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.     

Diphenhydramine as a Protective Agent in a Rat Model of Acute, Lethal Organophosphate Poisoning

OBJECTIVE: To evaluate the effects of diphenhydramine chloride (DPH) on mortality in a rat model of acute, severe organophosphate poisoning (OP). METHODS: Wistar rats (n = 40) were randomized to pretreatment with either normal saline (controls), 5 mg/kg atropine, 3 mg/kg DPH, 15 mg/kg DPH, or 30 mg/kg DPH given as a single intramuscular injection 5 minutes prior to a subcutaneous injection of 25 mg/kg dichlorvos (n = 8 per group). The primary endpoint was 10-minute survival. Survival at 24 hours was a secondary endpoint. Comparison of survival rates between groups was carried out by ANOVA and the Student-Newman-Keuls test. RESULTS: Dichlorvos exposure resulted in profound fasciculations within 2 minutes of injection in all cohorts. In controls, fasciculations were followed by respiratory arrest within 10 minutes (0% survival). The rats receiving atropine pre-treatment exhibited similar fasciculations (nicotinic effects) without subsequent respiratory arrest, resulting in a significant improvement in survival (88%, p < 0.001). The DPH-treated rats exhibited a significant dose-dependent reduction in mortality, with the 3 mg/kg, 15 mg/kg, and 30 mg/kg groups demonstrating 0%, 25%, and 100% survival, respectively. There was no additional mortality between 10 minutes and 24 hours in any group. There was no significant difference in survival between the high-dose DPH and the atropine groups. CONCLUSIONS: Diphenhydramine chloride significantly reduced mortality in rats with acute, severe dichlorvos exposure.     

Multiple Centrally Acting Antidotes Protect against Severe Organophosphate Toxicity

Background: Accumulation of acetylcholine in the central nervous system is believed to account for the rapid lethality of organophosphate pesticides and chemical nerve agents. Diazepam is known to supplement atropine therapy, but its specific mechanism of action is uncertain.
Objectives: To test four centrally acting agents for early antidotal efficacy in severe dichlorvos poisoning in the murine model.
Methods: The up-and-down method was used to dose four candidate antidotes: diazepam, xylazine, morphine, and ketamine. Antidotes were administered subcutaneously to unsedated adult Sprague-Dawley rats who were pretreated with 3 mg/kg intraperitoneal glycopyrrolate. All animals received 20 mg/kg of dichlorvos subcutaneously 5 minutes later. A blinded observer adjudicated the outcomes of 10-minute mortality and survival time.
Results: All animals pretreated with either no antidote (8/8 deaths) or glycopyrrolate alone (8/8) died within 10 minutes of dichlorvos injection. Pretreatment with diazepam (3/9 deaths), or xylazine (3/9), decreased lethality substantially (Fisher p = 0.007; median effective doses, 0.12 mg/kg and 3.0 mg/kg, respectively). Intermediate doses of morphine (3.1 to 5.5 mg/kg) resulted in survival, but higher doses did not, presumably because of excessive respiratory depression (7/11 deaths; p = 0.09). Ketamine (7/8 deaths) was ineffective as an antidote. Survival times also were prolonged in the diazepam and xylazine groups (log-rank p < 0.001) and, to a lesser degree, the morphine group (p = 0.07).
Conclusions: Doses of diazepam, xylazine, and morphine below those used for deep sedation protect against severe dichlorvos poisoning, implying that several distinct central mechanisms are each sufficient to avert lethality. These findings suggest new possibilities for prophylaxis or therapy.     

Respiratory failure in acute organophosphorus pesticide self-poisoning

BACKGROUND: 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. AIM: To describe the clinical patterns of OP-induced respiratory failure, and to determine whether the two syndromes are clinically distinct. DESIGN: Prospective study of 376 patients with confirmed OP poisoning. METHODS: Patients were observed throughout their admission to three Sri Lankan hospitals. Exposure was confirmed by butyrylcholinesterase and blood OP assays. RESULTS: 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. DISCUSSION: 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.     

