Routine administration of intravenous calcium during exchange blood transfusion for treatment of severe neonatal hyperbilirubinaemia: a systematic review of quantitative evidence protocol.

REVIEW QUESTION/OBJECTIVE: The objective of this review is to assess the effectiveness of intravenous calcium given during exchange blood transfusion (EBT) in neonates.More specifically, the objectives of the review are to determine whether:

BACKGROUND

Neonatal hyperbilirubinaemia is an abnormally high level of bilirubin in the circulating blood, resulting in clinically visible icterus or jaundice. A serum bilirubin level above 5 mg per dL (86 μmol per L) is a frequently encountered problem worldwide and is a common reason for neonates to present to the emergency department.Unconjugated bilirubin is toxic to infants' brains when the concentration exceeds a certain level. An unconjugated serum bilirubin concentration at toxicity level is described as 'severe hyperbilirubinaemia'. The concentrations that define toxic level vary, depending on the gestational age of the neonates and fetal maturity.Severe hyperbilirubinaemia can cause encephalopathy if not promptly treated, with significant complications such as athetoid cerebral palsy, sensorineural hearing loss, paralysis of upward gaze, dental enamel dysplasia and death.Recent reports indicate that these conditions, though rare, are still occurring despite the availability of efficient methods for treatment of hyperbilirubinaemia and its prevention.These complications can be prevented if the level of bilirubin is reduced rapidly with exchange blood transfusion.Exchange blood transfusion (EBT) is the most rapid and effective method for lowering serum bilirubin concentrations, but it is rarely needed when intensive phototherapy is effective.In the presence of hemolytic disease, severe anaemia, or a rapid rise in the total serum bilirubin level (greater than 1 mg per dL per hour in less than six hours), EBT is the recommended treatment. EBT also removes partially hemolyzed and antibody-coated erythrocytes and which is then replaced with uncoated donor red blood cells. If intensive phototherapy fails to lower the bilirubin level, then EBT is always considered as the next line of treatment in any newborn with non-hemolytic jaundice.Complications of EBT can include hypocalcaemia, seizures and even death within 24 hours. The potential seriousness of these complications makes clinicians consider intensive phototherapy before EBT.However, the option of intensive phototherapy may not be feasible and could be quite ineffective in resource limited settings where the required facilities and electrical power supply are inadequate. Under these circumstances neonates with severe hyperbilirubinaemia will most likely be treated with EBT.Exchange transfusion of blood collected with acid-citrate-dextrose (ACD) containing bags may produce hypocalcaemia.To decrease the morbidity from chelation of divalent cations by citrate, routine administration of calcium gluconate during EBT was advocated,but tetany, convulsion and death may still occur when ACD blood is used.However, there are controversies about the effectiveness of intravenous calcium in reducing these calcium-related morbidities. A preliminary search for systematic reviews in MEDLINE, the Cochrane Library, Campbell Library and the Joanna Briggs Database of Systematic Reviews and Implementation Reports failed to identify any existing publications on this topic. As a result, this review will examine current quantitative evidence regarding the effectiveness of routine administration of intravenous calcium during EBT in the treatment of severe hyperbilirubinaemia, with specific aim to describe incidences of hypocalcaemia, seizures and deaths after such a transfusion.