用等渗阿托品抢救重度有机磷农药中毒22例

用等渗阿托品抢救重度有机磷农药中毒２２例刘玉玲孙志国王增发阿托品为抢救重度有机磷农药中毒的常用抗胆碱药，其用量需根据中毒程度和病情变化而定。１９９３年７月～１９９７年５月，我们用等渗阿托品一次剂量阿托品化抢救２２例重度有机磷农药中毒患者，取得了良好的...     

“盐酸戊乙奎醚”与阿托品治疗急性有机磷农药中毒的临床观察比较

目的研究盐酸戊乙奎醚（长托宁）与阿托品治疗急性有机磷农药中毒的临床疗效和安全性比较。方法120例6小时内口服有机磷农药中毒者随机分成盐酸戊乙奎醚组（60例）和阿托品组（60例），均配伍用氯磷定，分别按照胆碱酯酶数值划分的轻中重度程度给予不同剂量的盐酸戊乙奎醚及阿托品，对两组患者的有效治愈率，死亡率，平均住院时间进行比较。结果盐酸戊乙奎醚组有效治愈率96．6％，死亡率3．4％，平均住院时间2．8d，阿托品组有效治愈率91．6％，死亡率8．4％，平均住院时间4．9d，两组比较有显著性差异（P〈0．01），且盐酸戊乙奎醚作用持续时间长，特别适用于毒理作用持续较长或中毒胆碱酯酶易老化的有机磷农药中毒，延长给药时间间隔，减少服药频度，减轻护士的工作强度．结论盐酸戊乙奎醚治疗急性有机磷农药中毒安全有效，疗效优于阿托品．     

再析抢救有机磷农药中毒的阿托品化

基层医院抢救的农药中毒以急性有机磷农药中毒(AOIP)最为常见。以阿托品为代表的抗胆碱药可对抗体内蓄积的乙酰胆碱所致的毒蕈碱样毒性作用，也可对抗呼吸中枢抑制。阿托品对治疗有机磷农药中毒发挥了非常重要的作用，在胆碱酯酶复活剂出现之前，阿托品曾经是AOIP的唯一解毒剂。而病人达到阿托品化时间的长短对治疗有机磷农药中毒的成败起着决定性的作用，     

应用长托宁联合氯磷定治疗有机磷农药中毒的临床观察

目的探讨阿托品与长托宁（盐酸戊乙奎醚）两种药物联合氯磷定治疗有机磷农药中毒的疗效。方法将收治的急性有机磷农药中毒患者23例,除1例入院时已死亡外,其余22例随机分成两组,分别采用阿托品和长托宁治疗。阿托品组用大剂量阿托品加氯磷定,长托宁组采用长托宁加氯磷定。结果长托宁组抢救成功率90.9%,阿托品组72.7%,两组比较差异有统计学意义（P〈0.05）。结论新型抗胆碱药长托宁联合氯磷定治疗有机磷农药中毒疗效确切,与阿托品比较具有作用时间长,选择性强,不良反应少,剂量易掌握等优点。     

甲胺磷重复染毒大鼠膈肌损害及突击量氯磷定对其保护作用

目的 探讨甲胺磷重复染毒大鼠膈肌损害及突击量氯磷定对其保护作用。方法 对96只SD大鼠皮下重复注射甲胺磷制备有机磷中毒模型，并给予不同治疗-阿托品或阿托品 突击量氯磷定，观察各组大鼠不同治疗情况下，染毒后不同时间膈肌组织病理学和超微结构的改变。结果 给予突击量氯磷定治疗组大鼠膈肌病理损害较单用阿托品组轻，病变恢复快。结论 急性甲胺磷中毒可致膈肌损害。突击量氯磷定治疗可减轻中毒大鼠膈肌形态学损害。     

长托宁治疗有机磷中毒病人的临床护理

有机磷农药中毒是急诊科常见的急危重症病例。具有病情急,发展快,致死率高的特点。抢救必须准确及时,当确诊后应马上给予足量的胆碱酯酶重活剂和抗胆碱药[1]。长托宁为卫生部"十年百项计划"推广应用药物,是新一代的抗胆碱药,它具有副反应少、有效剂量小、抗胆碱作用强等优点,改进了有机磷农药救治方法,提高有机磷农药中毒救治水平,减少中毒病人死亡。我科从2007年6月开始使用长托宁联合氯磷定对有机磷农药中毒病人进行临床急救,与以往用阿托品治疗进行比较,结果显示长托宁疗效确切,毒副反应少,病死率低,效果优于阿托     

