The Diagnostic Value Of Butyrylcholinesterase In Acute Organophosphorus Pesticide Poisoning

Organophosphorus pesticides (OP) poisoning is a clinical and social problem the whole world concerning about. The statistics data by WHO showed that there are millions cases of organophosphorus poisoning every year, mostly in China, India and other developing countries.The diagnosis of acute organophosphorus pesticide poisoning (AOPP) mainly depends on the patient's contact history, typical symptoms signs and biochemical and toxicological detection. However, in most primary hospitals the poison detection is often not as a routine way because of the lack of equipments. As the target enzyme of organophosphate poisons, the acetylcholinesterase (AChE) is the current diagnostic criteria for clinical diagnosis and classification of AOPP. However, AChE, mainly existing in the neuromuscular junction and red cell membrane, will be inactivated rapidly, and the protocol for preparing specimen is complicated. Therefore, AChE is not easy for clinical application. Although not as the target enzyme, butyrylcholinesterase (BuChE), mainly existing in plasma (or serum), is often as a diagnostic criteria because of its stable nature, easy-to-sample, reproducible and simple dectection procedure. However, a large number of clinical works discovered that BuChE is unreasonable to be applied as diagnostic indicator according to the existing standard of AChE mechanically. The controversy on the diagnostic value of BuChE was continued while without conclusion. Thus, whether BuChE can be used as a diagnostic indicator of AOPP is a pressing problem to physicians in emergency department.This study, based on the existing groundwork including animals exposed to OP in vivo and human blood exposed to OP in vitro, aimed to evaluate the diagnosis and classification valuation of BuChE to AOPP by selecting AOPP patients in our hospital emergency department as research objects. Firstly, we detected the normal activity range of AChE and BuChE in heathy adults and then analysised the relationship between BuChE activity the the current "golded standard"—AChE in vivo in AOPP patients. To further validate the clinical value of BuChE, we have analysised the relationship between BuChE activity and some important clinical indicators by reviewing the medical records of 113 AOPP patients.At present, there is no uniform standard among the various methods for determination of ChE activity of which results have large gap. The activity assay for ChE especially for AChE not only is easy to inactivate but also needs complex sample handling which brought a number of problems and challenges to clinical laboratory. At the same time, during the sample collection process, there are many clinical factors affecting determination of ChE. For example, patients often take in multi-drug ingredients during the treatment which has an adverse impact on the detection system. According to literatures, clinical circumstances and medical ethics, we have established and optimized a set of convenient protocal for blood collection and ChE activity detection based on the modified Ellman assay.The ideal method for study the relationship between AChE and BuChE should compare ChE activity of patients with self-control before poisoning which is difficult to apply in practice. Therefore, we selected healthy young male volunteers to establish normal activity range of AChE in whole blood and BuChE activity in plasma which were 105±33U/Hb and 15807±3495U/L respectively.We studied 21 cases of AOPP patients hospitalized from April, 2009 to September, 2009 of which 8 males, 13 females, at the age of 35.6±14.5. There are 13 cases of dichlorvos, parathion1 case, omethoate 2 cases, phorate 4 cases, phoxim 1 case devided by pesticide poisoning types. We simultaneous monitored the AChE and BuChE activity of these patients at the time of diagnosed and different time after poisoning inorder to further analyze the AChE-BuChE activity relationship. The results showed as follows. Firstly, activity of AChE and BuChE in vivo of AOPP patients were not a significant linear regression relationship, the reason of which would be individual differences and sensitivity difference of AChE and BuChE to different OP. In most cases, BuChE activity is lower than that of AChE. Statistics results showed that BuChE activity less than 10% correspond to AChE activity lower than 30% and BuChE activity less than 20% correspond to AChE activity lower than 50%. Therefore, we propose that when BuChE is used as criteria, the threshold of moderate or severe AOPP can be delimited at 20% or 10 % , according to the existing AChE classification criteria (moderate or severe at 50% or 30%). Secondly, during the recovery process, the activities of AChE and BuChE were different but both trends were basically consistent. The upswing of BuChE activity was often accompanied with AChE increasing. Therefore, we believe that BuChE, just liked AChE, can be used as indicators for tracking progression of disease which is positive for dynamic monitoring of disease and for judgment of prognosis. Thirdly, it was discovered that different types of OP had different suppression capability on AChE and BuChE activity which is concluded from observation of patients of phorate and dichlorvos poisoning. Now, phorate and other highly toxic pesticides are restricted by the goverment, thus the number of this kind poisoning is decreasing. Physicians should pay special attention to this kind of poisioning, and its diagnostic criteria should be more stringent in the case of using BuChE as indicator. During the recovery process of dichlorvos poisoning patients with with ideal prognosis, BuChE activity was linear rise at the rate of about 2.54% daily.To further validate the clinical value of BuChE, we observe the relationship of BuChE activity and other major clinical index retrospectively by analyzing the 113 cases of AOPP patients hospitalized from January 2008 to April 2009. We found some useful informations. Firstly, the inhibition degree of BuChE activity was associated with the degree of OP exposure which provided important diagnostic clues and reference for specific toxicological detection especially for patients with difficult cases taking or suspected cases. Secondly, analysis of clinical cases showed that BuChE activity was significantly correlated with concentration of OP pesticides in blood of AOPP patients. When the BuChE activity was declining or keeping lower indicated the concentrations of OP in patients maintained at a high level. The BuChE activity will recovery only when blood concentration of OP decreased to a certain extent. Therefore, the biological activity of BuChE may prompt the body's metabolism of pesticides. Thirdly, dynamic change of BuChE activity was more significant than a single result for judgments of disease condition. For example, the recovering of BuChE activity after bottoming out, even though still low, indicated that conditions have gradually improved and the patients need more close observation and adjusting doses of anticholinergics in time, otherwise atropine poisoning would easily occurred. Therefore, we think that AOPP patients should be classified based on the activity of BuChE at preliminary diagnosis and in the course of treatment dynamic curve trend of BuChE activity should be observed according which adjust the treatment in time. Fourthly, in the recovery process of AOPP patients with ideal prognosis, BuChE activity was linear rise, the daily recovery rate was greater than 2.5%. Fifthly, activity of BuChE keeping less than 5% often indicated large amount of OP taking (mostly highly toxic class) and high OP concentration in serum. Such AOPP patients need be paid enough attention because they were always accompany with respiratory failure, difficult treatment, long hospital staying, needing a lot of anti-drug to maintenance, multiple complications and high mortality.In summary, this study initially demonstrated the value of BuChE activity as the diagnostic and classification criteria for AOPP and its feasibility for estimating severity and prognosis of AOPP. The conclusion of this study is that BuChE activity can be used as clinical criteria for the diagnosis and classification of AOPP but numerus is lower than the standard AChE activity values. The classification criteria of moderate or severe poisoning can be classified by BuChE activity at 20% or 10% of normal and need be combined with pesticides types. Dynamic change of BuChE activity was more significant than a single result for judgment of disease condition. Patients need more close observation and adjusting doses of anticholinergics in time after BuChE activity bottoming out followed with upswing. Test continuing less than 5% for the BuChE activity indicated patients with high blood concentration in vivo, treatment difficulties, complications and high mortality characteristics, and need to be focused on. The patients need be paid enough attention when the activity of BuChE keeped less than 5% which indicated high serum concentration of OP, difficult treatment, multiple complications and high mortality.