丙戊酸钠静脉滴注治疗癫痫持续状态的疗效分析

目的探讨丙戊酸钠静脉滴注治疗癫痫持续状态（statusepilepticus,SE）的有效性及安全性。方法60例sE患者随机分为治疗组和对照组各30例,治疗组使用丙戊酸钠注射液,首剂以15mg／kg剂量缓慢静脉推注,推注时间5分钟。然后以1mg／（k·hr）的速度静滴。对照组使用地西泮注射液,首剂以10mg缓慢静脉推注,推注时间5分钟。随后以地西泮100mg溶于生理盐水500ml中,于12小时内缓慢静脉滴注。结果两组控制例数差异无统计学意义（P〈0．05）。治疗组复发率低于对照组,差异具有统计学意义（P〈0．05）。治疗组对呼吸、意识的影响小,差异具有统计学意义（P〈0．05）。结论静脉滴注丙戊酸钠治疗sE是一种有效的方法,不良反应少,值得临床推广应用。     

抗癫痫药物相互作用加重癫痫发作1例

患者,男,36岁,主因“发作性抽搐、神志不清20d,发热咳嗽5d”,门诊以“症状性癫痫（大发作）、腑炎、肺部感染”收入院。既往体健,否认其他疾病病史及酗酒史,否认食物、药物过敏史。     

反复咪达唑仑和咪达唑仑联合丙戊酸钠在小儿惊厥性癫痫持续状态治疗中的效果观察

目的探究反复咪达唑仑和咪达唑仑联合丙戊酸钠在小儿惊厥性癫痫持续状态(CSE)治疗中的效果。方法回顾性分析2014年2月至2017年8月经我院治疗的CSE患儿60例,根据随机数字表法分为对照组30例,研究组30例。对照组采用反复咪达唑仑静脉注入治疗,研究组采用咪达唑仑联合丙戊酸钠静脉泵入治疗。比较两组治疗前后STESS评分,治疗后临床治疗效果、药物起效时间和惊厥控制时间、不良反应发生率。随访12个月,观察并记录两组视力障碍、智力低下、偏瘫和肢体瘫痪等后遗症发生情况。结果治疗后,两组STESS评分均较治疗前降低,差异有统计学意义(P<0.05);治疗后,研究组的STESS评分低于对照组,差异有统计学意义(P<0.05);研究组的总有效率(93.33%,28/30)高于对照组(73.33%,22/30),差异有统计学意义(P<0.05);研究组的药物起效时间和惊厥控制时间均短于对照组,差异有统计学意义(P<0.05);研究组的不良反应发生率(6.67%,2/30)低于对照组(26.67%,8/30),差异有统计学意义(P<0.05);随访18个月后,研究组的后遗症发生率(10.00%,3/30)低于对照组(30.00%,9/30),差异有统计学意义(P<0.05)。结论咪达唑仑联合丙戊酸钠治疗小儿惊厥性癫痫持续状态有较好的效果,安全可靠,能够有效降低后遗症发生率。     

4种抗癫痫药物单用与合用的疗效观察

报道128例癫痫患者4种抗癫痫药单用与合用的临床疗效以及中毒情况,对128例癫痫患者的血药浓度监测结果进行了分析,着重分析了PHT中毒病例与血药浓度的关系.举例说明TDM工作有助于诊断、处理药物过量中毒;对合并用药的合理性具有指导作用,建议尽量避免多药合用;同时必须密切注意PHT的饱和动力学特征.     

