Abstract
BackgroundInhaled nitric oxide (iNO) is a rescue therapy for severe hypoxemia in patients with acute respiratory distress syndrome (ARDS). Pooled data from clinical trials have signaled a renal safety warning for iNO therapy, but the significance of these findings in daily clinical practice is unclear. We used primary data to evaluate the risk of iNO-associated renal dysfunction in patients with ARDS.MethodsWe conducted a cohort study using data from a tertiary teaching hospital to evaluate the risk of incident renal replacement therapy (RRT) in iNO users compared with that of non-users. Propensity score matching and competing-risks regression were used for data analysis. Residual confounding was assessed by means of a rule-out approach. We also evaluated effect modification by pre-specified factors using stratified analysis.ResultsWe identified 547 patients with ARDS, including 216 iNO users and 331 non-users. At study entry, 313 (57.2%) patients had moderate ARDS and 234 (42.8%) had severe ARDS. The mean patient age was 63 ± 17 years. The crude hazard ratio of the need for RRT in iNO users compared with non-users was 2.23 (95% CI, 1.61–3.09, p < 0.001). After propensity score matching, there were 151 iNO users matched to 151 non-users. The adjusted hazard ratio was 1.59 (95% CI, 1.08–2.34, p = 0.02). In the stratified analysis, we found that older aged patients (≥65 years) were more susceptible to iNO-associated kidney injury than younger patients (p = 0.05).ConclusionsThis study showed that iNO substantially increased the risk of renal dysfunction in patients with ARDS. Older aged patients were especially susceptible to this adverse event.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1566-0) contains supplementary material, which is available to authorized users.
Highlights
Inhaled nitric oxide is a rescue therapy for severe hypoxemia in patients with acute respiratory distress syndrome (ARDS)
We found that among patients with ARDS, exposure to Inhaled nitric oxide (iNO) significantly increased the risk of need for renal replacement therapy (RRT), and that patients ≥65 years old were especially prone to this hazard
Our results are consistent with the data from prior randomized controlled trial (RCT), which have shown that iNO therapy increases the risk for renal dysfunction in patients with ARDS by 50% [11, 26]
Summary
Inhaled nitric oxide (iNO) is a rescue therapy for severe hypoxemia in patients with acute respiratory distress syndrome (ARDS). Inhaled nitric oxide gas administered via a gas mixture with the patient’s inhaled breath reaches only normally ventilated lung units and causes selective dilatation of the vessels surrounding normal alveoli [1]. This improves the ventilation-perfusion mismatch in patients with hypoxaemic respiratory failure due to acute lung injury. A clinical trial of ARDS published in 1999 reported that iNO potentially doubled the risk of the need for renal replacement therapy (RRT) compared
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