Ultrastructural changes in rat liver treated with pralidoxime following acute organophosphate poisoning

We investigated the ultrastructural effects of methamidophos and the positive effects of 2-pralidoxime (2-PAM) on the liver. Male Wistar-albino rats were assigned to 4 groups and all were treated per os: Group 1 (n=10) received 30 mg/kg methamidophos; Group 2 (n=7) (serving as controls for Group 1) received physiologic NaCl; Group 3 (n=10) received 30 mg/kg methamidophos and was treated with 2-PAM and atropine when cholinergic symptoms were noted; and Group 4 (n=7) (serving as controls for Group 3) was treated with physiologic NaCl. Plasma cholinesterase was measured using radioimmunoassay. Liver tissues were prepared for electron microscopic studies. Methamidophos treatment of Group 1 led to serious changes in hepatocytes and organelles. These changes were not detected in Group 3. In Group 1, the chromatin content of some hepatocyte nuclei and cytoplasmic density increased; these cells also became vacuolar in appearance as a result of lysis in the mitochondrial matrices. In some cells, the lipid content constituted the majority of the cytoplasm. Furthermore, these cells were surrounded by glycogen accumulation. In some areas of the perisinusoidal zone, collagen fibers had increased to form bands. None of these changes were noted in Group 3. These findings suggest that acute organophosphate poisoning causes serious histopathological effects in rat liver, but that these changes are reversible with appropriate treatment strategies.     

Endocrine changes in patients with acute organophosphate poisoning

In critical illness, several drugs and various stressful conditions modify the functions of neurotransmitters which consequently affect the secretion of pituitary hormones. Although the role of neurotransmitters in the regulation of endocrine system is well known, cholinergic actions have been less investigated. In animals, cholinesterase inhibitors were shown to modify the pituitary-thyroid and pituitary-adrenal axes, and to affect prolactin levels. The aim of the present study was to determine the effect of the organophosphate compounds on endocrine system, particularly pituitary hormones. This prospective study was performed in Medical Intensive Care Unit of Erciyes University Medical School Hospital. Twenty-two consecutive patients (ten males and 12 females aged 28+/-8 years) with organophosphate poisoning were included in the study. ACTH (P<0.002), cortisol (P<0.0005) and PRL (P<0.005) levels were significantly higher during poisoning than after resolution of poisoning. FSH levels were significantly lower during poisoning (P<0. 05). Sick euthyroid syndrome was determined in seven patients (31. 8%). Two of them had low fT3 (with normal fT4 and TSH), two had low fT4 (with normal fT3 and TSH) and three had low TSH (with normal fT3 and fT4) levels. Serum levels of these hormones returned to normal values after resolution of poisoning. The present study demonstrated that organophosphate compounds affected PRL, ACTH and cortisol levels, but did not change LH levels. Organophosphate compounds may result in sick euthyroid syndrome. These conditions may be related to the effects of acetylcholine and direct effect of organophosphate compounds.     

配合抢救急性有机磷农药中毒的护理体会

有机磷中毒在基层医院一直是较常见的内科急症.提高抢救护理质量甚为重要.根据书本的理论知识和多年的实际工作经验,得出体会.     

Two cases of organophosphate poisoning with development of intermediate syndrome

Two cases of intermediate syndrome caused by organophosphorus poisoning are reported. Trichlorfon, propoxur (a carbamate pesticide) and fenthion were ingested in both attempts at suicide. After successful conventional therapy during the cholinergic phase, but before the time when the onset of delayed neuropathy might be expected, an intermediate syndrome developed. It affected the proximal limb muscles, neck flexors and respiratory muscles 2 d after pesticide ingestion. The two patients needed respiratory support. Recovery from the intermediate syndrome was complete in both patients, although one subsequently developed delayed neuropathy.     

