| Objective:1.To evaluate the efficacy of hemoperfusion(HP)for acute bromadiolone poisoning patients and the Beagle dogs;2.To compare the efficacy of activated carbon HP tank and resin carbon HP tank with acute bromadiolone poisoning patients and the Beagle dogs.Methods:1.The establishment of high performance liquid chromatographic(HPLC)method to measure the bromadiolone concentration in biological samples: The experiment was carried out by type 3200 liquid chromatography-tandem mass spectrometry.The chromatographic and mass spectrometry conditions were in accordance with the experimental standards and the methods for bromadiolone measurement.2.The clinical study of HP with acute bromadiolone poisoning patients: the retrospective analysis has been conducted on clinical data with acute bromadiolone poisoning patients.All data was collected on the patients who were admitted to the 307 Hospital of People's Liberation Army due to acute bromadiolone poisoning,inclusion criteria were patients who were admitted to emergency room(ER)and agreed to receive HP,blood and urine samples were obtained after admission.A total of 21 cases were included.The clinic data of those patients who were treated with HP(activated charcoal HP tank)were analyzed,the change of concentration of bromadiolone before and after each HP also were compared.To observe the single clearance rate and the total clearance rate to evaluate the effectiveness of HP.3.The Establishment of bromadiolone-Beagle-Dog Model: Three Beagle dogs(weight9-11kg)were randomly assigned to give 150 mg,50mg and 10 mg bromadiolone solution by intraperitoneal injection.The presentations of poisoning Beagle dogs were observed,and the peripheral venous blood samples at the 1st day,2nd day,3rd day,4th day,5th day and 6th day were collected for detecting bromadiolone concentration.4.The comparison study of the efficacy of HP with activated charcoal HP tank and resinHP tank,respectively,with bromadiolone poisoning Beagle dogs: the 15 Beagle dogs(weight 9-11kg)were randomly divided into three groups: control group(only bromadiolone poisoning),experimental group one(treated with the activated charcoal HP 6 hours after poisoning)and experimental group two(treated with the resin HP 6hours after poisoning),each group had 5 Beagle dogs.All Beagle dogs were given bromadiolone solution 4.5mg/kg by intraperitoneal injection.All blood samples were collected from the peripheral venous,the plasma bromadiolone concentration was detected after exposed 0.5h,2h,4h,6h,8h,12 h,24h and 30 h.The change of bromadiolone concentration after HP were observed,and the efficacy of HP with activated charcoal HP tank and resin HP tank,respectively,were evaluated.Results:1.The establishment of high performance liquid chromatographic(HPLC)method to measure the bromadiolone concentration in biological samples: The results showed that the time of maximum plasma bromadiolone at 200ng/m was 5.4 min.Besides,and the sensitivity,accuracy and precision all met the experimental requirements,the results showed that the method could be used for this study.2.Clinical study: The symptoms of all 21 acute bromadiolone poisoning cases had been improved after activated charcoal HP(CHP).There were statistical signifcance in the change of plasma bromadiolone concentration before and after CHP(p<0.01).The more the CHP treatments,the more the total clearance of plasma bromadiolone increased,while the clearance of plasma bromadiolone of the single HP treatment could achieve as high as 30%.3.Beagle Dogs experimental study: According to the previous studies,three different doses of bromadiolone were administrated to Beagle dogs by intraperitoneal injection.The results showed: high dose of poisoning(150mg)Beagle dog had appeared despressed on 2 hours after poisoning,gingival bleeding and hematochezia on 24 hours and died on day 3,respectively.While low dose of poisoning(10mg)Beagle dog had no significantly change,however,medium dose of poisoning(50mg)Beagle dog had hematochezia,but no death,thence,we selected 50mg(4.5mg/kg)as the animal experimental study of poisoning dose.4.The comparison study of the efficacy of HP with activated charcoal HP tank and resinHP tank,respectively,with bromadiolone poisoning Beagle dogs: The results showed:HP could significantly accelerate the removal of the bromadiolone in the Beagle dogs' bodies,in the detection of each point,there were statistically significant difference among the three groups of the bromadiolone clearance,of which the experimental group2 had the biggest clearance(p < 0.05).The toxicokinetics parameters were worked out by plasma bromadiolone concentration,the results showed that the elimination half-life had statistically significant difference among the three groups(170 h vs.90 h vs.43 h,p< 0.05)and the clearance of the three groups also had statistically significant difference(66.58 ml/h vs.225.0 ml/h vs.493.3 ml/h,p < 0.05).What's more,the time-concentration area under the curve(AUC)of bromadiolone was statistically significant difference among the groups(663790 h * ng/ml vs.356830 h * ng/ml vs.137910 h *ng/ml,p < 0.05),while the peak maximum concentration(Cmax)and the average retention time(MRT)had no statistically significant difference(p > 0.05).From the results,the clearance of bromadiolone in experimental group 2 was higher than the other two groups.Conclusions:1.HP can effectively reduce the bromadiolone concentration in patients with bromadiolone poisoning(or toxic animals),and the clearance rate of bromadiolone in single HP can achieve as high as 30% or even more.Repeated HP also can significantly improve the overall clearance rate.More importantly,there have less adverse,which can significantly shorten the course of disease and reduce the risk of re-bleeding and other complications.2.Activated charcoal HP tank and resin HP tank can effectively remove the bromadiolone in bodies,while the resin HP tank has mor effective.All the results show that HP treatment combination with gastrointestinal toxic clearing should be done as early as possible with acute bromadiolone poisoning patients,and when conditions permitted,the resin HP tank is preferred. |
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