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Critical Care
Published in: Critical Care 1/2016

Open Access 01-12-2016 | Research

Inhaled nitric oxide and the risk of renal dysfunction in patients with acute respiratory distress syndrome: a propensity-matched cohort study

Authors: Sheng-Yuan Ruan, Hon-Yen Wu, Hsien-Ho Lin, Huey-Dong Wu, Chong-Jen Yu, Mei-Shu Lai

Published in: Critical Care | Issue 1/2016

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Abstract

Background

Inhaled 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.

Methods

We 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.

Results

We 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).

Conclusions

This 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.
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Literature
1.
Griffiths MJ, Evans TW. Inhaled nitric oxide therapy in adults. N Engl J Med. 2005;353(25):2683–95.CrossRefPubMed
2.
Adhikari NK, Dellinger RP, Lundin S, Payen D, Vallet B, Gerlach H, Park KJ, Mehta S, Slutsky AS, Friedrich JO. Inhaled nitric oxide does not reduce mortality in patients with acute respiratory distress syndrome regardless of severity: systematic review and meta-analysis. Crit Care Med. 2014;42(2):404–12.CrossRefPubMed
3.
Bein T, Grasso S, Moerer O, Quintel M, Guerin C, Deja M, Brondani A, Mehta S. The standard of care of patients with ARDS: ventilatory settings and rescue therapies for refractory hypoxemia. Intensive Care Med. 2016;42(5):699–711.CrossRefPubMedPubMedCentral
4.
Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315(8):788–800.CrossRefPubMed
5.
Meade MO, Jacka MJ, Cook DJ, Dodek P, Griffith L, Guyatt GH. Survey of interventions for the prevention and treatment of acute respiratory distress syndrome. Crit Care Med. 2004;32(4):946–54.CrossRefPubMed
6.
Germann P, Braschi A, Della Rocca G, Dinh-Xuan AT, Falke K, Frostell C, Gustafsson LE, Herve P, Jolliet P, Kaisers U, et al. Inhaled nitric oxide therapy in adults: European expert recommendations. Intensive Care Med. 2005;31(8):1029–41.CrossRefPubMed
7.
McMahon TJ, Doctor A. Extrapulmonary effects of inhaled nitric oxide: role of reversible S-nitrosylation of erythrocytic hemoglobin. Proc Am Thorac Soc. 2006;3(2):153–60.CrossRefPubMedPubMedCentral
8.
Dellinger RP, Zimmerman JL, Taylor RW, Straube RC, Hauser DL, Criner GJ, Davis Jr K, Hyers TM, Papadakos P. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group. Crit Care Med. 1998;26(1):15–23.CrossRefPubMed
9.
Taylor RW, Zimmerman JL, Dellinger RP, Straube RC, Criner GJ, Davis Jr K, Kelly KM, Smith TC, Small RJ. Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial. JAMA. 2004;291(13):1603–9.CrossRefPubMed
10.
Lundin S, Mang H, Smithies M, Stenqvist O, Frostell C. Inhalation of nitric oxide in acute lung injury: results of a European multicentre study. The European Study Group of Inhaled Nitric Oxide. Intensive Care Med. 1999;25(9):911–9.CrossRefPubMed
11.
Ruan SY, Huang TM, Wu HY, Wu HD, Yu CJ, Lai MS. Inhaled nitric oxide therapy and risk of renal dysfunction: a systematic review and meta-analysis of randomized trials. Crit Care. 2015;19:137.CrossRefPubMedPubMedCentral
12.
Kane-Gill SL, Goldstein SL. Drug-Induced Acute Kidney Injury: A focus on risk assessment for prevention. Crit Care Clin. 2015;31(4):675–84.CrossRefPubMed
13.
Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526–33.PubMed
14.
Schneeweiss S. A basic study design for expedited safety signal evaluation based on electronic healthcare data. Pharmacoepidemiol Drug Saf. 2010;19(8):858–68.CrossRefPubMedPubMedCentral
15.
Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993;270(24):2957–63.CrossRefPubMed
16.
Murray JF, Matthay MA, Luce JM, Flick MR. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis. 1988;138(3):720–3.CrossRefPubMed
17.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41.CrossRefPubMed
18.
19.
Rubin DB. Estimating causal effects from large data sets using propensity scores. Ann Intern Med. 1997;127(8 Pt 2):757–63.CrossRefPubMed
20.
Austin PC. Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat. 2011;10(2):150–61.CrossRefPubMed
21.
Bakoyannis G, Touloumi G. Practical methods for competing risks data: a review. Stat Methods Med Res. 2012;21(3):257–72.CrossRefPubMed
22.
Fine J, Gray R. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.CrossRef
23.
Schneeweiss S. Sensitivity analysis and external adjustment for unmeasured confounders in epidemiologic database studies of therapeutics. Pharmacoepidemiol Drug Saf. 2006;15(5):291–303.CrossRefPubMed
24.
Rewa O, Bagshaw SM. Acute kidney injury-epidemiology, outcomes and economics. Nat Rev Nephrol. 2014;10(4):193–207.CrossRefPubMed
25.
26.
Adhikari NK, Burns KE, Friedrich JO, Granton JT, Cook DJ, Meade MO. Effect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review and meta-analysis. BMJ. 2007;334(7597):779.CrossRefPubMedPubMedCentral
27.
28.
Sharfuddin AA, Molitoris BA. Pathophysiology of ischemic acute kidney injury. Nat Rev Nephrol. 2011;7(4):189–200.CrossRefPubMed
29.
Husain-Syed F, Slutsky AS, Ronco C. Lung-kidney cross-talk in the critically ill patient. Am J Respir Crit Care Med. 2016;194(4):402–14.CrossRefPubMed
30.
Hall SV, Johnson EE, Hedley-Whyte J. Renal hemodynamics and function with continuous positive-pressure ventilation in dogs. Anesthesiology. 1974;41(5):452–61.CrossRefPubMed
31.
Mekontso Dessap A, Boissier F, Charron C, Begot E, Repesse X, Legras A, Brun-Buisson C, Vignon P, Vieillard-Baron A. Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: prevalence, predictors, and clinical impact. Intensive Care Med. 2016;42(5):862–70.CrossRefPubMed
32.
Troncy E, Francoeur M, Blaise G. Inhaled nitric oxide: clinical applications, indications, and toxicology. Can J Anaesth. 1997;44(9):973–88.CrossRefPubMed
33.
34.
Blanchard B, Dendane M, Gallard JF, Houee-Levin C, Karim A, Payen D. Oxidation, nitrosation, and nitration of serotonin by nitric oxide-derived nitrogen oxides: biological implications in the rat vascular system. Nitric Oxide. 1997;1(6):442–52.CrossRefPubMed
35.
Han M, Guo Z, Li G, Sang N. Nitrogen dioxide inhalation induces genotoxicity in rats. Chemosphere. 2013;90(11):2737–42.CrossRefPubMed
Metadata
Title
Inhaled nitric oxide and the risk of renal dysfunction in patients with acute respiratory distress syndrome: a propensity-matched cohort study
Authors
Sheng-Yuan Ruan
Hon-Yen Wu
Hsien-Ho Lin
Huey-Dong Wu
Chong-Jen Yu
Mei-Shu Lai
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2016
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-016-1566-0

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