Extrapyramidal syndrome as a delayed and reversible complication of acute dichlorvos organophosphate poisoning

We describe 4 cases of delayed extrapyramidal disorder following acute dichlorvos poisonings. All patients were seriously poisoned since all exhibited profound coma and respiratory failure, and they were all tracheally intubated and mechanically ventilated. On admission, plasma cholinesterase activity was greaty decreased, < 10 micromol/ml/h at 37 C in all patients (< 10% of normal for our laboratory). Extrapyramidal symptoms occurred between 5 and 15 d and were characterized by dystonia of arms and legs, resting tremor, cogwheel rigidity, and hypereflexia. With bromocriptine therapy the features of extrapyramidal syndrome disappeared progressively with complete recovery in all patients. Our observations suggest a delayed extrapyramidal syndrome should be taken into account during the course of acute dichlorvos organophosphate poisonings.     

Serum acetylcholinesterase and prognosis of acute organophosphate poisoning

OBJECTIVE: The aim of this study is to investigate the prognostic value of serum acetylcholinesterase levels and their relationship with neurological syndromes (Type 1 syndrome, intermediate syndrome, and delayed polyneuropathy) in acute organophosphate poisoning. MATERIALS AND METHODS: Thirty-two consecutive patients with acute organophosphate poisoning admitted to the Ondokuz Mayis University Emergency Department from June 1999 to January 2001 were evaluated. Patients were assessed according to admission time, symptoms, and results of clinical exams and their serum acetylcholinesterase levels were determined on days 1, 2, 3, 7, and the last day. RESULTS: There was no significant difference between the first-day serum acetylcholinesterase of the patients with severe poisoning (n = 22, 68.75%) and of the patients with mild poisoning (n = 10, 31.25%; NS). There was no discernible difference between the serum acetylcholinesterase obtained on days 1 and 3 after poisoning from the patients with intermediate syndrome (n = 5, 15.6%; means: 0.90 +/- 0.65 vs. 0.88 +/- 0.53, 19.35 vs. 18.92%; NS, sensitivity = 80%; specificity = 87.5%). There was a significant difference between the serum acetylcholinesterase obtained on days 1 and 3 from the patients with nonintermediate syndrome (n = 24, 75%; means: 1.05 +/- 0.24 vs. 1.68 +/- 0.29, 22.58 vs. 36.12%; p < 0.001). There was no discernible significant difference in serum acetylcholinesterase between the patients with organophosphorus-induced delayed polyneuropathy (n = 7, 21.8%) and nonorganophosphorus-induced delayed polyneuropathy. In the patients who died (n = 5, 15.6%), serum acetylcholinesterase showed no discernible increase day 1-the last day (means: 0.50 +/- 0.25 vs. 0.46 +/- 0.26, 10.75 vs. 9.89%; NS). There was a significant difference between the serum acetylcholinesterase levels obtained on days 1 and the last day from the patients who survived (n = 27, 84.3%; means: 1.14 +/- 0.25 vs. 2.32 +/- 0.26, 24.51 vs. 49.89%; p < 0.001). CONCLUSION: In the acute phase of organophosphate poisoning, low serum acetylcholinesterase (> 50% of minimum normal value) supports the diagnosis of organophosphate poisoning but it does not show a significant relationship to the severity of poisoning (NS). The serum acetylcholinesterase activity may be a useful parameter in following the acute prognosis of organophosphate poisoning.     

Antidotal therapy of severe acute organophosphate poisoning: A multihospital study

Out of 859 consecutive cases treated for exposure to organophosphate (PO) insecticides, 53 were included in the study. Criteria for inclusion were severe OP poisoning necessitating artificial ventilation, intensive care monitoring and treatment according to a standard protocol. The protocol was based on relatively high doses of obidoxime, relatively low doses of atropine and overriding with a pacemaker in cases of ventricular arrhythmias and prolonged Q-T interval. Seven patients died during hospitalization. Thirty-two patients (60%) had major central nervous system (CNS) involvement. Five (9.4%) presented severe psychiatric sequelae. Twenty-two patients (41.5%) presented cardiac arrhythmias. Five (9.4%) had liver dysfunction. High frequency of cardiac arrhythmias was observed in patients who received high cumulative doses of atropine and obidoxime; impairment of liver functions was significantly higher in patients who received high cumulative doses of obidoxime. We conclude that each drug should be titrated separately: atropine dosage should be adjusted to the severity of tracheobronchial secretions and bronchospasm, while full doses of obidoxime are justified for the period before “aging” sets in.     

