Naff Neal J, Hanley Daniel F, Keyl Penelope M, Tuhrim Stanley, Kraut Michael, Bederson Joshua, Bullock Ross, Mayer Stephan A, Schmutzhard Eric
Department of Neurosurgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Neurosurgery. 2004 Mar;54(3):577-83; discussion 583-4. doi: 10.1227/01.neu.0000108422.10842.60.
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.
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.
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).
Intraventricular thrombolysis with urokinase speeds the resolution of intraventricular blood clots, compared with treatment with ventricular drainage alone.
动物模型和临床研究表明，脑室内溶栓可改善脑室内出血患者的血凝块溶解情况及临床预后。然而，这种干预措施可能会增加再出血和感染的发生率。为评估脑室内溶栓的安全性和有效性，我们开展了一项前瞻性、随机、双盲、对照、多中心研究。
需要进行脑室造瘘术的脑室内出血患者被随机分组，每隔12小时接受一次脑室内注射生理盐水或尿激酶（25000国际单位）。根据预先设定的临床标准，持续注射直至停止脑室引流。每天进行头部计算机断层扫描，以定量测定脑室内出血量。估算每组的血凝块溶解率。
共纳入12名受试者（尿激酶组7例患者；安慰剂组5例患者）。尿激酶的商业撤市导致无法再纳入更多受试者。尿激酶组和安慰剂组在年龄（49.6岁对55.2岁，P = 0.43）和初始格拉斯哥昏迷量表评分（7.14对8.00，P = 0.72）方面相似。随机分配至尿激酶治疗组（P = 0.02）和女性性别（P = 0.008）对血凝块溶解率有积极影响。与安慰剂组相比，尿激酶治疗组经性别调整后的血凝块半衰期缩短了44.6%（4.69天对8.48天）。
与单纯脑室引流治疗相比，尿激酶脑室内溶栓可加速脑室内血凝块的溶解。
