Gao Yan, Chen Yi-lu, Deng Hui-ying, Zhong Fu, Li Ying-jie
Department of Nephrology, Guangzhou Children's Hospital, Guangzhou 510120, China.
Zhonghua Er Ke Za Zhi. 2007 Sep;45(9):661-4.
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.
Fourteen dogs were given intraperitoneal FAM at a dose of 0.3 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 degrees C. The concentration of the poison was measured by gas chromatography (GC). The clinical symptoms of all the dogs were observed for one day.
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 (chi(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 t(1/2) 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.
Charcoal HP was an effective treatment for severe FAM poisoning. T(1/2) 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.
过去，仅采用传统疗法治疗的重度氟乙酰胺（FAM）中毒患者的死亡率和后遗症发生率很高。近十年来，作者采用血液灌流（HP）治疗重度FAM中毒患儿，取得了较好的效果。然而，由于缺乏前瞻性随机对照临床研究，尚无足够证据表明在不进行传统治疗的情况下，HP能降低死亡率和后遗症发生率。因此，设计了FAM中毒犬模型，以研究HP的治疗效果、高效时间、HP后组织中毒释放时间，并探讨治疗过程中及HP后毒物的毒代动力学。
给14只犬腹腔注射0.3mg/kg体重的FAM。对9只中毒犬在中毒后30 - 120分钟进行HP。每次操作持续4小时。采集9只中毒犬在HP前、HP期间的30、60、90、120、180、240分钟以及HP后2、6、24小时的血样。从血样中分离出血浆，保存在-20℃。采用气相色谱（GC）法测定毒物浓度。观察所有犬一天的临床症状。
中毒犬HP前及HP期间60、120、180、240分钟血样中FAM浓度（ng/ml）分别为230.11±52.48、184.56±62.57、141.00±44.83、126.78±61.04、113.11±54.65。差异有统计学意义（χ² = 31.978，P < 0.0005）。HP前与HP 1小时之间的离散计数为45.55，1小时与2小时之间为43.56，2小时与3小时之间为14.22，3小时与4小时之间为13.67。与HP前相比，HP 2小时、3小时、4小时时FAM值分别下降了38.7%、45.0%和5(0).8%。HP 1、2、3、4小时期间每小时FAM的清除率分别为19.79%、23.6%、10.09%和10.78%。HP期间2小时内HP的清除效果较高。HP后6小时FAM浓度略有再次升高。与HP前水平相比，HP后[24小时FAM水平下降。HP期间每小时FAM水平的降低率高于HP后（12.71%对0.27% - 2.22%）。有HP和无HP时FAM的t(1/2)分别为(4.50±1.20)小时和(49.60±10.56)小时。5只未进行HP治疗的中毒犬全部死亡。然而，6只进行HP治疗的中毒犬在HP后存活。3只犬在HP后4小时再次频繁惊厥。HP后用0.9%盐水冲洗炭罐，冲洗液中未检测到FAM。
血液灌流是治疗重度FAM中毒的有效方法。HP可缩短毒物的t(1/2)，加快毒物清除率。HP高效时间为2 - 2.5小时。活性炭能强力吸附毒物，HP后用0.9%盐水回输血液至体内可行且安全。