不同用药救治有机磷中毒的疗效

目的比较长托宁与阿托品治疗有机磷中毒的疗效。方法将66例急性有机磷农药中毒的患者按入院先后时间分为2组,2009年1月至2011年8月收治的急性有机磷中毒患者为长托宁组（32例）,2007年1月至2008年12月收治患者为阿托品组（34例）。长托宁组根据患者轻、中、重度中毒程度的不同,使用长托宁首次用药量分别为2、4、6 mg肌内注射,首次用药后30～60 min如中毒症状未完全消失,胆碱酯酶（CHE）活力〈50%,再给予首次量的半量,达＂长托宁化＂后,应用维持量维持,CHE活力恢复至50%～60%时可停药观察,同时给予常规量胆碱酯酶复能剂。阿托品组根据有机磷农药中毒程度的不同给予不同剂量的阿托品5～20 mg,每5～30 min可重复给药,直到＂阿托品化＂后再延长给药时间或减量。同时给予常规量胆碱酯酶复能剂。对2组患者用药后中毒症状改善时间、CHE活力恢复时间、用药频次、住院时间、治愈率和病死率进行比较。结果长托宁组中毒症状改善时间、CHE活力恢复所用时间、用药频次、住院时间、病死率及不良反应均明显低于阿托品组（均P〈0.05）;长托宁组治愈率为96.9%,阿托品组治愈率为67.6%,2组比较差异有统计学意义（P〈0.05）。结论长托宁治疗急性有机磷农药中毒的临床疗效优于阿托品,治愈率高,病死率低。     

阿托品两种给药方法的效果比较

有机磷农药中毒是临床上常见的急性中毒之一.有机磷农药中毒的特效解毒剂为胆碱脂酶复能剂及抗胆碱药物阿托品,阿托品的用药浓度、剂量、给药时间直接关系到抢救治疗效果.我们将传统的人工定时推药的方法改进为采用微量泵持续匀速给药(注),取得了较好的治疗经验,现总结如下.     

长托宁取代阿托品治疗有机磷农药中毒临床观察

目的：观察长托宁治疗有机磷农药中毒的疗效。方法：对急性有机磷农药中毒患者随机分为长托宁治疗组与阿托品对照组。采用推荐剂量按轻、中、重分组治疗，比较其疗效。结果：15例急性有机磷农药中毒患者治愈率100％。平均住院4天。结论：长托宁治疗有机磷农药中毒优于阿托品，是较为理想的新型抗胆碱药。     

急性有机磷农药中毒96例临床分析

目的：为了提高对急性有机磷农药中毒的抢救治疗水平。方法：对96例急性有机磷农药中毒患者使用阿托品剂量进行统计分析。结果：早期及时足量、持续阿托品化一刷后逐渐减量，是救治成功因素之一。结论：达阿托品化状态越早，足量维持时间越长（1—2周）是抢救急性有机磷农药中毒的重要治疗措施之一。     

Studying long-term effect of phenytoin either alone or combined with ascorbic acid on the anesthetic effect of urethane in rats

Phenytoin is an anticonvulsant drug known to interact with many other drugs. Previous data suggest that chronic administration of phenytoin delays urethane-induced loss of righting reflex (LRR) and this phenomenon being potentiated by concomitant administration of ascorbic acid (ASC). Therefore, we examined how phenytoin at two different doses combined or not with ASC (fixed dose) interact with both the latency to, and the duration for urethane-induced LRR in experimental rats. The results showed that lower dose of phenytoin (60 mg/kg rat b.i.d.) has significantly shortened the duration of LRR while higher dose of the drug (120 mg/kg b.i.d.) has delayed the latency to LRR (cut-off period of 15 min). Furthermore, addition of ASC to any of the two doses of phenytoin gave results similar to that observed for latency to and duration of LRR when phenytoin was given alone at the higher dose (120 mg/kg b.i.d.). Our data suggest a resistant effect of chronic administration of phenytoin on latency to and/or duration of loss righting reflex induced by urethane in experimental animals. A dose-response relationship of phenytoin in this regard is expected and needs further investigations. The resistant effect of phenytoin on righting reflex has been augmented when ASC was chronically given in combination. This result supports a possible interaction between the two drugs and needs further investigations at both experimental and clinical levels.     

