toxreviewТоксикологический вестникToxicological Review0869-79223034-4611Federal Scientific Center of Hygiene named after F.F. Erisman10.36946/0869-7922-2017-4-40-49toxreview-86Research ArticleСтатьиПРОБЛЕМА ПРОМЕЖУТОЧНОГО СИНДРОМА ПРИ ОТРАВЛЕНИЯХ АНТИХОЛИНЭСТЕРАЗНЫМИ СОЕДИНЕНИЯМИTHE PROBLEM OF THE INTERMEDIATE SYNDROME FOLLOWING POISONING WITH ANTI-CHOLINESTERASE AGENTSТюнинМ. А.TyuninM. A.noemail@neicon.ruЧепурС. В.ChepurS. V.noemail@neicon.ruГоголевскийА. С.GogolevskyA. S.noemail@neicon.ruСеливановД. В.SelivanovD. V.noemail@neicon.ruБурцеваН. И.BurtsevaN. I.noemail@neicon.ruИльинскийН. С.IlyinskiyN. S.noemail@neicon.ruФГБУ «Государственный научноисследовательский испытательный институт военной медицины» Министерства обороны Российской ФедерацииРоссияState Research and Test Institute of Military Medicine , S.M. Kirov Medical Military AcademyRussian Federation201728082017044049Copyright © Тюнин М.А., Чепур С.В., Гоголевский А.С., Селиванов Д.В., Бурцева Н.И., Ильинский Н.С., 20172017Тюнин М.А., Чепур С.В., Гоголевский А.С., Селиванов Д.В., Бурцева Н.И., Ильинский Н.С.Tyunin M.A., Chepur S.V., Gogolevsky A.S., Selivanov D.V., Burtseva N.I., Ilyinskiy N.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.toxreview.ru/jour/article/view/86

В обзоре рассмотрены современные представления об этиологии и патогенезе промежуточного синдрома при отравлениях антихолинэстеразными соединениями (фосфорорганические соединения, карбаматы). Представлена характеристика клинической картины синдрома и методов его диагностики с использованием электромиографии. Проанализированы и обобщены данные об опыте применения широко используемых базисных средств антидотной (реактиваторы холинэстеразы, M- и N-холинолитики) и патогенетической терапии отравлений. Для решения проблемы в качестве приоритетных направлений исследований определены поиск механизмов формирования недеполяризационного нервно-мышечного блока и разработка способов профилактики и лечения с использованием препаратов, воздействующих на N-холинорецепторы.

Etiology and pathogenesis current concepts of the intermediate syndrome in cases of poisoning with anticholinesterase compounds (organophosphorus compounds, carbamates) are considered in the review. Characteristics of the syndrome clinical picture and its diagnostics methods using electromyography are presented.. Data on the experience of broadly used basic antidotal agents (cholinesterase reactivators, M – and N-cholinoreceptors) and pathogenic therapy of poisonings were analyzed and summarized. To solve the problem, priority research directions were determined, such as search for formation mechanisms of the nondepolarizing neuromuscular blocker and development of methods for prophylaxis and therapy using drugs targeting N-cholinoreceptors.

