Endosulfan Poisoning with Intravascular Hemolysis

The Journal of Emergency Medicine, Vol. 34, No. 3, pp. 295–297, 2008 Copyright © 2008 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/08 $–see front matter

doi:10.1016/j.jemermed.2007.02.039

Selected Topics: Toxicology

ENDOSULFAN POISONING WITH INTRAVASCULAR HEMOLYSIS Shankar Ramaswamy,

MD,

Goverdhan Dutt Puri,

MD, PhD,

and Subramanyam Rajeev,

MD

Department of Anaesthesia and Intensive Care, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India Reprint Address: G. D. Puri, Department of Anaesthesia & Intensive Care, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh 160012, India

e Abstract—We describe a 26-year-old female patient, who had attempted suicide with Endosulfan, and who presented to the Emergency Department with status epilepticus. She subsequently developed hypotension refractory to inotropes, intravascular hemolysis, disseminated intravascular coagulation (DIC), metabolic acidosis and, finally, cardiac arrest and death. Endosulfan is a chlorinated insecticide that causes central nervous system hyperstimulation. It is absorbed from the gastrointestinal tract, skin, and respiratory tract, and leads to nausea, vomiting, paraesthesia, giddiness, convulsion, coma, respiratory failure, and congestive cardiac failure. Hepatic, renal and myocardial toxicity, agranulocytosis, aplastic anemia, cerebral edema, DIC, thrombocytopenia, and skin reaction also have been reported. Management includes decontamination of skin and gastrointestinal tract, supportive care including treatment of status epilepticus, dysrhythmias, and mechanical ventilation. Mortality and morbidity rates are very high and there is no specific antidote. Atropine and catecholamines should be avoided. © 2008 Elsevier Inc.

status epilepticus, cardiac failure, disseminated intravascular coagulation (DIC), and intravascular hemolysis.

CASE REPORT A 26-year-old previously healthy woman with status epilepticus was brought to the Emergency Department by her family. She was immediately intubated and the seizure was controlled with diazepam, phenytoin, and midazolam infusion. There was no clinical evidence of aspiration. She was alleged to have taken 30 – 40 mL of Baygon (Propoxur, an organophosphate compound), a common household insecticide. Accordingly, she was managed as a case of propoxur poisoning, based on the history given by her relatives. Her heart rate was 80 beats/min, blood pressure 140/90 mm Hg, and the pupils were constricted at the time of presentation. Atropine infusion was started and titrated to heart rate, secretions, and pupil size. Within an hour she developed hypotension, which was managed with fluids, noradrenaline, and dopamine. She was subsequently transferred to the intensive care unit (ICU) for mechanical ventilation and further management. In the ICU, a central line and an arterial line were inserted. Atropine titrating to the same end points and midazolam (2– 4 mg/h) infusion were continued. Systolic blood pressure fell to around 70 mm Hg and heart rate increased to 180 beats/min (sinus tachycardia) despite receiving adequate fluids (titrated to central venous pressure), and inotropes including dopamine,

e Keywords— endosulfan; organochloride; poisoning; status epilepticus; insecticide

INTRODUCTION Organochloride insecticides like endosulfan are highly toxic compounds that are responsible for several intoxications and deaths worldwide. We report a fatal case of acute intentional endosulfan intoxication presenting with

RECEIVED: 19 September 2005; FINAL ACCEPTED: 8 November 2006

SUBMISSION RECEIVED:

9 June 2006;

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Table 1. Laboratory Results Investigations

On Admission

In ICU

Hb S. K S. Cr RBS PT aPTT D-dimer pH PaO2/FiO2 PaCO2 S. bicarbonate Base excess P. Hb U. Hb Platelet count

10.2 4.2 1.6 — — — — — — — — — —

7.8 7.3 — 257 ⬎120 ⬎120 Positive 7.2 136 24 9 ⫺17 Positive Positive —

—

Hb ⫽ hemoglobin (g/dL); S. K ⫹ serum potassium (mEq/dL); S. Cr ⫽ creatinine (mg/dL); RBS ⫽ random blood sugar (g/dL); PT ⫽ prothrombin time (seconds); aPTT ⫽ activated partial thromboplastin time (seconds); PaO2 ⫽ partial pressure of oxygen (mm Hg); FiO2 ⫽ fractional inspired oxygen concentration (%); PaCO2 ⫽ partial pressure of carbondioxide (mm Hg); BE ⫽ base excess; P. Hb ⫽ plasma hemoglobin; U. Hb ⫽ urine hemoglobin.

