Deadly drop--cholinergic syndrome from wearing a laundered uniform.

Unintentional organophosphate compound poisoning, although known, contamination of organophosphate compound through laundered uniform and subsequent transcutaneous absorption, in 30 children is reported herewith for its rarity. Emergency physicians have to recognize such entities clinically, confirm by laboratory means wherever possible, and intervene with appropriate measures.

Whole blood transfusion in the treatment of an acute organophosphorus poisoning--a case report.

BACKGROUND: Organophosphorus compounds (OP) are a group of substances used in agriculture as pesticides and are also used as military poisoning agents (MPA). Intoxication by these agents may cause severe systemic disturbances related to both the exposure time and lethal agent concentration. Toxic effects result from an excess of the endogenous neurotransmitter, acetylcholine (ACh), because decomposition of Ach by cholinesterases is blocked by OP. CASE REPORT: The authors describe a case in which an acute OP poisoning was managed both conventionally and with cholinesterase substitution by blood transfusion. CONCLUSIONS: Whole blood transfusion could be beneficial in the treatment of these life-threatening medical conditions.

OpdA, a bacterial organophosphorus hydrolase, prevents lethality in rats after poisoning with highly toxic organophosphorus pesticides.

Organophosphorus (OP) pesticides poison more than 3,000,000 people every year in the developing world, mostly through intentional self-poisoning. Advances in medical therapy for OP poisoning have lagged, and current treatment is not highly effective with mortality of up to 40% in even the most advanced Western medical facilities. Administration of a broadly active bacterial OP hydrolase to patients in order to hydrolyze OPs in circulation might allow current therapies to be more effective. The objective of this work was to evaluate the efficacy of a new recombinant bacterial OP hydrolase (OpdA), cloned from Agrobacterium radiobacter, in rat models of two chemically distinct but highly toxic and rapidly acting OP pesticides: dichlorvos and parathion. Without OpdA treatment, median time to death in rats poisoned with 3x LD(50) of dichlorvos or parathion was 6 min and 25.5 min, respectively. Administration of a single dose of OpdA immediately after dichlorvos resulted in 100% survival at 24h, with no additional antidotal therapy. After parathion poisoning, OpdA alone caused only a delay to death. However, an additional two doses of OpdA resulted in 62.5% survival at 24 h after parathion poisoning. In combination with pralidoxime therapy, a single dose of OpdA increased survival to 75% after parathion poisoning. Our results demonstrate that OpdA is able to improve survival after poisoning by two chemically distinct and highly toxic OP pesticides.

Organophosphorus pesticide poisoning: cases and developments.

Self-poisoning with organophosphate pesticides is a major health problem world-wide. Through the inhibition of acetylcholinesterase, organophosphorus poisoning is characterised by the clinical picture of acute cholinergic crisis. Other manifestations are the intermediate neurotoxic syndrome and delayed polyneuropathy. In the Western world, the occurrence of organophosphorus poisoning is less prevalent due to the declining availability of organophosphate pesticides, which could render the recognition of this particular type of intoxication and its specific treatment more difficult. In this article we discuss some recent developments and treatment dilemmas, illustrated by cases from our clinic, followed by a review of the current recommendations in the treatment of organophosphate poisoning.

Is beta-glucuronidase a clinical useful biomarker for an acute organophosphorus poisoning?

beta-glucuronidase is considered a sensitive biomarker for acute organophosphorus poisoning. In this well-documented study, multiple plasma samples over time were collected. A decrease in plasma concentration of beta-glucuronidase was surprisingly observed, even within normal range. These findings do not support the hypothesis that beta-glucuronidase is a useful biomarker for acute organophosphorus poisoning in humans.

Organophosphate poisonings with parathion and dimethoate.

OBJECTIVE: Organophosphate toxicity is the leading cause of morbidity and death in poisoning by insecticides. The clinical symptoms of pesticide toxicity range from the classic cholinergic syndrome to flaccid paralysis and intractable seizures. The mainstays of therapy are atropine, oximes, benzodiazepines and supportive care. The toxicokinetics vary not only with the extent of exposure, but also with the chemical structure of the agent. PATIENTS: We report two cases of poisoning with parathion-ethyl and dimethoate. The patients developed a cholinergic syndrome immediately, accompanied by bradycardia and hypotension. INTERVENTIONS: The patients were admitted to the intensive care unit (ICU) a few hours after ingestion. Atropine was administered according to the cholinergic symptoms. The patients recovered in the ICU after 10-12 days and were discharged after 3 and 4 weeks. MEASUREMENTS AND RESULTS: Organophosphate blood and urine levels were determined on admission and during hospitalisation. The pesticides were rapidly distributed and slow elimination rate of the poisons was documented. In the case of parathion-ethyl the distribution half-life estimated was t(1/2alpha) = 3.1h while the terminal half-life was t(1/2beta) = 17.9 h. Using a one-compartment model for dimethoate the elimination half-life was t(1/2beta) = 30.4 h in plasma and 23.8 h in urine. The serum pseudo-cholinesterase activity was below the limit of detection at admission and recovered during the following 3weeks.