фосфорорганические соединенияпромежуточный синдромэлектромиографиядиагностикалечениеorganophosphorus compoundsintermediate syndromeelectromyographydiagnosticstherapyReferencesAbdollahi M. Poisoning with anticholinesterase insecticides in Iran. In: Satoh T., Gupta R.C., eds. Anticholinesterase pesticides: metabolism, neurotoxicity, and epidemiology. John Wiley & Sons, Inc.; 2011: 433–446.Abdollahi M. Poisoning with anticholinesterase insecticides in Iran. In: Satoh T., Gupta R.C., eds. Anticholinesterase pesticides: metabolism, neurotoxicity, and epidemiology. John Wiley & Sons, Inc.; 2011: 433–446.Vasconcellos L.F., Leite A.C., Nascimento O.J. Organophosphate-induced delayed neuropathy: case report. Arq. Neuropsiquiatr. 2002; 60: 1003–1007.Vasconcellos L.F., Leite A.C., Nascimento O.J. Organophosphate-induced delayed neuropathy: case report. Arq. Neuropsiquiatr. 2002; 60: 1003–1007.Чепур С.В. Отдаленные органофосфатные нейропатии: патогенез, профилактика и лечение. Токсикологический вестник. 2010; 3: 42-43.Чепур С.В. Отдаленные органофосфатные нейропатии: патогенез, профилактика и лечение. Токсикологический вестник. 2010; 3: 42-43.Senanayake N., Karalliedde L. Neurotoxic effects of organophosphorus insecticides. An intermediate syndrome. N. Engl. J. Med. 1987; 316(13): 761–763Senanayake N., Karalliedde L. Neurotoxic effects of organophosphorus insecticides. An intermediate syndrome. N. Engl. J. Med. 1987; 316(13): 761–763Leon-S F.E., Pradilla-A G., Gamboa N., Vesga E. Multiple system organ failure, intermediate syndrome, congenital myasthenic syndrome, and anticholinesterase treatment: the linkage is puzzling (letter; comment). Journal of Toxicology – Clinical Toxicology. 1996; 34 (2): 245-247.Leon-S F.E., Pradilla-A G., Gamboa N., Vesga E. Multiple system organ failure, intermediate syndrome, congenital myasthenic syndrome, and anticholinesterase treatment: the linkage is puzzling (letter; comment). Journal of Toxicology – Clinical Toxicology. 1996; 34 (2): 245-247.Karalliedde L., Wheeler H., Maclehose R., Murray V. Possible immediate and long-term health effects following exposure to chemical warfare agents. Public Health. 2000; 114 (4): 238-248.Karalliedde L., Wheeler H., Maclehose R., Murray V. Possible immediate and long-term health effects following exposure to chemical warfare agents. Public Health. 2000; 114 (4): 238-248.Colak Ş., Erdoğan M.Ö., Baydin A., Afacan M.A., Kati C., Duran L. Turk. Epidemiology of organophosphate intoxication and predictors of intermediate syndrome. J. Med. Sci. 2014; 44 (2): 279- 282.Colak Ş., Erdoğan M.Ö., Baydin A., Afacan M.A., Kati C., Duran L. Turk. Epidemiology of organophosphate intoxication and predictors of intermediate syndrome. J. Med. Sci. 2014; 44 (2): 279- 282.Закурдаев В.В. Токсическая миопатия при острой интоксикации ФОС. Воен.-мед. журн. 1986; 10: 49-51.Закурдаев В.В. Токсическая миопатия при острой интоксикации ФОС. Воен.-мед. журн. 1986; 10: 49-51.De Bleecker J., Van Den Neuoker K., Willens J. The intermediate syndrome in organophosphate poisoning: presentation of a case and review of the literature. Journal of Toxicology – Clinical Toxicology. 1992; 30 (3): 321 – 329.De Bleecker J., Van Den Neuoker K., Willens J. The intermediate syndrome in organophosphate poisoning: presentation of a case and review of the literature. Journal of Toxicology – Clinical Toxicology. 1992; 30 (3): 321 – 329.Indira M., Andrews M.A., Rakesh T.P. Incidence, predictors, and outcome of intermediate syndrome in cholinergic insecticide poisoning: a prospective observational cohort study. Clin. Toxicol. (Phila). 