纳洛酮治疗重型颅脑损伤大剂量与小剂量的比较

纳洛酮小剂量(0.4～0.8mg)为常用量,肌注或静脉注射能迅速翻转吗啡的作用,大剂量(4.8～16mg)能有效增加呼吸频率,促使昏迷清醒.我院自1999年9月至2001年9月收治重型颅脑损伤病人160例,随机分为两组,分别用大剂量与小剂量纳洛酮治疗重型颅脑损伤各80例,经临床治疗观察.     

小剂量rt-PA静脉溶栓治疗急性脑梗死临床分析

目的美国及欧洲缺血性脑卒中治疗指南建议0.9mg.kg-1为重组组织型纤维酶原激活剂(rt-PA)静脉溶栓标准治疗剂量。鉴于国人尤其是我国南方人在种族、体质及脑梗死危险因素等方面的不同,也按0.9mg.kg-1国际标准剂量治疗是否完全适合,有很大争议。本试验比较小剂量rt-PA 0.7mg.kg-1与0.9mg.kg-1标准剂量治疗急性脑梗死的疗效、安全性及预后。方法 28例急性脑梗死患者,发病时间窗为4.5h内,具有溶栓指征,无溶栓禁忌症。随机分为小剂量组rt-PA(0.7mg.kg-1,最高剂量50mg)和对照组(0.9mg.kg-1,最高剂量90mg)。比较两组治疗前、治疗后24h及14d的NIHSS评分,颅内出血率、死亡率以及90d mRS评分。结果两组治疗前的基本临床资料比较差异无统计学意义。各组均能有效改善神经功能,各组治疗后NIHSS评分与治疗前相比有显著差异。但治疗后24h及14d时两组比较差异无统计学意义。两组90d mRS评分比较差异无统计学意义。小剂量0.7mg.kg-1组颅内出血发生率为7.1%,0.9mg.kg-1组为14.3%,两组比较差异无统计学意义。0.9mg.kg-1组死亡1例,小剂量组无死亡病例,两组死亡率比较差异无统计学意义。结论 rt-PA静脉溶栓0.7mg.kg-1剂量安全有效,该剂量可能更适合国人,尤其是南方人。     

金尔伦治疗急性颅脑损伤的剂量效应研究

目的探讨金尔伦(盐酸纳洛酮)在治疗大鼠液压脑损伤后神经功能恢复和病理损害程度的剂量效应.方法将104只SD大鼠随机分为4组,伤后早期分别腹腔注射0.03 mg/Kg(小剂量组)、0.3 mg/Kg(中剂量组)、3 mg/Kg(大剂量组)金尔伦和等量生理盐水(对照组),连续7 d.结果中、大剂量组动物伤后脑神经功能恢复、脑水肿减轻程度及光、电镜检查显著优于对照组及小剂量组.结论伤后早期使用中剂量和大剂量金尔伦(盐酸纳洛酮)对大鼠液压颅脑损伤有明显的治疗效果.     

两种剂量纳洛酮治疗重型颅脑损伤的疗效观察

目的比较盐酸纳洛酮在治疗重型脑损伤中两种剂量的治疗效果。方法126例重型脑损伤病人随机分为甲乙两组,甲组每天给予纳洛酮0.4mg/kg体重,用平衡液500ml稀释后微泵24h持续静滴,连用3d后统一减量为4.8mg/d,连用7d后停药;乙组按同样方法给予每天0.4mg/kg体重,连用7d后停药;观察第10d GCS和GOS。结果第10d的GCS和GOS甲组分别为9.41和3.23±1.71,乙组为10.52和3.97±1.64,有显著性差异(P<0.05)。结论治疗重型脑损伤中延长大剂量纳洛酮的治疗时间可提高疗效。     

纳络酮治疗重型颅脑损伤病人的疗效观察

目的观察重型颅脑损伤病人不同时期使用纳洛酮对预后的影响。方法重型颅脑损伤病人41例分为早期治疗组(伤后12h内足量或大剂量使用纳洛酮)12例,晚期治疗组(伤后7～10d使用纳洛酮)14例,对照组15例,比较观察各组病人的疗效。结果早期治疗组较晚期治疗组、对照组的意识复苏时间明显缩短(P<0.05),拔气管导管时间明显提前(P<0.01),肺部感染率则无明显差别(P>0.05);晚期治疗组与对照组上述各项指标则无显著差异(P>0.05)。结论早期足量或大剂量使用阿片受体阻滞剂纳洛酮能明显减轻重型颅脑损伤病人的继发损伤,缩短意识复苏时间及气管导管滞留时间。     