Survival pattern in patients with acute organophosphate poisoning receiving intensive care

BACKGROUND: Approximately 35% of patients acutely poisoned with organophosphates (OP) in developing countries like Sri Lanka require intensive care and mechanical ventilation. However, death rates remain high. OBJECTIVE: To study the outcomes and predictors of mortality in patients with acute OP poisoning requiring intensive therapy at a regional center in Sri Lanka over a period of 40 months. METHODS: Retrospective analysis of all intensive care records of patients with acute OP poisoning admitted to the Intensive Care Unit (ICU) between March 1998 and July 2001. RESULTS: During the study period, 126 subjects were admitted to the ICU with acute OP poisoning. Records of 10 patients were lost and those of 37 were incomplete and hence were excluded. All the remaining 71 patients (59 male) had required endotracheal intubation and mechanical ventilation for a period of four (median) days (range 1-27) in addition to gastric lavage and standard therapy with atropine and oximes and adequate hydration. Of these 71 patients, 36 (28 male) had died. Life table analysis demonstrated a steep decline in the cumulative survival to 67% during the first three days. Systolic blood pressure of < 100 mmHg and FiO2 of >40% to maintain a SpO2 of >92% within the first 24 h were recognized as poor prognostic indicators among mechanically ventilated patients. CONCLUSION: Mortality following OP poisoning remains high despite adequate respiratory support, intensive care, and specific therapy with atropine and oximes. One-third of the subjects needing mechanical ventilation and reaching intensive care units die within the first 72 h of poisoning. Systolic blood pressure of less than 100 mmHg and the necessity of a FiO2>40% to maintain adequate oxygenation are predictors of poor outcome in patients mechanically ventilated in the ICU.     

急性羰基镍染毒大鼠血清镍水平变化探讨

目的 探讨急性羰基镍染毒大鼠血清镍水平的变化规律,为临床救治急性羰基镍中毒患者提供实验室支持依据.方法 以羰基镍250 mg./in3、500 mg/m3两个剂量组给予SPF级大鼠各54只静态吸入30 min,分别于染毒后30 min、2h、4h、8h、12h、24 h、48 h、72 h、7d将大鼠以乙醚在15 s内麻醉,立即剖腹暴露腹主动脉,采集2 ～3 mL血液,分离0.5 ～1 mL血清,用美国PE公司AA800原子吸收仪（石墨炉法）检测血清镍含量,并与健康大鼠相比较.结果 250 mg/m3剂量组30 min、2h、4h、8 h、12 h、24h、48 h、72 h、7d血清镍含量平均值分别为（33.69±2.59） μg/L、（24.61 ±3.03） μg/L、（27.83±5.69）μg/L、（21.36±4.14）μg/L、（20.39 ±4.14） μg/L、（18.80±7.02）μg/L、（14.51±8.21） μg/L、（13.58±5.78）μg/L、（12.83±4.41）μg/L,30 min为峰值,为对照组的5.30倍,各时间段与健康大鼠差异均有统计学意义（t值分别为5.959、5.958、5.990、5.998、5.997、5.994、5.990、4.317、4.347,均P＜0.01）.500 mg/m3剂量组30 min、2h、4h、8h、12 h、24h、48 h、72 h、7d血清镍含量平均值分别为（72.22±1.62） μg/L、（57.78±12.99） μg/L、（42.25±7.25）μg/L、（103.77±11.ll）μg/L、（79.04±12.26） μg/L、（26.35±6.56）μg/L、（18.58±4.92）μg/L、（17.22±9.73） μg/L、（14.59±5.27） μg/L,8h为峰值,为健康大鼠的16.33倍,各时间段与健康大鼠差异均有统计学意义（t值分别为5.960、5.947、5.978、5.927、5.948、5.959、3.143、2.447、2.440,均P＜0.05）.两组30 min、2h、4h、8h、12h等时间段差异均有统计学意义（t值分别为5.208、2.447、2.449、5.959、5.959,P值分别为0.001、0.049、0.042、0.000、0.000）.结论 急性羰基镍染毒大鼠血清镍含量与染毒剂量呈明显的剂量-效应关系;羰基镍或其代谢产物的排出主要在24h内.     

