血液灌流治疗急性重度敌敌畏中毒的疗效研究
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摘要
目的:本实验拟通过敌敌畏染毒比格犬,运用统计学分析,评估活性炭血液灌流(HP)对体内已吸收的敌敌畏的清除效果、对毒物代谢动力学的影响及治疗急性重度敌敌畏中毒的疗效。
方法:10只比格犬随机分成对照组(常规治疗)和HP组(常规治疗+HP),通过静脉推注敌敌畏进行染毒,HP组于染毒后1小时行活性炭血液灌流治疗2小时。动态检测两组犬血中毒物浓度及丁酰胆碱酯酶(BuChE)的变化;检测炭肾洗脱液中毒物浓度;观察临床疗效;检测各主要脏器中毒物的含量。利用DAS 2.1.1软件进行毒物代谢动力学分析,采用SPSS 13.0统计软件进行成组t检验。
结果:敌敌畏在比格犬体内的分布和清除符合二室开放模型,主要的毒物代谢动力学参数为表观分布容积(Vd)(17.803±10.345)L/Kg、表观血浆半衰期(t1/2)(6.260±3.078)h、血浆毒物总清除率(Cl)(1.955±0.757)L/h/Kg;行HP治疗期间两组代谢动力学参数有显著性差异,平均驻留时间(MRT)、t1/2明显缩短,Cl明显增高;但观察48小时两组血中毒物浓度及代谢动力学参数无显著性差异;活性炭可高效地吸附血中的敌敌畏,但洗脱量仅占机体负荷量的极小部分(<2‰);两组BuChE的变化无显著性差异;观察期间阿托品的用量、出现呼吸衰竭时间、辅助呼吸时间及死亡率均无明显差异。
结论:单次HP治疗急性重度敌敌畏中毒的疗效可能不理想。
Purpose: To assess the efficacy of hemoperfusion (HP) treatment for beagles with acute severe dichlorvus poisoning by statistic analysis.
Methord: Ten beagles with intravenous administration of dichlorvus were divided randomly into control group (without hemoperfusion treatment)and HP group (with hemoperfusion treatment). Serum concentration of dichlorvus and the activity of butyrylcholinesterase were dynamicly measure, the clinical effects were judged, and the amount of toxicant in the main tissue was tested. Toxicodynamics was analyzed by DAS 2.1.1, and the data were statistically analyzed by two-tailed t-test.
Results: First, the distribution of dichlorvus fits two-compartment model, the main parameters of toxicodynamics were V(d17.803±10.345)L/Kg,t1/2(6.260±3.078)h and Cl(1.955±0.757)L/h/Kg. Second, comparison of toxicodynamics parameters of two groups was different during two-hour HP treatment, but that was not different during 48 hours. Activated charcoal which could efficiently absorbe the dichlorvus in blood only remove a very little( < 2‰) total body burden of dichlorvus.The activity of butyrylcholinesterase in two groups was not different. During the observation, the cumulative dosages of atropine required, at the beginging of breath failure,the endurance of mechanical ventilation and morality in two groups were not different.
Conclusion: One hemoperfusion of activated charcoal may not an ideal therapeutic method for acute severe dichlorvus poisoning.
方法:10只比格犬随机分成对照组(常规治疗)和HP组(常规治疗+HP),通过静脉推注敌敌畏进行染毒,HP组于染毒后1小时行活性炭血液灌流治疗2小时。动态检测两组犬血中毒物浓度及丁酰胆碱酯酶(BuChE)的变化;检测炭肾洗脱液中毒物浓度;观察临床疗效;检测各主要脏器中毒物的含量。利用DAS 2.1.1软件进行毒物代谢动力学分析,采用SPSS 13.0统计软件进行成组t检验。
结果:敌敌畏在比格犬体内的分布和清除符合二室开放模型,主要的毒物代谢动力学参数为表观分布容积(Vd)(17.803±10.345)L/Kg、表观血浆半衰期(t1/2)(6.260±3.078)h、血浆毒物总清除率(Cl)(1.955±0.757)L/h/Kg;行HP治疗期间两组代谢动力学参数有显著性差异,平均驻留时间(MRT)、t1/2明显缩短,Cl明显增高;但观察48小时两组血中毒物浓度及代谢动力学参数无显著性差异;活性炭可高效地吸附血中的敌敌畏,但洗脱量仅占机体负荷量的极小部分(<2‰);两组BuChE的变化无显著性差异;观察期间阿托品的用量、出现呼吸衰竭时间、辅助呼吸时间及死亡率均无明显差异。
结论:单次HP治疗急性重度敌敌畏中毒的疗效可能不理想。
Purpose: To assess the efficacy of hemoperfusion (HP) treatment for beagles with acute severe dichlorvus poisoning by statistic analysis.
