Acute Organophosphorus Pesticide Poisoning Research Articles

Effect of joint of activated charcoal and mannitol on the efficacy of treating acute organophosphorus pesticide poisoning.

Objective To study the effect of oral administration of activated charcoal and mannitol on removing toxicant after acute organophosphorus pesticide poisoning (AOPP). Method A total of 41 patients with severe AOPP were randomly divided into experiment group (activated charcoal used as adsorbent and mannitol used as cathartics, n =21)and control group (without adsorbent and cathartics, n = 20). Patients of both groups received routine treatment for AOPP after admission to hospital. The differences in duration of atropinization, the length of hospitalization and the success rate of treatment were compared between two groups. Results There were significant differences in duration of atropinization, the success rate of treatment and hospitalization time between the two groups. Conclusions The combination of activated charcoal and mannitol is more effective than the conventional gastric lavage on removal of organophosphorus pesticides from G-I tract, shorting the duration of atropinization time and hospital stays, and enhancing the success rate of rescue as well as improving the outcome of patients after organophosphorus pesticide poisoning. Key words: Activated carbon; Mannitol; Acute organophosphorus pesticide poisoning(AOPP); Remove

Plasma cholinesterase: double-edged parameter in the diagnosis of acute organophosphorus poisoning

Biochemical markers are one of the mainstays in the diagnosis of ill health. Plasma cholinesterase is one such marker of the ill health caused by acute organophosphorus pesticide poisoning. Organophosphorus pesticides are powerful inhibitors of plasma cholinesterase; consequently, the reduced level of this biochemical marker has been used in the diagnosis of cases of acute poisoning. But how dependable is this biochemical marker in the diagnosis of suspected organophosphorus pesticide poisoning without adequate clinical signs and symptoms? In the case reported here, the low level of plasma cholinesterase which was suspected to be due to organophosphorus poisoning was found to be caused by pulmonary Koch's and hepatitis B with associated malnutrition.

Clinical trial on standard treatment of acute organophosphorus poisoning

To explore the norms of treatment of acute organophosphorus pesticide poisoning (AOPP), and observe the curative effect. On basis of the pre-research, the norms of treatment of AOPP were summarized, and a multi-center clinical trial was performed in 6 hospitals selected from high incidence of AOPP in Shandong Province. 422 patients of AOPP in 6 hospitals in observation period were treated and observed by the norms of treatment. Among them, the proportion of oral poisoning was 97.16%, middle and severe degree were 87.44%. Compared with themselves 2 years ago before standard treatment, the curative effect of the norms of treatment for AOPP was much better than before. The mortality rate of AOPP declined from 9.87% to 1.66% (Chi2 = 27.92, P < 0.01), that was much better than the average therapeutic effect level of all our province in the same period (the mortality rate: 8.92%) (Chi2 = 26.05, P < 0.01). The average amount of atropine [(37.54 +/- 17.76) mg], dropped greatly [(1280.70 +/- 69.22) mg] (U = 439.22, P < 0.01).The usage of atropine by continuous intravenous injection with venous pump was better than ordinary intravenous injection. The mean dosage of pralidoxime chloride increased twice than the previous (U = 19.48, P < 0.01). There was no drug poisoning. The standard treatment of AOPP is urgently needed in our country, especially in rural area. By this trial, the satisfactory effect of the norms of treatment for AOPP summarized is observed and it reduces the fatality rate remarkably.

The diagnostic value of butyrylcholinesterase in acute organophosphorus pesticide poisoning

