Hyperbilirubinaemia: Trials of albumin infusion pre-exchange transfusion for severe neonatal jaundice have reported heterogeneous results. Chan et al [10] compared albumin 1 g/kg versus no treatment pre-exchange in 42 infants with severe neonatal jaundice and reported no difference in albumin-binding capacity, bilirubin, albumin or red cell bilirubin at pre- and one-hour post-albumin infusion in the primed infants. All infants received an exchange transfusion. Shahian et al [11] in 50 infants with severe jaundice compared 5 mL/kg of albumin 20% (1 g/kg) to no treatment pre-exchange transfusion. Bilirubin concentration was lower than at 6 and 12 hours post-exchange (P<0.001), duration of phototherapy was reduced (8.6 vs. 25 hours; P<0.001) and none of 25 needed repeat exchange transfusion compared to 4/25 in the control group.
Dash et [12] compared 5 mL/kg of 20% human albumin (n=23) versus saline (n=27) infusion one hour prior to exchange transfusion. Phototherapy duration was not different [Median 29 vs. 33 hours; P=0.76], serial changes in total serum bilirubin following exchange transfusion and need for repeat exchange transfusion were similar (2/23 versus 2/27).
A systematic review [13] compared IV fluid supplementation versus no fluid supplementation in newborn infants with unconjugated hyperbilirubinaemia who required phototherapy. Duration of phototherapy was significantly shorter for fluid-supplemented infants, (MD -10.70 hours, 95%CI -15.55 to -5.85; participants = 218; studies = 3; I² = 67%) and fluid-supplemented infants were less likely to require exchange transfusion (RR 0.39, 95% CI 0.21 to 0.71; participants = 462; studies = 6; I² = 72%). There was no evidence that IV fluid supplementation affected important clinical outcomes such as bilirubin encephalopathy, kernicterus or cerebral palsy.
Conclusion: Heterogeneous evidence suggests intravenous fluid treatment may reduce serum bilirubin levels and exchange transfusion requirements in infants with unconjugated hyperbilirubinaemia, although there is no evidence of a reduction in bilirubin encephalopathy, kernicterus or cerebral palsy [11, 13]. [LOE I GOR C] There is no evidence that albumin solutions are more efficacious than saline for reducing bilirubin or repeat exchange transfusion in infants undergoing exchange transfusion for hyperbilirubinaemia [12]. [LOE II GOR C]
Safety
There are insufficient data from RCTs in newborn infants to determine the safety of albumin infusion for any indication, although no adverse events attributable to albumin infusion were reported in trials in newborn infants [3, 14, 15]. Human albumin contains no preservatives and undergoes a rigorous pasteurisation process to ensure pathogen inactivation. It does not contain isoagglutinins or blood group substances; hence the risk of minor or major incompatibility is impossible. Additionally, hypersensitivity reactions such as flushing, urticaria, fever and nausea rarely occur following its administration, since albumin preparations are considered non-immunogenic [5]. However, possible harms associated with albumin infusion in neonates include fluid overload (pulmonary oedema, impaired gas exchange, worsening oxygenation, chronic lung disease, patent ductus arteriosus, myocardial dysfunction especially for infants with birth asphyxia), neurological injury (cerebral oedema, intraventricular haemorrhage due to rapid bolus administration), salt loading and fluid retention, and higher cost compared with crystalloids [5].
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