Methord: Ten beagles with intravenous administration of dichlorvus were divided randomly into control group (without hemoperfusion treatment)and HP group (with hemoperfusion treatment). Serum concentration of dichlorvus and the activity of butyrylcholinesterase were dynamicly measure, the clinical effects were judged, and the amount of toxicant in the main tissue was tested. Toxicodynamics was analyzed by DAS 2.1.1, and the data were statistically analyzed by two-tailed t-test.
Results: First, the distribution of dichlorvus fits two-compartment model, the main parameters of toxicodynamics were V(d17.803±10.345)L/Kg,t1/2(6.260±3.078)h and Cl(1.955±0.757)L/h/Kg. Second, comparison of toxicodynamics parameters of two groups was different during two-hour HP treatment, but that was not different during 48 hours. Activated charcoal which could efficiently absorbe the dichlorvus in blood only remove a very little( < 2‰) total body burden of dichlorvus.The activity of butyrylcholinesterase in two groups was not different. During the observation, the cumulative dosages of atropine required, at the beginging of breath failure,the endurance of mechanical ventilation and morality in two groups were not different.
Conclusion: One hemoperfusion of activated charcoal may not an ideal therapeutic method for acute severe dichlorvus poisoning.
引文
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[2]He F, Xu H, Qin F, Xu L,et al.Intermediate myasthenia syndrome following acute organophosphates poisoning-an analysis of 21 cases.Hum Exp Toxicol,1998,17:40-45.
[3]Yamashita M,Yamashita M,Tanaka J,et al.Human mortality in organophosphate poisonings.Vet Hum Toxicol,1997,39(2):84-85.
[4]Peng A,Meng FQ,Sun LF,et al.Therapeutic efficacy of charcoal hemoperfusion in patients with acute severe dichlorvos poisoning. Acta Pharmacol Sin,2004,25(1):15-21
[5]Iwaki Y,Ohtami M..Poison elimination methods in acute poisonin.Nippon Geka Gakkai Zasshi,2000,101(11):787.
[6]苑鑫,何跃忠,孙成文,等. 活性炭血液灌流对有机磷农药敌敌畏和解毒药阿托品的作用.中华急诊医学杂志,2005,14(4):279-281.
[7]陈雁君,卢英华,闫慧芳,等.血中敌敌畏的测定及灌流吸附毒物的定量清除效率.中华预防医学杂志,2005,39(3):208-209.
[8]于笑霞,王立新,田俊阁,等. 血液灌流对有机磷农药的清除作用. 中华急诊医学杂志,2005,14(4):282-285.
[9]于笑霞,韩和平,李培新,等.血液灌流治疗急性有机磷农药中毒中间综合征的疗效研究.中国危重病急救医学,2006,18 (1):54-55.
[10]张鸿民,夏淑琴,万永平,等.子目囊活性炭血液灌流对于农药甲胺磷及其解毒药物吸附作用的实验研究. 中国危重症急救医学, 1998,10(11):661-664.
[11] 张亚荣,刘永泉.血液灌流治疗重度有机磷农药中毒临床分析.中国血液净化.2002,1(2):15-17.
[12] 杨瑞丽,李文荣,赵跃青,等.血液灌流抢救急性重度有机磷农药中毒的临床研究.中华内科杂志.2002,41(12):833-834.
[13] 陈洁文,徐海燕,李玉权.血液灌流救治重度有机磷中毒的疗效观察.中国新医药,2003,2(10):72-73.
[14]杜柏华,马铁铮.血液灌流在有机磷中毒抢救中的应用.首都医药,2004,2(1):30-31.
[15]Okonek S, Tonnis J, Baldamus et al.Hemoperfusion versus hemodialysis in the management of patients severely poisoned by organophosphorus insecticides and bipyridyl herbicides. Artif Organs,1979,3(4):341-345.
[16]王勇强,史晓峰,张磊,等.血液灌流、换血疗法治疗急性中重度有机磷农药中毒效果评价.天津医药,2003 31(2):92-93.
[17]黎磊石,季大玺.连续性血液净化.东南大学出版社.2004.11. 第一版.104.
[18]Extracorporeal therapies for acute intoxications. Crit Care Clin, 2002,18(2):393-420.
[19]关广聚,时一民.临床血液净化学. 山东科学出版社. 2003.7.第一版. 222.