2013; 51 (9): 838-845.Indira M., Andrews M.A., Rakesh T.P. Incidence, predictors, and outcome of intermediate syndrome in cholinergic insecticide poisoning: a prospective observational cohort study. Clin. Toxicol. (Phila). 2013; 51 (9): 838-845.Hulse E.J., Davies J.O.J., Simpson A.J., Sciuto A.M., Eddleston M. Respiratory complications of organophosphorus nerve agent and insecticide poisoning implications for respiratory and critical care. American Journal of Respiratory and Critical Care Medicine. 2014; 12 (190): 1342-1354.Hulse E.J., Davies J.O.J., Simpson A.J., Sciuto A.M., Eddleston M. Respiratory complications of organophosphorus nerve agent and insecticide poisoning implications for respiratory and critical care. American Journal of Respiratory and Critical Care Medicine. 2014; 12 (190): 1342-1354.Coulson J. Predicting the intermediate syndrome in organophosphorus poisoning. Indian J. Crit. Care Med. 2015; 19 (7): 377–378.Coulson J. Predicting the intermediate syndrome in organophosphorus poisoning. Indian J. Crit. Care Med. 2015; 19 (7): 377–378.Abdollahi M., Karami-Mohajeri S. A comprehensive review on experimental and clinical findings in intermediate syndrome caused by organophosphate poisoning. Toxicol. Appl. Pharmacol. 2012; 258 (3): 309-314.Abdollahi M., Karami-Mohajeri S. A comprehensive review on experimental and clinical findings in intermediate syndrome caused by organophosphate poisoning. Toxicol. Appl. Pharmacol. 2012; 258 (3): 309-314.Karami-Mohajeri S., Nikfar S., Abdollahi M. A systematic review on the nerve–muscle electrophysiology in human organophosphorus pesticide exposure. Human and Experimental Toxicology. 2014; 33 (1): 92–102.Karami-Mohajeri S., Nikfar S., Abdollahi M. A systematic review on the nerve–muscle electrophysiology in human organophosphorus pesticide exposure. Human and Experimental Toxicology. 2014; 33 (1): 92–102.Peter J.V., Jerobin J., Nair A., Bennett A., Samuel P., Chrispal A. Clinical profile and outcome of patients hospitalized with dimethyl and diethyl organophosphate poisoning. Clin. Toxicol. 2010; 48 (9): 916-923.Peter J.V., Jerobin J., Nair A., Bennett A., Samuel P., Chrispal A. Clinical profile and outcome of patients hospitalized with dimethyl and diethyl organophosphate poisoning. Clin. Toxicol. 2010; 48 (9): 916-923.Lee F., Lin J.L. Intermediate syndrome after organophosphate intoxication in patient with end-stage renal disease. Ren. Fail. 2006; 28 (2): 197-200.Lee F., Lin J.L. Intermediate syndrome after organophosphate intoxication in patient with end-stage renal disease. Ren. Fail. 2006; 28 (2): 197-200.De Bleecker J.L. The intermediate syndrome in organophosphate poisoning: an overview of experimental and clinical observations. Journal of Toxicology – Clinical Toxicology. 1995; 33(6): 683-686.De Bleecker J.L. The intermediate syndrome in organophosphate poisoning: an overview of experimental and clinical observations. Journal of Toxicology – Clinical Toxicology. 1995; 33(6): 683-686.De Bleecker J., Van den Neucker K., Colardyn F. Intermediate syndrome in organophosphorus poisoning: a prospective study. Crit. Care Med. 1993; 21(11): 1706-1711.De Bleecker J., Van den Neucker K., Colardyn F. Intermediate syndrome in organophosphorus poisoning: a prospective study. Crit. Care Med. 1993; 21(11): 1706-1711.Ray D., Leicester U.K. Organophosphorus esters: an evaluation of chronic neurotoxic effects. Institute for Environment and Health; 19Ray D., Leicester U.K. Organophosphorus esters: an evaluation of chronic neurotoxic effects. Institute for Environment and Health; 19Kwong T.C. Organophosphate pesticides: biochemistry and clinical toxicology. Therapeutic Drug Monitoring. 