Polyneuropathy after massive exposure to parathion.

Many organophosphorus compounds, including the organophosphate insecticides, may cause polyneuropathy of delayed onset. An exception is parathion, which has been considered the prototype of nonneurotoxic cholinesterase inhibitors. Nevertheless, we describe a patient with delayed polyneuropathy after suicidal ingestion of parathion.

Pancuronium improves the neuromuscular transmission defect of human organophosphate intoxication.

Two patients with acute severe organophosphate intoxication showed (1) single evoked compound muscle action potentials (CMAP) with repetitive discharges and (2) prominent decremental responses of CMAP with 20 and 50 Hz supramaximal nerve stimulation. Following the intravenous injection of single small doses of pancuronium, marked improvement in these abnormalities occurred and persisted for several hours. We postulate that the physiologic improvement following low-dose pancuronium results from blockade of acetylcholine receptors, especially those located on the terminal axon responsible for antidromic backfiring.

Quantitative histochemistry of acetylcholinesterase in rat and human brain postmortem.

A quantitative analysis of acetylcholinesterase (AChE) activity in histochemically stained sections of rat and human brain can be achieved through the use of internal standards and computerized image analysis. Tissue standards containing known amounts of a highly purified AChE preparation are sectioned and incubated under the same conditions as experimental sections. A computerized image analyzer is used to convert the optical density of the stain to units of enzyme content via the standard curve. The method generates reliable and reproducible quantitative values from very small brain regions and nuclei, combining the quantitative character of a radiometric assay with the superior anatomical resolution of histochemistry.

Serum beta -- lipoproteins: studies in a patient and in guinea pigs after the ingestion of organophosphorus compounds.

A patient admitted to this hospital with Parathion poisoning had a marked reduction in serum cholinesterase activity and concentration of low density lipoprotein. The enzyme and the lipoprotein levels returned to normal with clinical recovery. Guinea pigs treated with phospholine iodide showed depressed levels of serum cholinesterase and beta-lipoprotein. It is suggested that the decrease in beta-lipoproteins is due to the decrease in cholinesterase activity.

Brain acetylcholinesterase after parathion poisoning: a comparative quantitative histochemical analysis post-mortem.

The regional distribution of AChE inhibition by parathion in the human brain was examined in a comparative study of the brains of 2 victims of lethal parathion intoxication and 2 control brains matched for age and sex. AChE activity in discrete brain regions was studied by quantitative histochemistry of 40 microns-thick sagittal or coronal cryostat sections from the 4 brains. The inhibition of human brain AChE by parathion is regionally selective. The biggest decreases were observed in the cerebellum, some thalamic nuclei and cortex. Only a moderate decrease (10-30%) was observed in the substantia nigra and basal ganglia, while no effect at all was seen in white matter regions. Detailed knowledge of the brain regions affected by parathion poisoning may explain some of the clinical manifestations of organophosphate poisoning.

Modern strategies in therapy of organophosphate poisoning.

Considering the various microscopic reactions as well as toxicokinetic and pharmacokinetic principles in therapy of organophosphate poisoning, the administration of obidoxime by an initial bolus dose followed by continuous infusion appears rational. Using this protocol, six patients each with parathion or oxydemeton methyl poisoning were treated. In parathion poisoning, reactivation was possible up to 7 days. At paraoxon concentrations > 0.1 microM obidoxime only partially reactivated acetylcholinesterase (AChE) of erythrocytes in vivo although reactivation could be assessed in vitro, which roughly fitted theoretical calculations. AChE-inhibitory material was detected up to 5 days. Cholinergic signs soon subsided when AChE was above 20% of normal, and atropine plasma levels could be kept below 7 ng/ml. In one patient brain damage persisted. Oxydemeton methyl poisoning responded to obidoxime therapy only when the oxime was instituted shortly after poisoning. Out of six patients one died. No intermediate syndrome and no signs of permanent hepatic dysfunction were found in the 12 patients.

Human parathion poisoning. A toxicokinetic analysis.

