Published online April 2, 2007
PEDIATRICS Vol. 119 No. 5 May 2007, pp. e1071-e1078 (doi:10.1542/peds.2006-2841)

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ARTICLE

Randomized Clinical Trial of Prevention of Hydrocephalus After Intraventricular Hemorrhage in Preterm Infants: Brain-Washing Versus Tapping Fluid

Andrew Whitelaw, MD^a,b, David Evans, MD^b, Michael Carter, MD^c, Marianne Thoresen, MD^d, Jolanta Wroblewska, MD^e, Marek Mandera, MD^f, Janusz Swietlinski, MD^e, Judith Simpson, MD^g, Constantinos Hajivassiliou, MD^h, Linda P. Hunt, PhD^d and Ian Pople, MD^c

^a Department of Clinical Science at North Bristol
^d South Bristol, University of Bristol, Bristol, United Kingdom
^b Neonatal Intensive Care Unit, Southmead Hospital, Bristol, United Kingdom
^c Department of Neurosurgery, Frenchay Hospital, Bristol, United Kingdom
^e Department of Neonatal Intensive and Special Care
^f Division of Pediatric Neurosurgery, Medical University of Silesia, Katowice, Poland
^g Neonatal Intensive Care Unit, Queen Mother's Hospital, Glasgow, United Kingdom
^h Department of Surgical Paediatrics, Royal Hospital for Sick Children, Glasgow, United Kingdom

OBJECTIVE. Hydrocephalus is a serious complication of intraventricular hemorrhage in preterm infants, with adverse consequences from permanent ventriculoperitoneal shunt dependence. The development of hydrocephalus takes several weeks, but no clinical intervention has been shown to reduce shunt surgery in such infants. The aim of this study was to test a new treatment intended to prevent hydrocephalus and shunt dependence after intraventricular hemorrhage.

METHODS. We randomly assigned 70 preterm infants who had gestational ages of 24 to 34 weeks and were progressively enlarging their cerebral ventricles after intraventricular hemorrhage to either (1) drainage, irrigation, and fibrinolytic therapy to wash out blood and cytokines or (2) tapping of cerebrospinal fluid by reservoir as required to control excessive expansion and signs of pressure (standard treatment). We evaluated outcomes at 6 months of age or hospital discharge (if later).

RESULTS. Of 34 infants who were assigned to drainage, irrigation, and fibrinolytic therapy, 2 died and 13 underwent shunt surgery (dead or shunt: 44%). Of 36 infants who were assigned to standard therapy, 5 died and 14 underwent shunt surgery (dead or shunt: 50%). This difference was not significant. Twelve (35%) of 34 infants who received drainage, irrigation, and fibrinolytic therapy had secondary intraventricular hemorrhage compared with 3 (8%) of 36 in the standard group. Secondary intraventricular hemorrhage was associated with an increased risk for subsequent shunt surgery and more blood transfusions.

CONCLUSIONS. Despite its logical basis and encouraging pilot data, drainage, irrigation, and fibrinolytic therapy did not reduce shunt surgery or death when tested in a multicenter, randomized trial. Secondary intraventricular hemorrhage is a major factor that counteracts any possible therapeutic effect from washing out old blood.

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Key Words: hydrocephalus • randomized prospective trial • neurosurgery • intraventricular hemorrhage

Abbreviations: IVH—intraventricular hemorrhage • PHVD—posthemorrhagic ventricular dilation • CSF—cerebrospinal fluid • ICP—intracranial pressure • rTPA—recombinant tissue plasminogen activator • DRIFT—drainage, irrigation, and fibrinolytic therapy • LP—lumbar puncture

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Accepted Oct 31, 2006.

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