Frequency of sustained intracranial pressure elevation during treatment of severe intraventricular hemorrhage.

BACKGROUND: Elevated intracranial pressure (ICP) is an important marker of neurological deterioration. The occurrence and significance of elevated ICP and low cerebral perfusion pressure (CPP) in aggressively treated spontaneous intraventricular hemorrhage (IVH) are not defined. METHODS: We performed a secondary longitudinal exploratory data analysis of a randomized multicenter trial of urokinase (UK) versus placebo (Pcb) as a treatment for IVH. Eleven IVH patients who required an external ventricular drain (EVD) were randomized to receive either intraventricular UK or Pcb every 12 h until clinical response permitted EVD removal. ICP and CPP were recorded every 4 or 6 h, as well as before and 1 h after EVD closure for administration of study agent. ICP, CPP and the proportion of ICP readings above 20, 30, 40 and 50 mm Hg were analyzed. RESULTS: Six UK and 5 Pcb patients aged 39-74 years (mean +/- standard deviation; 53 +/- 11 years) were enrolled. Initial ICP ranged from 0 to 38 mm Hg (10.9 +/- 11.0), initial CPP from 65 to 133 mm Hg (100.5 +/- 17.7). We recorded 472 ICP readings over the entire monitoring period. Of these 65 (14%) were >20 mm Hg, 23 (5%) >30 mm Hg, 9 (2%) >40 mm Hg and 3 (<1%) >50 mm Hg. Only 2 of 141 intraventricular injections of study agent with EVD closure were not tolerated and required reopening of the EVD. CONCLUSIONS: In the intensive care unit, initial ICP measured with an EVD was uncommonly elevated (1/11 patients) in this group of severe IVH patients despite acute obstructive hydrocephalus. Frequent monitoring reveals ICP elevation >20 mm Hg in 14% of observations during use of EVD. ICP elevation, though it can occur, is not routinely associated with EVD closure for thrombolytic treatment with UK.

Intraventricular thrombolysis speeds blood clot resolution: results of a pilot, prospective, randomized, double-blind, controlled trial.

OBJECTIVE: Animal models and clinical studies suggest that intraventricular thrombolysis improves clot resolution and clinical outcomes among patients with intraventricular hemorrhage. However, this intervention may increase the rates of rebleeding and infection. To assess the safety and efficacy of intraventricular thrombolysis, we conducted a pilot, randomized, double-blind, controlled, multicenter study. METHODS: Patients with intraventricular hemorrhage requiring ventriculostomy were randomized to receive intraventricular injections of normal saline solution or urokinase (25000 international units) at 12-hour intervals. Injections continued until ventricular drainage was discontinued according to prespecified clinical criteria. Head computed tomographic scans were obtained daily, for quantitative determinations of intraventricular hemorrhage volumes. The rate of clot resolution was estimated for each group. RESULTS: Twelve subjects were enrolled (urokinase, seven patients; placebo, five patients). Commercial withdrawal of urokinase precluded additional enrollment. The urokinase and placebo groups were similar with respect to age (49.6 versus 55.2 yr, P = 0.43) and presenting Glasgow Coma Scale scores (7.14 versus 8.00, P = 0.72). Randomization to the urokinase treatment arm (P = 0.02) and female sex (P = 0.008) favorably affected the clot resolution rate. The sex-adjusted clot half-life for the urokinase-treated group was reduced 44.6%, compared with the value for the placebo group (4.69 versus 8.48 d). CONCLUSION: Intraventricular thrombolysis with urokinase speeds the resolution of intraventricular blood clots, compared with treatment with ventricular drainage alone.