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N-Acetylcysteine plus Deferoxamine for Patients with Prolonged Hypotension Does Not Decrease Acute Kidney Injury Incidence: A Double Blind, Randomized, Placebo-Controlled Trial
Fraga C, Tomasi C, Damasio D, et al. Crit Care. 2016; 20: 331.
Study Question: Does the use of IV n-acetylcysteine (NAC) plus IV deferoxamine (DFX) prevent AKI in patients with shock?
Study Description: This single-center, double-blind, randomized, placebo-controlled, parallel-group trial included patients with new onset hypotension (MAP <60 mmHg) that did not improve with fluid boluses or required vasopressors. The study arm received a loading dose of NAC 50 mg/kg followed by a continuous infusion of 100 mg/kg/day for two consecutive days plus DFX 1000 mg for one dose. The primary outcome was the incidence of AKI as defined by the Kidney Disease Improving Global Outcomes (KIDGO) Guidelines. The study was stopped short of meeting its pre-specified sample size due to slow enrollment.
Results: A total of 40 patients were randomized to receive NAC + DFX and 40 patients to placebo. There was no difference in the incidence of AKI (RR 0.89, 95% CI 0.35-2.2). NAC + DFX reduced the incidence of stage 2/3 AKI (RR 0.4, 95% CI 0.16-0.98), duration of AKI days (0.5 vs. 1, p = 0.04), and serum creatinine levels at discharge (0.7 vs. 1.1, p = 0.05). There was no difference in the need for renal replacement therapy, ICU or hospital mortality. NAC + DFX did reduce anti-inflammatory markers measured.
Conclusion(s): The combination of NAC + DFX did not reduce the incidence of AKI in critically ill patients with shock.
Perspective: There is conflicting data on the potential benefit of NAC + DFX in shock patients. Previous studies have shown benefit but there is no consensus on appropriate dosing strategies. Due to the complexity and multi-factorial processes of each subset of shock, further studies should limit their evaluation to a single subset of shock and other inflammatory mediated processes.