The Journal of Emergency Medicine, Vol. 41, No. 5, pp. 507512, 2011 Copyright 2011 Elsevier Inc.

. Printed in the USA. All rights reserved 0736-4679/$ - see front matter

doi:10.1016/j.jemermed.2010.05.072

Selected Topics: Toxicology

ACUTE ABDOMEN ASSOCIATED WITH ORGANOPHOSPHATE POISONING

Sahin Aslan, MD,* Zeynep Cakir, MD,* Mucahit Emet, MD,* Mustafa Serinken, MD, Ozgur Karcioglu, MD, Hayati Kandis, MD,* and Mustafa Uzkeser, MD*
*Department of Emergency Medicine, Atatu rk University, School of Medicine, Erzurum, Turkey; Department of Emergency Medicine, Pamukkale University, School of Medicine, Denizli, Turkey; and Department of Emergency Medicine, Acibadem University, School of Medicine, Bakirkoy, Istanbul, Turkey Reprint Address: Mustafa Serinken, MD, Department of Emergency Medicine, Pamukkale University Medical School, Denizli 20070, Turkey

, AbstractBackground: 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 1670 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 uid. Pancreatitis and peritonitis developed in one case. Atropine treatment was administered for approximately 2436 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 ndings in our study suggest that these patients should undergo routine abdominal ultrasonography,

especially in cases with abdominal pain along with other abdominal complaints. 2011 Elsevier Inc. , Keywordsacute abdomen; abdominal pain; organophosphate; carbamate; poisoning; intoxication

INTRODUCTION Pesticides are extensively used in developed and developing countries throughout the world. The compounds possess the potential to cause serious harm and even death in human beings (1). Exposure to carbamates and organophosphates can have acute, chronic, and long-term effects. Organophosphates are highly toxic compounds that are readily absorbed through the skin, mucous membranes, and gastrointestinal and respiratory tracts (2,3). The toxic effects of organophosphate poisoning are due primarily to the inhibition of acetylcholinesterase (AChE), resulting in accumulation of acetylcholine at the cholinergic synapses of the central nervous system, neuromuscular junction, parasympathetic nerve endings, and some of the sympathetic nerve endings such as sweat glands (muscarinic effects); and somatic nerves and ganglionic synapses of autonomic ganglia (nicotinic effects) (4). Carbamates are reversible AChE inhibitors, whereas organophosphates are irreversible inhibitors of the enzyme. Additionally, the carbamates have less penetration across the blood-brain barrier than the

RECEIVED: 23 September 2009; FINAL SUBMISSION RECEIVED: 18 February 2010; ACCEPTED: 17 May 2010
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organophosphates (5). Poisoning with carbamate or organophosphate compounds and an acute abdomen rarely have been cited as associated conditions (6). The present study was designed to evaluate the clinical course of patients with carbamate or organophosphate poisoning admitted to our University-based emergency department (ED), with special emphasis on acute abdominal conditions. MATERIALS AND METHODS All consecutive patients who presented to our Universitybased ED due to intoxication with carbamate or organophosphate compounds over a 24-month study period were prospectively entered into the study. The study was approved by the Institutional Review Board before the commencement of the research. The diagnosis of acute poisoning with organophosphate or carbamate compounds was based on the following criteria: a history of exposure or contact with either pesticide; characteristic clinical signs and symptoms; and improvement in signs and symptoms after treatment with atropine and pralidoxime. Patients under 16 years old, those who were unable to supply adequate information on the substance ingested or their medical history, those with other medical and traumatic conditions affecting acute abdominal pain, and those with concurrent drug overdose and organophosphate ingestion were excluded from the study. The demographic characteristics, vital signs, the origin and nature of pesticide intake, the causes of poisoning, and ndings on physical examination were recorded. Glasgow Coma Scale score, electrocardiographic ndings, complete blood count, peripheral arterial blood gases, lactate dehydrogenase and amylase, electrolytes (Na and K), and liver and kidney function tests were recorded and evaluated in all cases. Nasogastric tubes were inserted and gastric lavage was performed, and 1 g/kg activated charcoal and repeated doses of atropine sulphate were administered to all patients. Ultrasonographic examination was performed by a certied emergency physician in patients with abdominal pain and intact consciousness. All data obtained in the study were recorded and analyzed using the Statistical Package for Social Sciences for Windows, Version 11 (SPSS Inc., Chicago, IL). Numerical variables were given as mean 6 standard deviation, and categorical variables were noted as N and percentages. RESULTS In the 24-month study period, 49 consecutive patients (23 males, 26 females) were diagnosed with carbamate or organophosphate poisoning. The mean age of the patients was 32 6 13.1 years (range 1670 years). The mean time

