N-acetylcysteine plus deferoxamine for patients with prolonged hypotension does not decrease acute kidney injury incidence: a double blind, randomized, placebo-controlled trial

Cassiana Mazon Fraga, Cristiane Damiani Tomasi, Danusa de Castro Damasio, Francieli Vuolo, Cristiane Ritter, Felipe Dal-Pizzol, Cassiana Mazon Fraga, Cristiane Damiani Tomasi, Danusa de Castro Damasio, Francieli Vuolo, Cristiane Ritter, Felipe Dal-Pizzol

Abstract

Background: The aim was to test the primary hypothesis that in patients suffering from shock, treatment with N-acetylcysteine (NAC) plus deferoxamine (DFX) decreases the incidence of acute kidney injury (AKI).

Methods: A double-blind, randomized, placebo-controlled trial was conducted in a general intensive care unit in an academic hospital. Patients were included if they had new-onset hypotension, defined as mean arterial blood pressure <60 mmHg or requirement for vasopressor medication. A loading dose of NAC or placebo of 50 mg/kg in 4 h was administered intravenously. After the loading dose, patients received 100 mg/kg/day for the next 48 h. DFX or placebo was administered once at 1000 mg at a rate of 15/mg/kg/h. The primary outcome was the incidence of AKI.

Results: A total of 80 patients were enrolled in the study. The incidence of AKI was 67 % in the placebo arm and 65 % in the treatment group (relative risk (RR) 0.89 (0.35-2.2)). Furthermore, NAC plus DFX was effective in decreasing the severity and duration of AKI, and patients in the treatment group had lower serum creatinine levels at discharge. No severe adverse event associated with treatment was reported. The effects of NAC plus DFX could be secondary to the attenuation of early inflammatory response and oxidative damage.

Conclusion: The administration of NAC plus DFX to critically ill patients who had a new episode of hypotension did not decrease the incidence of AKI.

Trial registration: Clinicaltrials.gov NCT00870883 (Registered 25 March 2009.).

Keywords: Acute kidney injury; Antioxidants; Inflammation; Oxidative stress; Shock.

Figures

Fig. 1
Fig. 1
Screening, randomization, and follow up
Fig. 2
Fig. 2
Oxidative and inflammatory parameters. Blood was collected on enrollment and on the morning of the subsequent 2 days for the measurement of thiobarbituric acid reactive species (TBARS) (a), interleukin (IL)-6 (b), IL-8 (c), IL-10 (d), and protein carbonyls (e). *Different from time 0, same group. #Difference between groups at the same time point NAC + DFX N-acetylcysteine plus deferoxamine, MDA malondialdehyde

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