2002; 24 (1): 144-149.Kwong T.C. Organophosphate pesticides: biochemistry and clinical toxicology. Therapeutic Drug Monitoring. 2002; 24 (1): 144-149.Khan S., Hemalatha R., Jeyaseelan L., Oommen A., Zachariah A. Neuroparalysis and oxime efficacy in organophosphate poisoning: a study of butyrylcholinesterase. Human & Experimental Toxicology. 2001; 20 (4): 169-174.Khan S., Hemalatha R., Jeyaseelan L., Oommen A., Zachariah A. Neuroparalysis and oxime efficacy in organophosphate poisoning: a study of butyrylcholinesterase. Human & Experimental Toxicology. 2001; 20 (4): 169-174.Sedgwick E.M., Senanayake N. Pathophysiology of the intermediate syndrome of organophosphorus poisoning. J. Neurol. Neurosurg. Psychiatry. 1997; 62 (2): 201−202.Sedgwick E.M., Senanayake N. Pathophysiology of the intermediate syndrome of organophosphorus poisoning. J. Neurol. Neurosurg. Psychiatry. 1997; 62 (2): 201−202.Karalliedde L., Baker D., Marrs T.C. Organophosphate-induced intermediate syndrome: aetiology and relationships with myopathy. Toxicol. Rev. 2006; 25 (1): 1−14.Karalliedde L., Baker D., Marrs T.C. Organophosphate-induced intermediate syndrome: aetiology and relationships with myopathy. Toxicol. Rev. 2006; 25 (1): 1−14.De Wilde V., Vogelaers D., Colardyn F., Vanderstraeten G., Van den Neucker K., De Bleecker J. Postsynaptic neuromuscular dysfunction in organophosphate induced intermediate syndrome. Klin. Wochenschr. 1991; 69 (4): 177−183.De Wilde V., Vogelaers D., Colardyn F., Vanderstraeten G., Van den Neucker K., De Bleecker J. Postsynaptic neuromuscular dysfunction in organophosphate induced intermediate syndrome. Klin. Wochenschr. 1991; 69 (4): 177−183.John M., Oommen A., Zachariah A. Muscle injury in organophosphorous poisoning and its role in the development of intermediate syndrome. Neurotoxicology. 2003; 24 (1): 43−John M., Oommen A., Zachariah A. Muscle injury in organophosphorous poisoning and its role in the development of intermediate syndrome. Neurotoxicology. 2003; 24 (1): 43−Dandapani M., Zachariah A., Kavitha M.R., Jeyaseelan L., Oommen A. Oxidative damage in intermediate syndrome of acute organophosphorus poisoning. Ind. J. Med. Res. 2003; 117: 253–259.Dandapani M., Zachariah A., Kavitha M.R., Jeyaseelan L., Oommen A. Oxidative damage in intermediate syndrome of acute organophosphorus poisoning. Ind. J. Med. Res. 2003; 117: 253–259.Perayre Badia M., Leiva Badosa E., Pastó Cardona E., Jódar Massanés R.. Intermediate syndrome after organophosphate poisoning despite continuous infusion of pralidoxime. An. Med. Interna. 2007; 24 (3): 129-131.Perayre Badia M., Leiva Badosa E., Pastó Cardona E., Jódar Massanés R.. Intermediate syndrome after organophosphate poisoning despite continuous infusion of pralidoxime. An. Med. Interna. 2007; 24 (3): 129-131.Khan S., Hemalatha R., Jeyaseelan L., Oommen A., Zachariah A. Neuroparalysis and oxime efficacy in organophosphate poisoning: a study of butyrylcholinesterase. Hum. Exp. Toxicol. 2001; 20 (4): 169-1Khan S., Hemalatha R., Jeyaseelan L., Oommen A., Zachariah A. Neuroparalysis and oxime efficacy in organophosphate poisoning: a study of butyrylcholinesterase. Hum. Exp. Toxicol. 2001; 20 (4): 169-1Jin Y.H., Jeong T.O., Lee J.B. Isolated bilateral vocal cord paralysis with intermediate syndrome after organophosphate poisoning. Clin. Toxicol. 2008; 46 (5): 482-484.Jin Y.H., Jeong T.O., Lee J.B. Isolated bilateral vocal cord paralysis with intermediate syndrome after organophosphate poisoning. Clin. Toxicol. 2008; 46 (5): 482-484.He F., Xu H., Qin F., Xu L., Huang J., He X. Intermediate myasthenia syndrome following acute organophosphates poisoning—an analysis of 21 cases. Hum. Exp. Toxicol. 