Abstract:
Epidemiology: Acute organophosphate insecticide (OPI) poisoning is still an important cause of morbidity and mortality, especially in developing countries. It is estimated that 300000 people die each year, most of them due to deliberate OPI poisoning. Since January 1998 till December 2007, in Serbian National Poison Control Centre 29723 patients were treated, among them 11174 were hospitalized. Pesticide poisonings were registered in 526 patients. Within this group of patients with pesticide poisoning, OP compounds were detected in 296, carbamates in 21, and pesticides having other chemical structures in 209.
Pathophysiology: Better understanding of OPI mechanism of action – irreversible inhibition of acetylcholinesterase, butyrilcholinesterase and all esterase type enzymes, followed by metabolic dysbalance, enforced the development of complex therapeutic regimens.
Therapeutic principles: Patients with acute exposures to organophosphorus compounds should undergo immediate assessment and management of disturbances in airway, breathing, and circulation. Further steps are based on risk assessment and observations during continuous monitoring, including dose ingested, time since ingestion, clinical features, patient factors, and available medical facilities. Patients with moderate or severe organophosphorus poisoning should be admitted to an intensive care unit after resuscitation in order to provide careful titration of antidotes, intubation, ventilation, and inotropes or vasopressors if required. Careful observation is also required because rapid clinical deterioration and death are reported in patients who seemed to be recovering from the acute cholinergic crisis. High quality intensive medical care is a priority as hospital stay may be prolonged, with secondary complications which are an important cause of morbidity and mortality.
Current therapeutic scheme for management of acute poisoning with anticholinesterase pesticides includes general supportive measures (decontamination, respiratory support) and specific pharmacological treatment (atropine, oxime, diazepam). Gastric lavage is the most commonly used form of decontamination in OP poisoning. Since the rate of absorption of OP containing P=O bond from the human bowel is rapid, as indicated by the appearance of symptoms of OP poisoning within a few minutes, gastric lavage should be performed as soon as possible, preferably within 2 hours post ingestion. Administration of oral activated charcoal, in conventional doses, may be considered for reducing further absorption of OP pesticides. However, recent clinical trials designed to evaluate the effectiveness of single and multiple doses of activated charcoal failed to find a significant benefit of either regimen over placebo. Atropine is the mainstay of treatment of effects mediated by muscarinic sensitive receptors, but it is ineffective at the nicotine sensitive synapses, it has limited antimuscarinic effects in CNS and counteracting of convulsions is possible only immediately after exposure. Some toxicologists prefer glycopyrrolate and hyoscine (scopolamine) methylbromide: These agents do not enter the CNS and they are not effective against coma and reduced respiratory drive in patients with anticholinesterase poisoning. Diazepam is used in counteracting convulsions, and it also improves atropine tolerance, reduces central nervous system damage and central respiratory weakness. Oximes reactivate phosphorylated AChE by displacing the phosphoryl moiety from the enzyme by virtue of their high affinity for the enzyme and their powerful nucleophilicity. The rate of reactivation depends on the structure of the phosphoryl moiety bound to the enzyme, the source of the enzyme, the structure and concentration of oxime which is present at the active site, and the rate of aging. Several oximes have been developed, but two (Pralidoxime chloride and Obidoxime) are more commonly used for acute organophosphorus poisoning. They are administered as an infusion which continues until recovery.
Serbian NPCC experience: During the different phases of development of the NPCC in Belgrade, many pyridinium oximes were used in experimental and clinical studies, as well as in routine clinical practice, such as pralidoxime chloride, pralidoxime methylsulphate, trimedoxime, obidoxime, and HI-6. Oxime HI-6 was introduced in clinical practice in Serbia in early 1980s. It was administered to more than 200 patients (with OP poisoning and volunteers). A clinical study with HI-6, administered intramuscularly at doses up to 500 mg, performed in 22 healthy volunteers, revealed no adverse effects, whereas in patients poisoned by several OP insecticides, HI-6 ensured fast reactivation of AChE in almost all cases except in dimethoate and phosphamidon poisoning. Contrary to these findings, the reports from Asia indicated that pralidoxime treatment was not sufficiently effective in their patients. Despite this controversy we could still recommend oxime use in moderate and severe OPI poisoning. Acute poisoning with organophosphorus pesticides is not frequent in Serbia, however, it represent important clinical feature due to severity, possible complications and their impact on duration and costs of hospitalization. Initial treatment involves prevention of further absorption and provision of supportive care, followed by administration of specific antidotes (carefully titrated atropine, oxime and diazepam).
New therapeutic regimens: Many other treatments have been trialled for use in patients with acute organophosphorus poisoning (á-2 adrenergic receptor agonists-clonidine, butyrylcholinesterase replacement therapy, extracorporeal blood purification, including haemodialysis, haemofiltration, and haemoperfusion, magnesium sulphate, oganophosphorus hydrolases and sodium bicarbonate), but at present high quality data are insufficient to make evidence based recommendations and further investigations are necessary.

Brief Biography of the Speaker:
Slavica Vucinic MD PhD is an associated professor of internal medicine and clinical toxicology at the Clinic of Emergency and Clinical Toxicology of the National Poison Control Centre, Military Medical Academy in Belgrade, Serbia. Her area of expertise is acute organophosphate poisoning. Besides being an author and co-author of 155 papers, she wrote 6 chapters in different books of emergency medicine and one book in the field of clinical toxicology. She is a Head of two scientific projects in Military Medical Academy concerning the therapy of acute organophosphate poisoning. She is the Head of the Clinic of Emergency and Clinical Toxicology. For the last 7 years she has been a General Secretary of Serbian association of toxicologists. Moreover she is a member of the European Association of Poison Control Centres and Clinical Toxicologists.