The mortality rate of suicidal parathion poisoning is particularly high, the onset of fulminant cholinergic signs, and the patients frequently present to the emergency physician with life-threatening symptoms. Despite this uniformity, subsequent clinical course differs significantly among patients, mostly not as a result of different delays in treatment or insufficiency of primary care. Probably, the differences depend on the amount of poison absorbed and/or the disposition of the active poison, paraoxon. We followed the toxicokinetics of parathion and tried to quantify the actual poison load. To this end, we monitored parathion-intoxicated patients (patients requiring artificial ventilation) for plasma levels of parathion and paraoxon along with the activity of erythrocyte acetylcholinesterase and its reactivatability. Plasma obidoxime concentrations were followed as well as the cumulative urinary para-nitrophenol conjugate excretion as a measure of total poison load. All patients received a standard obidoxime scheme of a 250 mg bolus dose intravenously, followed by continuous infusion with 750 mg per 24 hours as long as reactivation could be expected (usually 1 week). All other treatment was instituted as judged by the physician. It was recommended to use atropine at low doses to achieve dry mucous membranes, no bronchoconstriction and no bradycardia. Usually 1-2 mg/h were sufficient. Seven selected cases are presented exemplifying toxicokinetic peculiarities. All patients were severely intoxicated, while the amount of parathion absorbed varied widely (between 0.12 and 4.4 g; lethal dose 0.02-0.1 g) and was generally much lower than anticipated from the reports of relatives. It remains open whether the discrepancies between reports and findings were due to exaggeration or to effective decontamination (including spontaneous vomiting, gastric lavage and activated charcoal). Absorption of parathion from the gastrointestinal tract was sometimes retarded, up to 5 days, resulting in fluctuating plasma profiles. The volume of distribution at steady-state (Vdss) of parathion was around 20 L/kg. Post-mortem analysis in one patient revealed a 66-fold higher parathion concentration in fat tissue compared with plasma, 16 days after ingestion. Biotransformation of parathion varied widely and was severely retarded in one patient receiving fluconazole during worsening of renal function, while phenobarbital (phenobarbitone) sedation (two cases) had apparently no effect. The proportion of plasma parathion to paraoxon varied from 0.3-30, pointing also to varying paraoxon elimination, as illustrated by one case with particularly low paraoxonase-1 activity. Obidoxime was effective at paraoxon concentrations below 0.5 microM, provided aging was not too advanced. This concentration correlated poorly with the paration concentration or the poison load. The data are discussed in light of the pertinent literature.

Enhancement of intestinal glucose transport following chronic parathion poisoning.

Chronic administration of parathion to male rats stimulated glucose (p less than 0.05) but not calcium (p greater than 0.05) transport in the everted duodenal gut sac preparation. Chronic parathion stimulation was not reduced by concurrent administered of atropine. Acutely applied parathion or paraoxon, its active metabolite, did not increase glucose transport in this preparation.

[Pneumonitis with fatal pulmonary fibrosis (Hamman-Rich syndrome) due to parathion-(E-605-) poisoning]. / Pneumonitis mit letaler Lungenfibrose (Hamman-Rich-Syndrom) bei Parathion-(E-605-) Vergiftung.

A patient with chronic Parathione (E 605) poisoning was observed over a period of 55 days. During that time he developed progressive changes, which were identical to those of progressive idiopathic pulmonary fibrosis. The rapid development of an alveolitis, followed by a lethal pulmonary fibrosis, differed in no way, macroscopically nor microscopically, from the lung changes in paraquat poisoning (paraquat lung). The radiological course has been correlated with the clinical and post mortem findings.

[Exogenous-toxic bilateral basal ganglia necroses in computer tomography]. / Exogen-toxische bilaterale Stammgangliennekrosen im Computertomogramm.

By means of cranial computer tomography, it is possible to demonstrate the cerebral consequences of severe intoxications in vivo. A variety of different toxic agents produce similar disease patterns, which are thought to be due to fall in blood pressure caused by the toxin. The lesions are mainly localised in the basal ganglia at the borders of contiguous vascular territories. Six patients observed by the authors are described.

Clinical observation and comparison of the effectiveness of several oxime cholinesterase reactivators.

After passing toxicity and experimental therapeutic tests, four oxime cholinesterase reactivators [PAM (pyridine aldoxime methiodide), PAC (pralidoxime, pyridine aldoxime methylchloride), TMB4 (trimedoxime), and DMO4 (obidoxime, Toxogonin, LüH6)] were compared in clinical trials. All of them proved capable of restoring erythrocyte cholinesterase activity and relieving symptoms and signs of organophosphate insecticide poisoning. Mildly and moderately poisoned patients can be treated by several injections of any one of these drugs alone, but severe cases need the synergistic action of atropine, as well as treatments for two to three consecutive days. Although response to treatment is stronger with TMB4 and DMO4, they are not recommended for routine treatment because of their dangerous adverse side effects.

Prevention of acute parathion and demeton poisoning in farmers around Shanghai.

After the occurrence of poisoning episodes among commune members who handled the insecticides parathion and demeton during the first few years of application in the early 1960s, a series of surveys was conducted and comprehensive regulatory actions were adopted. The surveys showed that the cause of most of the poisoning cases was percutaneous absorption of toxicant as a consequence of skin contamination during careless operating. As a result of a comprehensive program carried out by large numbers of administrators, health workers, and commune members, the incidence of intoxication quickly declined, starting in 1965, to a negligible level and has remained so to the present, even though parathion and demeton use has increased greatly. It is suggested that the experience obtained might be helpful to other areas in the People's Republic of China and in some developing countries.