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Nitric oxide for respiratory failure in infants born at or near term

  • Review
  • Intervention

Authors


Abstract

Background

Nitric oxide is a major endogenous regulator of vascular tone. Inhaled nitric oxide gas has been investigated as a treatment for persistent pulmonary hypertension of the newborn.

Objectives

To determine whether treatment of hypoxaemic term and near-term newborn infants with inhaled nitric oxide (iNO) improves oxygenation and reduces the rates of death, the requirement for extracorporeal membrane oxygenation (ECMO), or affects long term neurodevelopmental outcomes.

Search methods

Electronic and hand searching of pediatric/neonatal literature and personal data files. In addition we contacted the principal investigators of articles which have been published as abstracts to ascertain the necessary information.

Selection criteria

Randomized and quasi-randomized studies of inhaled nitric oxide in term and near term infants with hypoxic respiratory failure. Clinically relevant outcomes, including death, requirement for ECMO, and oxygenation.

Data collection and analysis

Trial reports were analysed for methodologic quality using the criteria of the Cochrane Neonatal Review Group. Results of mortality, oxygenation, short term clinical outcomes (particularly need for ECMO), and long term developmental outcomes were tabulated.

Statistics: For categorical outcomes, typical estimates for relative risk and risk difference were calculated. For continuous variables, typical estimates for weighted mean difference were calculated. 95% confidence intervals were used. A fixed effect model was assumed for meta-analysis.

Main results

Fourteen eligible randomized controlled studies were found in term and near term infants with hypoxia.
Seven of the trials compared iNO to control (placebo or standard care without iNO) in infants with moderate or severe severity of illness scores.
Four of the trials compared iNO to control, but allowed back up treatment with iNO if the infants continued to satisfy the same criteria for severity of illness after a defined period of time.
Two trials enrolled infants with moderate severity of illness score (OI or AaDO2) and randomized to immediate iNO treatment or iNO treatment only if they deteriorated to more severe criteria.
One trial studied only infants with congenital diaphragmatic hernia (Ninos 1997), and one trial enrolled both preterm and term infants (Mercier 1998), but reported the majority of the results separately for the two groups.

Inhaled nitric oxide appears to improve outcome in hypoxaemic term and near term infants by reducing the incidence of the combined endpoint of death or need for ECMO. The reduction seems to be entirely a reduction in need for ECMO; mortality is not reduced. Oxygenation improves in approximately 50% of infants receiving nitric oxide. The Oxygenation Index decreases by a (weighted) mean of 15.1 within 30 to 60 minutes after commencing therapy and PaO2 increases by a mean of 53 mmHg. Whether infants have clear echocardiographic evidence of persistent pulmonary hypertension of the newborn (PPHN) or not does not appear to affect outcome.

The outcome of infants with diaphragmatic hernia was not improved; indeed there is a suggestion that outcome was slightly worsened.

The incidence of disability, incidence of deafness and infant development scores are all similar between tested survivors who received nitric oxide or not.

Authors' conclusions

On the evidence presently available, it appears reasonable to use inhaled nitric oxide in an initial concentration of 20 ppm for term and near term infants with hypoxic respiratory failure who do not have a diaphragmatic hernia.

