Angiotensin II for the Treatment of Refractory Shock: A Matched Analysis*

Abstract

OBJECTIVES: To determine if angiotensin II is associated with improved outcomes as measured by 30- and 90-day mortality as well as other secondary outcomes such as organ dysfunction and adverse events. DESIGN: Retrospective, matched analysis of patients receiving angiotensin II compared with both historical and concurrent controls receiving equivalent doses of nonangiotensin II vasopressors. SETTING: Multiple ICUs in a large, university-based hospital. PATIENTS: Eight hundred thirteen adult patients with shock admitted to an ICU and requiring vasopressor support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Angiotensin II use had no association with the primary outcome of 30-day mortality (60% vs 56%; p = 0.292). The secondary outcome of 90-day mortality was also similar (65% vs 63%; p = 0.440) as were changes in Sequential Organ Failure Assessment scores over a 5-day monitoring period after enrollment. Angiotensin II was not associated with increased rates of kidney replacement therapy (odds ratio [OR], 1.39; 95% CI, 0.88–2.19; p = 0.158) or receipt of mechanical ventilation (OR, 1.50; 95% CI, 0.41–5.51; p = 0.539) after enrollment, and the rate of thrombotic events was similar between angiotensin II and control patients (OR, 1.02; 95% CI, 0.71–1.48; p = 0.912). CONCLUSIONS: In patients with severe shock, angiotensin II was not associated with improved mortality or organ dysfunction and was not associated with an increased rate of adverse events.

Is It Time to Reconsider the Concept of “Salvage Therapy” in Refractory Shock?*

“…Indeed, shock refractory to high doses of vasopressors is associated with extraordinarily high mortality rates, ranging from 60% to greater than 90% (7). These high mortality rates are consistent with those observed by Smith et al (4) in their sample of patients with a mean baseline NEE vasopressor dose of approximately 0.62 mcg/kg/min. This poses additional questions, such as, in the hostile chemical environment of refractory shock requiring extremely high doses of vasopressors, has the opportunity to meaningfully intervene passed, such that the concept of applying a “salvage therapy” could be considered inherently flawed?…”

“…Importantly, a similar relationship was not seen when the baseline vasopressor dose was high (> 0.25 mcg/kg/min). Taken altogether, these data suggest that contrary to the environment in which Smith et al (4) assessed angiotensin II, potential benefits of the addition of alternative vasopressors, including angiotensin II, to catecholamine vasopressors such as norepinephrine, may be realized in settings where progression to refractory shock has not yet occurred.…”

“…In this issue of Critical Care Medicine , Smith et al (4) report a retrospective observational analysis of persons with refractory distributive shock who received angiotensin II in a so-called “salvage” fashion, which they compared with a matched angiotensin II-unexposed group. Importantly, the mean baseline vasopressor dose in norepinephrine equivalents (NEE) was 0.62 mcg/kg/min, which was the only criterion used to identify the matched group, leaving multiple differences between the treatment groups, such that angiotensin II recipients appeared to be sicker than the control group with higher Sequential Organ Failure Assessment scores (12 vs 10; p < 0.001), higher lactate concentrations (8.5 vs 5.9 mmol/L; p < 0.001), lower mean arterial pressures (69 vs 73 mm Hg; p = 0.004), and greater frequency of various comorbid conditions, suggesting they may be, at baseline, more likely to experience a suboptimal outcome than the control group.…”

“…In their multivariable model, receipt of angiotensin II did not alter odds of 30-day mortality (odds ratio [OR], 0.95; 95% CI, 0.61–1.48), nor the odds of new kidney replacement therapy or mechanical ventilation, or the propensity to experience thrombotic complications. The report by Smith et al (4) suggests that administering angiotensin II in patients with distributive shock that is refractory to high-dose vasopressors may not change outcomes, but leaves critically unanswered questions including: 1) is refractory shock the optimal setting to apply alternative vasopressors and 2) should we reconsider the concept of “salvage therapy” in shock?…”

“…As we continue to investigate the optimal settings and approaches to vasopressor treatment in shock, the findings of Smith et al (4) should remind us that we must critically reconsider the potentially flawed concept of “salvage therapy” and seek every opportunity possible to prevent progression to refractory shock.…”