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Brain and Nerve No to Shinkei Volume 44, Issue 11 （November 1992）

Brain and Nerve 脳と神経 44巻11号（1992年11月発行）

Japanese English

原著

クモ膜下出血後の脳血管攣縮に対する遺伝子組換えヒトt-PA（TD−2061）の初期臨床試験 Preliminary Clinical Trial of Intrathecal rt-PA (TD-2061) for the Prevention of Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage 佐々木富男 ¹ , 太田富雄 ² , 菊池晴彦 ³ , 高倉公朋 ¹ , 臼井雅昭 ⁴ , 近藤明悳 ⁵ , 田邊治之 ⁶ , 中村順一 ⁷ , 山田恭造 ² Tomio Sasaki ¹ , Tomio Ohta ² , Haruhiko Kikuchi ³ , Kintomo Takakura ¹ , Masaaki Usui ⁴ , Akinori Kondoh ⁵ , Harusi Tanabe ⁶ , Jun-ichi Nakamura ⁷ , Kyozou Yamada ² ¹東京大学医学部脳神経外科 ²大阪医科大学脳神経外科 ³京都大学医学部脳神経外科 ⁴総合会津中央病院脳神経外科 ⁵北野病院脳神経外科 ⁶大阪府三島救命救急センター脳神経外科 ⁷中村記念病院脳神経外科 ¹Department of Neurosurgery, Tokyo University School of Medicine ²Department of Neurosurgery, Osaka Medical College ³Department of Neurosurgery, Kyoto University School of Medicine ⁴Department of Neurosurgery, Aizu Central Hospital ⁵Department of Neurosurgery, Kitano Hospital ⁶Department of Neurosurgery, Misima Critical Care Medical Center ⁷Department of Neurosurgery, Nakamura Memorial Hospital キーワード： aneurysmal subarachnoid hemorrhage , vasospasm , fibrinolytic therapy , thrombolytic therapy , tissue plasminogen activator , t-PA , rt-PA , TD−2061 Keyword: aneurysmal subarachnoid hemorrhage , vasospasm , fibrinolytic therapy , thrombolytic therapy , tissue plasminogen activator , t-PA , rt-PA , TD−2061 pp.1001-1008

発行日 1992年11月1日 Published Date 1992/11/1

DOI https://doi.org/10.11477/mf.1406900404

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Abstract 文献概要
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　脳動脈瘤破裂によりクモ膜下出血を来した患者で，術前におけるFisherのCT分類がgroup 3または4およびHunt and Kosnikの重症度分類がgrade IIからIVの年齢42歳から69歳までの17例を対象とし，術後24時間以降に遺伝子組換えヒトt-PA（TD−2061）（25 KIU, 75 KIU, 200 KIU, 600 KIU／回，4回／日×3日）を脳槽内に投与し，その安全性並びに血腫溶解効果および遅発性脳血管攣縮の発現の有無を検討した。その結果，安全性に関しては副作用として，頭痛，出血，精神症状障害の発現がみられ，その発現頻度は用量に依存して増加した。一方，血腫溶解効果はいずれの投与群にも認められ，群間に大差はなかった。また，75KIU／回投与群では脳血管攣縮（血管写および症候性）の発現頻度は他の3投与群に比べて少なく，脳血管攣縮の発現に対して抑制効果が認められた。

　以上より，遺伝子組換えヒトt-PA（TD−2061）を1日4回，3日間脳槽内に投与した時の安全量は75 KIU／回（300 KIU／日）前後と考えられた。また，75 KIU／回，4回／日の3日間脳槽内投与が有効量と考えられた。

The results of preliminary clinical trial (a multicenter, open-label, dose escalation study) of intrathecal recombinant tissue plasminogen activator (rt-PA) for the prevention of cerebral vasospasm were reported. Seventeen patients ad-mitted within 48 hours of subarachnoid hemorrhage (SAH) were enrolled in this study. Patients ranged from 42 to 69 years of age. All cases enrolled were classified in clinical grade II, III or IV according to the classification of Hunt and Kosnik and in group 3 or 4 according to Fisher's CT grading scale.

Surgery for clipping the aneurysms were perfor-med and a small silicone catheter was left in the subarachnoid space. Twenty four hours after the surgery intrathecal bolus infusion of rt-PA was started through the silicone catheter at 6-hour inter-vals for 3 days. Patients were divided into 4 groups based on the dosage of rt-PA for each infusion. The dosage of rt-PA for each infusion and number of cases in each group was as follows ; 25 KIU in 4 cases, 75 KIU in 6 cases, 200 KIU in 4 cases and 600 KIU in 3 cases.

There was no significant difference in the clea-rance of subarachnoid clots between four groups. However, the occurrence of both symptomatic and angiographic vasospasm was less in the 75 KIU group than in other three groups.

Intracranial bleeding complications were noted in 4 patients (1/6 in the 75 KIU group, 2/4 in the 200 KIU group and 1/3 in the 600 KIU group). Serial coagulation studies demonstrated no evidence of systemic fibrinolysis. Disorientation was noted in 2 out of 3 patients of the 600 KIU group.

These results suggest that intrathecal administra-tion of 75 KIU of rt-PA at 6-hour intervals for 3 days is safe and effective in preventing the occur-rence of vasospasm.