Clonidine protection from the toxicity of soman, an organophosphate acetylcholinesterase inhibitor, in the mouse

Mice pretreated with the centrally active alpha-2 adrenergic agonist, clonidine, were protected from several of the toxic manifestations of soman, an organophosphate acetylcholinesterase inhibitor. The protection resulted in increased survival rates and a reduction in centrally mediated symptoms of soman, including tremor and straub tail, as well as one peripheral muscarinic symptom, excessive salivation. Doses of clonidine between 0.1 and 1 mg/kg, administered between 5 and 40 min before LD80 to LD90 doses of soman, produced significant protection. Pretreatment with atropine (25 mg/kg) also protected against soman toxicity. When atropine was combined with clonidine, the degree of protection afforded by the combination was greater than that predicted for a simple additive effect. Mice protected by atropine from the initial toxicity of soman frequently died within 24 h; no such delayed lethality was observed with protective doses of clonidine. Clonidine noncompetitively inhibited acetylcholinesterase activity in vitro and after in vivo administration at protective doses. At brain concentrations obtained after in vivo administration in protective doses, clonidine also inhibited ligand binding to cortical muscarinic receptors in vitro. The protective effects of clonidine are likely to involve multiple effects, including blockade of acetylcholine release and postsynaptic muscarinic receptors and transient inhibition of acetylcholinesterase.     

急性有机磷农药中毒阿托品用量探讨

目的探讨急性有机磷农药中毒（AOPP）时,阿托品用量对AOPP转归的影响。方法将中度中毒以上患者分成中度中毒组、重度中毒组及濒死组,观察三组中阿托品首剂量、阿托品化量、阿托品总量、阿托品过量例数及死亡率。再将重度中毒组及濒死纽中阿托品过量患者归为阿托品过量组,阿托品不过量者为阿托品适量纽,比较两纽中毒的时相发展、并发症及死亡率。结果阿托品化量及阿托品总量濒死组〉重度中毒组〉中度中毒组（P〈0．05）。阿托品过量组中的中间综合征（IMS）、中毒性心肌炎的发生率明显低于阿托品适量组（P〈0．05）。结论AOPP时,中毒程度不同,阿托品的用量也不同,阿托品化量及首剂量也不同。维持阿托品化时易致阿托品过量,但轻度阿托品过量不会增加开．亡率及并发症．     

Mechanism of the clonidine-induced protection against acetylcholinesterase inhibitor toxicity

Clonidine, an alpha-2 adrenergic agonist can inhibit the release of acetylcholine from central and peripheral cholinergic neurons. This study was designed to examine the ability of clonidine to protect animals from the toxic manifestations of cholinesterase poisoning. Physostigmine, a central and peripheral cholinesterase inhibitor produced tremors, and at high doses death, by respiratory paralysis. Mice were injected with physostigmine at a dose (0.75 mg/kg) which evoked tremors in 100% and death in 90% of the animals. Clonidine pretreatment (0.3 mg/kg) increased the onset latency to tremor from 5 to 20 min, increased the onset latency to death from 12 to 24 min and increased the percentage of survivors to 50%. Yohimbine (1 mg/kg) reversed these protective effects of clonidine. The physostigmine-induced accumulation of forebrain and hindbrain acetylcholine also was reduced by 50% in both brain regions in clonidine-pretreated mice. Neostigmine, a selective peripheral cholinesterase inhibitor, induced respiratory paralysis which was not affected by clonidine pretreatment. These findings indicate that central cholinergic neurons involved in the regulation of respiration and fine motor control, but not peripheral motor neurons, are inhibited by clonidine acting on alpha receptors.     

Tonic cholinergic inhibition of spinal mechanical transmission.

