Langelaar G, Leeuwenkamp O R, Sterkman L G, Torreman M, Hesselink J M
Westeinde Hospital, Hague, The Netherlands.
J Int Med Res. 1996 Sep-Oct;24(5):425-32. doi: 10.1177/030006059602400504.
The clinical effects of nimodipine monotherapy were compared with the effects of nimodipine combined with ketamine and lignocaine (combination therapy) in a single-centre, one investigator, open study in patients with proven aneurysmal subarachnoid haemorrhage (aSAH). After clipping of the aneurysm, nimodipine was administered intravenously until day 5-7 after clipping. Thereafter the intravenous nimodipine was substituted by oral doses of nimodipine. These were decreased gradually and then discontinued within the following 6 days. For combination therapy, nimodipine was given together with both a bolus injection of 1 microgram/kg ketamine followed by an infusion of the drug at a rate of 3 micrograms/kg/min and a bolus injection of 1.5 mg/kg lignocaine followed by an infusion of the drug at a rate of 12 micrograms/kg/min. During the study period, 173 patients were admitted to the hospital with subarachnoid haemorrhage (SAH). Of these patients, 115 with a proven aneurysm were operated on and evaluated: 66 patients received nimodipine monotherapy and 49 were given nimodipine combined with ketamine and lignocaine. These subgroups were comparable in terms of the baseline characteristics (age, Hunt and Hess score). The (baseline corrected) Hunt and Hess scores after surgery and a 0-5 clinical outcome score were applied as indices for clinical effects. Patients receiving nimodipine monotherapy and combined therapy showed a significant clinical improvement compared to baseline (P = 0.001 and P = 0.006, respectively). The beneficial effect of nimodipine monotherapy is in line with previous double-blind, placebo-controlled studies. Although nimodipine monotherapy seems to be more effective than combined treatment, this was not statistically significant. Our data indicate that combined treatment with ketamine and lignocaine is not more effective than nimodipine monotherapy in patients with mild aSAH, but this does not rule out an effect in severe cases. There was no indication of a pharmacodynamic interaction between nimodipine and co-medication. No serious or clinically relevant adverse reactions were noted during the study.
在一项单中心、由一名研究者开展的开放性研究中，对尼莫地平单药治疗与尼莫地平联合氯胺酮和利多卡因（联合治疗）在确诊为动脉瘤性蛛网膜下腔出血（aSAH）患者中的临床效果进行了比较。动脉瘤夹闭术后，静脉注射尼莫地平直至夹闭术后第5 - 7天。此后，静脉注射的尼莫地平被口服尼莫地平替代。口服剂量逐渐减少，然后在接下来的6天内停用。对于联合治疗，尼莫地平与单次静脉注射1微克/千克氯胺酮随后以3微克/千克/分钟的速率输注该药物以及单次静脉注射1.5毫克/千克利多卡因随后以12微克/千克/分钟的速率输注该药物同时给予。在研究期间，173例蛛网膜下腔出血（SAH）患者入院。其中，115例确诊为动脉瘤的患者接受了手术并进行评估：66例患者接受尼莫地平单药治疗，49例患者接受尼莫地平联合氯胺酮和利多卡因治疗。这些亚组在基线特征（年龄、Hunt和Hess评分）方面具有可比性。术后（基线校正后的）Hunt和Hess评分以及0 - 5临床结局评分被用作临床效果指标。与基线相比，接受尼莫地平单药治疗和联合治疗的患者临床均有显著改善（分别为P = 0.001和P = 0.006）。尼莫地平单药治疗的有益效果与先前的双盲、安慰剂对照研究一致。虽然尼莫地平单药治疗似乎比联合治疗更有效，但这在统计学上并不显著。我们的数据表明，在轻度aSAH患者中，氯胺酮和利多卡因联合治疗并不比尼莫地平单药治疗更有效，但这并不排除在严重病例中有效果。没有迹象表明尼莫地平与联合用药之间存在药效学相互作用。研究期间未观察到严重或临床相关的不良反应。