Role of penehyclidine in acute organophosphorus pesticide poisoning

BACKGROUND:Penehyclidine is a newly developed anticholinergic agent.We aimed to investigate the role of penehyclidine in acute organophosphorus pesticide poisoning(OP)patients.METHODS:We searched the Pubmed,Cochrane library,EMBASE,Chinese National Knowledge Infrastructure(CNKI),Chinese Biomedical literature(CBM)and Wanfang databases.Randomized controlled trials(RCTs)recruiting acute OP patients were identifi ed for meta-analysis.Main outcomes included cure rate,mortality rate,time to atropinization,time to 60%normal acetylcholinesterase(AchE)level,rate of intermediate syndrome(IMS)and rate of adverse drug reactions(ADR).RESULTS:Sixteen RCTs involving 1,334 patients were identifi ed.Compared with the atropineor penehyclidine-alone groups,atropine combined with penehyclidine significantly increased the cure rate(penehyclidine+atropine vs.atropine,0.97 vs.0.86,RR 1.13,95%CI[1.07–1.19];penehyclidine+atropine vs.penehyclidine,0.93 vs.0.80,RR 1.08,95%CI[1.01–1.15])and reduced the mortality rate(penehyclidine+atropine vs.atropine,0.015 vs.0.11,RR 0.17,95%CI[0.06–0.49];penehyclidine+atropine vs.penehyclidine,0.13 vs.0.08,RR 0.23,95%CI[0.04–1.28]).Atropine combined with penehyclidine in OP patients also helped reduce the time to atropinization and AchE recovery,the rate of IMS and the rate of ADR.Compared with a single dose of atropine,a single dose of penehyclidine also signifi cantly elevated the cure rate,reduced times to atropinization,AchE recovery,and rate of IMS.CONCLUSION:Atropine combined with penehyclidine benefi ts OP patients by enhancing the cure rate,mortality rate,time to atropinization,AchE recovery,IMS rate,total ADR and duration of hospitalization.Penehyclidine combined with atropine is likely a better initial therapy for OP patients than atropine alone.     

Acid-base interpretation can be the predictor of outcome among patients with acute organophosphate poisoning before hospitalization

Objectives

Acute organophosphate (OP) poisoning causing alteration in acid-base equilibrium was reported before. Hence, different acid-base statuses may present in patients with acute poisoning due to OP exposure. This study aims to determine the impact of acid-base interpretation in patients with acute OP poisoning before hospitalization in medical care units and to describe the pattern of mortality with different acid-base statuses.

Design and Patients

Over a 9-year retrospective study, from July 1996 to August 2005, a total of 82 consecutive patients with acute OP poisoning were admitted to the China Medical University Hospital (Taichung, Taiwan) within 24 hours after exposure to OP and were enrolled into this study.

Results

Patients with acute OP poisoning were divided into 4 groups: without acidosis, metabolic acidosis, respiratory acidosis, and mixed acidosis. Overall survival (Kaplan-Meier curves) among groups was statistically significant (P < .0001). The mortality rate of acute OP poisoned patients with metabolic acidosis was 25%, and 75% of those patients died of cardiovascular failure. The mortality rate of acute OP poisoning with respiratory acidosis was 50%, and 50% of those patients died of respiratory failure.

Conclusions

Acid-base interpretation can be effective in quick diagnosis and prediction of the outcome of patients with acute OP poisoning (without acidosis < metabolic acidosis < respiratory acidosis < mixed acidosis) before hospitalization. Major causes of death are different between the respiratory acidosis and metabolic acidosis groups of patients with acute OP poisoning.     

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.     

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.     

Intensive care management of organophosphate insecticide poisoning

Introduction  

Organophosphate (OP) insecticides inhibit both cholinesterase and pseudo-cholinesterase activities. The inhibition of acetylcholinesterase causes accumulation of acetylcholine at synapses, and overstimulation of neurotransmission occurs as a result of this accumulation. The mortality rate of OP poisoning is high. Early diagnosis and appropriate treatment is often life saving. Treatment of OP poisoning consists of intravenous atropine and oximes. The clinical course of OP poisoning may be quite severe and may need intensive care management. We report our experience with the intensive care management of serious OP insecticide poisonings.     

