Phase 1 trial of prevention of hydrocephalus after intraventricular hemorrhage in newborn infants by drainage, irrigation, and fibrinolytic therapy.
OBJECTIVE
Treatment of posthemorrhagic ventricular dilation in premature infants is fraught with failures and complications. We have piloted a new treatment aimed at removing intraventricular blood and the cytokines associated with hydrocephalus.


METHODS
Twenty-four infants were enrolled with ventricular width enlarged to 4 mm over the 97th centile after a large intraventricular hemorrhage. Sixteen had parenchymal brain lesions before treatment. Median gestation was 28 weeks, and birth weight was 1150 g. At a median postnatal age of 17 days, 2 ventricular catheters (1 right frontal, 1 left occipital) were inserted with 13 infants also having a reservoir frontally. Tissue plasminogen activator 0.5 mg/kg was given intraventricularly 8 hours before the ventricles were irrigated with artificial cerebrospinal fluid at 20 mL/h for a median of 72 hours.


RESULTS
Seventeen of 23 survivors (74%) did not require a ventriculoperitoneal shunt. One infant (of 23 weeks' gestation) died. Two infants developed reservoir-associated infection, and 2 infants had a second intraventricular hemorrhage. Of the 19 survivors aged >12 months postterm, 8 were normal, 7 (37%) had single disability, and 4 (21%) had multiple disabilities.


CONCLUSIONS
Shunt surgery was reduced compared with historical controls with similar treatment criteria. Mortality and single and multiple disability rates all showed downward trends. Reducing pressure, free iron, and proinflammatory and profibrotic cytokines may reduce periventricular brain damage and permanent hydrocephalus. Additional advances will require a controlled trial and better knowledge of the mechanisms of hydrocephalus.
Whitelaw
Andrew
A
Division of Child Health, University of Bristol, Bristol, United Kingdom. andrew.whitelaw@bristol.ac.uk
Pople
Ian
I
Cherian
Shobha
S
Evans
David
D
Thoresen
Marianne
M
D001925:Brain Damage, Chronic / Q000453:epidemiology; D002404:Catheterization / Q000009:adverse effects / Q000379:methods; D002543:Cerebral Hemorrhage / Q000150:complications / Q000601:surgery / Q000628:therapy*; D002552:Cerebral Ventricles / Q000473:pathology / Q000601:surgery; D004322:Drainage / Q000009:adverse effects / Q000379:methods; D017707:Erythrocyte Transfusion / Q000379:methods; D006801:Humans; D006849:Hydrocephalus / Q000517:prevention & control*; D007223:Infant; D007231:Infant, Newborn; D009017:Morbidity; D010865:Pilot Projects; D011183:Postoperative Complications / Q000453:epidemiology; D007507:Therapeutic Irrigation / Q000009:adverse effects / Q000379:methods; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome; D017287:Ventriculoperitoneal Shunt / Q000379:methods; D014696:Ventriculostomy / Q000009:adverse effects / Q000379:methods