Inhaled nitric oxide for the management of pulmonary hypertension after surgery in infants and children with congenital heart disease

Bizzarro M, Gross I

Published Online:

October 8, 2008

Although inhaled nitric oxide (iNO) has been studied as a postsurgical therapy in children with heart disease to assist recovery, this review showed no benefits with its use.
Elevated pulmonary arterial pressure, or pulmonary hypertension, can affect various patient populations and cause significant morbidity and mortality. In particular, infants and children with congenital heart disease necessitating surgical repair can develop life-threatening pulmonary hypertensive crises in the postoperative period. Inhaled nitric oxide is a therapy which causes a selective reduction in pulmonary arterial pressures and, therefore, may have a treatment benefit in this population. This review examined the results of four randomised controlled trials comparing iNO with placebo or conventional management in the postoperative treatment of infants and children with congenital heart disease. No clinical benefits were apparent with the use of iNO. In addition, no significant alterations in haemodynamics were observed comparing treatment and control groups.

Abstract (click to read)

Background:

Nitric oxide (NO) is a prevalent molecule in humans responsible for many physiologic activities including pulmonary vasodilation. An exogenous, inhaled form (iNO) exists that mimics this action without affecting systemic blood pressure. This therapy has been implemented in the treatment of pulmonary hypertension. This review examines the efficacy of iNO in the postoperative management of infants and children with congenital heart disease (CHD).

Objectives:

To compare the effects of postoperative iNO versus placebo or conventional management , or both, on infants and children with CHD. The primary outcome was mortality. Secondary outcomes included length of hospital stay; neurodevelopmental disability; number of pulmonary hypertensive crises (PHTC); changes in mean pulmonary arterial pressure (MPAP), mean arterial pressure (MAP), and heart rate (HR); changes in oxygenation measured as the ratio of arterial oxygen tension (PaO2) to fraction of inspired oxygen (FiO2); and measurement of maximum methaemoglobin level as a marker of toxicity.

Search strategy:

We originally searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2004, Issue 3), MEDLINE (1966 to 2004), and EMBASE (1980 to 2004). In this updated version we extended the CENTRAL search to 2007, Issue 4 of The Cochrane Library, and MEDLINE and EMBASE through to November 1, 2007. We included abstracts and all languages.

Selection criteria:

We included randomized and quasi-randomized controlled trials comparing iNO with placebo or conventional management, or both. Trials included only children with CHD requiring surgery complicated by pulmonary hypertension.

Data collection and analysis:

Data were collected on mortality; number of PHTC; changes in MPAP, MAP, HR, and PaO2:FiO2; and maximum methaemoglobin level. Data on long-term mortality, neurodevelopmental disability, and length of hospital stay were unavailable. We performed subgroup analysis by method of control (placebo or conventional management).

Main results:

We included four randomized trials and observed no differences in mortality (P = 0.50); PHTC (P = 0.79); changes in MPAP (P = 0.36), MAP (P = 0.40), HR (P = 1.00), or PaO2:FiO2 (P = 0.46). There was a significant increase in the methaemoglobin level (P < 0.00001) in patients treated with iNO, although levels did not reach toxicity.

Authors' conclusions:

We observed no differences with the use of iNO in the outcomes reviewed. No data were available for several clinical outcomes including long-term mortality and neurodevelopmental outcome. We found it difficult to draw valid conclusions given concerns regarding methodologic quality, sample size, and heterogeneity.

This record should be cited as:

Bizzarro M, Gross I. Inhaled nitric oxide for the postoperative management of pulmonary hypertension in infants and children with congenital heart disease. Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD005055. DOI: 10.1002/14651858.CD005055.pub2

Assessed as up to date:

November 6, 2007

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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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Inhaled nitric oxide for the management of pulmonary hypertension after surgery in infants and children with congenital heart disease

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