Changes in the hemodynamic state of patients with acute lethal organophosphate poisoning

The main cause of death due to acute organophosphate poisoning is believed acute respiratory failure caused by peripheral and central cholinergic actions. Today, advances in respiratory management and intensive care make it possible to maintain the respiratory function of patients with organophosphate poisoning, but it is still difficult to maintain their circulation, and some patients with acute organophosphate poisoning die of metabolic acidosis. The present study clarified the hemodynamics of patients with acute lethal organophosphate poisoning. Subjects were patients with severe acute organophosphate poisoning accompanied by hypotension in whom hemodynamics were monitored by pulmonary artery catheterization. In this study, the medical records of these patients were reviewed. Four patients with severe acute organophosphate poisoning accompanied by hypotension and metabolic acidosis died. In 3/4 patients respiration was maintained favorably. In all 4 patients cardiac output was maintained, but systemic vascular resistance index (SVRI) was significantly reduced. Catecholamine administration was ineffective and did not increase SVRI.     

急性冠脉综合征患者血清同型半胱氨酸水平的变化

目的研究急性冠脉综合征（ACS）患者血清同型半胱氨酸水平的变化。方法选取2010年6月．2012年6月于本院心内科住院的105例患者作为ACS组,另选取同期本院心内科稳定性心绞痛（SA）患者60例作为SA组,再选取同期于本院进行体检的健康者60例作为对照组,分别测定各组患者的血清Hey水平。结果ACS组105例患者血清Hey为（44．56±3．58）μmol／L,SA组60例患者Hey为（26．85±4．17）μmol／L,对照组60例患者Hey为（13．67±3．91）μmol／L。ACS组Hey水平较SA组高,SA组Hey水平较对照组高。结论急性冠脉综合征患者血清同犁半胱氡酸水平较正常要高．可作为该疾病预测的一个指标．     

急性有机磷农药中毒患者在院前急救中的护理效果分析

目的:探讨急性有机磷农药中毒患者在院前急救中的护理.方法:对60例有机磷农药中毒患者的临床资料及院前急救过程进行回顾性分析,观察其效果并总结经验.结果:经过积极的抢救和护理,58例中毒患者全部治愈,2例因中毒时间过长延误了抢救时机而死亡.结论:对急性有机磷农药中毒患者进行及时规范的院前急救,准确的病情评估,实施有效的抢救措施,合理的使用解毒药物,可明显提高抢救成功率.     

急性有机磷农药中毒53例救治体会

目的探讨救治急性有机磷中毒的方法和经验总结。方法回顾分析2008年至2010年期间的53例有机磷农药中毒病例的一般资料,中毒药物种类,救治的方法。结果 48例经综合治疗后痊愈,5例死亡。结论尽早、快速、彻底清除毒物,早期足量、联合、重复应用解毒剂和复能剂是抢救有机磷中毒患者的关键环节和措施。     

