Cardiogenic shock with first-degree heart block in a patient with glyphosate-surfactant poisoning

Introduction

Glyphosate is an N-phosphonomethyl glycine. It is an organic compound and non-selective herbicide-containing phosphorus. ¹ As north India is a major agricultural area, it is used extensively there. Though it is considered as less toxic than other herbicides, significant amount of ingestion can be fatal. A major cause of mortality is circulatory shock. ² Some investigators have reported that shock may be due to hypovolemia, which usually responds to intravenous fluids and vasopressors. ³ Others have reported that this type of shock may not always respond to fluids and pressor therapy. ⁴ We present a case of glyphosate poisoning who developed cardiogenic shock with reduced ejection fraction (EF), which improved within four days, and shock was resolved, thus indicating transient myocardial depression in this patient.

Case Report

A 34-year-old male gentleman, resident of Punjab, India, presented to emergency department with complaints of throat pain, nausea, vomiting and epigastric pain for the preceding 2 h. On examination, he was conscious but sweating profusely, and hypotensive with a blood pressure of 96/50 mm Hg. Oral examination showed, buccal mucosal congestion with multiple small ulcers. The pupils were bilaterally symmetrical and reacting to light. There was a diffuse mild respiratory wheeze, with muffled heart sounds, and mild epigastric tenderness. The electrocardiogram (ECG) was normal, and cardiac enzymatic markers were negative.

Further enquiry revealed that he had ingested 200 ml of a herbicide which was later found to be glyphosate, and gastric lavage was initiated immediately. Arterial blood gas analysis revealed metabolic acidosis (pH of 7.268 with bicarbonate of 16.2). Supportive treatment with intravenous fluids and anti-emetics was continued, but his blood pressure fell further to 70/40 mm Hg over the next 6 h, and urine output were low at 150 ml during the previous 12 h. Central venous pressure (CVP) was elevated (22 cm of H₂O), and noradrenaline infusion, dobutamine infusion, intravenous hydrocortisone and nebulisation with bronchodilator for bronchospasm were given. On the second day, his liver function test showed mild derangement (SGOT-51, SGPT-60) and mildly raised bilirubin of 39.3umol/L, and the creatinine level 115umol/L. He showed persistent metabolic acidosis. Blood pressure remained low at 80/56 mm Hg with a CVP of 18 cm of H₂O. An echocardiogram revealed global hypokinesia with an ejection fraction (EF) of 20–25% with mild mitral regurgitation. Repeat ECG showed first-degree atrio-ventricular block. Over the next two days, his symptoms settled with supportive therapy, liver and renal function returned to normal, and the metabolic acidosis resolved. His blood pressure increased to 116/70 mm Hg and CVP normalised at 13 cm of H₂O. Inotropes were tapered and stopped. Repeat echocardiography on sixth day of admission revealed normal left ventricular function with an EF of 55–60%. Repeat ECG was normal. The patient was discharged on the seventh day of admission.

Discussion

Glyphosate surfactant (GlySH) is a herbicide. In Asian countries, the usual formulation of glyphosate herbicide products contain 41% of glyphosate as an isopropylamine salt, water and a variable amount of surfactant, most commonly polyoxyethyleneamine (POEA). ⁵ The surfactant POEA is more toxic than glyphosate alone. Formulations containing GlySH and POEA cause more severe toxicity. ⁶ The proposed mechanisms for severe toxic effects of this combination are due to GlySH-mediated oxidative phosphorylation of mammalian cells by enhancing adenosine triphosphatase activity and POEA-mediated direct cardiotoxicity.^7,8 About 30–36% of GlySH is absorbed after oral ingestion. Peak concentration occurs in 6 h. It undergoes little metabolism in the body and is mostly excreted unchanged in the faeces and secondarily in the urine. ⁹ Significant toxicity occurs when >85 ml of GlySH is ingested. ⁴

Glyphosate affects many organs. It most commonly affects the gastro-intestinal system. Sore throat, nausea, vomiting, diarrhoea, abdominal pain and dysphagia are most commonly seen. Gastritis, duodenitis may occur due to its corrosive effect. ⁴ Respiratory involvement such as bronchospasm, aspiration and its consequences may occur. Renal and hepatic impairment (elevated liver enzyme and bilirubin) occurs in many patients. ⁴ Central nervous system manifestations include dilated pupil, confusion and convulsion. ² Fever, leucocytosis, metabolic acidosis and hyperkalemia can occur.

Glyphosate affects the cardiovascular system significantly. Cardiovascular collapse is the primary cause of death. ² Most probably, POEA component in GlySH is primarily responsible for the cardiovascular toxicity by causing mitochondrial dysfunction. ¹⁰ Cardiovascular involvement includes shock, sinus tachycardia and sinus bradycardia conduction abnormalities like first-degree AV block, ventricular tachycardia. ⁴ In glyphosate poisoning, shock is sometimes due to hypovolemia, so that it responds to fluids and vasopressor therapy. ³ The clinical scenario may, however, be different, where shock does not respond to fluid and pressor therapy. Our patient had increased CVP, shock, conduction disturbances and myocardial suppression as evidenced by echocardiography; all occurred simultaneously. Shock did not improve with fluids or vasopressor therapy. It improved simultaneously with improvement of cardiac function, as evidenced by repeat echocardiography. This indicates that transient myocardial depression is probably the reason for shock. As glyphosate has short half-life and when it is gradually decomposed in the circulation, cardiac function gradually improved. ¹¹ These findings substantiate studies ¹² where electrophysiological changes and conduction blocks correlated well with serum levels of glyphosate.

There is no antidote for glyphosate poisoning. Treatment is supportive. Decontamination should be carried out if patient presents early. Haemodialysis may be necessary. Intubation and mechanical ventilation may be necessary in respiratory failure. There is increasing evidence in support of intralipid fat emulsion (IFE) in refractory whose effectiveness has already been demonstrated. ¹³ It lowers the serum concentration of the free surfactant POEA component of GlySH. In our patient, shock improved gradually without the need for IFE.