急性有机磷农药中毒并发呼吸衰竭原因分析及临床对策

目的:探讨急性有机磷农药中毒(AOPP)并发呼吸衰竭(RF)的发生原因及临床对策。方法:回顾性分析33例AOPP并发RF的临床表现及治疗情况。结果:AOPP并发RF原因有多方面,除有机磷的直接毒性作用外,还有阿托品中毒、脑水肿、中间综合征及中毒反跳等因素的影响。早期合理使用阿托品及复能剂,早期气管插管呼吸机辅助呼吸是治疗的关键,避免阿托品的过量使用,预防和治疗脑水肿,配合血液灌流,输新鲜血等综合性治疗措施有利于预防和治疗呼吸衰竭。结论:AOPP并发RF原因多方面,早期发现和识别,采取针对性的防治措施,可明显提高抢救成功率。     

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.     

Electrophysiological correlates of respiratory failure in acute organophosphate poisoning: Evidence for differential roles of muscarinic and nicotinic stimulation

Background. Respiratory failure in acute organophosphate (OP) poisoning can occur early and also relatively late in the clinical course, and the pathophysiology of respiratory failure at these different phases may have important clinical implications. Objective. To compare the electrophysiological findings in patients with early and late respiratory failure following acute OP poisoning. Methods. A prospective observational case series of consenting symptomatic patients with acute OP poisoning were assessed with daily physical examinations and repetitive nerve stimulation (RNS) studies. RNS was done on right and left median and ulnar nerves at 1, 3, 10, 15, 20, and 30 Hz. Outcomes such as need for ventilation and development of intermediate syndrome (IMS) were noted. Early respiratory failure was defined as occurring within 24 hours of ingestion. Results. Seventy-eight patients were recruited for the clinical and electrophysiological study and of those 59 (75.6%) patients had ingested chlorpyrifos. Seven patients developed respiratory failure within 24 hours of ingestion with overt muscarinic signs. They had no electrophysiological abnormalities at median and ulnar nerves before intubation. Three of them later developed “forme fruste” IMS. Five other patients developed late respiratory failure after 24 hours of ingestion, and all of them showed progressive RNS changes indicating severe IMS prior to intubation. Conclusion. The normal RNS in all patients developing early respiratory failure suggests that it is due to a central nervous system (CNS) and muscarinic effect. This emphasizes the need for early rapid atropinisation as a priority, combating the nicotinic effects being less urgent. This is in contrast with the late respiratory failure, which has been shown to be associated with neuromuscular dysfunction. Further studies are needed to quantify CNS and muscarinic dysfunction to assist in the development of better treatments for the severe and early OP poisoning.     

The Effects of Fresh Frozen Plasma on Cholinesterase Levels and Outcomes in Patients with Organophosphate Poisoning

Objective: The aim of this study is to determine the effects of fresh frozen plasma, as a source of cholinesterase, on butyrylcholinesterase (BuChE; plasma or pseudo cholinesterase) levels and outcomes in patients with organophosphate poisoning. Materials and Methods: This prospective study was performed at the Department of Intensive Care of Erciyes University Medical School. Over 2 yrs, patients admitted to the ICU for OP poisoning were entered into the study. OP poisoning was diagnosed on the basis of history and BuChE levels. All patients received atropine. Fresh frozen plasma was given to 12 patients. The study was approved by the Ethical Committee, and verbal informed consent was obtained. Results: Thirty‐three patients were included in the study. BuChE levels measured at admission and the pralidoxime and atropine doses administered were not different between groups (p > 0.05). Although intermediate syndrome developed in 28.6% of patients receiving pralidoxime, there were no intermediate syndrome cases in patients receiving plasma prior to developing intermediate syndrome. The mortality rates were 14.3% in the pralidoxime group and 0% in the plasma + atropine + pralidoxime group. Two patients received plasma after developing the intermediate syndrome, and one patient who received only atropine died. BuChE levels of fresh frozen plasma were 4069.5 ± 565.1 IU/L. Every two bags of plasma provided an increase in BuChE levels of approximately 461.7 ± 142.1 IU/L. Conclusion: Fresh frozen plasma therapy increases BuChE levels in patients with organophosphate poisonings. The administration of plasma may also prevent the development of intermediate syndrome and related mortality. Plasma (fresh frozen or freshly prepared) therapy may be used as an alternative or adjunctive treatment method in patients with organophosphate pesticide poisoning, especially in cases not given pralidoxime. Further randomized controlled and animal studies are required to infer a definitive result.     

