Abstract
IntroductionInhaled nitric oxide (iNO) is an important therapy for acute respiratory distress syndrome (ARDS), pulmonary hypertension and pediatric hypoxemic respiratory failure. Safety concerns regarding iNO and renal dysfunction have been reported; however, there are currently no systematic reviews on this issue. Our objective was to evaluate published randomized controlled trials (RCTs) to ascertain the risk of renal dysfunction associated with iNO therapy in patients with and without ARDS.MethodsA systematic review of databases was performed to identify RCTs which compared iNO with controls up to September 2014. Effect estimates for risk ratio (RR) of acute kidney injury (AKI) were pooled using a random-effects model.ResultsTen RCTs involving 1363 participants were included. Inhaled nitric oxide significantly increased the risk of AKI compared with controls (RR, 1.4, 95%CI, 1.06 to 1.83, p = 0.02). In the stratified analysis, a high cumulative-dose of iNO significantly increased the risk of AKI (RR, 1.52, 95%CI, 1.14 to 2.02, p = 0.004), whereas medium and low cumulative-doses did not (RR, 0.64, 95%CI, 0.23 to 1.81 and RR, 0.56, 95%CI, 0.11 to 2.86 respectively). In subgroup analysis by study population, an increased risk of AKI was observed in patients with ARDS (RR, 1.55, 95%CI, 1.15 to 2.09, p = 0.005) but not in those without (RR, 0.90, 95%CI, 0.49 to 1.67, p = 0.75).ConclusionsThe available data show that iNO therapy may increase the risk of renal dysfunction, especially with prolonged use and in patients with ARDS. The risk in pediatric population is unknown owing to limited data. We suggest monitoring renal function during iNO therapy, and that future trials of iNO should evaluate renal safety.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0880-2) contains supplementary material, which is available to authorized users.
Highlights
Inhaled nitric oxide is an important therapy for acute respiratory distress syndrome (ARDS), pulmonary hypertension and pediatric hypoxemic respiratory failure
According to our predefined inclusion and exclusion criteria, 10 randomized controlled trial (RCT) involving a total of 1,363 patients were included in the final analysis [12,20,21,22,23,24,25,26,27,28]
Quality assessment of the included studies suggested a low risk of bias, except for one study which was published with an abstract [21]
Summary
Inhaled nitric oxide (iNO) is an important therapy for acute respiratory distress syndrome (ARDS), pulmonary hypertension and pediatric hypoxemic respiratory failure. A safety concern about renal dysfunction for nitric oxide inhalation was reported in a metaanalysis designed to evaluate the efficacy of iNO in ARDS [13]. This finding contradicts earlier evidence that iNO has favorable effects on renal and splanchnic perfusion [8]. This adverse effect, as a class effect of iNO therapy, was not observed in non-ARDS populations.
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