To assess the value of butyrylcholinesterase (BuChE) in the diagnosis of acute organophosphorus pesticide poisoning (AOPP), and to investigate the relationship between the activity of whole blood acetylcholinesterase (AChE) and plasma BuChE in patients of AOPP in order to re-evaluate the diagnostic value of BuChE. An improved Ellman method was employed to determine the activity of AChE and BuChE in 21 AOPP inpatients due to different kinds of pesticides (from April to September in 2009) during the course of the illness, with 26 healthy volunteers as normal control. The relationship between BuChE activity and other clinical indicators of 113 inpatients (from January 2008 to April 2009) was also retrospectively analyzed. The normal value of AChE and BuChE were (105 + or - 33) U/Hb and (15 807 + or - 3 495) U/L . The inhibition levels of these two enzymes were different. When the AChE activity was lower than 50%, 30% or 20%, the activity of BuChE was lower than 20%, 10% or 5% correspondingly. The tendency of changes in the two enzymes was similar and coincided well with the clinical symptoms after poisoning. The results of sequential detection showed that a significant decrease or persistent inhibition of BuChE activity by less than 5% indicated a high level of organophosphorus pesticide in the body. However, an elevation of BuChE indicated a favorable outcome. BuChE is one of the ideal diagnostic and classification criteria for AOPP. When the inhibition level of BuChE reaches 20%, AOPP is of moderate degree, when it reaches 10%, severe AOPP can be diagnosed, with different kinds of organophosphorus pesticides taken into consideration.

The Significance of the Measurement of Serum Xanthine Oxidase and Oxidation Markers in Patients with Acute Organophosphorus Pesticide Poisoning

This study investigated whether xanthine oxidase (XO) plays an important role in the mechanism of toxicity of acute organophosphorus pesticide poisoning (AOPP). The serum activities of XO, superoxide dismutase (SOD), paraoxonase-1 (PON1), butyrylcholinesterase (BChE) and malondialdehyde (MDA) were compared in 49 patients with AOPP and 50 age- and gender-matched healthy controls. Serum XO and MDA activities were higher and the serum SOD, PON1 and BChE activities were lower in the AOPP patients compared with the controls. Pearson correlation analysis demonstrated a significant negative correlation between XO activity and the SOD, PON1 and BChE activities, but a significant positive correlation between XO activity and MDA. These results suggest that increased activity of XO and decreased antioxidant enzyme activity contribute to the development of oxidative injury in AOPP patients. Thus, effective antioxidant therapy may be a therapeutic option following AOPP.

The protection effect of benthiactzine on gut-barrier in acute organophosphorus pesticide poisoning

Objective To investigate the change of gut-barrier function of mice in acute organophosphorus poisoning and the protection effect of benthiactzine. Method A total of 65 Kunming mice, female and male both half, were randomly assigned to five groups: normal group, DDVP poisoning(model) group, and benthiactzine 2, sured by spectrophotometric assay at 3 hours after DDVP poisoning. The variance analysis was used to deal the quantitative data. Results The DAO activity in model group significantly increased compared with normal group (P < 0.01). Whereas, the DAO activity in all pretreatment groups were significantly decreased compared with concentration of D-lactate in model group was significantly increased compared with normal group (P < 0.01). However, the concentration of D-lactate in pretreatment groups was significantly decreased compared with model group(all P < 0.01). The concentration of D-lactate could be decreased dose-dependently by the administration of benthiactzine. Conclusions The diamine oxidase activity and concentration of D-lactate were significantly in-creased in the DDVP poisoning mice, which means the gnt-barrier function was severely damaged. And the admin-istration of benthiactzine could alleviate the injury to the gut-barrier function. Key words: DDVP; Mice; Benthiactzine; Atropine; Diamine oxidase; D-lactate; The gut-barrier; Multi-ple organ dysfimction syndrome

Therapy with continous intravenous infusim pralidoxime chloride therapy in acute organophosphorus pesticide poisoning

Objective To investigate the therapeutic effect of continuous intravenous pralidoxime chloride infusion in acute organophosphorus pesticide poisoning(AOPP).Methods The patients with severe AOPP were randomly divided into 3 groups:(1)group 1(n =51)received a bolus injection of pralidoxime chloride 2.Og followed by continuous intravenous infusion at 0.25 g/h.(2)group 2(n = 51)received a bolus injection of pralidoxime 2.Og followed by continuous intravenous infusion at 0.5g/h.(3)group 3(n = 50)received intravenous drip of pralidoxime 2.Og for 3 times a day.Efficacy was compared among 3 groups on the basis of time to reach atropinization,recovery of cholinesterase activity .cumulative amount of atropine,incidence of recurrence of pesticide poisoning,intermediate syndrome,and hospitalization days,etc.Results Efficacy in patients receiving continuous intravenous therapy was significantly different from the third group.But there was no significant difference in efficacy between the first and second groups.Conclusion The patients with AOPP can be effectively treated by a loading dose followed with continous intravenous pralidoxime chloride infusion. Key words: Pralidoxime chloride; Continuous infusion therapy; Organophosphorus pesticide; Poisoning