盐酸纳洛酮联合醒脑静对重度颅脑损伤患者术后颅内压及脑功能的保护作用

目的探讨盐酸纳洛酮联合醒脑静对重度颅脑损伤患者术后颅脑内压及脑功能的保护作用。方法选取医院收治的重度颅脑损伤患者86例为研究对象,采用数字随机对照表分为对照组和观察组各43例,对照组给予盐酸纳洛酮治疗,观察组在对照组基础上给予醒脑静治疗,记录2组治疗前后血浆一氧化氮(NO)、超氧化物歧化酶(SOD)、过氧化脂质(LOP)水平的变化,对比2组入院2周颅内压变化,行格拉斯哥昏迷评分(GCS)和格拉斯哥预后评分(GOS),记录2组术后15d清醒率。结果观察组治疗15dGCS评分为(12.08±3.84)分显著高于对照组,3个月后GOS评分为(4.01±1.30)分显著高于对照组,差异均具有统计学意义(P0.05);观察组治疗后颅内压、LOP显著低于对照组,NO、SOD显著高于对照组,差异有统计学意义(P0.05);治疗15d后观察组清醒率62.79%显著高于对照组的39.53%,差异有统计学意义(P0.05)。结论盐酸纳洛酮联合醒脑静能降低重度颅脑损伤患者术后颅内压,减少对脑组织的损伤。     

五酯胶囊对肾移植受者他克莫司浓度的影响及临床意义

目的 探讨五酯胶囊对肾移植受者他克莫司全血浓度的影响及临床意义。方法 将38例采用他克莫司+霉酚酸酯（MMF）+泼尼松（Pred）三联免疫方案的首次肾移植受者作为研究对象，21例同时服用五酯胶囊的受者为实验组，17例未服用五酯胶囊的受者为对照组，检测并比较两组第1、3、6个月达到治疗窗他克莫司全血浓度时他克莫司剂量（mg.kg-1.d-1）和肾功能（血清肌酐）, 观察两组术后6月内急性排斥(AR)发生率、肝肾功能、糖尿病发生率。结果 对照组和实验组第1月达到治疗窗他克莫司全血浓度的他克莫司剂量分别是（0.087±0.018 mg.kg-1.d-1与0.062±0.024mg.kg-1.d-1）,两组间他克莫司剂量差异有统计学意义（p＜0.05），第3月分别为（0.072±0.01 mg.kg-1.d-1与0.046±0.019mg.kg-1.d-1），第6月分别为（0.054±0.012 mg.kg-1.d-1与0.033±0.014mg.kg-1.d-1）两组间剂量差异均有统计学意义（p＜0.05），两组间肾功能、肝功能损害发生率、AR发生率、糖尿病发生率差异无统计学意义(P＞0.05)。结论 五酯胶囊能明显提高肾移植受者他克莫司全血浓度，减少他克莫司服用量，减少他克莫司的毒性作用，具有重大的临床意义。     

早期应用亚低温联合纳洛酮治疗重型颅脑损伤的疗效观察

目的探讨早期应用亚低温联合纳洛酮治疗重型颅脑损伤的临床效果。方法选取2006-12—2011-12在我院接受治疗的重型颅脑损伤患者(GCS计分≤8分)120例,随机分为治疗组和对照组各60例。对照组常规治疗,治疗组在常规治疗的基础上加用亚低温与纳洛酮进行联合治疗。结果治疗组的治疗效果明显优于对照组,治疗组的病死率20.0%,与对照组的31.7%相比,差异有统计学意义(P<0.05)。治疗后的第7、21天,治疗组GCS评分均明显高于对照组,差异有统计学意义(P<0.05)。治疗后3个月GOS评定,治疗组生存质量明显优于对照组,差异具有统计学意义(P<0.05)。结论早期给予患者亚低温与纳洛酮联合治疗重型颅脑损伤,能降低病死率,有效改善患者的GCS评分,加快恢复进程,提高患者的生存质量。     

