Early Death Due to Severe Organophosphate Poisoning Is a Centrally Mediated Process

OBJECTIVE: To distinguish whether early death from severe organophosphate (OP) poisoning with dichlorvos is mediated through peripheral or central nervous system (CNS) actions. METHODS: Wistar rats (n = 72) were randomized to pretreatment with either: normal saline (controls), peripheral anticholinergics (glycopyrrolate [low, medium, or high dose] or nebulized ipratropium bromide), or CNS + peripherally acting anticholinergics (diphenhydramine, nebulized atropine, or injected atropine). All treatments were given prior to a subcutaneous injection of 25 mg/kg dichlorvos (n = 8 per group). Survival was assessed at 10 minutes (early death) and 24 hours (delayed death). Kaplan-Meier (95% confidence intervals [95% CIs]) and chi-squared analysis was then performed to determine differences between treatments. RESULTS: Regardless of treatment, all animals exhibited profound nicotinic effects (fasciculations) without obvious seizures within 2 minutes of poisoning. In rats pretreated with peripherally acting agents, the fasciculations were rapidly followed by reduced motor activity, sedation, and death. Mortality at 10 minutes for saline controls, glycopyrrolate, and ipratropium was 88%, 96%, and 100%, respectively. The single control animal surviving beyond 10 minutes went on to develop peripheral cholinergic manifestations, including hypersalivation, urination, and defecation. Only one of 24 animals treated with injected atropine, nebulized atropine, or diphenhydramine died during the early phase of poisoning; all others survived to 24 hours (p < 0.01). CONCLUSIONS: Death in acute, severe OP poisoning is prevented by pretreatment with anticholinergic agents that cross the blood-brain barrier, but not by agents with only peripheral actions. Early death due to OP poisoning appears to be a centrally mediated process.     

盐酸戊乙奎醚治疗急性有机磷中毒临床观察

目的：比较盐酸戊乙奎醚（长托宁）与阿托品治疗急性有机磷中毒（AOPP）的疗效。方法：将67例AOPP患者随机分为两组,以阿托品＋氯解磷定为对照组（32例）,长托宁＋氯解磷定为治疗组（35例）,比较两组的治疗效果。结果：治疗组中毒症状消失时间、CHE恢复程度、用药总量、治愈时间、反跳率均优于对照组（P〈0.05）。结论：长托宁是治疗AOPP较为理想的药物。     

Acute Abdomen Associated with Organophosphate Poisoning

Background

Pesticides are extensively used in developed and developing countries.

Objectives

The present study was designed to evaluate the clinical course of patients with carbamate or organophosphate poisoning presenting to a University-based emergency department (ED).

Methods

All consecutive patients admitted to our ED due to intoxication with carbamate or organophosphate compounds over a 2-year period were enrolled prospectively.

Results

A total of 49 consecutive patients (26 females) were diagnosed with carbamate or organophosphate poisoning in the 24-month study period. The mean age of the patients was 32 ± 13.1 years (range 16-70 years). Signs and symptoms most frequently noted in patients with organophosphate or carbamate poisoning were perspiration, vomiting, and bronchorrhea. Abdominal pain was reported by 65.3% of the patients. Abdominal ultrasonography was performed in 22 patients who complained of abdominal pain as a leading symptom. Among these, 63.6% were found to have abdominal free fluid. Pancreatitis and peritonitis developed in one case. Atropine treatment was administered for approximately 24-36 h, with a mean total dose of 13.75 ± 6.75 mg. Pralidoxime was administered to 70.9% of patients with organophosphate poisoning, but was not used in patients intoxicated with carbamates. Endotracheal intubation and mechanical ventilatory support were required in 14.2% of the patients. Mean duration of mechanical ventilation was 3.7 ± 2.2 days. The overall mortality rate was 10.2%.

Conclusion

Patients with a diagnosis of organophosphate poisoning should be screened for acute abdomen. The findings in our study suggest that these patients should undergo routine abdominal ultrasonography, especially in cases with abdominal pain along with other abdominal complaints.     

