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Three Part Question

In [the absence of asphyxia or hypovolaemia in a newborn infant with metabolic acidosis] does [an intravenous bolus of normal saline or albumin] improve [the following: pH, base deficit, mortality, morbidity, length of hospital stay, neurodevelopmental disability]?

Clinical Scenario

At the age of 4 hours, a tachypnoeic, well hydrated, well perfused and normotensive 34-week preterm neonate born develops a metabolic acidosis (arterial pH 7.25, base deficit minus 10 mmol/L). There was no history of perinatal blood loss or sepsis risk factors. No resuscitation was required at birth, and the cord blood pH was 7.3. According to departmental protocol, volume expansion with an intravenous bolus of 10-20 ml/kg of normal saline or 4.5% albumin is advised. You wonder as to the value of this volume expansion.

Search Strategy

PubMed (1975-2003). Cochrane Library, Issue 3, 2003. SumSearch.
("metabolic acidosis") AND ("therapy" OR "fluid" OR "albumin" OR "colloid" OR "sodium chloride") using Clinical Queries methodological filters category (therapy, prognosis) and emphasis (sensitivity, specificity). Limits-Newborn.

Search Outcome

Medline: 87 papers, of which 2 were relevant.
Cochrane Library (Issue 3, 2003): 1 protocol – Two control trials in CENTRAL, of which 1 was relevant.
SumSearch – 96 articles, 1 protocol
2 articles were deemed relevant (all the above relevancies picked up by Pubmed)

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Dixon et al, 1999, UK	Randomised control trial using 10 ml/kg 4.5% albumin (20 babies) versus sodium bicarbonate (16 neonates) with metabolic acidosis without hypotension	RCT (level 1b)	Improvement in pH	Change in median pH following bicarbonate (0.10 units) was over twice that in the albumin group (0.04 units)*	In normotensive neonates, bicarbonate was more effective than albumin to correct the metabolic acidosis
Belgaumkar et al, 1998	10 ml/kg 4.5% albumin infusion in 26 ventilated normotensive neonates with metabolic acidosis	Retrospective cohort (level 4)	Improvement in pH and base deficit	Improvement in pH and base deficit up to 6 hours later (p<0.05), no change in blood pressure*

Comment(s)

* Results did not allow risk reduction and NNT to be calculated. Previous studies of administering parenteral fluid and/or alkali therapy to neonates with metabolic acidosis have included infants with clinically suspected poor perfusion (e.g. low blood pressure, poor cutaneous perfusion). Other studies of the effect of early volume expansion on mortality and morbidity have included unselected preterm infants not known to have metabolic acidosis. We found only two studies addressing the benefit of administering intravenous bolus of albumin or normal saline to normovolaemic neonates with metabolic acidosis. They do not however provide a clear answer to the main question of this article in view of few methodological weaknesses. The first study was not blinded. The second study was not randomised and no placebo group was available. Although both studies reported an improvement in the pH and base deficit with volume expansion (although less marked than with bicarbonate), none of these reports included the following outcomes: survival, morbidity, length of hospital stay or neurodevelopment disability. The effect of the resulting correction of the metabolic acidosis on those clinically important outcomes remains therefore unknown. In the absence of outcome-based data, there is currently no evidence to support the routine administration of intravenous bolus of albumin or normal saline to normovolaemic neonates with metabolic acidosis. In addition, as administration of volume expansion was found to be associated with increased mortality in preterm neonates, it is recommended that, in the absence of clear hypovolaemia, caution should be exercised when prescribing volume expansion (Ewer et al). A Cochrane protocol (Lawn and Weir) reviewing base administration or fluid bolus for preventing morbidity and mortality in pre-term infants with metabolic acidosis is currently underway and may provide the appropriate answers.

Clinical Bottom Line

The effect of administration of intravenous bolus of albumin or normal saline to normovolaemic neonates with metabolic acidosis on mortality, morbidity and neurodevelopmental outcome in this group of infants is not known. There is no evidence to support the benefit of this therapy for such infants.

References

1. Dixon H, Hawkins K, Stephenson T. Comparison of albumin versus bicarbonate treatment for neonatal metabolic acidosis. Eur J Pediatr 1999;158(5):414-5.
2. Belgaumkar A, Greenough A, Kavvadia V, et al. Metabolic acidosis: response to albumin infusion. Eur J Pediatr 1998;157:520-1.
3. Lawn CJ, Weir FJ. Base administration or fluid bolus for preventing morbidity and mortality in pre-term infants with metabolic acidosis (Protocol for a Cochrane Review). In: The Cochrane Library, Issue 3, 2003. Oxford: Update Software. Chichester, UK: John Wiley & Sons, Ltd.
4. Ewer AK, Tyler W, Francis A, et al. Excessive volume expansion and neonatal death in preterm infants born at 27-28 weeks gestation. Paediatr Perinat Epidemiol 2003;17(2):180-6.