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

  • Review
  • Intervention

Authors


Abstract

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 methods

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.

摘要

背景

吸入性一氧化氮應用於先天性心臟病之嬰兒與兒童的術後肺動脈高壓

一氧化氮是人體中分布相當廣泛的分子並且負責許多生理功能包括肺動脈的血管擴張。外生性、吸入型的一氧化氮也具有類似的功效,但不會影響全身的血壓。吸入性一氧化氮的治療在過去已經應用於治療肺動脈高壓。本篇文章將回顧吸入性一氧化氮的功效,主要應用於處理先天性心臟病嬰兒與兒童的術後肺動脈高壓。

目標

比較先天性心臟病的病童於術後使用吸入性一氧化氮與吸入性安慰劑、傳統治療或是安慰劑與傳統治療合併使用的功效。主要結果是探討死亡率,次要結果是評估住院天數,神經發展狀況,發生肺動脈高壓危機的次數,比較平均肺動脈壓、平均血壓與心跳的改變,分析血氧分壓與吸入的氧氣分壓比值的改變,並測量變性血紅素的量當作中毒測量因子。

搜尋策略

我們從以下的資料庫搜尋相關資料: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2004, Issue 3), MEDLINE (1966to 2004), and EMBASE (1980 to 2004). 在這個更新版本,我們擴展到以下資料: the CENTRAL search to 2007, Issue4 of The Cochrane Library, and MEDLINE and EMBASE through to November 1, 2007. 這些搜尋的資料並包括所有語言。

選擇標準

我們囊括了隨機與半隨機對照試驗,比較吸入性一氧化氮與吸入性安慰劑、傳統治療或是安慰劑與傳統治療合併使用的功效。這些試驗侷限於先天性心臟病的孩童,在接受手術後產生肺動脈高壓之併發症。

資料收集與分析

資料收集包括:死亡率,發生肺動脈高壓危機的次數,平均肺動脈壓、平均血壓、心跳以及動脈血氧分壓與吸入氧氣分壓比值(PaO2:FiO2)的改變,以及最大變性血紅素的數值。關於長期死亡率,神經發展的狀況或是住院天數的結果並無法從資料中取得。我們以方法控制的方式進行分組分析(安慰劑與傳統治療)。

主要結論

我們收集到四個隨機對照試驗並觀察到以下的情況並無顯著差異:死亡率(P = 0.50),肺動脈高壓危機次數(P = 0.79),平均肺動脈壓的改變(P = 0.36),肺動脈壓(P = 0.40),心跳(P = 1.00)以及PaO2:FiO2(P = 0.46)。但血中異化血紅素的量在吸入性一氧化氮的的病患身上是有顯著增加的(P<0.00001),但是濃度尚未到達中毒劑量。

作者結論

我們從文章中觀察到使用吸入性一氧化氮的預後結果並無顯著差異。至於與臨床相關的結果,例如長期死亡率、神經發展預後,並無足夠的資料足以分析。我們認為根據分析方法學上的品質,樣本大小與異質性很難得出正確的結論。

翻譯人

本摘要由慈濟醫院李佳玲翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

吸入性一氧化氮用來處理先天性心臟病之嬰兒與兒童之術後肺動脈高壓。雖然說吸入性一氧化氮已經被使用於心臟病童的術後復原,但根據文章的回顧,吸入性一氧化氮並無任何優點。肺動脈壓升高或是肺性高血壓可能影響不同病患族群並可能造成重大併發症及死亡。特別是患有先天性心臟病且需要手術治療的嬰兒與兒童,容易在術後發生威脅生命的肺動脈高壓危機。吸入性一氧化氮能夠有選擇性的降低肺動脈壓;因此,在這一群病患應該能有所助益。這篇回顧性文章檢視四篇隨機對照試驗,比較先天性心臟病嬰兒與兒童於術後吸入性一氧化氮與吸入性安慰劑或傳統治療的結果。使用一氧化氮並沒有臨床上顯著的優點。除此之外,無論是在治療組或是控制組,兩組在血液動力學上並無任何顯著差異。

Plain language summary

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

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.