Efficacy and outcomes of lipid resuscitation on organophosphate poisoning patients: A systematic review and meta-analysis

ObjectiveOrganophosphate (OP) pesticides are still widely available in developing countries, leading to numerous accidental or suicidal poisonings every year. Lipid emulsion treatments are commonly used in resuscitating OP poisoning patients but few studies regarding their use have been reported. Our meta-analysis aimed to analyze the efficacy and outcomes of lipid resuscitation on OP poisoning patients.MethodsA systematic search for associated studies was conducted in Pubmed, EMBASE, MEDLINE, the Cochrane Library and the Chinese National Knowledge Infrastructure. Collected data was pooled using Revman v5.3. Outcomes included prognosis (cured vs. mortality rates), hepatic function (serum ALT, AST, Total Bilirubin (TBIL) level), serum acetylcholinesterase (AchE) level and respiratory function (rate of respiratory muscular paralysis).ResultsSeven randomized controlled studies consisting of 630 patients meeting inclusion criteria were identified. Lipid emulsion helped to improve the cure rate [OR = 2.54, 95% CI (1.33, 4.86), p = 0.005] and lower the mortality rate [OR = 0.31, 95% CI (0.13, 0.74), p = 0.009]. Serum ALT, AST and TBIL in patients undergoing lipid resuscitation were lower than those in the control groups [ALT, SMD = ?1.52, 95% CI (?2.64, 0.40), p = 0.008; AST, SMD = ?1.66, 95% CI (?3.15, 0.16), p = 0.03; TBIL, SMD = ?1.26, 95% CI (?2.32, 0.20), p = 0.02]. Serum AchE level were increased in patients treated with lipid emulsion [SMD = 2.15, 95% CI (1.60, 2.71), p < 0.00001]. Rate of respiratory muscular paralysis was lower in patients undergoing lipid resuscitation than those in the control groups [OR = 0.19, 95% CI (0.05, 0.71), p = 0.01].ConclusionBased on our meta-analysis of included RCT reports, lipid resuscitation seems likely to help improve prognosis and liver function of OP poisoning patients. However, larger multi-center RCTs are still recommended.     

