or ≥ 0.25 mcg/kg/min. The primary outcome was time-to-vasopressor discontinuation (hours). Secondary outcomes included 28-day in-hospital mortality, intensive care unit (ICU) length of stay (LOS), fluid balance after 72 hours, and the change in NEE at 12 hours. RESULTS: A total of 302 patients were included in this study. After propensity-score matching, 73 patients in each group were identified for analysis. There was no significant difference in the time-to-vasopressor discontinuation (hours) between the groups (88.8 [55-187.5] vs 86.7 [47-172]); p = 0.7815). Fluid balance (mL) at 72 hours was significantly lower when vasopressin was initiated at NEE < 0.25 mcg/kg/min (1769 [71-7287] vs 5762 [1463-8813]; p = 0.0077). A multivariable linear regression showed shorter time to shock resolution with earlier vasopressin initiation, defined as within 4 hours (p < 0.05). CONCLUSION: In this propensity-score matched cohort, vasopressin initiation at NEE < 0.25 mcg/kg/min was not associated with shorter vasopressor duration. There was a lower fluid balance at 72 hours when vasopressin was initiated at lower NE doses.

Esmolol, vector change, and dose-capped epinephrine for prehospital ventricular fibrillation or pulseless ventricular tachycardia.

BACKGROUND: Refractory ventricular fibrillation (VF) and pulseless ventricular tachycardia (pVT) cardiac arrest describes a subset of patients who do not respond to standard Advanced Cardiac Life Support (ACLS) interventions and are associated with poor outcomes. Esmolol administration and vector change defibrillation have shown promise in improving outcomes in these patients, however evidence is limited. OBJECTIVES: This study compares clinical outcomes between patients with prehospital refractory VF/pVT who received an Emergency Medical Service (EMS) bundle, comprised of esmolol administration, vector change defibrillation, and dose-capped epinephrine at 3 mg, to patients who received standard ACLS interventions. METHODS: This multicenter, retrospective, cohort study evaluated medical records between October 18, 2017 and March 15, 2022. Patients were enrolled if they experienced a prehospital cardiac arrest with the rhythm VF or pVT, had received at least three standard defibrillations, at least 3 mg of epinephrine, and 300 mg of amiodarone. Patients who received the EMS bundle after its implementation were compared to patients who received standard ACLS interventions prior to its implementation. The primary outcome was sustained return of spontaneous circulation (ROSC), defined as ROSC lasting 20 min without recurrence of cardiac arrest. Secondary outcomes included the incidence of any ROSC, survival to hospital arrival, survival at hospital discharge, and neurologically intact survival at hospital discharge. RESULTS: Eighty-three patients were included in the study. Thirty-six were included in the pre-EMS bundle group and 47 patients were included in the post-EMS bundle group. Patients in the pre-EMS bundle group achieved significantly higher rates of sustained ROSC (58.3% vs 17%, p < 0.001), any ROSC (66.7% vs 19.1%, p < 0.001), and survival to hospital arrival (55.6% vs 17%, p < 0.001). The rates of survival to hospital discharge (16.7% vs 6.4%, p = 0.17) and neurologically intact survival at hospital discharge (5.9% vs 4.3%, p = 1.00) were not significantly different between groups. CONCLUSIONS: Patients who received the EMS bundle achieved sustained ROSC significantly less often and were less likely to have pulses at hospital arrival. The incidence of neurologically intact survival was low and similar between groups.

Current and investigational therapies for the treatment of refractory ventricular fibrillation.

PURPOSE: Esmolol, dual sequential defibrillation, vector change defibrillation, and left stellate ganglion block are presented and reviewed for the treatment of refractory ventricular fibrillation. SUMMARY: Although no formal definition has been established for refractory ventricular fibrillation, the literature describes it as a pulseless ventricular arrhythmia that persists despite 3 standard defibrillation attempts, administration of amiodarone 300 mg intravenously, and provision of three 1-mg intravenous doses of epinephrine. Evolving literature surrounding resuscitation in this particular subset of cardiac arrest challenges the efficacy of traditional therapies, such as epinephrine, and suggests that other treatment modalities may improve outcomes. Case reports, case series, and small retrospective studies have pointed to benefit when utilizing a variety of therapies, namely, esmolol, dual sequential defibrillation, vector change defibrillation, or left stellate ganglion block, in patients with refractory ventricular fibrillation arrest. CONCLUSION: A mounting, although limited, body of evidence suggests that esmolol, dual sequential defibrillation, vector change defibrillation, or left stellate ganglion block may be effective at terminating refractory ventricular fibrillation and improving patient outcomes. Further evidence is required before these therapies can be adopted as standard practice; however, as key members of the code response team, it is imperative for pharmacists to be familiar with the supporting evidence, safety considerations, and logistical challenges of utilizing these treatments during arrest.

An 18-month single-center observational study of real-world use of andexanet alfa in patients with factor Xa inhibitor associated intracranial hemorrhage.

OBJECTIVE: Intracranial hemorrhage is a life threatening complication of factor Xa inhibitors. Except for results of the open-label, single-arm ANNEXA-4 study, published real-world utilization of andexanet alfa is limited. We present our experience with andexanet alfa use in factor Xa inhibitor associated intracranial hemorrhage. The objective of this study was to assess the hemostatic efficacy and safety following early implementation of andexanet alfa use in factor Xa inhibitor associated intracranial hemorrhage. METHODS: Single center, retrospective, observational study at a large community teaching hospital and Comprehensive Stroke Center. Consecutive patients with factor Xa inhibitor associated intracranial hemorrhage, spontaneous or traumatic, treated with andexanet alfa. Primary outcome was hemostatic efficacy established by categories of hematoma growth between baseline and follow-up head computerized tomography after andexanet alfa treatment. Safety outcomes included inpatient mortality and 30-day readmission due to a thromboembolic event. Consecutive factor Xa inhibitor associated intracranial hemorrhage treated with andexanet alfa presenting between June 2018 and December 2019 were included. RESULTS: Thirty-nine patients with mean age of 81.9 years and median baseline Glasgow Coma Score of 14 were evaluated. Median (IQR) baseline intracerebral hematoma volume was 7.1 mL (2.3-28.5), while baseline thickness for subdural hemorrhage was 12.5 mm (8.0-19.3). In 35 of 39 patients with repeat computerized tomography prior to surgical intervention, excellent/good hemostatic efficacy was seen in 29 (82.9%). Excluded from the hemostatic efficacy estimate were four trauma patients who underwent hematoma evacuation prior to repeat head computerized tomography, nevertheless they had excellent hemostatic effectiveness without perioperative complications or rebleeding. Four (10.3%) patients died during hospitalization and two (5.1%) thrombotic events were observed. CONCLUSIONS: In this cohort of a real-world utilization of andexanet alfa for reversal of factor Xa inhibitors in patients presenting with intracranial hemorrhage, we observed a high excellent/good hemostatic efficacy rate and lower than reported inpatient mortality and 30-day readmission due to thromboembolism consistent with the findings reported in ANNEXA-4 study. Despite the lack of comparative group, our outcomes, most noticeably hemostatic efficacy and inpatient mortality are consistent with those reported in the literature.