丙戊酸钠静脉注射治疗小儿惊厥持续状态的临床体会

惊厥持续状态是小儿神经科常见的急症之一。我科2002年以来应用丙戊酸钠静脉注射控制20例惊厥持续状态的患儿．并与地西泮做对照，取得较好的效果，现报道如下。     

左乙拉西坦治疗惊厥性癫痫持续状态效果观察

目的 分析左乙拉西坦辅助治疗惊厥性癫痫持续状态的效果。方法 选择中国人民解放军联勤保障部队第九八八医院于2017年3月-2022年3月期间收治的92例符合纳入标准的病例进行探讨,随机分组为2个组别,对照组使用丙戊酸钠治疗,观察组使用左乙拉西坦治疗,比较治疗效果。结果 观察组总有效45例,有效率97.83%,明显高于对照组82.61%,P <0.05;观察组治疗后STESS评分低至1.49±0.16分,显著低于对照组2.77±0.19分,P <0.05;观察组发生不良反应5例,发生率10.87%,显著低于对照组34.78%,P <0.05。观察组患者退热时间为25.25±1.67 (h)、惊厥消失时间4.19±0.36 (h)、药物起效时间70.49±5.36 (min)以及住院时间5.22±1.44 (d),均显著低于对照组,P <0.05。结论 左乙拉西坦对惊厥性癫痫持续状态患者疗效较好,并且没有出现严重不良反应。值得推广。     

丙戊酸钠对比地西泮治疗成人癫痫持续状态有效性和安全性的Meta分析

目的:系统评价丙戊酸钠对比地西泮治疗成人癫痫持续状态的有效性和安全性,以为临床治疗提供循证参考。方法:计算机检索Medline、EMBase、Pub Med、Cochrane图书馆、中国期刊全文数据库、中文科技期刊数据库、中国生物医学文献数据库和万方数据库,收集丙戊酸钠(试验组)对比地西泮(对照组)治疗成人癫痫持续状态的随机对照试验(RCT)或半随机对照试验(q RCT),提取数据并进行质量评价后,采用Rev Man 5.0统计软件进行Meta分析。结果:共纳入5项RCT,合计276例患者。Meta分析结果显示,试验组患者48 h癫痫复发率显著低于对照组[OR=0.39,95%CI(0.16,0.96),P=0.04],而2 h内控制癫痫的有效率[OR=1.76,95%CI(0.88,3.52),P=0.11]和肝损害发生率[RR=1.19,95%CI(0.38,3.70),P=0.77]与对照组比较,差异无统计学意义。结论:丙戊酸钠治疗成人癫痫持续状态疗效和安全性与地西泮相当,而控制患者复发效果优于地西泮。受纳入研究方法学的限制,该结论有待大样本、高质量的RCT进一步证实。     

抗癫痫药物对儿童脑电图影响的初步探讨

目的探讨癫痫患儿应用卡马西平(CBZ)和丙戊酸钠(VPA)对脑电图的影响。方法对31例单独应用CBZ和35例单独应用VPA,临床发作缓解的两组病例进行脑电图(EEG)分析。结果CBZ组48.4%病人痫样放电减少或消失。22.6%痫样放电反而增加。VPA组80%病人痫样放电明显减少或消失。结论CBZ和VPA可使临床发作控制,但CBZ组却有22.6%的病人痫样放电增加,同时引起EEG背景活动慢化,表现为α活动减少,θ波增加,δ波增加,因此脑电图不能作为卡马西平治疗有效的一种指标。     

安定联合苯巴比妥治疗小儿惊厥的疗效及安全性分析

目的采用地西泮(商品名:安定)联合苯巴比妥治疗小儿惊厥的临床疗效与安全性。方法 30例小儿惊厥患儿为研究对象,采用随机数字表法分为对照组和观察组,各15例。对照组患儿采用安定治疗,观察组患儿在对照组基础上加用苯巴比妥治疗。对比两组患儿惊厥症状控制时间、治疗效果、复发情况与不良反应发生情况。结果观察组惊厥症状控制时间(11.3±2.5)min明显短于对照组的(15.7±4.6)min,差异有统计学意义(P<0.05)。观察组治疗总有效率93.3%明显高于对照组的60.0%,差异有统计学意义(P<0.05)。观察组总复发率6.7%明显低于对照组的40.0%,差异有统计学意义(P<0.05)。两组患儿除个别止惊后嗜睡,未见其他不良反应。结论采用安定联合苯巴比妥对惊厥患儿进行治疗,临床疗效确切,复发率低,安全性高,建议大力推广。     

