Drainage, irrigation and fibrinolytic therapy (DRIFT) for posthaemorrhagic ventricular dilatation: 10-year follow-up of a randomised controlled trial.

BACKGROUND: Progressive ventricular dilatation after intraventricular haemorrhage (IVH) in preterm infants has a very high risk of severe disability and death. Drainage, irrigation and fibrinolytic therapy (DRIFT), in a randomised controlled trial (RCT), reduced severe cognitive impairment at 2 years. OBJECTIVE: To assess if the cognitive advantage of DRIFT seen at 2 years persisted until school age. PARTICIPANTS: The RCT conducted in four centres recruited 77 preterm infants with IVH and progressive ventricular enlargement over specified measurements. Follow-up was at 10 years of age. INTERVENTION: Intraventricular injection of a fibrinolytic followed by continuous lavage, until the drainage was clear, and standard care consisting of control of expansion by lumbar punctures and if expansion persisted via a ventricular access device. PRIMARY OUTCOME: Cognitive quotient (CQ), derived from the British Ability Scales and Bayley III Scales, and survival without severe cognitive disability. RESULTS: Of the 77 children randomised, 12 died, 2 could not be traced, 10 did not respond and 1 declined at 10-year follow-up. 28 in the DRIFT group and 24 in the standard treatment group were assessed by examiners blinded to the intervention. The mean CQ score was 69.3 (SD=30.1) in the DRIFT group and 53.7 (SD=35.7) in the standard treatment group (unadjusted p=0.1; adjusted p=0.01, after adjustment for the prespecified variables sex, birth weight and IVH grade). Survival without severe cognitive disability was 66% in the DRIFT group and 35% in the standard treatment group (unadjusted p=0.019; adjusted p=0.003). CONCLUSION: DRIFT is the first intervention for posthaemorrhagic ventricular dilatation to objectively demonstrate sustained cognitive improvement. TRIAL REGISTRATION NUMBER: ISRCTN80286058.

Posthemorrhagic ventricular dilation in the neonate: development and characterization of a rat model.

Intraventricular hemorrhage is a common complication of prematurity. Posthemorrhagic ventricular dilation (PHVD) has a high rate of disability and no safe and effective treatment. Its pathogenesis is poorly understood, largely because of the lack of a satisfactory animal model. We have developed a model of neonatal PHVD in the rat. Seven-day-old (P7) Wistar rat pups were given 80-microl injections of citrated rat blood or artificial cerebrospinal fluid (CSF) into alternate lateral ventricles on P7 and P8. Intracranial pressure was monitored and increased briefly by over 8-fold. Some rats received further 10-microl intraventricular injections of India ink on P21. Animals were weighed daily and simple neurologic tests performed. On P21 (or P22 if India ink had been injected), the rats were perfusion-fixed and blocks processed for paraffin histology. Sixty-five percent of pups injected with blood and 50% injected with artificial CSF developed dilated lateral ventricles, with patchy loss of ependyma, marked astrocytic gliosis, and rarefaction of periventricular white matter. India ink injection revealed slow transit of CSF from the dilated lateral ventricles but eventual passage into the subarachnoid space. Pups that had received intraventricular injections but did not develop ventricular dilation nonetheless had lighter brains than littermate controls (p < 0.001). Body weights were not significantly different from controls. Hydrocephalic animals had reduced motor performance as assessed by a grip traction test (p = 0.0002). This model is well suited to studying the pathogenesis of PHVD.