尼莫地平联合甘露醇对大鼠弥漫性轴索损伤治疗效果

目的观察尼莫地平联合甘露醇对大鼠弥漫性轴索损伤(DAI)的治疗效果。方法将170只SD雄性大鼠随机分为对照组、损伤组、甘露醇组、尼莫地平组和联合干预组,后4组制作大鼠颅脑DAI模型。甘露醇组尾静脉注射甘露醇1g.kg-1.d-1及腹腔注射等量生理盐水替代尼群地平;尼莫地平组予以尼莫地平0.5mg.kg-1.d-1及等量生理盐水替代甘露醇;联合干预组予以尼莫地平及甘露醇,对照组和损伤组仅以等量的生理盐水替代甘露醇和尼莫地平。后4组伤后2～75h内每隔2.5h处死1只大鼠测脑组织含水量;受伤后2、6、24、72、168h观察动物行为。结果各实验组行为学评分在伤后2、6、24、72、168h各时相点组间有显著差异,F值分别为为:10.89、28.39、12.18、27.50、15.28(P<0.01)。除甘露醇与联合组间脑水含量差异无统计学意义外,其他各组间比较差异均有统计学意义(P<0.05)。结论尼莫地平联合甘露醇治疗DAI,有助于减轻大鼠DAI后继发性脑损害,促进神经功能恢复。     

特麦角脲对线索诱发海洛因自身给药行为重建的影响

目的观察D2受体部分激动剂特麦角脲对线索诱发大鼠海洛因觅药行为复发的影响。方法建立大鼠海洛因固定比率自身给药行为模型,大鼠随机分为4组各8只:特麦角脲0.1mg/kg、0.2mg/kg、0.4mg/kg干预组(0.1mg/kg组、0.2mg/kg组、0.4mg/kg组)、生理盐水干预组(对照组)。戒断后第15d给予生理盐水或特麦角脲相应剂量腹腔注射,观察条件线索引燃海洛因觅药行为。结果①0.1mg/kg组各项行为指标与对照组相比,差异均无统计学意义(P>0.05);②0.2mg/kg组和0.4mg/kg组的总有效鼻触、第2h有效鼻触、获得条件刺激数均较对照组低(P<0.01);③大鼠活动度、无效鼻触各组之间差异均无统计学意义(P>0.05)。结论特麦角脲剂量依赖性地降低海洛因觅药行为重建,对运动功能无明显影响,有用于戒毒治疗的前景。     

Repeated naloxone administration in schizophrenia

A double-blind study of repeated subcutaneous administrations of 20 mg naloxone was performed in 10 schizophrenic patients as part of a World Health Organization collaborative project. No clinically obvious treatment effects were observed. None of the analyzed psychopathological symptoms, including hallucinations and unusual thought content, showed a distinct improvement during the 4 consecutive days of naloxone treatment. A slight but statistically significant decrease of symptomatology was found shortly after placebo injection on the first 2 days of treatment. This effect was not present following naloxone treatment. These findings are discussed in view of the hypothesis that increased endorphin activity contributes to the symptomatology of schizophrenic syndromes.     

The effect of naloxone on normal human sleep

Placebo and naloxone (4, 8, and 12 mg) were infused on separate nights in a double-blind fashion over a 20-min period between the 25th and 45th min of sleep in normal volunteers. Naloxone produced a dose-dependent increase in REM latency (the time from onset of sleep until the first REM period), and duration of the first REM period and second NREM period. The number of REM periods was also reduced.     

纳洛酮治疗抗精神病药中毒疗效观察

目的:观察纳洛酮对急性抗精神病药中毒的疗效. 方法:回顾性比较分析85例急性抗精神病药中毒者的临床资料.纳洛酮组加用纳洛酮治疗,常规组以常规治疗. 结果:纳洛酮组有效率明显高于常规组(P<0.01),病死率明显低于常规组(P<0.01),催醒时间明显短于常规组(P<0.01). 结论:纳洛酮治疗急性抗精神病药中毒疗效可靠,不良反应不明显,催醒作用明显,能有效提高急性抗精神病药中毒患者抢救成功率.     