interval from poisoning to admission was 6.7 6 7.13 h (range 136 h). The poisoning resulted from a suicide attempt in 38 cases (77.6%), whereas the remaining 11 (22.4%) were reported as accidental ingestions. Oral ingestion was the route of intake in the majority of the patients (83.6%, n = 41). Organophosphates accounted for 63.3% (n = 31) of the intoxications, and carbamate was the culprit in 36.7% (n = 18). Clinical signs and symptoms of organophosphate and carbamate poisonings are shown in Table 1. The signs and symptoms most frequently noted in organophosphate and carbmate poisonings were perspiration (80.6% and 72.2%, respectively), vomiting (77.4% and 66.6%, respectively), and bronchorrhea (77.4% and 61.1%, respectively). Abdominal pain was reported by 32 patients (65.3%). Abdominal ultrasonography was performed in 22 patients who complained of moderate to severe abdominal pain as a leading symptom. Serious muscarinic symptoms accompanied abdominal pain in these 22 patients. Among them, 14 (63.6%) were found to have abdominal free uid (Table 2). Massive abdominal free uid collection was observed throughout the abdomen in two cases (14.2%). An ultrasound image of a 25-year old man is shown in Figure 1. Three (21.4%) of the 14 patients found to have abdominal free uid were pregnant. Their gestational ages were established with ultrasound as 9, 15, and 28 weeks, respectively. The latter two women were found to have intrauterine fetal demise. The pregnant patients underwent therapeutic abortion due to morbid clinical presentations. Pancreatitis and peritonitis developed in one case. This patient had overt manifestations of muscarinic poisoning associated with hard signs of acute abdominal conditions (i.e., rebound tenderness and guarding). Abdominal ndings persisted despite resolution in muscarinic signs after the treatment. In this case, lactate dehydrogenase and amylase were signicantly high (2445 U/L and 750 U/L, respectively). Ultrasound examination revealed peripancreatic uid, decreased echogenicity, and minimal enlargement of the gland. He was followed-up for 20 days. Leaving this case out, the in-hospital management and follow-up lasted between 3 and 4 (3.4 6 6.7) days. Study patients mean white blood cell count was 14,975 6 7523 mm3 (range 680036,500/mm3). Serum amylase level was signicantly high in one case (750 U/L) and mildly elevated in 4 women who also had severe muscarinic signs (between 280 U/L and 350 U/L). The serum amylase was not elevated in the pregnant patients. Other laboratory ndings were within normal limits. Gastric lavage was performed, and 1 g/kg activated charcoal was administered to all patients. In addition, 14 mg atropine sulphate was administered intravenously in repeated doses to all patients with muscarinic signs (n = 22, 60%) and bradycardia (n = 8, 40%). Atropine

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Table 1. Clinical Signs and Symptoms of the Patients Organophosphate Poisoning (n = 31) Signs Muscarinic Bronchial hypersecretions bronchorrhea Miosis Sweating Diarrhea Urinary incontinence Abdominal pain Nausea/vomiting Respiratory distress Nicotinic Fasciculations Tremors Central nervous system Impaired consciousness Seizures Cardiac Sinus tachycardia (> 100 beats/min) Sinus bradycardia (< 60 beats/min) Others Fever n 24 21 25 13 9 22 24 4 15 2 19 1 19 8 10 % 77.4 67.7 80.6 41.9 29.0 70.9 77.4 12.9 48.3 5.2 61.2 3.2 61.2 25.8 32.2 Carbamate Poisoning (n = 18) n 11 10 13 7 3 10 12 1 8 1 3 0 9 1 2 % 61.1 55.5 72.2 38.8 16.6 55.5 66.6 5.5 44.4 5.5 16.6 0 50.0 5.5 11.1