The present study examined the role of spinal cholinergic modulation of spinal mechanical and thermal transmission. Intrathecal administration of the cholinergic muscarinic receptor antagonists atropine or scopolamine in awake rats produced a dose-dependent decrease in the nociceptive mechanical withdrawal threshold of the rat tail. Pirenzepine, a selective muscarinic receptor type 1 antagonist, produced a similar effect at greater doses while mecamylamine, a nicotinic receptor antagonist, was without effect. The nociceptive tail flick (TF) reflex evoked by noxious heating was unaffected by the above drugs. Intrathecal administration of the cholinesterase inhibitor physostigmine produced a rapid, reversible and significant increase in the mechanical withdrawal threshold; TF latency was increased slightly but not significantly. Intrathecal administration of morphine, carbachol or clonidine all produced dose-dependent increases in TF latency; morphine and carbachol, but not clonidine, also increased the mechanical withdrawal threshold significantly. Intrathecal pretreatment with atropine reversed carbachol-produced increases in TF latency and the mechanical withdrawal threshold but did not affect increases in TF latency produced by intrathecal morphine or clonidine. The morphine-produced increase in the mechanical withdrawal threshold, however, was shifted rightward in a parallel fashion by intrathecal pretreatment with atropine. Intrathecal pretreatment with yohimbine did not affect the inhibitory effect of carbachol on either TF latency or the mechanical withdrawal threshold. These results suggest that a tonic, endogenous cholinergic muscarinic influence in the spinal cord, independent of spinal adrenergic mechanisms, modulates spinal mechanical transmission.     

Kinetics of drug action in disease states. VII. Effect of experimental renal dysfunction on the pharmacodynamics of ethanol in rats

This investigation was designed to determine if renal dysfunction is associated with an increased sensitivity to the CNS depressant effect of ethanol. Adult female Lewis rats were given injections of either 2 or 5 mg/kg of uranyl nitrate (saline for controls) or had both ureters ligated (sham operation for controls) to provide different experimental models of renal dysfunction. Normal and renal dysfunction (ureter-ligated) rats were infused i.v. with ethanol at rates of 8.1, 16.3 or 32.6 mg/min; concentrations of ethanol in cerebrospinal fluid, serum and brain at onset of loss of righting reflex were independent of infusion rate in both groups, indicating rapid equilibration of ethanol between the sampling sites and the biophase. Ethanol concentrations in cerebrospinal fluid at onset and offset (after approximately 110 min of sleep) of loss of righting reflex were not significantly different, reflecting negligible acute tolerance development under the experimental conditions. Ethanol concentrations at onset of loss of righting reflex in cerebrospinal fluid, serum and brain of rats with severe renal dysfunction (5 mg/kg of uranyl nitrate-treated and ureterligated groups) were slightly but statistically significantly lower than in normal controls. This difference was relatively much smaller than the difference in phenobarbital concentrations observed in a similar preceding study, which is consistent with the different mechanisms of action of alcohols and barbiturates.     

Kinetics of drug action in disease states. IV. Effect of pregnancy on phenobarbital concentrations at onset of loss of righting reflex in rats

This investigation was designed to determine if the acute hypnotic activity of a barbiturate is altered by advanced pregnancy. Twenty-day-pregnant rats and nonpregnant rats of the same age received an i.v. infusion of phenobarbital, 0.824 mg/min/rat, until they lost their righting reflex. The concentrations of total and free phenobarbital in serum at that time were significantly lower in pregnant than in nonpregnant animals. However, pregnancy had no effect on the concentrations of phenobarbital in the brain and cerebrospinal fluid at onset of loss of righting reflex. The difference of the serum phenobarbital concentrations was due to the slower rate of phenobarbital infusion received by the pregnant rats when normalized for body weight. The lack of difference of phenobarbital concentrations in cerebrospinal fluid, a site that reflects the concentration of the free drug at the sites of action, indicates that advanced pregnancy has no apparent effect on the central nervous system response to phenobarbital.     