丙戊酸钠个体化剂量治疗癫痫的临床分析

目的 :探讨丙戊酸钠 (VPA)个体化剂量治疗癫痫 ,减少药物不良反应。方法 :总结我院癫痫门诊 1999年 8月～ 2 0 0 1年 10月应用VPA单药治疗癫痫患儿 6 1例。结果 :年龄 9月～ 14岁 ,全身发作 4 2例 ,部分发作 19例 ;VPA治疗剂量 11 2 5～ 4 8 4 9mg/ (kg·d) ,平均剂量 (2 2 92± 7 83)mg/ (kg·d) ,服药至目标剂量后 4～ 9d血浓度值 (谷浓度 )为 2 4 5 0～ 16 3 0 0mg/L ,平均 (6 9 75± 2 0 75 )mg/L。结论 :VPA是广谱抗癫痫药 ,服药剂量存在明显的个体差异 ,早期测定药物稳态浓度很有必要。     

Evaluation of a proposed method for phenytoin maintenance dose prediction following an intravenous loading dose

Summary A large clinical study, designed to investigate the induction of theophylline metabolism by phenytoin, provided the opportunity to test a previously proposed method for estimating dose requirements of phenytoin. This method involves prediction of the oral maintenance dosage from data obtained following the administration of an intravenous loading dose.In 30 subjects, trough plasma concentration at steady-state were 12.0±4.9 µg·ml^–1 (mean ±SD) and differed by –2.7±39.3% from a mean target plasma concentration of 12.5±1.5µg·ml^–1.A Bayesian regression programme was used to forecast an estimate of each subject's individual pharmacokinetics. These were then used to predict the steady-state plasma concentrations which would be expected from a standard dosing regimen (4 mg per kg per day). When compared to the results expected from the use of this standard dosage, the proposed method gave acceptable steady-state plasma phenytoin concentrations with significant reductions in deviations from target concentrations.This method for the rapid individualization of phenytoin dosage requirements provides an improvement over more traditional methods of choosing an arbitrary dose adjusted for body weight followed by dosage adjustments based on achieved plasma concentration.     

不同负荷剂量氯吡格雷对植入药物洗脱支架患者术后影响

目的 探讨药物洗脱支架(DES)植入后予不同剂量氯吡格雷的安全性及术后主要不良心脏事件(MACE).方法 176例接受DES植入患者随机进入氯吡格雷300、450、600、750 mg负荷剂量组,术前6～24 h服药,服药前及服药后4、24、48 h监测血小板聚集率(PA),服药前、后24 h监测血小板计数.临床随访6个月.结果 氯吡格雷600、750 mg组PA抑制明显,维持时间长,发生氯吡格雷抵抗病例少,MACE发生少; 严重出血事件各组之间无差别,600、750 mg组轻微出血事件增高,750 mg组血小板计数明显下降.结论 600、750 mg组抑制PA效果更明显,作用时间更长,MACE发生更少; 600 mg负荷剂量优势更明显.     

负荷剂量氯吡格雷治疗非心源性急性脑梗死疗效观察

目的探讨负荷剂量氯吡格雷治疗非心源性急性脑梗死的疗效。方法 将242例非心源性急性脑梗死患者随机分为负荷组120例（给予氯吡格雷首剂300mg,之后改为75mg/d）和标准组122例（给予氯吡格雷75mg/d）,均连用14d。治疗后比较2组卒中量表（NHISS）评分、凝血指标、血常规及药物不良反应。结果 2组治疗后NHISS评分均低于治疗前,差异有统计学意义（P〈0.05）;且负荷组治疗后NHISS评分低于标准组,差异有统计学意义（P〈0.05）。2组治疗前后凝血指标差异无统计学意义（P〉0.05）。2组均未发生危及生命的中枢神经系统出血及严重的皮肤黏膜出血,对血液系统均无明显影响（P〉0.05）。结论 负荷剂量氯吡格雷治疗非心源性急性脑梗死疗效优于常规剂量,且无明显安全性问题,值得临床进一步推广。     