1998; 17 (1): 40-He F., Xu H., Qin F., Xu L., Huang J., He X. Intermediate myasthenia syndrome following acute organophosphates poisoning—an analysis of 21 cases. Hum. Exp. Toxicol. 1998; 17 (1): 40-De Bleecker J., Willems J., Van Den Neucker K., De Reuck J., Vogelaers D. Prolonged toxicity with intermediate syndrome after combined parathion and methyl parathion poisoning. J. Toxicol-Clin. Toxicol. 1992; 30: 333–345.De Bleecker J., Willems J., Van Den Neucker K., De Reuck J., Vogelaers D. Prolonged toxicity with intermediate syndrome after combined parathion and methyl parathion poisoning. J. Toxicol-Clin. Toxicol. 1992; 30: 333–345.Palimar V. Intermediate syndrome in organophosphorous poisoning. JIAFM. 2005; 27 (1): 28-30.Palimar V. Intermediate syndrome in organophosphorous poisoning. JIAFM. 2005; 27 (1): 28-30.Baker D.J., Sedgwick E.M. Single fibre electromyographic changes in man after organophosphate exposure. Hum. Exp. Toxicol. 1996; 15 (5): 369-375.Baker D.J., Sedgwick E.M. Single fibre electromyographic changes in man after organophosphate exposure. Hum. Exp. Toxicol. 1996; 15 (5): 369-375.Dongren Y., Tao L., Fengsheng H. Electroneurophysiological studies in rats of acute dimethoate poisoning. Toxicol. Lett. 1999; 107 (1-3): 249-254.Dongren Y., Tao L., Fengsheng H. Electroneurophysiological studies in rats of acute dimethoate poisoning. Toxicol. Lett. 1999; 107 (1-3): 249-254.Jayawardane P. The Spectrum of Intermediate Syndrome Following Acute Organophosphate Poisoning: A Prospective Cohort Study from Sri Lanka. PLoS Medicine. 2008; 5 (7): 1143-1153.Jayawardane P. The Spectrum of Intermediate Syndrome Following Acute Organophosphate Poisoning: A Prospective Cohort Study from Sri Lanka. PLoS Medicine. 2008; 5 (7): 1143-1153.Aygun D., Doganay Z., Altintop L., Guven H., Onar M., Deniz T. Serum acetylcholinesterase and prognosis of acute organophosphate poisoning. J. Toxicol. Clin. Toxicol. 2002; 40 (7): 903-910.Aygun D., Doganay Z., Altintop L., Guven H., Onar M., Deniz T. Serum acetylcholinesterase and prognosis of acute organophosphate poisoning. J. Toxicol. Clin. Toxicol. 2002; 40 (7): 903-910.Chetan Kumar G., Bhuvana K., Venkatarathnamma P.N., Sarala N. Serum creatine phosphokinase as predictor of intermediate syndrome in organophosphorus poisoning. Indian J. Crit. Care Med. 2015; 19 (7): 384–387.Chetan Kumar G., Bhuvana K., Venkatarathnamma P.N., Sarala N. Serum creatine phosphokinase as predictor of intermediate syndrome in organophosphorus poisoning. Indian J. Crit. Care Med. 2015; 19 (7): 384–387.Wan W.G., Jiang L., Zheng S.C., Qiu H.M., Xuan D.D., Zou H.J. Comprehensive analysis on variation of cardiac enzyme and troponin induced by acute organophosphorous poisoning. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2012; 30 (6): 452-455.Wan W.G., Jiang L., Zheng S.C., Qiu H.M., Xuan D.D., Zou H.J. Comprehensive analysis on variation of cardiac enzyme and troponin induced by acute organophosphorous poisoning. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2012; 30 (6): 452-455.Aygun D., Erenler A.K., Karatas A.D., Baydin A. Intermediate syndrome following acute organophosphate poisoning: correlation with initial serum levels of muscle enzymes. Basic Clin. Pharmacol. Toxicol. 200; 100 (3): 201-204.Aygun D., Erenler A.K., Karatas A.D., Baydin A. Intermediate syndrome following acute organophosphate poisoning: correlation with initial serum levels of muscle enzymes. Basic Clin. Pharmacol. Toxicol. 