Comparison on effects of penehyclidine hydrochloride and atropine on acute organophosphorus pesticide poisoning in children

目的 比较盐酸戊乙奎醚(长托宁)与阿托品在治疗小儿急性有机磷农药中毒中的疗效、不良反应.方法 将开封市儿童医院PICU 2005年5月至2007年12月收治的21例采用盐酸戊乙奎醚治疗的急性有机磷中毒患儿(盐酸戊乙奎醚组)与2003年5月至2005年4月收治的23例采用阿托品治疗的急性有机磷中毒患儿(阿托品组)进行比较.结果 与阿托品组相比,盐酸戊乙奎醚组症状消失快、胆碱酯酶恢复时间短、给药次数与住院天数少,且心动过速、躁动的发生率低,而呼吸衰竭、中间综合征发生率较低,未出现需采用血液灌流及透析的病例.结论 盐酸戊乙奎醚治疗小儿急性有机磷中毒疗效明显优于阿托品。

A phase II clinical trial to assess the safety of clonidine in acute organophosphorus pesticide poisoning

BackgroundAn estimated 2–3 million people are acutely poisoned by organophosphorus pesticides each year, mostly in the developing world. There is a pressing need for new affordable antidotes and clonidine has been shown to be effective in animal studies. Our aim was to determine the safety of clonidine given as an antidote in adult patients presenting with signs or symptoms of acute organophosphate ingestion.MethodsThis study was a dose finding, open-label, multicentre, phase II trial. Forty eight patients with acute organophosphate poisoning were randomized to receive either clonidine or placebo: Four to receive placebo and twelve to receive clonidine at each dose level. The first dose level was an initial loading dose of 0.15 mg followed by an infusion of 0.5 mg of clonidine over 24 hours. The initial loading dose was increased to 0.3 mg, 0.45 and 0.6 mg. at all dosing levels however the subsequent infusion remained at 0.5 mg of clonidine over 24 hours.ResultsThe baseline characteristics of both groups were similar. The trial was stopped after completion of the 3rd dosing level. At the 1st and 2nd dosing level there were no reported adverse drug reactions. At the 3rd dosing level 5 patients (42%) developed significant hypotension during clonidine treatment that responded to intravenous fluids. There were no statistical differences in ventilation rate, pre and post GCS, and mortality rates over all levels.ConclusionOur findings suggest use of moderate doses of clonidine in acute organophosphate poisoning can be used without causing frequent clinical problems but that higher doses are associated with a high incidence of hypotension requiring intervention. Further studies are needed to study the efficacy of clonidine as an antidote in organophosphate poisoning.Trial registrationCurrent Controlled Trial ISRCTN89917816.

Therapeutic effect of Penehyclidine on children's acute organophosphorus pesticide poisoning

目的 观察长托宁治疗小儿急性有机磷中毒的疗效.方法 有机磷中毒患儿36例,随机分为长托宁组和阿托品组,各18例.在常规治疗基础上,分别应用长托宁和阿托品治疗.对两组中毒症状消失时间、用药次数、胆碱酯酶恢复时间、住院天数及治愈率进行比较.结果 长托宁组全部治愈,3例出现躁动,1例瞳孔轻度扩大.阿托品组死亡1例,治愈17例,全部病例均有面部潮红,瞳孔扩大,心率增快,发热,其中高热5例,2例出现阿托品中毒症状.两组患儿在平均用药次数、胆碱酯酶恢复时间、平均住院天数方面差异均有非常显著性(P＜0.01),两组息儿中毒症状消失时间比较差异有显著性(P＜0.05).结论 长托宁治疗小儿有机磷中毒疗效肯定,不良反应少,是目前比较理想的抗胆碱药物。

Application of different airway opening approaches in patients with intermediate syndrome following severe acute organophosphorus pesticide poisoning

