Overview
Norepinephrine is a catecholamine that is the first-line vasopressor for septic shock. The addition of non-catecholamine vasopressors, including vasopressin and angiotensin-II may be used in adults with septic shock that have inadequate mean arterial pressure while on norepinephrine. Uncertainty exists regarding the timing of initiation of these agents and there is a lack of data comparing their safety and efficacy.
The current literature suggests that earlier initiation of angiotensin-II will have a more significant reduction on norepinephrine-equivalent dose compared to later initiation. In addition, approximately half of patients initiated on vasopressin do not have an early hemodynamic response 6 hours after initiation. The purpose of this study is to evaluate the efficacy of angiotensin-II when used as the second vasopressor agent for septic shock.
Description
- Objectives
Primary Objective:
- To evaluate the efficacy of ang-II when used as the second vasopressor agent for septic shock
Secondary Objectives:
- To assess the duration of response to ang-II
- To assess overall survival
- To assess the amount of time spent in the ICU
- To assess the need for renal replacement therapy
- To assess the overall duration of vasoactive medication use
- To assess toxicity and tolerability
Eligibility
Inclusion Criteria:
- Patients admitted to the ICU within 12 hours of presentation to the emergency department for septic shock requiring 15-25 mcg/min of norepinephrine. Septic shock will be defined as having a known or presumed infection with two or more criteria of systemic inflammatory response syndrome, a mean arterial pressure <65 mm Hg despite fluid resuscitation requiring vasopressor support, and a serum lactate >2 mmol/L. Criteria of systemic inflammatory response syndrome include a temperature >100.4°F or <96.8°F; heart rate >90/min; respiratory rate >20/min and a white blood cell count >12,000/mm3 or <4,000/mm3.
Exclusion Criteria:
- Age <18 years
- Pregnancy or lactation
- Known allergic reactions to angiotensin-II or hydrocortisone sodium succinate
- Requiring >25 mcg/min of norepinephrine or on any vasopressor other than norepinephrine at study enrollment
- Clinically significant bleeding precluding the use of chemical prophylaxis for venous thromboembolism
- Treatment with another investigational drug or other intervention during study timeframe