Study On The Protective Effects Of Peritoneal Dialysis On Multiple Organs Of Rabbits With Omethoate Poisoning

IntroductionAcute organophosphorus pesticide poisoning has been a global problem that is threatening health of human. How to take effective measures, reverse conditions of AOPP and decrease death rate is still one of the important subjects in emergency and first aid fields. Peritoneal dialysis has been used for AOPP several years, but there are still controversies on its curative effect. During these years, although many dates reported that PD has effects on AOPP, these are all clinical investigations without dates about whether PD remove poisons and influence the function of multiple organ.Objective Through detecting poisons in serum and fluid of peritoneal dialysis of AOPP rabbits, observing the levels of TNF-αand biochemical indexes of multiple orans injury and comparing the differences of control and PD group, to explore the mechanisms of the protection of PD to multiple organs ,supply science proofs for application of PD in clinic and new approach for the treatment of AOPP. Methods Model of rabbits with acute organophosphorus pesticide poisoning was made, by intragastric administration of 25 mg/kg(0.5LD50)40% omethoate. Rabbits of control group were given Pralidoxime Chloride and Atropine for intramuscular injection. Besides of these, animals of PD group were inserted in by peritoneal dialysis tube and given peritoneal dialysis for ten times. Blood plasma and liquid of peritoneal dialysis was remained and tested for qualitation of intoxicants. TNF-αand Biochemical indicators of cardiac creatase ,hepatic,renal and pancreatic function in serum were observed dynamically. Results We detected omethoate in the liquid of peritoneal dialysis and blood plasma with obvious difference six hour after intoxication in the detection ratio; After intoxication, TNF-αincreased, serum cholinesterase of both group declined obviously, and biochemical indicators of cardiac creatase ,hepatic,renal and pancreatic function in serum had changed also, and when comparing, TNF-αin PD group was lower than in control group ,the recovery of ChE was faster and these changes reflecting the injury of cardiac muscle,liver,kidney and pancreas were superior to control group.DiscussionAOPP is a common acute and severe disease in emergency department, which always lead to multiple organ injury, especially severe and dead cases are relational with MODS. It has significant sense to explore an effective method to protect the functions of multiple organ and decrease the case fatality and improve the prognosis of AOPP patients. MODS induced by AOPP also consist of primary MODS caused by primary injury and secondary MODS. A great deal of intoxicants make the organism in stress state and switch on immune system, and then generous cytokines are produced, leading to SIRS and MODS. Simultaneously there are hypoxia,shock,ischemical reperfusion injury and other causative factors of SIRS in AOPP, which also lead to uncontrolled release of cytokines and MODS.1. AOPP usually leads to cardiac injury, toxic myocarditis, and cardiac failure and malignant arrhythmia in severe cases. If founded in time and given early intervention, these can be improved. Cardiac injury usually occur in several hours after intoxication, hypoxia,electrolyte disturbances and acidosis are the main reasons. This experiment found that the level of CK-MB increased greatly after intoxication, achieved the peak at 12 hours, fall off after 24 hours and recover to the level of pre-poisoning after 48 to 72 hours. 2. When absorbed, organophosphorus pesticides will distribute in every organs, and have highest concentration in liver, in which they were transformed biochemically by the system of oxidation enzymes in hepatic microsomal and lead to injury and necrosis of hepatic cells, causing toxic hepatitis. The levels of ALT and AST in serum of both groups were significantly higher than normal value, which indicated that hepatic cells were injured to certain extent. They reached the peak at 12 or 24 hours later after intoxication, and then fall off. The level of total bilirubin was also increased.3. Although organophosphorous pesticides are broken down in livers and excreted from kidneys in toxicokinetics,there were less reports on acute renal injury in clinical. Because kidneys have powerful compensative function , minor injury has less infection