目的 比较急性有机磷农药中毒(AOPP)重型中间综合征(IMS)患者呼吸支持过程中选择不同气道开放方式对病程的影响.方法 选择2004年12月至2007年12月入住ICU的重型IMS患者73例,按气道开放方式分为:经口气管插管组22人,常规气管切开组25人,经皮扩张气管切开组26人,比较各组患者阿托品用量、氯解磷定用量、肺部感染、机械通气时间、留置人工气道时间、ICU住院时间的差异.结果 常规气管切开组、经皮扩张气管切开组机械通气时间分别为(9.2±2.5)、(8.6±2.5)d,留置人工气道时间分别为(13.6±2.5)、(13.7±2.1)d,ICU住院时间分别为(15.1±2.6)、(15.0±2.1)d,均明显低于经口气管插管组,差异均有统计学意义(P<0.05).结论 重型IMS患者尽早行气管切开术有利于其呼吸功能的恢复。

Therapeutic efficacy of hemoperfusion combined with comtinuous vein-vein hemofiltration in treatment of acute severe organophosphorus pesticide poisoning

目的 评价血液灌流加连续性静脉-静脉血液滤过治疗重度有机磷中毒的价值.方法 53例AOPP患者分为两组,对照组21例行传统治疗,治疗组32例在常规治疗基础上联合运用血液灌流及持续静-静脉血液滤过治疗.观察比较两组的治疗效果.结果 治疗组的昏迷持续时间、胆碱酯酶活力恢复时间、住院时间、阿托品应用总量均小于对照组,有显著性差异(P＜0.01).反跳发生率、中间综合症发生率均小于对照组,有显著性差异(P＜0.0 5).结论 血液灌流加连续性静脉-静脉血液滤过治疗重度有机磷中毒更为安全而有效。

Naloxone and acute organophosphorus pesticide poisoning-related respiratory failure

This study was to examine the influence of Naloxone on respiratory failure among patients with acute organophosphorus pesticide poisoning(AOPP). From June 1997 to May 2000, 106 AOPP-related respiratory failure patients were assigned to the control group. During June 2000 to September 2002, 83matched patients were assigned to the treatment group and obtained intravenous Naloxone injection. Duration of mechanical ventilation was recorded. In comparison to the treatment group, the control group showed prolonged mechanical ventilation[(342±123)h vs(235±89)h;t=6. 92, P＜0. 01], demonstrating that intravenous Naloxone injection may promote the reoccurrence of independence-breathing in AOPP-related respiratory failure patients. Key words: Poisoning; Naloxone

Risk factors of ventilator related pneumonia in acute organophosphorus pesticide poisoning

目的 探讨急性有机磷农药中毒(AOPP)患者机械通气治疗时呼吸机相关性肺炎的危险因素.方法 回顾分析本院收治的96例AOPP呼吸衰竭机械通气患者呼吸机相关性肺炎(VAP)及其临床观察指标.先以单因素分析筛选出有统计学意义的危险因素,再通过多元逐步Logistic回归分析确定VAP的独立危险因素.结果 VAP发生率为47.92%,病死率为7.29%.单因素分析显示,入院时意识障碍、应用广谱抗生素、原有慢性呼吸道疾病、留置胃管、使用抑酸剂及感染确定前使用阿托品总量是VAP的危险因素;多元Logistic回归分析显示,VAP的独立危险因素及其OR值和95%可信区间依次为原有慢性呼吸道疾病7.384(1.654～32.967)、使用抑酸剂5.151(1.527～17.381)、留置胃管3.983(1.024～14.312)、入院时意识障碍3.567(1.274～9.987).结论 原患有慢性呼吸道疾病、使用抑酸剂、留置胃管3 d以上、入院时意识障碍是AOPP患者发生VAP的危险因素。

Clinical observation of bedside hemoperfusion and repeated gastrolavage and purgation on acute severe organophosphorus pesticide poisoning

目的 研究血液灌流联合洗胃、导泻治疗急性重度有机磷农药中毒的效果.方法 回顾性分析自2003年7月至2006年6月重度有机磷农药中毒病历资料完整的72例临床资料.全部病例均在急诊科洗胃及内科常规处理后转入ICU并给予血液灌流治疗,将内科常规治疗、血液灌流同时再次反复洗胃、导泻的34例作为治疗组,将仅内科常规治疗、血液灌流,未再次洗胃、导泻的38例作为对照组.结果 治疗组治疗开始至清醒时间,氯磷定、阿托品用量,住院时间均较对照组明显减少,治愈率提高,两组比较差异有统计学意义.结论 内科常规治疗加早期血液灌流治疗急性重度有机磷农药中毒安全有效,早期血液灌流同时反复洗胃、导泻,可以进一步提高治愈率。

Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial

The role of oximes for the treatment of organophosphorus pesticide poisoning has not been conclusively established. We aimed to assess the effectiveness of a constant pralidoxime infusion compared with repeated bolus doses to treat patients with moderately severe poisoning from organophosphorus pesticides. 200 patients were recruited to our single-centre, open randomised controlled trial after moderately severe poisoning by anticholinesterase pesticide. All were given a 2 g loading dose of pralidoxime over 30 min. Patients were then randomly assigned to control and study groups. Controls were given a bolus dose of 1 g pralidoxime over 1 h every 4 h for 48 h. The study group had a constant infusion of 1 g over an hour every hour for 48 h. Thereafter, all patients were given 1 g every 4 h until they could be weaned from ventilators. Analysis was by intention to treat. Primary outcome measures were median atropine dose needed within 24 h, proportion of patients who needed intubation, and number of days on ventilation. The study is registered at http://www.clinicaltrials.gov with the identifier NCT00333944. 100 patients were assigned the high-dose regimen, and 100 the control regimen. There were no drop-outs. Patients receiving the high-dose pralidoxime regimen required less atropine during the first 24 h than controls (median 6 mg vs 30 mg; difference 24 mg [95% CI 24-26, p<0.0001]). 88 (88%) and 64 (64%) of controls and high-dose patients, respectively, needed intubation during admission to hospital (relative risk=0.72, 0.62-0.86, p=0.0001). Control patients required ventilatory support for longer (median 10 days vs 5 days; difference 5 days [5-6, p<0.0001]). A high-dose regimen of pralidoxime, consisting of a constant infusion of 1 g/h for 48 h after a 2 g loading dose, reduces morbidity and mortality in moderately severe cases of acute organophosphorus-pesticide poisoning.

Gastric lavage in acute organophosphorus pesticide poisoning (GLAOP)--a randomised controlled trial of multiple vs. single gastric lavage in unselected acute organophosphorus pesticide poisoning.

BackgroundOrganophosphorus (OP) pesticide poisoning is the most common form of pesticide poisoning in many Asian countries. Guidelines in western countries for management of poisoning indicate that gastric lavage should be performed only if two criteria are met: within one hour of poison ingestion and substantial ingested amount. But the evidence on which these guidelines are based is from medicine overdoses in developed countries and may be irrelevant to OP poisoning in Asia. Chinese clinical experience suggests that OP remains in the stomach for several hours or even days after ingestion. Thus, there may be reasons for doing single or multiple gastric lavages for OP poisoning. There have been no randomised controlled trials (RCTs) to assess this practice of multiple lavages. Since it is currently standard therapy in China, we cannot perform a RCT of no lavage vs. a single lavage vs. multiple lavages. We will compare a single gastric lavage with three gastric lavages as the first stage to assess the role of gastric lavage in OP poisoning.Methods/DesignWe have designed an RCT assessing the effectiveness of multiple gastric lavages in adult OP self-poisoning patients admitted to three Chinese hospitals within 12 hrs of ingestion. Patients will be randomised to standard treatment plus either a single gastric lavage on admission or three gastric lavages at four hour intervals. The primary outcome is in-hospital mortality. Analysis will be on an intention-to-treat basis. On the basis of the historical incidence of OP at the study sites, we expect to enroll 908 patients over three years. This projected sample size provides sufficient power to evaluate the death rate; and a variety of other exposure and outcome variables, including particular OPs and ingestion time. Changes of OP level will be analyzed in order to provide some toxic kinetic data.Discussionthe GLAOP study is a novel, prospective cohort study that will explore to the toxic kinetics of OP and effects of gastric lavage on it. Given the poor information about the impact of gastric lavage on clinical outcomes for OP patients, this study can provide important information to inform clinical practice.