Jimson Weed Extract as a Protective Agent in Severe Organophosphate Toxicity

Treatment of patients following an organophosphate (OP) exposure can deplete a hospital's entire supply of atropine. Given the possibility of multiple severe exposures after a terrorist attack using OP nerve agents, there exists a need for either greater atropine stores or the development of alternative antidotes. Jimson weed (Datura stramonium) contains atropine and other anticholinergic compounds and is common and readily available. It is used recreationally for its central anticholinergic effects and is made easily into an extract by boiling the crushed seeds. The extract has rapid onset of effects and may be useful for treatment of OP poisoning. OBJECTIVES: To determine whether pretreatment with an easily stored and prepared Datura seed extract (DSE) will increase survival following a severe OP poisoning. METHODS: Datura stramonium seeds were collected, crushed, and then heated in water to make a 2-mg/mL atropine solution (100 seeds contain approximately 6 mg of atropine or 0.007 mg/seed). Male rats were randomized to pretreatment with either saline (n = 10) or 7.5 mg/kg DSE (n = 10) given as a single intraperitoneal injection 5 minutes prior to a subcutaneous injection of 25 mg/kg of dichlorvos. The endpoint was time to death recorded by a blinded observer. RESULTS: The Kaplan-Meier estimates of the 24-hour survival rate was 90% (95% CI = 56% to 100%) for the DSE-pretreated group and 10% (95% CI = 0% to 45%) for the control group. The log-rank test revealed a statistically significant longer survival for the Datura-treated animals (p = 0.0002). Median survival time was 22 minutes 30 seconds for the control group and greater than 24 hours for the DSE-pretreated group. CONCLUSIONS: Pretreatment with DSE significantly increases survival following severe dichlorvos exposure.     

重度有机磷农药中毒78例临床分析

目的：探讨重度有机磷农药中毒的救治方法。方法：回顾性分析重度有机磷农药中毒78例的临床资料。结果：78例中痊愈71例,死亡7例。结论：早期、及时、足量阿托品,尽早阿托品化,仔细观察,呼吸衰竭者及时使用呼吸机可提高存活率。     

微泵注入与肌注氯解磷定对急性有机磷中毒的疗效比较

目的：比较氯解磷定微泵与肌注二种不同的给药方式在救治急性有机磷中毒中的治疗效果。方法：将42例急性有机磷农药中毒患者在常规对抗毒蕈碱样症状治疗基础上按就诊顺序单号和双号分为观察组和对照组各21例,观察组采用微泵注入氯解磷定的方式,对照组应用肌注氯解磷定的方式,比较两组患者的治疗效果和胆碱酯酶（ChE）的恢复情况。结果：观察组中胆碱酯酶的恢复时间、氯解磷定的总量、从昏迷到清醒时间和住院的平均时间均明显小于对照组（P〈0．05）。结论：微泵注入氯解磷定治疗急性有机磷中毒的效果明显优于肌注氯解磷定。     

未成年人有机磷中毒原因分析及健康教育

分析63例未成年有机磷中毒患者的中毒原因和途径。本组未成年有机磷中毒患者以消化道中毒多见,共40例（占63％）,其次是皮肤吸收中毒13例（占21％）,呼吸道吸收中毒7例（占11％）,其他3例。中毒原因：与儿童有关的包括误服、服毒自杀、在喷药环境中玩耍;与家长有关的包括用后未洗手、未更衣便接触儿童,误用农药作皮肤药或灭蚊剂等。认为有机磷农药管理有待加强,对监护人及年龄偏大患者进行相应的健康教育具有重大意义。健康教育包括：对家长和对未成年患者的预防知识宣教,如家长应正确保管、使用有机磷农药,儿童应认识其毒害性;中毒入院后用药、饮食等方面的知识指导,出院后加强休息和防止再次中毒等知识的指导。     

Calcium Neutralizes Fluoride Bioavailability in a Lethal Model of Fluoride Poisoning

Objectives: Acute systemic fluoride poisoning can result in systemic hypocalcemia, cardiac dysrhythmias, and cardiovascular collapse. Topical and intraarterial therapy with calcium or magnesium salts reduces dermal injury from fluoride burns. The mechanism of these therapies is to bind and inactivate the fluoride ion. The purpose of this study is to evaluate the effect of calcium and magnesium to decrease the bioavailability of fluoride in a lethal model of fluoride poisoning. Methods: In preliminary studies, we determined that fluoride 3.6 mM/kg intraperitoneally in the form of sodium fluoride was uniformly and rapidly fatal in a mouse model. Using this fluoride dose, we performed a controlled, randomized, blinded study of low-and high-dose calcium chloride (1.8 and 3.6 mM/kg intraperitoneally, respectively) and magnesium sulfate (3.6 mM/kg intraperitoneally) to decrease the bioavailability of the fluoride ion. After injection with sodium fluoride, animals were immediately treated with injections of sodium chloride (control), calcium chloride (low- or high-dose), or magnesium sulfate. The major outcome was 6-hour survival using a Cox Proportional Hazard model. Results: All untreated animals died within 60 minutes. Using a Cox Proportional Hazard model, each 1.8 mM/kg dose of calcium chloride administered reduced the risk of death by 33%. Magnesium sulfate treatment was not associated with a hazard reduction. Conclusion: Calcium chloride administered simultaneously with sodium fluoride reduces the bioavailability of fluoride poisoning in a mouse model. The equivalent dose of magnesium sulfate does not significantly decrease fluoride bioavailability.     