Isobolographic analysis of interactions between loreclezole and conventional antiepileptic drugs in the mouse maximal electroshock-induced seizure model

This study examined the interaction characteristics between loreclezole (LCZ) and various conventional antiepileptic drugs (phenytoin - PHT, carbamazepine - CBZ, valproate - VPA and phenobarbital - PB) in the mouse maximal electroshock (MES)-induced seizure model using isobolographic analysis. Drug-related adverse effects were ascertained by use of the chimney test (motor impairment) and the step-through passive avoidance task (learning and retrieval). It was observed that the combination of LCZ with VPA or PB, at the fixed ratio of 1:1, was supra-additive (synergistic) and the combination of LCZ with CBZ, at all fixed ratios tested (1:3, 1:1 and 3:1), was supra-additive against electroconvulsions. The remaining combinations evaluated, i.e., LCZ with PB or VPA at fixed ratios of 1:3 and 3:1, as well as all fixed-ratio combinations between LCZ and PHT, were additive in the MES test in mice. Pharmacokinetic characterization revealed that LCZ significantly increased both free plasma and brain concentrations of CBZ and PHT, but was without effect on PB. Moreover, a bi-directional pharmacokinetic interaction between LCZ and VPA was observed in that while LCZ increased free plasma, but not total brain VPA concentrations, VPA increased the total brain, but not free plasma LCZ concentrations. Adverse-effect testing revealed that for all antiepileptic drug combinations neither motor performance nor long-term memory was altered. Of the drug combinations investigated, only that of LCZ and PB at the fixed ratio of 1:1 was not associated with any pharmacokinetic interactions, and thus it may be concluded that the supra-additive (synergistic) isobolographic interaction was pharmacodynamic in nature. Furthermore, the fact that LCZ and PB have similar mechanisms of action would suggest that drugs with similar mechanisms of action may provide rational polytherapy regimens.The results of this study were presented in part at the 8th Congress of the European Federation of Neurological Societies, held in Paris, France, on 4--7 September 2004 [Abstract available in Eur J Neurol 11(Suppl 2): 227, 2004].     

常规与负荷剂量阿托伐他汀在治疗急性心肌梗死中的疗效对比

目的 探讨与比较阿托伐他汀的常规与负荷剂量在介入治疗急性心肌梗死中的疗效.方法 收集2015年6月至2016年6月入院的100例行介入治疗的急性心肌梗死患者随机分为两组,常规剂量组患者给予常规剂量阿托伐他汀,负荷剂量组患者则给予负荷剂量阿托伐他汀,比较两组患者相关临床指标、不良心血管事件与药物不良反应发生率.结果 常规剂量组患者术后24 h的TC、TG、LDL-C、CK-MB、cTn Ⅰ、hs-CRP、IL-6、Cr与ALT水平组间比较均显著高于负荷剂量组,HDL-C水平组间比较显著低于负荷剂量组,差异均有统计学意义(均P＜ 0.01);常规剂量组患者30 d MACE发生率明显高于对照组,差异有统计学意义(P＜0.05);两组患者治疗期间总体药物不良反应发生率比较差异均无统计学意义(均P＞ 0.05).结论 负荷剂量的阿托伐他汀在降低介入治疗术后炎症反应与稳定血脂的效果优于常规剂量,并减少心血管事件发生概率,且并未提高药物不良反应,安全性较高,借鉴意义重大.     