摘要

背景

一氧化氮用於有呼吸衰竭之足月或接近足月兒

一氧化氮是調節血管張力的主要內生性調控者。吸入性一氧化氮已被研究用來治療新生兒的持續性肺高壓。

目標

本篇主要是要探討吸入性一氧化氮用於足月及接近足月的缺氧嬰孩身上,對改善其血中氧合程度、減少死亡率、使用體外循環機 (ECMO) 的需求及長期的神經學預後之影響。

搜尋策略

運用電腦及人工尋找兒童和新生兒相關文獻及個人資料檔案。除此之外,我們與文章被發表的主要研究者連絡以取得需要的相關資料。

選擇標準

選擇在有缺氧性呼吸衰竭之足月產及接近足月產兒身上,隨機或半隨機選用吸入性一氧化氮的研究。臨床上有關的預後包括死亡、是否需要體外循環機及氧合程度。

資料收集與分析

這些報告是藉由Cochrane Neonatal Review Group的定義來分析。關於死亡率、氧合程度、短期臨床預後(尤其是對體外循環機的需求),及長期發展預後都被製成圖表。統計資料:針對類別性的預後,計算相對風險及風險差異的典型預測值。針對連續性變數,計算加權平均差的典型預測值。在此使用95%信賴區間,並設定一個固定影響的模式來做後設研究(meta analysis)。

主要結論

有十四篇關於足月及接近足月產缺氧嬰兒的研究被搜尋到,這些都是符合規定且隨機分配的研究。其中七篇是有關中度或重度疾病嚴重度的嬰孩分別使用吸入性一氧化氮及對照組(安慰劑及沒有使用一氧化氮的標準照護)的比較。四篇是比較吸入性一氧化氮及對照組,但是如果病嬰經過一段時間的治療,仍持續維持在相同的疾病嚴重度,就可以採用吸入性一氧化氮的治療。其中兩篇是將中等嚴重度(OI or AaDO2)的病嬰隨機分為立即使用吸入性一氧化氮,或當他們臨床狀況變差才使用一氧化氮。有一篇是只探討有橫膈疝氣的嬰兒 (Ninos 1997) , 有一篇同時討論早產兒及足月兒 (Mercier 1998) ,但是關於主要結果是分開討論的。吸入性一氧化氮似乎能藉著減少死亡及需要使用體外循環機的機會來改善缺氧性足月兒及接近足月兒的預後。主要減少的是使用體外循環機的機率,死亡率並沒有減少。在使用一氧化氮者有50%其血中氧合程度得到改善。氧合係數在使用一氧化氮治療30 – 60分鐘後平均可下降15.1,而血中氧氣濃度平均可上升53mmHg。一個嬰孩是否有明確心臟超音波上持續肺高壓的證據並不會影響結果。有橫膈疝氣的嬰孩其預後並沒有因此改善,甚至有更差的可能。關於殘障或耳聾的發生率、嬰兒發展評分,無論是否使用一氧化氮的存活者,兩者的結果相當。

作者結論

由可獲得的證據顯示,在一個無橫膈疝氣疾病但是有缺氧性呼吸衰竭的新生兒,無論是足月或是接近足月產,使用初始劑量20ppm的一氧化氮是合理的。

翻譯人

本摘要由馬偕醫院曾至凡翻譯。

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

總結

在一些有呼吸衰竭且對一般支持療法無反應之足月產兒身上,吸入性一氧化氮是相當安全並有幫助的。 吸入性一氧化氮對那些有呼吸衰竭且對一般支持療法無反應之足月產兒是有幫助的。研究指出吸入性一氧化氮可以增加氧合程度及減少使用需高度技術性及具侵入性的體外循環機的機率。不幸的是,吸入性一氧化氮在因橫膈疝氣造成呼吸衰竭的嬰孩並無助益。使用吸入性一氧化氮目前並未發現有短期或長期的副作用。

Plain language summary

Nitric oxide for respiratory failure in infants born at or near term

Inhaled nitric oxide is safe and can help some full term babies suffering respiratory failure who have not responded to the usual methods of support. Inhaled nitric oxide can help some full term babies suffering respiratory failure who have not responded to the usual methods of support. Trials have shown that inhaled nitric oxide can increase the levels of oxygen in babies' blood and reduce the need for extracorporeal membrane oxygenation (ECMO), a highly technical and invasive therapy. Unfortunately, these benefits of inhaled nitric oxide care not seen in babies whose respiratory failure is due to a diaphragmatic hernia. Inhaled nitric oxide has not shown any short or longer term adverse effects.

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