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.     

Oral Treatment of Organophosphate Poisoning in Mice

OBJECTIVE: Organophosphates are used as pesticides, herbicides, and chemical warfare agents. Treatment of organophosphate poisoning is with intravenous atropine and pralidoxime in addition to supportive care. This study determined the efficacy of oral agents in preventing death from organophosphate poisoning. METHODS: The organophosphate paraoxon (8 mg/kg) was used in a murine model with lethality at four and 24 hours as an end point. For oral treatment, 15 male Balbc mice were given either atropine sulfate (4 mg/kg), or a combination of atropine sulfate (4 mg/kg) with pralidoxime (100 mg/kg), by oral gavage. A control group of 22 mice received water by oral gavage. Chi-square analysis was used to compare results in the different groups. RESULTS: Of the control group, six of 22 survived to four hours after paraoxon exposure. Of the exposed animals treated with oral atropine, eight of 15 survived to four hours. Of the exposed animals treated with a combination of atropine and pralidoxime, 13 of 15 survived to four hours. All animals surviving to four hours survived to 24 hours. The increased survival of animals in the atropine group relative to the control group was not significant (p = 0.09). Survival was significant in the group treated with atropine and pralidoxime relative to atropine alone (p = 0.02) and to the control group (p = 0.0002). All treated mice surviving at four hours were alive at 24 hours. CONCLUSIONS: Both oral atropine and a combination of oral atropine and pralidoxime improved survival, and combination therapy achieved statistical significance. Generalization of this result to other organophosphate pesticides, other doses of paraoxon, and other species cannot be made without further investigations.     

有创-无创序贯通气治疗急性有机磷农药中毒致中间期肌无力综合征

[目的]探讨有创-无创序贯通气治疗急性有机磷农药中毒(AOPP)致中间期肌无力综合征(IMS)合并急性呼吸衰竭(ARF)的可行性及疗效.[方法]AOPP致IMS合并ARF有创机械通气的45例患者,出现IMS控制窗后,随机分为有创机械通气治疗组(简称有创组,20例) 和有创-无创序贯通气治疗组(简称序贯组,25例).记录序贯组患者改无创通气治疗前、后2 h、24 h动脉血气、心率(HR)、呼吸(RR)、血氧饱和度(SpO2)值 ,并统计所有患者再次气管插管率、呼吸机相关性肺炎发生率及有创通气时间、总机械通气时间、住ICU时间及费用情况.[结果]序贯组患者改无创通气前、后2 h、24 h生命体征及动脉血气比较差异无显著性(P＞0.05);撤机后序贯治疗组在有创通气时间、总机械通气时间、住ICU 时间明显缩短(P＜0.05);住院费用明显下降(P＜0.05);呼吸机相关性肺炎(VAP)的发生率序贯治疗组明显下降(P＜0.05);序贯治疗组重新气管插管率明显低于对照组(P＜0.05).[结论]有创-无创序贯通气能有效治疗AOPP致IMS合并ARF,并较常规有创机械通气治疗减少再插管率、VAP发生率及机械通气时间及费用等,临床可积极尝试.     

Glasgow Coma Scale Score and QTc Interval in the Prognosis of Organophosphate Poisoning

OBJECTIVES: The aim of this study was to assess the applicability of the Glasgow Coma Scale (GCS) score and the Q-T interval corrected for heart rate (QTc interval) in predicting outcome and complications in patients with organophosphate (OP) poisoning. METHODS: This prospective, observational study included 65 patients older than 18 years. In the out-of-hospital setting, the end-tidal carbon dioxide (ETCO2), oxygen saturation (SaO2), QTc interval, and GCS score were monitored in each patient. A statistical comparison was then made between the group with respiratory failure and the group without this complication. RESULTS: The group with complications had significantly different values of measured parameters--a longer QTc interval and a lower GCS score, a higher number of intubations, and worse outcomes (p < 0.05). The two measures, GCS score and QTc interval, have been shown to be equally good in predicting respiratory failure and hospital mortality in patients with OP poisoning. CONCLUSIONS: In the initial out-of-hospital care of patients with OP poisoning, it is essential to monitor QTc interval and GCS score. These measures help with prognosis, and may suggest when to initiate precautions to prevent complications (i.e., respiratory failure). The simplicity and promptness of these methods allow providers to perform early and effective triage.     