Footshock-induced analgesia: Its opioid nature depends on the strain of rat

Previous studies have indicated that stressful footshock can induce both opioid, naloxone-sensitive, and non-opioid, naloxone-insensitive forms of analgesia, depending on stimulation parameters used with 30 min of intermittent footshock (3 mA, 1 s on, 5 s off) producing opioid analgesia and 3 min of continuous shock (3 mA) producing non-opioid analgesia. Using a local strain of Charles River (CR)-derived rats we conducted a parametric investigation of footshock-induced analgesia applying both AC and DC scrambled shock ranging from 1 to 4 mA, continuous shock of 1, 3 and 5 min in duration and intermittent shock lasting 1, 3, 5, 10, 20, 30 and 80 min. All shock parameters produced potent analgesia. In no case did 10 mg/kg of naloxone block this analgesia. Varying the dose of the antagonist (0.1-10 mg/kg) and testing the animals at different points in the diurnal cycle did not result in the emergence of naloxone-sensitive anangesia. Based on the assumption that non-opioid systems may mask the activity of opioid analgesia systems, we attempted to either enhance opioid analgesia by: preventing enkephalin degradation by the use of D-phenylalanine; increasing the entry of blood-borne opioids into the brain by the use of DMSO; and the attenuation of non-opioid analgesia by the use of reserpine. In no case did a naloxone-sensitive component of analgesia emerge. To test whether the animals possess an intact opioid analgesia system, both electrical stimulation of, and injection of opiates into the periaqueductal gray (PAG) were examined. Both procedures produced analgesia which was reversed by naloxone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Naloxone-induced reduction of schizophrenic symptoms

A schizophrenic patient was repeatedly treated with intravenous naloxone 0.04 mg or saline in a double-blind design. The Comprehensive Psychopathological Rating Scale was used to quantify the symptoms before and after each injection. Naloxone significantly reduced the symptoms temporarily, whereas saline was without effect.     

Sub-chronic exposure to opiates in the rat: effects on brain levels of substance P and calcitonin gene-related peptide during dependence and withdrawal.

Substance P (SP) and calcitonin gene-related peptide (CGRP) are putative transmitters in the central and peripheral (sensory) nervous systems. In this study, we examined the effects of dependence on and withdrawal from morphine and methadone on brain SP and CGRP content. Female Long Evans rats (70-100 g) were provided with plain drinking water or solutions containing opiate. No choice of drinking fluid was allowed. The maintenance level of each opiate (0.8 and 0.4 mg/ml for morphine and methadone, respectively) was continued for 4 days. Following an injection with naloxone (10 mg/kg i.p.) or saline, animals were decapitated 0, 20, or 60 min later and regional brain peptide content was measured by specific radioimmunoassays. SP and CGRP content in opiate-maintained and naive animals were similar following saline injection. However, following naloxone injection in morphine-maintained animals, SP content was elevated in the hypothalamus and midbrain at 20 min, but by 60 min was no longer distinguishable from basal (0 min) level. CGRP content was increased in the medulla oblongata and followed a comparable time course but, unlike SP, was not altered in the hypothalamus or midbrain. No alterations were observed in methadone-maintained animals. These results correlated with the peak of the behavioral morphine withdrawal syndrome and were consistent with the comparatively milder abstinence encountered in methadone medication.     

Differential responses in prolactin levels induced by naloxone in humans

The plasma prolactin (PRL) response to the opiate antagonist naloxone was tested in drug-free healthy volunteers (10 men, 18 regularly menstruating women who were in the late follicular phase of their ovarian cycles, and seven post-menopausal women). Naloxone hydrochloride (2 mg intravenous bolus) and placebo (normal saline) were administered on two different days in a double-blind fashion. Blood samples were collected at -15, 0, 30, 60, 120, 180 and 240 min after the injection. In the women of reproductive age, naloxone reduced plasma PRL concentrations, whereas in the post-menopausal women and the men, naloxone resulted in no significant change. However, in the post-menopausal women treated with estrogen (intramuscular 17-beta-estradiol), the opiate antagonist was able to lower plasma PRL concentrations. Thus, it appears that opiate effects on PRL secretion are influenced by the gonadal steroid environment and that estrogens may play a modulating role.     

Fluid consumption in water-deprived rats after administration of naloxone or quaternary naloxone

1. 1. Water-deprived male rats were given access to water, or to a 0.005M sodium saccharin solution, or to a 0.9% sodium chloride solution, during a 30 min test period.

2. 2. Naloxone (0.01–10.0 mg/kg) produced dose-dependent reductions in the consumption of each fluid. Saccharin-drinking was significantly reduced by 0.01 mg/kg naloxone, and water- and saline-drinking by 0.1 mg/kg naloxone. Quaternary naloxone (0.01–10.0 mg/kg) had no effect on drinking under any condition.

3. 3. Access to the saline solution resulted in hyperdipsia, due to a prolongation of the initial bout of avid drinking in the thirsty rats. Naloxone, in small doses, completely abolished this hyperdipsia. Since the quaternary compound had no effect, it was concluded that opiate antagonist suppression of saline-induced hyperdipsia was probably mediated at central opiate receptors.