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sulphate was administered until salivation and lacrimation were relieved (mean total dose 13.75 6 6.75 mg) (range 532 mg). Atropine treatment lasted for approximately 2436 h. Pralidoxime was administered to 22 (70.9%) patients with organophosphate poisoning but was not used in patients intoxicated with carbamates. Complications were observed in 13 (26.5%) patients, including respiratory failure in 8 (16.3%), aspiration pneumonia in 4 (8.2%), and septic shock in 1 (2.0%). Endotracheal intubation and mechanical ventilatory support were required in 7 patients (14.3%). The mean duration of mechanical ventilation was 3.7 6 2.2 days. Five patients (10.2%) expired in the follow-up period. Three patients who were mechanically ventilated died from sudden cardiorespiratory arrest, and 2 died from pneumonia complicated by adult respiratory distress syndrome. DISCUSSION Pesticide poisoning is the most common cause of organophosphate and carbamate poisoning because the vast majority of pesticides still contain organophosphates and carbamates. The most common cause of mortality in organophosphate and carbamate poisoning is respiratory failure; however, death is rare, occurring in 0.04 1% of typical pesticide poisonings (7). Exner and Ayala reported the mortality rate as 6% (8). The high mortality

rate found in the current study can be attributed to the preferential transfer of patients with morbid condition to the study hospital because it is the single institution in the region with a high capacity of beds and the highest technologic advancements available. Another reason for the high mortality may be the withdrawal of oxime therapy in patients with carbamate poisoning. This was done because .the administration of oximes, acetylcholinesterase reactivators, in carbamate poisoning is controversial due to the potential toxicity of oximes in conjunction with carbamate, especially in the case of the carbamatecarbaryl poisoning (9). Moreover, in accord with current procedures, oximes were not used for patients admitted with cholinergic crisis unless they were proven to have organophosphate poisoning. However, new guidelines state that when a poisoned patient presents with a cholinergic crisis and the poison is unknown, it is necessary to treat the patient with a combination of atropine and oximes (10,11). The most frequent signs associated with organophosphate poisoning have been reported to be miosis, vomiting, hypersalivation, respiratory distress, abdominal pain, depressed level of consciousness, and muscle fasciculation (1,12). In the present study, perspiration, nausea and vomiting, and bronchorrhea were the most common abnormal signs. Exner and Ayala reported on a 300patient study and found that the most common symptoms on presentation were abdominal pain (83%), nausea/ vomiting (79%), miosis (72%), bronchorrhea (44%), diarrhea (41%), and fasciculations (31%) (8). In the present study, the percentage of patients with abdominal pain was lower than in Exner and Ayalas report, at 70.9%, especially in patients with carbamate poisoning (55.5%). Organophosphate poisoning, abdominal pain, and abdominal free uid rarely have been cited as associated conditions (6). These patients may suffer from abdominal distress because muscarinic effects from post-ganglionic parasympathetic activity may cause smooth muscle contractions in all gastrointestinal organs. Secretions may be overt with the same mechanism due to stimulation from acetylcholine excess at cholinergic junctions of secretory glands. Another reason for free uid accumulation may be pancreatic inammation and stimulation of pancreatic secretion secondary to cholinergic stimulation (13). In fact, the characteristics of the free abdominal uid (exudate vs. transudate) should have been determined in this study, but unfortunately it was not possible. The exudate was thought to be secondary to inammation. However, although the mechanism of abdominal free uid identied in the fetus is not clear, it is attributed to the stimulation of the muscarinic receptors. In our study, 22 patients developed severe abdominal pain and 14 patients developed abdominal free uid, both of which were likely due to the direct toxic effect of organophosphate on the