QTc Prolongation as a Useful Prognostic Factor in Acute Paraquat Poisoning

Background

Acute paraquat poisoning has a high mortality rate. Several prognostic factors have been proposed to predict the mortality risk of paraquat-poisoned patients. However, these prognostic factors are complex and some require a laboratory. Corrected QT (QTc) has been used as a prognostic factor in several clinical conditions, such as acute organophosphate poisoning. In addition, the measurement can be obtained in a reasonable amount of time.

Study Objectives

This study's objective was to investigate whether QTc can predict mortality in paraquat-poisoned patients.

Methods

This was a retrospective study. Potential prognostic factors such as QTc, vital signs at admission, and certain biochemistry variables were analyzed with Cox regression analyses for their ability to predict a patient's survival from paraquat poisoning.

Results

Sixty acute paraquat-poisoned patients were admitted to the emergency department during the study period. The QTc of the survival group ranged from 0.35 to 0.48 s, whereas the nonsurvivor group ranged from 0.32 to 0.63 s. The nonsurvivor group contained a higher percentage of patients with QTc prolongation (≥0.45 s) compared with the survivor group (p = 0.04). The hazard ratio of QTc prolongation for a patient's death was found to be 2.47 (95% confidence interval [CI] 1.68–5.67) in patients with a lower potassium level (<3.2 mEq/L) and 3.71 (95% CI 1.53–8.97) in patients with a higher potassium level (≥3.2 mEq/L). In addition, hyperdynamic circulation was observed upon admission of these poisoned patients.

Conclusion

QTc prolongation is a useful prognostic factor for predicting death in acute paraquat-poisoned patients. Cardiovascular collapse may occur in some paraquat-poisoned patients. Physicians can use QTc as an indicator of a patient's severity of poisoning and mortality risk.     

The comparison of therapeutic effects of atropine and pralidoxime on cardiac signs in rats with experimental organophosphate poisoning

Organophosphate poisoning causes disturbances in cardiac conduction and potentially fatal severe cardiac rhythm abnormalities. This study investigated the cardiac effects of atropine and pralidoxime in the treatment of organophosphate poisoning in rats. Three groups of 10 adult male Wistar rats were anesthetized with an intraperitoneal injection of ketamine 100 mg/kg and xylazine 10mg/kg and connected to a computerized electrocardiographic monitor. Each rat was then injected intraperitoneally with the pesticide dichlorvos 70 mg/kg. Sixty seconds after the injection, 10 rats were injected with saline, 10 with pralidoxime mesylate 20 mg/kg, and 10 with atropine 10 mg/kg. During the computerized electrocardiographic monitoring, each rat’s heart rate and QT_c intervals were recorded and analyzed as the injections were administered. The heart rates in all 3 groups did not differ before the dichlorvos was administered, nor at 60 seconds afterward, but in the atropine group, the time elapsed before the first decline in heart rate was significantly longer than that in the control group (P< .05). In addition, the interval before death was significantly longer in the atropine group than in either the control group or the pralidoxime group (P< .05 for both). The QT_c was almost identical in each of the groups. Atropine has beneficial effects on the heart rate, prolongs the time before the heart rate declines, and delays death but has no effect on the QT_c interval. Further research about the toxic effects of organophosphate compounds on myocardial cells is warranted.     

中毒严重程度评分在急性有机磷农药中毒中的临床意义

目的：探讨中毒严重程度评分（PSS）在急性有机磷农药中毒（AOPP）患者病情严重程度评估中的意义,以指导临床决策。方法：我院急救医疗中心2004年1月至2012年7月收治急性有机磷农药中毒患者73例．根据患者入院时的PSS评分分为1、2、3三组,比较三组的临床资料。结果：PSS评分越高,并发症发生率越高,住院天数越长;PSS评分与APACHEⅡ评分有良好的相关性。结论：PSS评分能反映急性有机磷农药中毒患者的病情严重程度,指导临床正确决策和预后判断。     

综合性医院急性中毒患者的回顾性流行病学分析

目的了解武汉协和医院急性中毒的最新流行病学特点,为急性中毒的进一步防治提供科学依据。方法对2000年1月～2006年1月583例资料完整的急性中毒住院病例进行回顾性流行病学分析。结果所调查患者当中男289例（49．57％）,女294例（50．43％）,男女之比1：1．02;高发年龄段为21～40岁（42．20％）,且男女之比1：1．28（P〈0．05）;中毒患者职业排在前4位的依次是无业人员、农民、工人和儿童;中毒类型主要是药物中毒174例（29．85％）,其次是酒精中毒90例（15．44％）和农药中毒88例（15．09％）;中毒时间分布特点呈无规律性波动;自杀是中毒的主要原因（254例,占43．57％）;治愈或好转522例（89．54％）,未愈或死亡51例（8．75％）。结论急性中毒防治的关键在于强化人们身心健康教育以及提高急诊医疗救治水平。