200; 100 (3): 201-204.Bird S.B., Krajacic P., Sawamoto K., Bunya N., Loro E., Khurana T.S. Ann N.Y. Pharmacotherapy to protect the neuromuscular junction after acute organophosphorus pesticide poisoning. Acad. Sci. 2016; 1374 (1): 86-93.Bird S.B., Krajacic P., Sawamoto K., Bunya N., Loro E., Khurana T.S. Ann N.Y. Pharmacotherapy to protect the neuromuscular junction after acute organophosphorus pesticide poisoning. Acad. Sci. 2016; 1374 (1): 86-93.Eyer P., Worek F., Thiermann H., Eddleston M. Paradox findings may challenge orthodox reasoning in acute organophosphate poisoning. Chem. Biol. Interact. 2010; 187 (1−3): 270−Eyer P., Worek F., Thiermann H., Eddleston M. Paradox findings may challenge orthodox reasoning in acute organophosphate poisoning. Chem. Biol. Interact. 2010; 187 (1−3): 270−Buckley N.A., Eddleston M., Szinicz L. Oximes for acute organophosphate pesticide poisoning. Cochrane Database Syst. Rev. 2011; 2: CD005085.Buckley N.A., Eddleston M., Szinicz L. Oximes for acute organophosphate pesticide poisoning. Cochrane Database Syst. Rev. 2011; 2: CD005085.Rahimi R., Nikfar S., Abdollahi M. Increased morbidity and mortality in acute human organophosphate-poisoned patients treated by oximes: a meta-analysis of clinical trials. Hum. Exp. Toxicol. 2006; 25 (3): 157-162.Rahimi R., Nikfar S., Abdollahi M. Increased morbidity and mortality in acute human organophosphate-poisoned patients treated by oximes: a meta-analysis of clinical trials. Hum. Exp. Toxicol. 2006; 25 (3): 157-162.Chen J.G. The therapeutic effects of obidoxime chloride on intermediate syndrome following acute organophosphate poisoning. Zhonghua Xiandai Zhong Xi Yi Za Zhi (Chin. J. Curr. Tradit.Chen J.G. The therapeutic effects of obidoxime chloride on intermediate syndrome following acute organophosphate poisoning. Zhonghua Xiandai Zhong Xi Yi Za Zhi (Chin. J. Curr. Tradit.West Med.). 2004; 2: 945–946.West Med.). 2004; 2: 945–946.Thiermann H., Szinicz L., Eyer F., Worek F., Eyer P., Felgenhauer N. Modern strategies in therapy of organophosphate poisoning. Toxicol. Lett. 1999; 107 (1-3): 233-239.Thiermann H., Szinicz L., Eyer F., Worek F., Eyer P., Felgenhauer N. Modern strategies in therapy of organophosphate poisoning. Toxicol. Lett. 1999; 107 (1-3): 233-239.Johnson S., Peter J.V., Thomas K., Jeyaseelan L., Cherian A.M. Evaluation of two treatment regimens of pralidoxime (1 gm single bolus dose vs 12 gm infusion) in the management of organophosphorus poisoning. J. Assoc. Physicians India. 1996; 44 (8): 529-5Johnson S., Peter J.V., Thomas K., Jeyaseelan L., Cherian A.M. Evaluation of two treatment regimens of pralidoxime (1 gm single bolus dose vs 12 gm infusion) in the management of organophosphorus poisoning. J. Assoc. Physicians India. 1996; 44 (8): 529-5Besser R., Weilemann L.S., Gutmann L. Efficacy of obidoxime in human organophosphorus poisoning: determination by neuromuscular transmission studies. Muscle Nerve. 1995; 18 (1): 15-22.Besser R., Weilemann L.S., Gutmann L. Efficacy of obidoxime in human organophosphorus poisoning: determination by neuromuscular transmission studies. Muscle Nerve. 1995; 18 (1): 15-22.Paudyal B.P. Organophosphorus poisoning. JNMA J. Nepal Med. Assoc. 2008; 47 (172): 251-258.Paudyal B.P. Organophosphorus poisoning. JNMA J. Nepal Med. Assoc. 2008; 47 (172): 251-258.Abedin M.J., Sayeed A.A., Basher A., Maude R.J., Hoque G., Faiz M.A. Open-label randomized clinical trial of atropine bolus injection versus incremental boluses plus infusion for organophosphate poisoning in Bangladesh. J. Med. Toxicol. 2012; 8 (2): 108-117.Abedin M.J., Sayeed A.A., Basher A., Maude R.J., Hoque G., Faiz M.A. Open-label randomized clinical trial of atropine bolus injection versus incremental boluses plus infusion for organophosphate poisoning in Bangladesh. J. Med. Toxicol. 