to glomerular filtration rate, and the changes of BUN and CREA are usually not evident, but in severe cases, there are great accrescences. Our study found that after poisoning ,there were little change of CREA in both groups ,but the levels of BUN upgraded gradually after 24 hours and at 72 hours there was obvious difference than before poisoning, which may be for prerenal factors.4. OPs can lead to acute pancreatitis, most of which has not obvious clinical symptom, presenting a moderate and nonmalignant process, and can be masked by acute cholinergic symptom. In this study, the level of AMS increased gradually after 12 hours , reached the peak and recovered to the level of pre-poisoning; The level of APS increased promptly at 12 hours ,lasted longer time and did not recover to the level of pre-poisoning at 72 hours. Both of these can be used for the diagnosis of acute pancreatitis induced by AOPP. The incidence of acute pancreatitis induced by AOPP is actually high, and although this kind pancreatitis is considered to be inferior clinical state and self-limited, arbitrary development may lead to acute hemorrhagic and necrotizing pancreatitis, which should be pay great attention to.5. Besides of above mechanisms, inflammatory mediators play important role in the process of MODS. TNF-αis the main primary cytokines to activate cascade reaction of cytokines in SIRS, and plays important roles in the development of SIRS/CARS. It was similar to clinical study that the level of TNF-αincreased after poisoning in control group ,achieved the peak at 24 hours and did not decrease to the level of pro-poisoning, and the levels of TNF-αhad obvious positive correlation with CK-MB,ALT,TBIL,AMS and APS in serum ,which demonstrated that TNF-αis an important factor of MODS induced by AOPP.Peritoneal dialysis is a therapeutic approach ,which utilizes peritoneum as dislysis-membrane, waters prepared dialysate into abdominal cavity, exchanges uninterruptly and achieve the purpose to remove metabolic wastes,poisons and regulate the disturbance of water- electrolyte and acid-base balance through diffusion and ultra- filtration.Omethoate is a kind of high toxicity pesticide, and pure one is achromasy and transparent oily liquid. Its water solubility is high and can be dissolved in alcohol,acetone and other organic solvent. This experiment proved that peritoneal dialysis could get rid of internal omethoate for we detected poison in both serum and peritoneal liquid, and we could only detect poison in two of nine specimens in PD group, while seven of nine in control group at six hours ,which illustrated that PD could make the concentration of omethoate reduce, and is effective in toxicokinetics. It has been approved that continuous blood purification could remove inflammatory mediators, but recently some ones presumed that peritoneal dialysis may be another method to clean inflammatory mediators. We observed the dynamic changes of TNF-α,and confirmed that TNF-αplays a role in the process of MODS and PD can cut down the level of TNF-αin serum, adjust the balance of SIRS/CARS, and put off the process of MODS.This study confirmed that PD can lighten the injury of cardiac muscle,liver,kidney and pancreas through the following mechanisms:①to clean up intoxicants;②to remove inflammatory mediators ;③to get rid of toxic metabolites, for example ,bilirubin,blood ammonia,BUN,CERA and other middle and small molecules coming from dysfunction of liver and kidney;④through ultrafiltration and dehydration to lessen edema and hypoxia;⑤to correct dysfunction of water-electrolyte balance, and keep homeostasis. In summary ,peritoneal dialysis can be use for an effective approach to treat AOPP, especially in some basic hospitals ,where there are no HP,HD and other blood purification.Conclusion Organophosphorus pesticides can lead to toxic myocarditis,toxic hepatitis,acute pancreatitis and renal injury and TNF-αplay an important role in the process of MODS induced by AOPP; Peritoneal dialysis can get rid of OPs slowly and continuously; PD can cut down the level of pro-inflammatory mediator TNF-α, lessen systemic inflammatory reaction and injuries to organs; PD can protect multiple organ including heart,liver,kidney and pancreas, from injury through many mechanisms;peritoneal dialysis can be use for an effective approach to treat AOPP, especially in some basic hospitals ,where there are no HP,HD and other blood purification.