adrenaline, and noradrenaline. One hour later, the urine became dark colored, which was accompanied by a fall in blood hemoglobin (Hb) from 10.2 to 7.8 g/dL, suggesting intravascular hemolysis (Table 1). This was confirmed by a positive plasma and urine Hb. She also developed generalized oozing from the nasal cavity, central and arterial line sites, and endotracheal tube, and the coagulation parameters were grossly deranged (Table 1). The urine output was approximately 0.75 to 1 mL/kg/h until the end. A chest X-ray study revealed bilateral diffuse infiltrates suggestive of pulmonary edema. Platelet counts could not be obtained due to technical reasons. She developed severe metabolic acidosis and hyperkalemia, which were treated with glucose-insulin, sodium bicarbonate, and calcium chloride. Despite receiving six units of fresh frozen plasma and two units of platelet concentrates, she continued to bleed. When we insisted on seeing the poison bottle, the patient’s relatives brought an empty bottle of endosulfan. About 13 h after consumption of the poison, she developed ventricular fibrillation and she did not respond to cardiopulmonary resuscitation. Autopsy could not be performed in the absence of consent of the patient’s relatives.

DISCUSSION Endosulfan is a chlorinated insecticide similar to DDT. Its full name is 6,7,8,9,10,10- hexachloro- 1,5,5a,6,9,9ahexahydro- 6,9- methano- 2,4,3- benzo(e) dioxathiepin 3- oxide, and it is used as a pesticide (1). It is absorbed

from the gastrointestinal tract, respiratory system, and skin. Endosulfan acts as an antagonist to the inhibitory neurotransmitter Gama-aminobutyric acid (GABA) by inactivating GABA A-dependent chloride channels. Several cases of suicidal and accidental poisoning, as well as chronic poisoning, with endosulfan have been reported in the literature (1–10). Poisoning with endosulfan produces strong sulfur odors, and the clinical picture is comprised of three stages: the acute cardiac and convulsive stage, followed by the sub-acute pulmonary and convulsive stage, and finally, the slow recovery stage (2). The insecticide produces symptoms consistent with central nervous system stimulation, with generalized seizures being the most common presentation. Acute poisoning is usually accompanied with nausea, vomiting, parasthesia, giddiness, convulsion, coma, respiratory failure, and congestive cardiac failure. Hepatic, renal, and myocardial toxicity, agranulocytosis, aplastic anemia, cerebral edema, pulmonary edema, thrombocytopenia, metabolic disturbances such as metabolic acidosis and skin reaction also have been reported (3– 8,11). Other features that can hint toward a possible endosulfan poisoning include sulfur odor and an abdominal X-ray demonstrating radio-opacity due to the chlorine component (11). A case of fatal poisoning with DIC also has been reported (7). Common causes of death include pulmonary aspiration, myocardial insufficiency, pulmonary edema, and multi-organ failure. Residual psychiatric and neurological symptoms and renal failure have been reported in the survivors after exposure to either acute or chronic overdose of endosulfan (4,9,10). Management of endosulfan poisoning is mainly supportive and there is no antidote for it. Supportive care includes decontamination of skin with soap and water, gastric lavage, activated charcoal, cholestyramine, treatment of status epilepticus, and dysrhythmias. Cholestyramine removes endosulfan from enterohepatic circulation and enhances its elimination (11). Endotracheal intubation and mechanical ventilation may be required for airway protection and prevention of pulmonary aspiration. Atropine, epinephrine, dopamine, and noradrenaline should be avoided in the organochloride-sensitized myocardium (3,11). Benzodiazepines are the anti-epileptics of choice due to their specific GABA agonist activity. Phenobarbitone and propofol may be used as an alternative and are preferred over phenytoin. These drugs may be required in relatively larger doses than usual (11). In our patient, the case was initially wrongly diagnosed as propoxur poisoning based on the history given by the patient’s relatives, and the patient was treated with atropine. The seizures were controlled with midazolam infusion and phenytoin. The patient subsequently developed sinus tachycardia (up to 180 beats/min) and refractory myocardial failure, which could be due to the effect

Endosulfan Poisoning

of atropine and inotropes in the sensitized heart. The patient also developed intravascular hemolysis, which was confirmed with plasma and urine Hb reports. In conclusion, endosulfan is a highly toxic poison that produces central nervous system stimulation and status epilepticus. It can result in refractory myocardial failure, metabolic acidosis, and DIC. Our patient also had intravascular hemolysis. The clinical course could have been compounded by drugs like atropine and inotropes. There is no specific therapy and the management is only supportive care. Acute intravascular hemolysis after endosulfan poisoning has not been referred to in the literature. REFERENCES 1. Demeter J, Heyndrickx A, Timperman J, Lefevere M, De Beer J. Toxicological analysis in a case of endosulfan suicide. Bull Environ Contam Toxicol 1977;18:110 – 4. 2. Shemesh Y, Bourvine A, Gold D, Bracha P. Survival after acute endosulfan intoxication. J Toxicol Clin Toxicol 1988;26:265– 8.

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