Neonatology
Kernicterus
(Acute Bilirubin Encephalopathy)
Jon Palmer, VMD, Associate Professor, New Bolton Center, University of Pennsylvania
Kernicterus is an acute toxicity caused by bilirubin. Unbound, unconjugated bilirubin readily enters neurons and forms a deposit resulting in neurotoxicity and irreversible damage.
The amount of unbound unconjugated bilirubin increases as total unconjugated bilirubin increases. But the amount of unbound unconjugated bilirubin can’t be predicted by measuring the unconjugated bilirubin level, since it also depends on the availability of binding sites. The availability of binding sites depends on the albumin level, pH, and other substances (usually drugs) displacing bound bilirubin. Although there may be a danger of kernicterus as the total bilirubin climbs above 20 mg/dl, kernicterus is usually not seen in foals until the bilirubin is in the mid to high 20’s or 30’s.
Signs
Signs include extensor rigidity, a stiff gate, opisthotonus, and tonic seizures often with facial grimace. Seizures increase in severity and are not usually responsive to phenobarbital or diazepam. As the disease becomes established, the foal may be hyperresponsive, continue to have a stilted gate, develop head/body tremors, walk in circles, head press and have propulsive walking.
Although the signs from kernicterus tend to be permanent, the hemolytic anemia causing the hyperbilirubinemia may be severe enough to result in HIE. Neurologic signs from HIE are reversible. It is difficult to tell the relative contribution of each to the abnormal neurologic behavior, but the signs caused by HIE should resolve with time.
Treatment
The only viable treatment is prevention by treating severe hyperbilirubinemia before toxicity occurs. The most effective way is with an exchange transfusion. This is difficult under most circumstances because of the large volume of blood needed (2 times the foal’s total blood volume) and difficulty in exchanging rapidly enough (in human neonates its done over 60-90 minutes). This can be done by using a "push-pull" method giving or withdrawing 5 ml/kg at a time. Although this will remove 75-85% of albumin-bound bilirubin, because of mobilization from tissues, levels only drop 60% with each exchange.
Another temporary measure to consider is giving fresh albumin to provide more binding sites for the bilirubin. Since fractionated plasma is not currently available, whole plasma must be used. Use of large volumes may result in protein overload. The recommendation in human neonates is 1 gm/kg albumin 1 hour before the exchange transfusion.