Pharmacokinetics of a netilmicin loading dose on the first postnatal day in preterm neonates with very w gestational age

Objective Pharmacokinetic parameters are important for dose adjustment of aminoglycosides, but they are highly variable in neonates. In this study the pharmacokinetics of a netilmicin loading dose was investigated on the first postnatal day in preterm neonates with very low gestational age (GA).Methods In an open prospective study, 20 neonates with GA between 22.9 and 32.0 weeks and suspected postnatal bacterial infection received an intravenous loading dose of 5 mg/kg netilmicin over 1 h during the first postnatal day. Netilmicin serum concentrations were determined by an enzyme multiplied immunoassay.Results The systemic clearance of netilmicin normalized to body weight (BW) was not significantly different in three GA subgroups (0.59± 0.02 ml/min/kg for GA <24 weeks, 0.72±0.14 ml/min/kg for GA 24–27 weeks, and 0.62±0.19 ml/min/kg for GA 27–32 weeks, P=0.123). Similar results were also obtained for serum elimination half-time and for the distribution volume normalized to BW. Multiple regression analysis showed that systemic clearance and volume of distribution (both not normalized to BW) significantly correlated with BW (P<0.0001) but not with GA. In the entire group, 20% of peak concentrations were below the target of 6 mg/l, and 63% of trough concentrations were above the target of 2 mg/l.Conclusion In neonates with very low GA, the pharmacokinetic parameters of netilmicin determined after an intravenous loading dose were not dependent on GA when normalized to BW. A number of neonates did not reach targeted peak and trough netilmicin serum concentrations, suggesting that a higher loading dose and a prolonged dosing interval might enhance the effectiveness and safety of netilmicin in preterm neonates immediately after birth.     

The safety of rapid infusion levetiracetam: A systematic review

Epilepsy is a common diagnosis and can quickly progress to status epilepticus which requires rapid treatment. Levetiracetam is a frequent treatment choice in these situations. The approved administration of intravenous levetiracetam is an infusion over 15 min. In recent years, studies have been published on faster infusion rates of levetiracetam. The objective of this review is to discuss the safety of levetiracetam as an intravenous push at a rate quicker than recommended. A literature search using PubMed, Cochrane Library, ClinicalTrials.gov , and Google Scholar resulted in 192 articles. Inclusion criteria consisted of English language, human studies, use of levetiracetam administered intravenously at a rate faster than 15 min, discussion of safety, and full-text availability. After screening, nine articles remained for inclusion. Of the nine articles, one was a prospective, open-label study, six were retrospective studies, and two were open-label, randomized controlled trials. The most common rapid infusion speed was 5 min and doses ranged from 280 to 4500 mg. Some of these trials used undiluted levetiracetam and many reported that peripheral access was used for a portion or all of the administrations. There were few adverse effects, including specific adverse effects relating to medication concentration and speed of infusion, in all the studies. Administration of intravenous levetiracetam at a rate faster than recommended in the labeling information appears to be safe and tolerable and can be given via a peripheral line. Rapid infusion of levetiracetam is a beneficial method of administration in an acute care setting where patients need rapid attainment of therapeutic levels of antiepileptic medications. Additional research is needed to ensure that rapid administration of intravenous levetiracetam is as efficacious as the traditional dosing method.     

RP-HPLC法同时测定人血清中4种抗癫痫药的浓度

目的：建立同时测定人血清中拉莫三嗪(LTG)、苯巴比妥(PB)、苯妥英(PHT)和卡马西平(CBZ)浓度的高效液相色谱法。方法血清样品经甲醇沉淀蛋白后直接进样测定。色谱柱采用Waters Symmetry C18柱(250 mm×4.6 mm,5μm),流动相为甲醇-水(55∶45),检测波长235 nm。结果 LTG、PB、PHT和CBZ的线性范围分别是1.56~50、3.13~100、2.19~70、1.09~35μg/ml,平均回收率均>98%。结论本方法操作简便,结果准确,适用于临床治疗药物监测。