Outcomes in patients with vasodilatory shock and renal replacement therapy treated with intravenous angiotensin II
Critical Care Medicine
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Objective: Acute kidney injury (AKI) requiring renal replacement therapy (RRT; together referred to as AKI-RRT) in the setting of severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II (Ang II) treatment may play a specific physiological role in patients with AKI RRT by potentially restoring glomerular filtration rate and increasing urine output without decreasing intrarenal oxygenation. We analyzed the impact of Ang II on the outcomes of AKI patients treated with RRT. Design: Post-hoc analysis of the Angiotensin II for the Treatment of High-output Shock 3 (ATHOS-3). Setting: Intensive care units in North America, Australasia, and Europe. Patients: Patients with AKI treated with RRT at initiation of Ang II or placebo (n = 45 and n = 60, respectively). We excluded patients with a history of end stage renal disease from analyses. Interventions: We randomized patients with persistent vasodilatory shock, receiving > 0.2 μg/kg/min of norepinephrine equivalent dose, to receive additional intravenous Ang II or placebo. Measurements and Main Results: The primary endpoint was an increase in mean arterial pressure (MAP) from baseline of ≥ 10 mm Hg or an increase to ≥ 75 mm Hg. Secondary outcomes included 28 day mortality and renal recovery. The composite endpoint of being alive and RRT-free was assessed through a cumulative incidence model. The MAP endpoint was achieved in 53% (95% confidence interval [CI], 38% 68%) and 22% (95% CI, 12% 34%) of patients in the Ang II and placebo groups (p = .001), respectively. The 28-day mortality rates were 47% (95% CI, 33% 62%) and 70% (95% CI, 59%-81%) in the Ang II and placebo groups (p = .012), respectively. Patients in the Ang II group were more likely to discontinue RRT within 7 days (unadjusted hazard ratio [HR], 2.37; 95% CI, 1.06 5.32; p = .031). These results were consistent with cumulative incidence estimates of RRT that accounted for death as a competing risk (HR, 2.90; 95% CI, 1.29-6.52; p = .007). Conclusions: In patients with AKI-RRT at study drug initiation, MAP response was higher, 28 day mortality was lower, and rate of recovery to RRT liberation was greater in the Ang II group compared with placebo. These findings suggest that patients with vasodilatory shock and AKI RRT may preferentially benefit from Ang II, and that future studies should further elucidate this relationship.