Base administration or fluid bolus for preventing morbidity and mortality in preterm infants with metabolic acidosis

  • Review
  • Intervention




Metabolic acidosis in the early newborn period is associated with adverse outcomes in preterm infants. The most commonly used strategies to correct metabolic acidosis are intravascular infusion of base, for example sodium bicarbonate, and intravascular infusion of a fluid bolus, usually a crystalloid or colloid solution.


To determine the effect of either infusion of base or of a fluid bolus on mortality and adverse neurodevelopmental outcomes in preterm infants with metabolic acidosis.

Search methods

We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005), MEDLINE (1966 to January 2005), EMBASE (1980 to January 2005), CINAHL (1982 to January 2005).
The search was updated in 2010.

Selection criteria

Randomised or quasi-randomised controlled trials that evaluated the following treatments for preterm infants with metabolic acidosis:
1. Infusion of base versus no treatment;
2. Infusion of fluid bolus versus no treatment;
3. Infusion of base versus fluid bolus.

Data collection and analysis

We extracted the data using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors, and synthesis of data using relative risk and risk difference.

Main results

We found two small randomised controlled trails that fulfilled the eligibility criteria (Corbet 1977; Dixon 1999) and one unpublished pilot trial (Lawn 2005). Corbet 1977 compared treating infants with sodium bicarbonate infusion (N = 30) versus no treatment (N = 32) and did not find evidence of an effect on mortality [relative risk (RR) 1.39 (95% confidence interval 0.72 to 2.67)] or in the incidence of intra/periventricular haemorrhage [RR 1.24 (95% confidence interval 0.47 to 3.28)]. Addition of the unpublished data of Lawn 2005 does not change the overall estimate of effect on mortality [typical RR 1.45 (95%CI 0.82 to 2.56)]. Dixon 1999 compared treatment with sodium bicarbonate (N = 16) versus fluid bolus (N = 20). The primary outcome assessed was arterial blood pH/base excess two hours after the intervention. Other clinical outcomes were not reported. Neither trial assessed longer term neurodevelopmental outcomes.

Authors' conclusions

There is insufficient evidence from randomised controlled trials to determine whether infusion of base or fluid bolus reduces morbidity and mortality in preterm infants with metabolic acidosis. Further large randomised trials are needed.








我們使用Cochrane新生兒評價組的標準檢索方案。檢索包括Cochrane對照試驗中心註冊資料庫(CENTRAL,Cochrane 圖書館2005年第1期)、MEDLINE(1966年-2005年1月)、EMBASE(1980年−2005年1月)以及CINAHL(1982年- 2005年1月)。


評估以下治療代謝性酸中毒早產兒的隨機或半隨機對照試驗:1. 靜注鹼性液體與不治療進行比較。 2. 液體推注與不治 療進行比較。 3. 靜注鹼性液體與液體推注比較。




我們發現兩項小型隨機對照試驗符合合格標準(Corbet 1977; Dixon 1999)。 Corbet 1977年對使用碳酸氫鈉滴注治療的嬰兒(N = 30)與不治療(N = 32)進行比較,未發現影響死亡率[相對危險度1.39 (95% 可信區間0.72, 2.67),風險差0.12 (95% 可信區間−0.12,0.36)] 或腦室內/室週出血發生率[相對危險度1.24 (95% 可信區間0.47,3.28),風險差0.05 (95% 可信區間 0.16,0.25)] 的證據。 Dixon 1999年對碳酸氫鈉(N = 16)與推注液體(N = 20)治療進行比較。評估的主要結局是干預後二小時的動脈血pH/鹼剩餘。未報告其它臨床結局。沒有一項試驗評估遠期神經發育結局。





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










Cochrane Neonatal Review Groupの標準的検索戦略を用いた。これには、Cochrane Central Register of Controlled Trials(CENTRAL、コクラン・ライブラリ 2005年第1号)、MEDLINE(1966年から2005年1月まで)、EMBASE(1980年から2005年1月まで)、CINAHL(1982年から2005年1月まで)の検索があった。検索を2010年に更新した。




Cochrane Neonatal Review Groupの標準的方法を用いてデータを抽出した。2人のレビューアが別個に試験の質を評価し、データを抽出し、相対リスクとリスク差を用いてデータを合成した。


適格基準を満たした2件の小規模ランダム化比較試験(Corbet 1977;Dixon 1999)と1件の未発表パイロット試験(Lawn 2005)を見いだした。Corbet (1977)は、乳児に対する重炭酸ナトリウム輸注治療(N=30)と無治療(N=32)を比較し、死亡率[相対リスク(RR)1.39(95%信頼区間0.72~2.67)]や脳室内/脳室周囲出血の発生率[RR 1.24(95%信頼区間0.47~3.28)]に対する効果のエビデンスを見いださなかった。Lawn (2005)の未発表データを追加しても、死亡率に対する効果の総推定値は変わらなかった[typical RR 1.45(95%CI 0.82~2.56)]。Dixon (1999)は重炭酸ナトリウムによる治療(N=16)と輸液ボーラス投与(N=20)を比較した。評価した主要アウトカムは介入後2時間時点の動脈血pH/塩基過剰であった。他の臨床的アウトカムは報告されなかった。長期の神経発達アウトカムを評価した試験はなかった。




監  訳: 江藤 宏美,2011.7.12

実施組織: 厚生労働省委託事業によりMindsが実施した。

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Plain language summary

Base administration or fluid bolus for preventing morbidity and mortality in preterm infants with metabolic acidosis

Sick preterm infants are easily affected by reduced oxygen levels, cold and poor blood circulation. Their blood becomes acid with a build up of lactic acid (metabolic acidosis) that their kidneys cannot correct. Metabolic acidosis in preterm infants may cause bleeding in the brain (intra or periventricular haemorrhage) and problems with longer-term neurodevelopment (including hearing, vision and cognitive ability). Solutions of the alkaline sodium bicarbonate or tris-(hydroxymethyl) amino methane (THAM) can be given to correct the acidity. These solutions are more concentrated than blood (hyperosmolar), which can change blood flow and cause bleeding in the brain, especially when given rapidly or in large quantities. The rationale for their use is to prevent the adverse outcomes that are associated with acidosis in preterm infants.
The review authors searched the medical literature and found two small randomised controlled trials (98 infants) measuring/investigating the benefit of either infusion of base or of a fluid injection (bolus) in the treatment of preterm infants with metabolic acidosis. Infants were given an infusion of sodium bicarbonate on the first day of postnatal life, compared with no treatment or a fluid bolus with albumin. There was no clear evidence that the base infusion corrected metabolic acidosis more effectively. One of the studies (62 newborns) reported no difference in early deaths at one week or in the incidence of bleeding in the brain. Neither study assessed longer-term neurological disabilities.