Surfactant therapy and intracranial hemorrhage: review of the literature and results of new analyses.
OBJECTIVE
Surfactant replacement is a powerful therapy for newborns with respiratory distress syndrome, but limited observations suggest that alterations of cerebral blood flow can accompany the use of several available surfactants. An early European multicenter controlled study with beractant demonstrated an increased rate of intracranial hemorrhage in treated patients. Nine additional controlled studies were subsequently performed and included follow-up evaluations through 2 years adjusted age. This clinical experience provided a database of approximately 1700 infants to examine retrospectively for any relationship between surfactant therapy and intracranial hemorrhage.


METHODS
Cumulative incidence rates, hazard ratios, and 95% confidence intervals for intracranial hemorrhage were computed for each study and for appropriately pooled studies of similar design. Where an association between surfactant and the risk of intracranial hemorrhage was found, additional analyses were performed to attempt to identify intermediate physiologic events that might link administration of surfactant to the occurrence of intracranial hemorrhage. These analyses were guided by literature reports of hemodynamic changes observed in association with surfactant therapy.


RESULTS
During the controlled studies with beractant, treated newborns of 600 to 750 g birth weight were at higher risk for grades I and II intracranial hemorrhage than control newborns. There was no increased risk for grades III and IV hemorrhage among these newborns, nor was there increased risk of hemorrhage among any other patient groups. This finding did not result in increased morbidity for the affected patients; at 2 years adjusted age, they were not different from the control infants of 600 to 750 g birth weight. Retrospective examination of the database could not pinpoint the mechanism behind the finding, but it might have been related to changes in cerebral blood flow after surfactant uncompensated by ventilator management of oxygenation and ventilation.


CONCLUSIONS
Surfactant therapy may set in motion hemodynamic changes that could predispose to intracranial hemorrhage in certain circumstances, but this can probably be compensated by careful management of oxygenation and ventilation. A relationship between surfactant therapy and intracranial hemorrhage is probably not isolated to any particular surfactant preparation or method of delivery; studies comparing surfactants have shown no differences in rates of intracranial hemorrhage.
Gunkel
J H
JH
Ross Laboratories Division of Abbott Laboratories, Columbus, OH 43215.
Banks
P L
PL
D001688:Biological Products; D002543:Cerebral Hemorrhage / Q000209:etiology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D016001:Confidence Intervals; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D011663:Pulmonary Surfactants / Q000009:adverse effects* / Q000627:therapeutic use; D012127:Respiratory Distress Syndrome, Newborn / Q000628:therapy*; D012189:Retrospective Studies
D001688:Biological Products; D011663:Pulmonary Surfactants; C072197:beractant