Extrapyramidal effects of acute organophosphate poisoning

Background: There is limited information on extrapyramidal symptoms in acute organophosphate (OP) poisoning. We describe the course and outcome of severely poisoned patients who develop extrapyramidal manifestations. Methods: In this prospective observational study, spanning 8 months (Apr–Nov 2013) adult patients (>18 years) admitted with OP poisoning were enrolled. Patients on anti-psychotic therapy, those refusing consent or presenting with co-ingestions were excluded. Treatment included atropine and supportive care (e.g. ventilation and inotropes as indicated); oximes were not administered. The presence of rigidity, tremors, dystonia and chorea were assessed daily till discharge using modifications of the Unified Parkinson’s Disease rating scale and the Tremor rating scale. The presence of extrapyramidal manifestations was correlated with length of ventilation and hospital stay and mortality. Results: Of the 77 patients admitted with OP poisoning, 32 were enrolled; 17 (53.1%) developed extrapyramidal manifestations which included rigidity (94.1%), tremors (58.8%) and dystonia (58.8%). None developed chorea. The median (inter-quartile range) time of symptom onset was 8 (5–11) days; extrapyramidal features resolved in 11 (6–17) days. The median duration of intensive care stay in patients not developing extrapyramidal symptoms was 6 (2–8) days, indicating that most of these patients had recovered even before symptom onset in patients who developed extrapyramidal manifestations. Overall, 27/32 (84%) were ventilated. Hospital mortality was 6.25% (2/32). When compared with patients not developing extrapyramidal signs, those with extrapyramidal manifestations had significantly prolonged ventilation (5 versus 16 median days; p?=?0.001) and hospitalization (8 versus 21 days; p?<?0.001), reduced ventilator-free days (23 versus 12 days; p?=?0.023) and increased infections (p?=?0.03). The need for ventilation and mortality were not significantly different (p?>?0.6). Extrapyramidal symptoms were not observed in non-OP poisoned patients with prolonged ICU stay. Conclusion: In this small series of acute OP poisoning, extrapyramidal manifestations were common after 1 week of intensive care but self-limiting. They are significantly associated with longer duration of ventilation and hospital stay.     

Is oxygen required before atropine administration in organophosphorus or carbamate pesticide poisoning? – A cohort study

Background. Early and adequate atropine administration in organophosphorus (OP) or carbamate insecticide poisoning improves outcome. However, some authors advise that oxygen must be given before atropine due to the risk of inducing ventricular dysrhythmias in hypoxic patients. Because oxygen is frequently unavailable in district hospitals of rural Asia, where the majority of patients with insecticide poisoning present, this guidance has significant implications for patient care. The published evidence for this advice is weak. We therefore performed a patient cohort analysis to look for early cardiac deaths in patients poisoned by anticholinesterase pesticides. Methods. We analysed a prospective Sri Lankan cohort of OP or carbamate-poisoned patients treated with early atropine without the benefit of oxygen for evidence of early deaths. The incidence of fatal primary cardiac arrests within 3 h of admission was used as a sensitive (but non-specific) marker of possible ventricular dysrhythmias. Results. The cohort consisted of 1957 patients. The incidence of a primary cardiac death within 3 h of atropine administration was 4 (0.2%) of 1957 patients. The majority of deaths occurred at a later time point from respiratory complications of poisoning. Conclusion. We found no evidence of a high number of early deaths in an observational study of 1957 patients routinely given atropine before oxygen that might support guidance that oxygen must be given before atropine. The published literature indicates that early and rapid administration of atropine during resuscitation is life-saving. Therefore, whether oxygen is available or not, early atropinisation of OP- and carbamate-poisoned patients should be performed.     

COPD and asthma therapeutics for supportive treatment in organophosphate poisoning

Context: Nerve agents like sarin or VX have repeatedly been used in military conflicts or homicidal attacks, as seen in Syria or Malaysia 2017. Together with pesticides, nerve agents assort as organophosphorus compounds (OP), which inhibit the enzyme acetylcholinesterase. To counteract subsequent fatal symptoms due to acetylcholine (ACh) accumulation, oximes plus atropine are administered, a regimen that lacks efficacy in several cases of OP poisoning. New therapeutics are in development, but still need evaluation before clinical employment. Supportive treatment with already approved drugs presents an alternative, whereby compounds from COPD and asthma therapy are likely options. A recent pilot study by Chowdhury et al. included β2-agonist salbutamol in the treatment of OP-pesticide poisoned patients, yielding ambiguous results concerning the addition. Here, we provide experimental data for further investigations regarding the value of these drugs in OP poisoning.

Methods: By video-microscopy, changes in airway area were analyzed in VX-poisoned rat precision cut lung slices (PCLS) after ACh-induced airway contraction and subsequent application of selected anticholinergics/β2-agonists.

