尼莫地平预防儿童蛛网膜下腔出血后脑血管痉挛的疗效与安全性研究

Effectiveness and safety of nimodipine in preventing cerebral vasospasm after subarachnoid hemorrhage in children

目的评价尼莫地平预防儿童蛛网膜下腔出血(SAH)后脑血管痉挛的有效性及安全性。方法前瞻性、随机对照临床试验。以2015年1月至2018年10月首都医科大学附属北京儿童医院儿童重症监护病房(PICU)住院治疗的符合入组条件的SAH患儿43例为研究对象,应用随机数表随机分至尼莫地平预防用药组(24例)和对照组(19例),应用经颅多普勒超声(TCD)动态监测双侧大脑中动脉(MCA)血流速度、频谱形态等,观察尼莫地平对脑血管痉挛的预防作用,以及对患儿预后的影响。出院后28 d进行随访,应用儿童脑功能分类量表(PCPC)评价患儿脑功能。组间比较采用t检验、Mann-Whitney U检验或χ^2检验。结果除心率[(157±26)比(137±34)次/min,t=2.079,P=0.045]外,预防用药组和对照组患儿人口学基本资料、原发疾病、首发临床表现、出血部位差异无统计学意义(P均>0.05)。入院第5天预防用药组双侧MCA峰值流速低于对照组[左侧(136±34)比(158±23)cm/s,t=-2.890,P=0.006;右侧(129±34)比(176±27)cm/s,t=-3.717,P=0.001],入院第7天预防用药组左侧MCA峰值流速低于对照组[(127±45)比(152±13)cm/s,t=-2.903,P=0.007],右侧MCA峰值流速差异无统计学意义[(131±48)比(150±22)cm/s,t=-1.760,P=0.090]。共有11例患儿发生MCA痉挛,预防用药组6例(6/24,25%),对照组5例(5/19,26%),差异无统计学意义(χ^2=0.010,P=1.000)。其中8例在继续用药后痉挛得到完全缓解,1例院内死亡,另2例在离开PICU时痉挛仍未缓解。预防用药组和对照组患儿住院时间、机械通气比例、出院时格拉斯哥昏迷评分、出院存活率及出院28d存活率差异无统计学意义(P均>0.05)。预防用药组与对照组PCPC脑功能评价良好的比例分别为92%(22/24)和63%(12/19),两组之间差异有统计学意义(χ^2=5.208,P=0.030)。本研究中未发现与用药相关的低血压、皮疹、注射部位红肿等不良反应。结论预防性静脉应用尼莫地平未能减少儿童SAH后脑血管痉挛发生,但可能改善患儿的短期脑功能。儿童静脉应用尼莫地平安全性良好。

Objective To evaluate the effect of prophylactic nimodipine in vasospasm prevention and outcome improvement in children with subarachnoid hemorrhage (SAH).Methods A prospective,randomized controlled clinical trial which enrolled children with SAH who were admitted to pediatric intensive care unit (PICU) of Beijing Children′s Hospital from January 2015 to October 2018 was conducted.A total of 43 patients were randomly divided into nimodipine group (24 patients) and control group (19 patients) according to random number table.Transcranial Doppler (TCD) was used to dynamically monitor blood flow velocity and spectrum monography of bilateral middle cerebral artery (MCA) for vasospasm evaluation.Pediatric cerebral performance category (PCPC) scale was used to evaluate patients′ brain function on 28th day after discharge.Data were analyzed by t test,Mann-Whitney U test,χ^2 test.Results Except heart rate ((157±26) vs.(137±34) beats/min,t=2.079,P=0.045),no significant differences existed between the two groups in basic demographic characteristics,primary diseases,and clinical manifestations (all P>0.05).The peak velocities of bilateral MCA on the 5th day after admission were significantly lower in nimodipine group (left MCA (136±34) vs.(158±23) cm/s,t=-2.890,P=0.006;right MCA (129±34) vs.(176±27) cm/s,t=-3.717,P=0.001).Likewise,a lower peak velocity of left MCA was observed on the 7th day after admission in nimodipine group ((127±45) vs.(152±13) cm/s,t=-2.903,P=0.007),but no significant difference existed in that of right MCA ((131±48) vs.(150±22) cm/s,t=-1.760,P=0.090).Eleven patients suffered from vasospasm,25%(6/24) in nimodipine group and 26%(5/19) in control group (χ^2=0.010,P=1.000),within whom 8 patients had complete remission after continuing nimodipine treatment,one died in hospital and the other two′s vasospasm still existed at the time of discharge.No significant differences were found between the two groups in mean length of hospitalization,proportion of mechanical ventilation,Glasgow coma scale at discharge,survival rate at discharge or survival rate on 28th day after discharge (all P>0.05).However,nimodipine group had a higher proportion of favorable PCPC brain function (92%(22/24) vs.63%(12/19),χ^2=5.208,P=0.030).No side effects such as hypotension,rash or injection site erythema were observed.Conclusion Prophylactic nimodipine cannot reduce vasospasm incidence in children with SAH but may improve short-term brain function,without any significant safety issues.