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Inhaled nitric oxide therapy and risk of renal dysfunction: a systematic review and meta-analysis of randomized trials.

Ruan SY, Huang TM, Wu HY, Wu HD, Yu CJ, Lai MS - Crit Care (2015)

Bottom Line: 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).The risk in pediatric population is unknown owing to limited data.

View Article: PubMed Central - PubMed

Affiliation: Institute of Epidemiology and Preventive Medicine, National Taiwan University, No.17 Xu-Zhou Road, Taipei, 10020, Taiwan. syruan@ntu.edu.tw.

ABSTRACT

Introduction: Inhaled 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.

Methods: A 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.

Results: Ten 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).

Conclusions: The 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.

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Related in: MedlinePlus

Bubble plot with fitted meta-regression line depicting the relationship between the risk of renal dysfunction and cumulative dose of inhaled nitric oxide (Ino).
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Fig5: Bubble plot with fitted meta-regression line depicting the relationship between the risk of renal dysfunction and cumulative dose of inhaled nitric oxide (Ino).

Mentions: To test the dose-response relationship between iNO and the risk of AKI, we performed stratified analysis by duration and dosage of iNO therapy. Prolonged use of iNO (>7 days) significantly increased the risk of AKI (RR, 1.55, 95% CI, 1.15 to 2.09, P = 0.005, four studies), whereas short-term use did not (RR, 0.90, 95% CI, 0.49 to 1.67, P = 0.75, six studies). Notably, the four studies involving the prolonged use of iNO are all ARDS studies. Table 4 summarizes the risk of renal dysfunction for different iNO exposure levels. We classified the included studies into three groups according to the cumulative dose in the stratified analysis. High cumulative dose of iNO significantly increased the risk of renal dysfunction but medium and low cumulative doses did not (Table 4). Figure 5 depicts the relationship between the risk of renal dysfunction and cumulative dose of iNO. Visual inspection suggested a possible association between the cumulative dose and risk of renal dysfunction but statistical test by meta-regression analysis was not significant due to small sample size (P = 0.10).Table 4


Inhaled nitric oxide therapy and risk of renal dysfunction: a systematic review and meta-analysis of randomized trials.

Ruan SY, Huang TM, Wu HY, Wu HD, Yu CJ, Lai MS - Crit Care (2015)

Bubble plot with fitted meta-regression line depicting the relationship between the risk of renal dysfunction and cumulative dose of inhaled nitric oxide (Ino).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4384233&req=5

Fig5: Bubble plot with fitted meta-regression line depicting the relationship between the risk of renal dysfunction and cumulative dose of inhaled nitric oxide (Ino).
Mentions: To test the dose-response relationship between iNO and the risk of AKI, we performed stratified analysis by duration and dosage of iNO therapy. Prolonged use of iNO (>7 days) significantly increased the risk of AKI (RR, 1.55, 95% CI, 1.15 to 2.09, P = 0.005, four studies), whereas short-term use did not (RR, 0.90, 95% CI, 0.49 to 1.67, P = 0.75, six studies). Notably, the four studies involving the prolonged use of iNO are all ARDS studies. Table 4 summarizes the risk of renal dysfunction for different iNO exposure levels. We classified the included studies into three groups according to the cumulative dose in the stratified analysis. High cumulative dose of iNO significantly increased the risk of renal dysfunction but medium and low cumulative doses did not (Table 4). Figure 5 depicts the relationship between the risk of renal dysfunction and cumulative dose of iNO. Visual inspection suggested a possible association between the cumulative dose and risk of renal dysfunction but statistical test by meta-regression analysis was not significant due to small sample size (P = 0.10).Table 4

Bottom Line: 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).The risk in pediatric population is unknown owing to limited data.

View Article: PubMed Central - PubMed

Affiliation: Institute of Epidemiology and Preventive Medicine, National Taiwan University, No.17 Xu-Zhou Road, Taipei, 10020, Taiwan. syruan@ntu.edu.tw.

ABSTRACT

Introduction: Inhaled 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.

Methods: A 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.

Results: Ten 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).

Conclusions: The 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.

Show MeSH
Related in: MedlinePlus