Results: Glycopyrrolate and ipratropium efficiently antagonized an ACh-induced airway contraction in VX-poisoned PCLS (EC₅₀ glycopyrrolate 15.8?nmol/L, EC₅₀ ipratropium 2.3?nmol/L). β2-agonists formoterol and salbutamol had only negligible effects when solely applied in the same setting. However, combination of formoterol or salbutamol with low dosed glycopyrrolate or atropine led to an additive effect compared to the sole application [50.6?±?8.8% airway area increase after 10?nmol/L formoterol +1?nmol/L atropine versus 11.7?±?9.2% (10?nmol/L formoterol) or 8.6?±?5.9% (1?nmol/L atropine)].

Discussion: We showed antagonizing effects of anticholinergics and β2-agonists on ACh-induced airway contractions in VX-poisoned PCLS, thus providing experimental data to support a prospective comprehensive clinical study.

Conclusions: Our results indicate that COPD and asthma therapeutics could be a valuable addition to the treatment of OP poisoning.     

Bilateral loculated pleural effusion as a manifestation of acute parenteral organophosphate intoxication: a case report

BackgroundAcute organophosphate (OP) toxicity causes a wide range of clinical effects on the respiratory system, including pulmonary bronchoconstriction and bronchorrhea. Morbidity and mortality from acute OP toxicity correlate best with pulmonary secretions.ObjectiveIn this article, we report bilateral loculated pleural effusion as a rare pulmonary effect in a patient with acute parenteral OP toxicity.Case ReportA 25-year-old, previously healthy woman was transferred to our Poison Department 3 days after suicidal injection of malathion. At the time of presentation her vital signs were normal, except that her respiratory rate was 24 breaths/min. She complained of pleuritic chest pain and had a cough productive of yellow sputum. She had generalized chest wall tenderness, and breath sounds were decreased in the base of both lung fields. Standard therapy for OP toxicity, including atropine, pralidoxime, and diazepam, was initiated. Due to persistent pleuritic chest pain, a computed tomography (CT) scan was performed that showed bilateral loculated pleural effusions. Shortly after hospital admission, the patient developed respiratory distress, for which she was intubated and transferred to the Intensive Care Unit. She received continued medical therapy and was extubated on hospital day 3. A CT scan of the chest on hospital day 9, after completion of the treatment, documented resolution of the effusions.ConclusionParenteral OP toxicity occurs rarely, and in this case it was associated with bilateral loculated pleural effusions. In this regard, it should be considered in a patient with acute parenteral OP toxicity and persistent chest wall pain.     

盐酸戊乙奎醚对氧化乐果中毒大鼠的治疗作用

目的：研究盐酸戊乙奎醚（PCHE）对氧化乐果中毒大鼠的治疗作用及其诱发的循环抑制的影响。方法：将实验大鼠随机分为盐水对照组（SC组）、中毒对照组（OC组）、阿托品治疗组（OA组）和长托宁治疗组（OP组）,观察麻醉大鼠有机磷农药中毒症状,心率（HR）和血压（MBP）的变化,并检测肌酸激酶（CK）、乳酸脱氢酶（LDH）和胆碱酯酶（CHE）活力。结果：OC组出现分泌物增多、肌颤、呼吸困难,而OA组和OP组分泌物少,其中OP组大鼠的肌颤、呼吸困难程度较OA组轻,血流动力学稳定,CHE活力恢复快。结论：PCHE是一种理想的治疗有机磷农药中毒的解毒剂。     

盐酸戊乙奎醚对氧化乐果中毒大鼠心肌的作用

目的研究盐酸戊乙奎醚(penehyclidine hydrochloride,PCHE)对氧化乐果中毒大鼠的治疗效果及其对心脏病理改变的影响。方法将实验大鼠随机分为盐水对照组(SC组)、中毒对照组(OC组)、阿托品治疗组(OA组)和长托宁治疗组(OP组),观察实验大鼠有机磷农药中毒的治疗效果和心肌的病理改变。结果OC组大鼠迅速出现有机磷农药中毒症状并死亡,而OA组和OP组大鼠症状较轻,但OP组大鼠的肌颤、肌无力程度较OA组轻,且心肌的病理损害小。结论PCHE对有机磷农药中毒所引起的心肌损害有保护作用。