2012; 8 (2): 108-117.Samuel J., Thomas K., Jeyaseelan L., Peter J.V., Cherian A.M. Incidence of intermediate syndrome in organophosphorous poisoning. J. Assoc. Physicians India. 1995; 43 (5): 321-323.Samuel J., Thomas K., Jeyaseelan L., Peter J.V., Cherian A.M. Incidence of intermediate syndrome in organophosphorous poisoning. J. Assoc. Physicians India. 1995; 43 (5): 321-323.Pawar K.S., Bhoite R.R., Pillay C.P., Chavan S.C., Malshikare D.S., Garad S.G. Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. Lancet. 2006; 368 (9553): 2136−41Pawar K.S., Bhoite R.R., Pillay C.P., Chavan S.C., Malshikare D.S., Garad S.G. Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. Lancet. 2006; 368 (9553): 2136−41Vucinić S., Antonijević B., Ilić N.V., Ilić T.V. Oxime and atropine failure to prevent intermediate syndrome development in acute organophosphate poisoning. Vojnosanit. Pregl. 2013; 70 (4): 420-423.Vucinić S., Antonijević B., Ilić N.V., Ilić T.V. Oxime and atropine failure to prevent intermediate syndrome development in acute organophosphate poisoning. Vojnosanit. Pregl. 2013; 70 (4): 420-423.Choi P.T., Quinonez L.G., Cook D.J., Baxter F., Whitehead L. The use of glycopyrrolate in a case of intermediate syndrome following acute organophosphate poisoning. P Can. J. Anaesth. 1998; 45 (4): 337-340.Choi P.T., Quinonez L.G., Cook D.J., Baxter F., Whitehead L. The use of glycopyrrolate in a case of intermediate syndrome following acute organophosphate poisoning. P Can. J. Anaesth. 1998; 45 (4): 337-340.Turner S.R., Chad J.E., Price M., Timperley C.M., Bird M., Green A.C., Tattersall J.E.H. Protection against nerve agent poisoning by a noncompetitive nicotinic antagonist. [in special issue: Selected papers from the 13th Medical Chemical Defence Conference 2011: New Developments in the treatment of intoxications by chemical warfare agents with focus on neurotoxic agents] Toxicology Letters. 2011; 206 (1): 105-111.Turner S.R., Chad J.E., Price M., Timperley C.M., Bird M., Green A.C., Tattersall J.E.H. Protection against nerve agent poisoning by a noncompetitive nicotinic antagonist. [in special issue: Selected papers from the 13th Medical Chemical Defence Conference 2011: New Developments in the treatment of intoxications by chemical warfare agents with focus on neurotoxic agents] Toxicology Letters. 2011; 206 (1): 105-111.Бонитенко Ю.Ю., Бонитенко Е.Ю., Першин В.Н. Конкурентные миорелаксанты и отравления фосфорорганическими инсектицидами. Medline. 2004; 5 (9): 40-44.Бонитенко Ю.Ю., Бонитенко Е.Ю., Першин В.Н. Конкурентные миорелаксанты и отравления фосфорорганическими инсектицидами. Medline. 2004; 5 (9): 40-44.Pichamuthu K., Jerobin J., Nair A., John G., Kamalesh J., Thomas K., et al. Bioscavenger therapy for organophosphate poisoning – an open-labeled pilot randomized trial comparing fresh frozen plasma or albumin with saline in acute organophosphate poisoning in humans. Clin. Toxicol. 2010; 48 (8): 813-819.Pichamuthu K., Jerobin J., Nair A., John G., Kamalesh J., Thomas K., et al. Bioscavenger therapy for organophosphate poisoning – an open-labeled pilot randomized trial comparing fresh frozen plasma or albumin with saline in acute organophosphate poisoning in humans. Clin. Toxicol. 2010; 48 (8): 813-819.Güven M., Sungur M., Eser B., Sari I., Altuntaş F. The effects of fresh frozen plasma on cholinesterase levels and outcomes in patients with organophosphate poisoning. J. Toxicol. Clin. Toxicol. 2004; 42 (5): 617-623.Güven M., Sungur M., Eser B., Sari I., Altuntaş F. The effects of fresh frozen plasma on cholinesterase levels and outcomes in patients with organophosphate poisoning. J. Toxicol. Clin. Toxicol. 2004; 42 (5): 617-623.

The authors declare that there are no conflicts of interest present.