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.

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.

Read the full abstract...

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 strategy: 

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.