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Table 2. Main Clinical Characteristics of the Patients and their Ultrasonographic Findings Symptoms No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Sex/Age (Years) F/25 F/41 F/39 F/18 M/19 F/28 M/25 M/38 F/43 M/23 F/33 M/24 M/29 F/40 MS + + + + + + + + + + + + + + NS + + + + + CNSS + + + + + + + + + Atropine (Total Dose) 7 mg 5 mg 5 mg 27 mg 12 mg 5 mg 32 mg 9 mg 18 mg 10 mg 6 mg 7 mg 11 mg 8 mg PAM (Initial and Repeated Dose) 1g 1g 1g 1 g + 0.5 g 1g 1g 1 g + 0.5 g 1g 1 g + 0.5 g 1g 1g 1g 1g 1g

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Ultrasonographic Findings Volume of Free Fluid ++ + ++ +++ ++ ++ +++ + + ++ + + ++ + Location of Free Fluid Right and left lower quadrant Right lower quadrant Right lower quadrants Throughout the abdomen Right and left lower quadrant Left lower quadrant Throughout the abdomen Left lower quadrant Right and left lower quadrant Throughout the abdomen Right lower quadrant Right lower quadrant Right and left lower quadrant Right and left lower quadrant

MS = muscarinic symptoms; NS = nicotinic symptoms; CNSS = central nervous system symptoms; PAM = pralidoxime; M = male; F = female; + = minimal uid collection; ++ = moderate uid collection; +++ = massive uid collection.

muscarinic receptor (14). The patients suffering from abdominal pain were either the patients presenting to the ED late or the patients who did not receive enough treatment on their previous visit. The patients who came to the ED early recovered in a short period of time. These observa-

tions support an important role of early diagnosis and expedient treatment in the management of acute organophosphate and carbamate poisoning. One important effect of organophosphate or carbamate intoxication is the development of acute pancreatitis. The

Figure 1. Ultrasonographic examination with 7.5-MHz linear transducer shows free uid in the intraperitoneal and peri-intestinal area.

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incidence of acute pancreatitis in adults with organophosphate intoxication is approximately 12%, and vomiting and abdominal pain are among the most consistent clinical signs in patients with pancreatitis (15). In the presence of a patients severe abdominal distress along with high levels of serum amylase, pancreatitis should be suspected. The clinical picture is usually mild, and the development of important complications, such as pancreatic necrosis, is quite rare (16,17). Singh et al. conducted a prospective study on 79 patients with organophosphate poisoning and reported that serum amylase was elevated in 47% (18). They concluded that although acute pancreatitis is rare, mild elevation of serum amylase is common in these patients. Acute pancreatitis was diagnosed in only one of our patients. Sonographic ndings, along with elevated serum amylase, conrmed the diagnosis of acute pancreatitis. The clinical picture in this case was mild to moderate, which is consistent with the data from the literature. The literature suggests a high incidence of silent or elusive pancreatitis in patients with organophosphate poisoning (19). Limitations A prospective, community-based, multi-center study on abdominal conditions in association with organophosphate intoxication would give more detailed information on the topic than the present study can provide. The design of the present study, being conducted in a single center, is a major limitation per se. In addition, lack of abdominal ultrasonography as a standard diagnostic modality in each patient in the study also inhibits extrapolation of the results to the entire sample, or to other patients. Another potential limitation is the user-dependent nature of ultrasonography and difculties with performing the procedure (e.g., a fetus in the uterus). CONCLUSION Abdominal pain as an associated condition with organophosphate intoxication was encountered frequently in our study. Patients with a diagnosis of organophosphate intoxication should be screened for acute abdomen. The observations in the present study suggest that these patients should undergo routine abdominal ultrasonography,

especially in cases with abdominal pain along with suspect abdominal complaints. REFERENCES
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ARTICLE SUMMARY 1. Why is this topic important? Organophosphate poisoning has an important effect on community health, especially in developing countries widely involved in agriculture, yet the clinical course of the patients is still under investigation. 2. What does this study attempt to show? The aim of this study was to evaluate the clinical course of patients with carbamate or organophosphate poisoning admitted to the University-based emergency department (ED), with special emphasis on abdominal complications. 3. What are the key ndings? Abdominal pain was reported by 32 patients (65.3%), 14 (63.6%) of whom were found to have abdominal free uid. 4. How is patient care impacted? Patients with a diagnosis of organophosphate intoxication should be screened for abdominal pain.