Adjuvant Therapies for Hydrocephalus After Intraventricular Hemorrhage in Infants

A different group of interventions combines medical and surgical treatment options and is based on the theory that lowering the intraventricular CSF accumulation is not the definitive management for preventing PHH. Blood and blood degradation products have to be removed by means of fibrinolysis and draining.

Medical

Fibrinolysis

• Urokinase (and streptokinase) effective in adults: Experimental studies in animals have shown that infusion of urokinase into blood-filled ventricles of animals is effective in preventing hydrocephalus. Clinical studies in adults have shown the effectiveness and safety of its use for IVH caused by basal ganglia hypertensive extension (18, 28).
• No proven efficacy in infants: Several studies in infants have yielded different results. Upon randomization, two studies with streptokinase yielded similar results regarding shunt requirement and a significant risk for infection. The treatment in these studies was initiated after hydrocephalus was evident, several days after the IVH. The studies found that intraventricular fibrinolytic therapy with streptokinase in preterm neonates, when PHH was established, could not be recommended, and this practice has been abandoned (30, 36, 111).

Tissue plasminogen activator

• tPA effective for IVH in adults: Clinical studies of adults with IVH due to trauma and hemorrhages from aneurysms and AVMs have shown a positive effect of treatment with tPA.
• tPA controversial in children: tPA administration has been shown to increase the TGF-β1 concentration in CSF, an important factor in PHH pathogenesis (113).
• Drainage, irrigation and fibrinolytic therapy not proven: The procedure lasts usually for 3 days, until clear CSF is drained. Short-term data, at hospital discharge and at 6 months, have shown equivalent results in the treated group and control group regarding shunt requirement, but a significant reduction in severe cognitive disability was noticed in the group treated with drainage, irrigation and tPA at 2 years of follow-up. Doubts about overall safety of the intervention and small numbers of patients restrict this treatment option to specialized centers, and it has not found widespread use yet (107, 108, 112).

Diuretics

• Acetazolamide and furosemide reduce CSF production: The diuretics acetazolamide, furosemide, and, to a lesser extent, isosorbide and glycerol have been used in the management of PHH. Acetazolamide and furosemide reduce CSF production by almost half in some cases (63), but side effects (electrolyte disorders) and long-term administration (up to 6 months) make their use problematic. Results of large trials have shown that the combination of the two agents significantly increased the risk of impairment or disability at 1 year with no decrease in death or ventriculoperitoneal shunt requirement. These agents cannot be recommended as an option for the management of PHH (37, 109).