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At the age of 4 hours, a tachypnoeic, well hydrated, well perfused, and normotensive 34 week preterm neonate 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.
Structured clinical question
In the absence of asphyxia or hypovolaemia in a newborn infant with metabolic acidosis [patient] does an intravenous bolus of normal saline or albumin [intervention] improve the following [outcomes]: pH, base deficit, mortality, morbidity, length of hospital stay, neurodevelopmental disability?
The outcomes were defined as follows:
Mortality = neonatal mortality and mortality to discharge.
Morbidity = peri/intraventricular haemorrhage of any grade, periventricular leucomalacia, patent ductus arteriosus, renal impairment (raised serum creatinine, oliguria), air leak, chronic lung disease (at 28 postnatal days or near term postmenstrual age), necrotising enterocolitis, or retinopathy of prematurity of any grade.
Neurodevelopmental disability = neurological abnormality including cerebral palsy, developmental delay, or sensory impairment.
Search strategy and outcome
Exclusion criteria: trials including infants with clinically suspected poor perfusion (e.g. low blood pressure, poor cutaneous perfusion) or trials including unselected newborn infants (not known to have metabolic acidosis).
Secondary sources—Cochrane Library (Issue 3, 2003): one protocol—two control trials in CENTRAL, of which one was relevant.
PubMed (1975–2003): search words—(“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: 87 papers, of which two were relevant (one already retrieved by Cochrane).
SumSearch—96 articles, one protocol (already retrieved by PubMed and Cochrane).
Search results—three articles found, two relevant (already retrieved by PubMed and Cochrane).
See table 2.
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), neither 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 therefore remains 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.3 A Cochrane protocol4 reviewing base administration or fluid bolus for preventing morbidity and mortality in preterm infants with metabolic acidosis is currently underway and may provide the appropriate answers.
CLINICAL BOTTOM LINE
The effect of administration of an 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.
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