The Diagnostic Significance of Plasma Cardiotroponin I (cTnI) in Early Cardiac Damage With Acute Organophosphorus Pesticide Poisoning

Objective To explore the diagnostic significance of plasma cardiotroponin I （cTnI） in early cardiac damage with acute organophosphorus pesticide poisoning and it＇s detection effect of heart events incidece. Methods 50 cases with AOPP were divided into group A（mild）,groupB（moderate）,group C（severe）.cTnI, CK-MB and electrocadiogram（ECG） performed within 4 hours and the twenty-four hours afer admission .Plasma cTnI was compared as single index and other index, in order to obtain the difference with early detectable one for cardiac damage in patients with AOPP. Results The cTnI level in group C was signicance difference higher than in group B,A. The cTnI level in group B was signicance difference higher than in group A too. there was no signicance difference to CK-MB and ECG among the all groups（p〉0. 05）.The cases with elevated cTnI were signicantly higher than other cases with abnormal index（p〈0. 05）. Conclusion Mesuring plasma cWnI can improve the detectable rate to cardiac damage in patients with AOPP, and it＇s sensitivity were better than that of CK-MB and ECG. Mesuring plasma cTnI can predict heart events . Key words: Acute organophosphorus Pesticide poisoning Plasma cardiotroponin I Cardiac damage

Respiratory failure in acute organophosphorus pesticide self-poisoning

Acute organophosphorus (OP) pesticide poisoning is a major clinical problem in the developing world. Textbooks ascribe most deaths to respiratory failure occurring in one of two distinct clinical syndromes: acute cholinergic respiratory failure or the intermediate syndrome. Delayed failure appears to be due to respiratory muscle weakness, but its pathophysiology is unclear. To describe the clinical patterns of OP-induced respiratory failure, and to determine whether the two syndromes are clinically distinct. Prospective study of 376 patients with confirmed OP poisoning. Patients were observed throughout their admission to three Sri Lankan hospitals. Exposure was confirmed by butyrylcholinesterase and blood OP assays. Ninety of 376 patients (24%) required intubation: 52 (58%) within 2 h of admission while unconscious with cholinergic features. Twenty-nine (32%) were well on admission but then required intubation after 24 h while conscious and without cholinergic features. These two syndromes were not clinically distinct and had much overlap. In particular, some patients who required intubation on arrival subsequently recovered consciousness but could not be extubated, requiring ventilation for up to 6 days. Respiratory failure did not occur as two discrete clinical syndromes within distinct time frames. Instead, the pattern of failure was variable and overlapped in some patients. There seemed to be two underlying mechanisms (an early acute mixed central and peripheral respiratory failure, and a late peripheral respiratory failure) rather than two distinct clinical syndromes.

Development of antidotes: Problems and strategies

Antidotes against chemical warfare agents are “orphan drugs” given that these poisonings are rare. Therefore, they are of limited interest to the pharmaceutical industry. For this reason, and recognizing the increasing threat of terrorist or asymmetrical use of chemical warfare agents, the responsibility for research into medical countermeasures against these weapons is of primary interest to armies. Accordingly, the research activities of the Bundeswehr Institute of Pharmacology and Toxicology are dedicated to improving diagnosis, prophylaxis and therapy of individuals who are exposed to a chemical agent. Here, antidote development and testing are a high priority in the research program, particularly with respect to organophosphorus (OP) nerve agents and sulphur mustard. The Institute has been coordinating research activities undertaken in house and in collaboration with external researchers. The research program aims to develop primarily in vitro models to minimize the sacrifice of animals, using strategies, which involve human material early in antidote testing. An animal model using isolated mouse diaphragm demonstrated the correlation between AChE activity and neuromuscular function. A similar relationship was found between erythrocyte AChE and neuromuscular function in patients with acute OP pesticide poisoning. In vitro rate constants of the various reactions that are involved in enzyme inhibition and reactivation using human material were used for prediction of what would happen in vivo. This prediction could be confirmed in a patient with acute OP pesticide poisoning. Finally, computer models are being established to estimate the therapeutic effect of an antidote in various human poisoning scenarios. This approach is necessary to compensate for the lack of human clinical pharmacodynamic studies that are usually required for drug regulatory approval, given the obvious ethical issues preventing human volunteer studies with these agents.