Use of inhaled nitric oxide in acute respiratory failure patients with low blood oxygen does not improve survival

Afshari A, Brok J, Møller AM, Wetterslev J

Published Online:

December 8, 2010

There is a lack of knowledge from previous research to support the use of inhaled nitric oxide (INO) to improve the survival of patients with acute respiratory failure and low blood oxygen levels. In the present systematic review we set out to assess the benefits and harms of its use in patients with acute respiratory failure. We identified 14 randomized trials comparing INO with placebo or no intervention. We could not identify any beneficial effect of INO on our predefined outcomes or in any subgroups of patients. Despite signs of initial improvement, INO does not appear to improve survival and might be hazardous since it may cause kidney function impairment. Our analysis does not indicate reduced cost or decreased length of stay in either an intensive care unit or hospital.

Abstract (click to read)

Background:

Acute hypoxaemic respiratory failure (AHRF), defined as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), are critical conditions. AHRF results from a number of systemic conditions and is associated with high mortality and morbidity in all ages. Inhaled nitric oxide (INO) has been used to improve oxygenation but its role remains controversial.

Objectives:

To systematically assess the benefits and harms of INO in critically ill patients with AHRF.

Search strategy:

Randomized clinical trials (RCTs) were identified from electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 1); MEDLINE; EMBASE; Science Citation Index Expanded; International Web of Science; CINAHL; LILACS; and the Chinese Biomedical Literature Database (up to 31st January 2010). We contacted trial authors, authors of previous reviews, and manufacturers in the field.

Selection criteria:

We included all RCTs, irrespective of blinding or language, that compared INO with no intervention or placebo in children or adults with AHRF.

Data collection and analysis:

Two authors independently abstracted data and resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as relative risks (RR) with 95% confidence intervals (CI). Our primary outcome measure was all cause mortality. We performed subgroup and sensitivity analyses to assess the effect of INO in adults and children and on various clinical and physiological outcomes. We assessed the risk of bias through assessment of trial methodological components and the risk of random error through trial sequential analysis.

Main results:

We included 14 RCTs with a total of 1303 participants; 10 of these trials had a high risk of bias. INO showed no statistically significant effect on overall mortality (40.2% versus 38.6%) (RR 1.06, 95% CI 0.93 to 1.22; I2 = 0) and in several subgroup and sensitivity analyses, indicating robust results. Limited data demonstrated a statistically insignificant effect of INO on duration of ventilation, ventilator-free days, and length of stay in the intensive care unit and hospital. We found a statistically significant but transient improvement in oxygenation in the first 24 hours, expressed as the ratio of partial pressure of oxygen to fraction of inspired oxygen and the oxygenation index (MD 15.91, 95% CI 8.25 to 23.56; I2 = 25%). However, INO appears to increase the risk of renal impairment among adults (RR 1.59, 95% CI 1.17 to 2.16; I2 = 0) but not the risk of bleeding or methaemoglobin or nitrogen dioxide formation.

Authors' conclusions:

INO cannot be recommended for patients with AHRF. INO results in a transient improvement in oxygenation but does not reduce mortality and may be harmful.

This record should be cited as:

Afshari A, Brok J, Møller AM, Wetterslev J. Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) and acute lung injury in children and adults. Cochrane Database of Systematic Reviews 2010, Issue 7. Art. No.: CD002787. DOI: 10.1002/14651858.CD002787.pub2

Assessed as up to date:

June 8, 2010

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Primary Review Group:

Anaesthesia Group

Health topics:

Anaesthesia & pain control > Post-anaesthetic unit/intensive care unit > Respiratory care

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Independent high-quality evidence for health care decision making

Use of inhaled nitric oxide in acute respiratory failure patients with low blood oxygen does not improve survival

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