[20] 赵秀丽,栾丽君,赫梅生.家兔敌敌畏代谢动力学与胆碱酯酶抑制毒效动力学的关系.中国药理学与毒理学杂志,1997,11(1):59-62.
[21]侯云修,田东,吴淑华等.有机磷中毒家兔脑干损伤的病理机制探讨.中国急诊医学杂志,2003,12(6):391-393.
[22]王汉斌.急性有机磷农药致脏器损害与并发症的防治.中华急诊医学杂志,2001,10(4):285-287.
[23] 夏成云,周京国,谢建平,等.内皮素与急性有机磷农药中毒后多器官功能障碍的相关性研究.中华急诊医学杂志,2004,13(5):328-330.
[2]He F, Xu H, Qin F, Xu L,et al.Intermediate myasthenia syndrome following acute organophosphates poisoning-an analysis of 21 cases.Hum Exp Toxicol,1998,17:40-45.
[3]Yamashita M,Yamashita M,Tanaka J,et al.Human mortality in organophosphate poisonings.Vet Hum Toxicol,1997,39(2):84-85.
[4]Peng A,Meng FQ,Sun LF,et al.Therapeutic efficacy of charcoal hemoperfusion in patients with acute severe dichlorvos poisoning. Acta Pharmacol Sin,2004,25(1):15-21
[5]Iwaki Y,Ohtami M..Poison elimination methods in acute poisonin.Nippon Geka Gakkai Zasshi,2000,101(11):787.
[6]苑鑫,何跃忠,孙成文,等. 活性炭血液灌流对有机磷农药敌敌畏和解毒药阿托品的作用.中华急诊医学杂志,2005,14(4):279-281.
[7]陈雁君,卢英华,闫慧芳,等.血中敌敌畏的测定及灌流吸附毒物的定量清除效率.中华预防医学杂志,2005,39(3):208-209.
[8]于笑霞,王立新,田俊阁,等. 血液灌流对有机磷农药的清除作用. 中华急诊医学杂志,2005,14(4):282-285.
[9]于笑霞,韩和平,李培新,等.血液灌流治疗急性有机磷农药中毒中间综合征的疗效研究.中国危重病急救医学,2006,18 (1):54-55.
[10]张鸿民,夏淑琴,万永平,等.子目囊活性炭血液灌流对于农药甲胺磷及其解毒药物吸附作用的实验研究. 中国危重症急救医学, 1998,10(11):661-664.
[11] 张亚荣,刘永泉.血液灌流治疗重度有机磷农药中毒临床分析.中国血液净化.2002,1(2):15-17.
[12] 杨瑞丽,李文荣,赵跃青,等.血液灌流抢救急性重度有机磷农药中毒的临床研究.中华内科杂志.2002,41(12):833-834.
[13] 陈洁文,徐海燕,李玉权.血液灌流救治重度有机磷中毒的疗效观察.中国新医药,2003,2(10):72-73.
[14]杜柏华,马铁铮.血液灌流在有机磷中毒抢救中的应用.首都医药,2004,2(1):30-31.
[15]Okonek S, Tonnis J, Baldamus et al.Hemoperfusion versus hemodialysis in the management of patients severely poisoned by organophosphorus insecticides and bipyridyl herbicides. Artif Organs,1979,3(4):341-345.
[16]王勇强,史晓峰,张磊,等.血液灌流、换血疗法治疗急性中重度有机磷农药中毒效果评价.天津医药,2003 31(2):92-93.
[17]黎磊石,季大玺.连续性血液净化.东南大学出版社.2004.11. 第一版.104.
[18]Extracorporeal therapies for acute intoxications. Crit Care Clin, 2002,18(2):393-420.
[19]关广聚,时一民.临床血液净化学. 山东科学出版社. 2003.7.第一版. 222.
[20] 赵秀丽,栾丽君,赫梅生.家兔敌敌畏代谢动力学与胆碱酯酶抑制毒效动力学的关系.中国药理学与毒理学杂志,1997,11(1):59-62.
[21]侯云修,田东,吴淑华等.有机磷中毒家兔脑干损伤的病理机制探讨.中国急诊医学杂志,2003,12(6):391-393.
[22]王汉斌.急性有机磷农药致脏器损害与并发症的防治.中华急诊医学杂志,2001,10(4):285-287.
[23] 夏成云,周京国,谢建平,等.内皮素与急性有机磷农药中毒后多器官功能障碍的相关性研究.中华急诊医学杂志,2004,13(5):328-330.