急性有机磷中毒患者并发心肌损害55例临床分析

目的探讨急性有机磷中毒患者并发心肌损害的心电图及心肌酶学的变化情况。方法对我院1999年1月-2009年1月所收治55例急性有机磷中毒致心肌损害患者的情况进行回顾性分析。结果当心率分别为60～120次/min、120～140次/min、〉150次/min时,中重度中毒患者的心率改变比轻度患者变化明显（P〈0.05）;所有患者中心电图异常17例（30.91%）,心肌酶学均有不同程度的升高。结论有机磷中毒患者,尤其是重症患者,密切观察心肌的损害及损害程度,早期保护心脏功能,将有助于降低病死率。     

有机磷中毒中间综合征患者血栓前状态的研究

目的了解急性有机磷中毒中间综合征（IMS）患者血栓前状态变化情况。方法对23例IMS患者血清P-选择素（Ps）、尿激酶型纤溶酶原激活物（uPA）、纤溶酶原激活物抑制物（PAI）和血管性血友病因子（vWF）水平进行检测,并与21例健康体检者（对照组）和20例急性有机磷中毒非中间综合征组（AOPP组）比较。结果IMS组血清Ps、uPA和vWF水平分别为（42.38±14.12）pg／L、（1.68±0.52）μg/L、（164.33±33.16）％;AOPP组分别为（31.57±12.31）pg／L、（1.23±0.41）μg／L、（135.45±31.21）％;对照组分别为（21.62±12.27）pg／L、（0.61±0.42）μg／L、（112.27±31.41）％。IMs组高于对照组和AOPP组（P〈0.01或P〈0.05）;PAI：IMs组为（1.36±0.38）Au／ml,AOPP组为（0.93±0.31）Au／ml,对照组为（0.74±0.29）Au／ml,IMS组低于对照组和AOPP组（P〈0.01或P〈0.05）。结论IMS患者机体纤溶功能受损,表现为纤溶亢进,其受损程度较AOPP患者重。     

甲氯酚酯治疗儿童急性重度有机磷中毒疗效观察

目的：探讨甲氯酚酯用于儿童急性有机磷农药中毒的临床治疗效果。方法：将近10年我科收治的急性有机磷农药中毒患儿58例,随机分为治疗组30例（女10例）,对照组28例（女9例）,对照组采用洗胃、静脉推注阿托品、解磷定、吸氧、保持呼吸道通畅等常规方法。治疗组在常规治疗的基础上静脉滴注甲氯酚酯（剂量60～100mg/次,2次,d）观察两组儿童的治疗效果。结果：治疗组治愈26例,治愈率86．7％;对照组治愈19例,治愈率67．9％两组比较P〈O．05。结论：在抢救重度有机磷农药中毒时,及时应用甲氯酚酯能明显提高抢救成功率,值得临床推广使用。     

The effect of plasmapheresis on plasma cholinesterase levels in a patient with organophosphate poisoning

OBJECTIVE: To describe the role of plasmapheresis in management of organophosphate poisonings. DESIGN: Case report. SETTING: A medical intensive care unit of a medical faculty. PATIENT: A patient with organophosphate poisoning whose cholinesterase levels continuously decline and then increase up to a normal level after plasmapheresis is performed for his sepsis. INTERVENTIONS: Plasmapheresis with fresh frozen plasma. MEASUREMENTS AND MAIN RESULTS: Baseline plasma cholinesterase (ChE) level was 4001 IU/L (normal values: 4000-10000 IU/L). Aspiration pneumonia was developed on day 3, and sepsis occurred on day 5. During this period, ChE levels gradually decreased. On day 5, plasmapheresis was performed for sepsis. Interestingly, plasma ChE levels increased from 2101 IU/L to 6144 IU/L after plasmapheresis. Atropine and pralidoxime were stopped, and a high level of ChE continued during hospitalization. The patient was successfully weaned from mechanical ventilation 3 days after plasmapheresis. CONCLUSION: Plasma exchange therapy may be considered for patients with organophosphate poisoning unresponsive to atropine and pralidoxime.