Body temperature differentially affects ethanol sensitivity in both inbred strains and selected lines of mice

Offsetting ethanol-induced hypothermia in five inbred strains of mice changed ethanol sensitivity within strains and markedly reduced differences between strains in brain sensitivity to hypnotic ethanol doses. The present study extended this work to mice selectively bred for sensitivity and resistance to ethanol-induced loss of righting reflex (LORR) and hypothermia. In all experiments LORR duration and ethanol concentrations at return of righting reflex were measured after i.p. hypnotic ethanol doses and exposure to 22 or 34 degrees C. In experiment 1, C57BL/6J, A/HeJ, 129/J, LS/lbg and SS/lbg mice were given 4.2 g/kg ethanol. In experiment 2, the same mouse genotypes were tested with different ethanol doses (2.5-4.9 g/kg) selected to produce an equivalent degree of impairment (60 min LORR duration). In experiment 3, HOT and COLD lines of mice were given 4.0 g/kg ethanol. In agreement with previous work, offsetting hypothermia reduced differences between genotypes in ethanol sensitivity. Comparisons within genotypes indicated that ethanol sensitivity in C57, A/He, SS, HOT and COLD mice increased as body temperature increased. In contrast, ethanol sensitivity in 129 and LS mice decreased as body temperature increased. These results extend previous findings indicating that body temperature during intoxication contributes to differences between genotypes in ethanol sensitivity. The present findings also suggest that there are qualitative differences in the effects of temperature on ethanol sensitivity within genotypes.     

Comparison of subcutaneous and intramuscular ketamine-medetomidine with and without reversal by atipamezole in Dutch belted rabbits (Oryctolagus cuniculus).

Forty male Dutch belted rabbits (Oryctolagus cuniculus) enrolled in a minimally invasive pharmacokinetics study were used to compare the efficacy of an anesthetic combination delivered through 2 injection routes. Rabbits were randomly assigned to 4 groups (n = 10/group) to determine the sedative and physiologic effects of ketamine (25 mg/kg)-medetomidine (0.5 mg/kg) given either intramuscularly (IM) or subcutaneously (SC). Palpebral, pedal, ear pinch, and righting reflexes, as well as cardiopulmonary parameters (heart rate, respiratory rate, and arterial blood oxyhemoglobin saturation), were recorded every 5 min. In addition, the reversal effects of an intravenous dose of atipamezole (1 mg/kg), an alpha 2 adrenoreceptor antagonist, were assessed by comparing the return of the righting reflex in rabbits given the reversal agent with those that recovered spontaneously. Compared with the IM route, SC ketamine-medetomidine effectively induced chemical restraint with less than a 2-min difference in onset of anesthesia and markedly less resistance (for example, fl inching, kicking, and so forth) during the injection. In all groups, the anesthetic regimen, regardless of the route of administration, provided an adequate level of anesthesia. Reversal with atipamezole improved arterial hemoglobin oxygen saturation for both the SC and IM groups; however, an enhanced rate of recovery from anesthesia was clinically apparent only for animals given the combination by the IM route.     

序贯阿托品疗法与常规阿托品疗法治疗有机磷农药中毒疗效分析

目的：探讨有机磷农药中毒患者阿托品使用方法,提高抢救成功率。方法：对2005年6月至2009年6月我院收治的有机磷农药中毒病人281例进行分组,所有患者均使用阿托品疗法,A组为2007年以后132例序贯阿托品疗法患者,B组2007年以前为常规使用静推继之肌注阿托品疗法149例患者,根据有机磷农药对胆碱酯酶复能剂的疗效分为高效组和低效组,并结合病情严重程度共分为重度有机磷农药中毒胆碱酯酶复能剂高效组、重度有机磷农药中毒胆碱酯酶复能剂低效组,轻度有机磷农药中毒胆碱酯酶复能剂高效组、轻度有机磷农药中毒胆碱酯酶复能剂低效组4组,分别从达到阿托品化时间、维持阿托品化效果、反跳和中间综合征发生率、开始撤药平均时间、总住院费用、总住院平均时间、护士劳动强度进行总结和分析。结果：维持阿托品化疗效A组与B组间有显著差异,P值〈0.01,开始撤药平均时间、总住院平均时间、总住院费用、护士劳动强度A组与B组间均有差异,P值〈0.05,发生反跳和中间综合征发生率、达到阿托品化时间在高效组间比较无差异,低效组间比较无差异,高效组与低效组比较有显著差异,P值〈0.01,主要与中毒药物种类和病情严重程度有关,其次与阿托品治疗方法有关。结论：序贯阿托品疗法治疗有机磷农药中毒优于常规使用静推继之肌注阿托品疗法。