Angiotensin II Infusion for Shock: A Multicenter Study of Postmarketing Use.

BACKGROUND: Vasodilatory shock refractory to catecholamine vasopressors and arginine vasopressin is highly morbid and responsible for significant mortality. Synthetic angiotensin II is a potent vasoconstrictor that may be suitable for use in these patients. RESEARCH QUESTION: What is the safety and effectiveness of angiotensin II and what variables are associated with a favorable hemodynamic response? STUDY DESIGN AND METHODS: We performed a multicenter, retrospective study at five tertiary medical centers in the United States. The primary end point of hemodynamic responsiveness to angiotensin II was defined as attainment of mean arterial pressure (MAP) of ≥ 65 mm Hg with a stable or reduced total vasopressor dosage 3 h after drug initiation. RESULTS: Of 270 included patients, 181 (67%) demonstrated hemodynamic responsiveness to angiotensin II. Responders showed a greater increase in MAP (+10.3 mm Hg vs +1.6 mm Hg, P < .001) and reduction in vasopressor dosage (-0.20 µg/kg/min vs +0.04 µg/kg/min; P < .001) compared with nonresponders at 3 h. Variables associated with favorable hemodynamic response included lower lactate concentration (OR 1.11; 95% CI, 1.05-1.17, P < .001) and receipt of vasopressin (OR, 6.05; 95% CI, 1.98-18.6; P = .002). In severity-adjusted multivariate analysis, hemodynamic responsiveness to angiotensin II was associated with reduced likelihood of 30-day mortality (hazard ratio, 0.50; 95% CI, 0.35-0.71; P < .001). Arrhythmias occurred in 28 patients (10%) and VTE was identified in 4 patients. INTERPRETATION: In postmarketing use for vasopressor-refractory shock, 67% of angiotensin II recipients demonstrated a favorable hemodynamic response. Patients with lower lactate concentrations and those receiving vasopressin were more likely to respond to angiotensin II. Patients who responded to angiotensin II experienced reduced mortality.

Impact of Multiple Daily Clinical Pharmacist-Enforced Assessments on Time in Target Sedation Range.

OBJECTIVES: Incorporation of a single daily assessment by a clinical pharmacist to improve adherence with a sedation protocol is associated with reduced duration of mechanical ventilation and intensive care unit (ICU) length of stay (LOS). We test the feasibility of incorporating a clinical pharmacist into more frequent sedation assessments and observed whether there are any potential differences in the sedatives administered. METHODS: Prospective, quasi-experimental, pilot study of patients admitted to the medical ICU. Patients were included in the analysis if ≥18 years of age within the first 24 hours of initiation of mechanical ventilation. Our primary intent was to test the clinical feasibility surrounding more frequent sedation assessments by a clinical pharmacist by evaluating potential differences in time in target sedation range and sedative administration. Exploratory efficacy end points included time in target sedation range (0 to -2) using the Richmond Agitation Sedation Scale (RASS) and sedative exposure. Patients were assigned to receive either 3 assessments with a clinical pharmacist per day (intervention) or a single assessment by a clinical pharmacist per day (standard of care). During the assessments, clinical pharmacists participated in the RASS administration and made dosing adjustments according to an established sedation protocol. MAIN RESULTS: Seventeen patients were enrolled (n = 6 intervention group, n = 11 standard of care). Duration of mechanical ventilation was similar in the 2 groups (intervention 100.0 hours [52.5-197.5] vs control 76.0 hours [46.0-201.0], P = .95), but patients in the intervention group exhibited a greater percentage time in the target RASS range (intervention 76.0% [53.7-81.5%] vs control 45.2% [35.3-67.0], P = .11) that was not statistically significant. Patients in the intervention group received less fentanyl per day (820.9 µg [227.3-1579.4] vs 1997 µg [1648.2-2477.2], P = .02) than in the control group. CONCLUSION: Incorporating a clinical pharmacist into more frequent daily sedation assessments was associated with a reduction in fentanyl administration. There were no observed differences in time in target sedation range or reduction in duration of mechanical ventilation.