活性炭血液灌流在治疗犬实验性氟乙酰胺中毒中的价值

Evaluation of charcoal hemoperfusion in dogs with acute fluoroacetamide poisoning

目的观察活性炭血液灌流(Hemoperfusion,HP)在犬氟乙酰胺(fluoroacetamide,FAM)中毒的治疗效果,最佳效能时间,组织毒物再释放时间;HP 前后的毒代动力学。方法 14只犬腹腔内注射 FAM,其中9只进行了 HP 治疗,分别留取 HP 前,HP30、60、90、120、180、240 min,HP 后2、6、24 h 的血2 ml;气相色谱法检测血浆 FAM 浓度。观察所有中毒犬的临床中毒症状1 d。结果 HP前、HP 治疗60、120、180、240 min 9只实验犬血浆 FAM 量(ng/ml)分别是230.11±52.48,184.56±62.57,141.00±44.83,126.78±61.04,113.11±54.65(P<0.0005)。HP 后4 h FAM 下降50.85%,其中第1 h 毒物清除率是19.79%,第2 h 是23.60%,第3和第4 h 分别是10.09%和10.78%。HP后毒物的下降速度平均每小时仅0.27%～2.22%,与 HP 中平均每小时清除速度(12.71%)比较明显减慢。HP 治疗阶段和非 HP 治疗阶段,实验犬 FAM 的代谢消除半衰期(t_(1/2))分别为(4.50±1.20)h和(49.60±10.56)h。HP 结束后冲洗炭罐,冲洗液中不能测出 FAM 量。HP 治疗犬的中毒症状明显好转,而未实施 HP 的5只犬中毒后5 h 内全部死亡。结论 HP 使 FAM 毒物代谢消除 t_(1/2)明显缩短,能安全、有效地治疗中毒患者;最佳 HP 时间是2 h;HP 间隔时间至少4～6 h;活性炭吸附毒性物质牢固,生理盐水回血可行和安全。

Objective In the past the mortality and sequelae rate of the patients with severe fluoroacetamide（FAM） poisoning treated only with traditional remedies was high. During the recent ten years the authors treated children with severe FAM poisoning with charcoal hemoperfusion（HP） and achieved better results. However evidence was not sufficient to show that reduced mortality and sequelae rates were obtained from HP without traditional treatment because of lack of prospective randomized, controlled clinical studies. Thus, a dog model for FAM poisoning was designed in order to study the therapeutic effect, high-efficiency time of HP, the time of tissue-poisoning to release after HP, and to investigate the toxicokinetics of the poison in the course of treatment and after HP. Method Fourteen dogs were given intraperitoneal FAM at a dose of0. 3 mg/kg body weight. HP was performed on 9 poisoned dogs for 30-120 minutes post intoxication. Each procedure lasted for 4 hours. Blood samples of the 9 poisoned dogs were collected before HP and 30, 60, 90, 120, 180, 240 minutes during HP and 2, 6, 24 hours after HP. Blood plasma was separated from blood samples and stored at -20℃. The concentration of the poison was measured by gas chromatography （GC）. The clinical symptoms of all the dogs were observed for one day. Results The FAM concentration （ng/ml） of blood samples in poisoned dogs before HP, and 60, 120, 180, 240 minutes during HP were 230. 11 ± 52.48,184. 56 ± 62. 57,141.00 ± 44. 83,126. 78 ± 61.04,113.11 ± 54. 65 respectively. The differences were significant （χ^2 = 31. 978, P 〈 0. 0005 ）. The dispersion count between pre-HP and HP for 1 was 45.55, between 1 h and 2 h was 43.56, between 2 h and 3 h was 14. 22 and between 3 h and 4 h was 13.67. The values of FAM had declined by 38. 7% ,45.0% and 50. 8% respectively at 2 h, 3 h, 4 h of HP compared with pre-HP. The rate of cleaning efficacy of FAM of every hour during HP were 19. 79% , 23.6% , 10. 09% and 10. 78% respectively during HP 1,2,3,4 h. The cleaning efficacy of HP was high within 2 hours during HP. The concentration of FAM slightly rose again 6 h after HP. The level of FAM had declined at 24 hour after HP when compared with pre-HP level. The reduction rate of FAM level for every hour during HP was higher than that after HP （ 12.71% vs 0. 27%-2. 22% ）. The t1/2 of FAM with and without HP were （4. 50 ± 1.20） h and （49. 60 ± 10. 56） h. All the 5 poisoned dogs not treated with HP died. However 6 poisoned dogs treated with HP kept alive after HP. Three dogs had frequent seizures again 4h after HP. After HP the charcoal container was washed by 0. 9% saline and FAM could not be detected in the douche. Conclusions Charcoal HP was an effective treatment for severe FAM poisoning. Tl/2 of the poison was shortened, and the poison clearing rate was accelerated by HP. The high-efficiency time of HP was 2-2. 5 h. Activated charcoal can adsorb the poison vigorously, and return of blood to the body after HP by using 0. 9% saline was feasible and safe.