Glyphosate poisoning - a case report.

Glyphosate is the most commonly used broad-spectrum, non-selective herbicide in the world. The toxicity is supposed to be due to uncoupling of oxidative phosphorylation and the surfactant polyoxyethylene amine (POEA)- mediated cardiotoxicity. Clinical features of this herbicide poisoning are varied, ranging from asymptomatic to even death. There is no antidote and aggressive supportive therapy is the mainstay of treatment for glyphosate poisoning. We present a 69-year-old female patient with suicidal consumption of around 500 ml of Glycel®. Initially, gastric lavage was done and intravenous fluids were given. Within two hours of presentation, the patient developed respiratory distress needing intubation, hypotension needing vasopressor support, and severe lactic acidosis. She also developed acute respiratory distress syndrome, hypokalemia, hypernatremia, and aspiration pneumonia. Our patient was critically ill with multiple poor prognostic factors, but with timely aggressive supportive management, the patient gradually recovered.

Introduction

Glyphosate is the most commonly used broad-spectrum, non-selective herbicide in the world. It is widely available in India as a formulation containing 41% Isopropyl amine salt of Glyphosate and 15% surfactant Polyoxyethylene amine (POEA) with water. The toxicity is supposed to be due to uncoupling of oxidative phosphorylation and POEA mediated cardiotoxicity. Toxic manifestations can range from gastrointestinal disturbance to acute respiratory distress syndrome (ARDS), arrhythmias, renal failure, and even death. There is no antidote for this herbicide poisoning and the treatment is mainly aggressive supportive therapy. We report a case of glyphosate poisoning who developed ARDS, shock, and severe metabolic acidosis recovered with timely supportive management.

Case History

A 69-year-old female (weight- 68 kg) brought to the emergency department with an alleged history of suicidal consumption of around 500 ml of Glycel® (41% Glyphosate and 15% POEA) [Figure 1a and b]. This was followed by multiple episodes of vomiting. On examination she was conscious and oriented with a Glasgow coma scale of 15/15, blood pressure (BP) of 140/70 mm Hg, heart rate of 120 beats per minute, and oxygen saturation (SpO2) of 99% in room air. Her systemic examination was normal. As she was brought to the emergency within 20 minutes of consumption of the poison gastric lavage was done immediately and activated charcoal was given. Poison Centre was contacted and the fact that no antidote is available for this particular poison was confirmed. She was hydrated with normal saline. Within two hours of presentation, the patient developed respiratory distress with hypoxia and she was intubated and put on mechanical ventilator. Also, vasopressor support was started (Noradrenaline at 0.5 μg/kg/min) to maintain the blood pressure as it dropped to 80 mm Hg systolic. Her arterial blood gas (ABG) analysis revealed severe metabolic acidosis with raised lactate levels [Table 1]. ECG showed QT prolongation [Figure 2]. Initial investigations revealed a high total leukocyte count, high amylase and lipase, creatinine of 1.3 mg/dl, and potassium of 2.5 mEq/L [Table 2]. A consolidation was found in the posterior segment of the right upper lobe and superior segment of the right lower lobe in the CT thorax [Figure 3]. The patient was started on cefoperazone sulbactam and clindamycin in view of aspiration pneumonia. She was started on potassium supplementation. On day two, we were able to reduce the fraction of inspired oxygen (FIO2) to 50% and noradrenaline dose to half. Her serum sodium was 149 mEq/L and normal saline was switched to half normal saline. On day three, x-ray revealed bilateral inhomogenous opacities in the lower zones with ABG showing moderate ARDS (PaO2/FiO2 of 186) [Table 1]. As her blood pressure stabilized without noradrenaline support, IV fluid support was reduced and lung-protective ventilation was given. After which there was a gradual improvement in the PaO2 levels and thus she was extubated to BiPAP (bi-level positive airway pressure) support on day four. During the entire course, her urine output was fair and there was no evidence of liver or kidney injury. She was then discharged in stable condition on day six.

Figure 1

(a and b) Glyphosate is available commercially as an aqueous mixture of 40.6% isopropyl amine salt of glyphosate and 15% surfactant polyoxyethylene amine (POEA)

Table 1

Daily arterial blood gas (ABG) comparison of the patient

Oxygen support	Day 0 ( Day of presentation)			Day 1	Day 2	Day 3	Day 4	Day 5
	At presentation	2 h after presentation	After intubation
	Room air	10 liters of oxygen	FiO2=100%	FiO2=50%	FiO2=50%	FiO2=50%	FiO2=40%	Room air
pH	7.42	7.18	7.36	7.35	7.41	7.39	7.37	7.45
paCO2 (mmHg)	22	34	36	37	32	34	31	30
paO2 (mmHg)	86	77	77	135	150	93	106	65
HCO3- (mmol/L)	14.3	12.5	20.3	20.4	20	20.6	17.9	20.9
SpO2 (%)	97	91	95	99	99	97	98	93
Lactate (mmol/L)	2.5	2	2.6	0.6	0.5	0.6	0.6	0.8

Figure 2

Twelve lead ECG showing a prolonged QT interval

Table 2

Day-wise laboratory investigation reports of the patient

Lab parameter (units)	Day 1	Day 2	Day 3	Day 4	Day 5
Hemoglobin (gm/dl)	13.4	14	—	—	—
Total leucocyte count (cells/ mm3)	19.8	18.4	13.7	—	7.8
Platelet count (lakhs/ mm3)	2.9	2.9	—	—	—
Blood urea (mg/dl)	39	26	39	29	24
Serum creatinine (mg/dl)	1.3	0.9	0.9	0.7	0.7
Serum sodium (mEq/L)	140	145	149	144	141
Serum potassium (mEq/L)	2.5	3.6	3.6	3.5	3.8
Total bilirubin (mg/dl)	0.8	—	—	1.1	—
Direct bilirubin	0.5	—	—	0.6	—
AST (IU/L)	21	—	—	18	—
ALT (IU/L)	18	—	—	16	—
ALP (IU/L)	78	—	—	60	—
Serum amylase (U/L)	178	—	98	—	—
Serum lipase (U/L)	315	—	124	—	—

Figure 3

Chest CT scan image showing consolidation in the posterior segment of the right upper lobe and superior segment of the right lower lobe (red arrow)

Discussion

Glyphosate is a general-purpose and nonselective Herbicide. It is commercially available as an aqueous mixture of 41% or more Isopropyl amine salt of Glyphosate and 15% surfactant Polyoxyethylene amine (POEA). It works through the shikimic acid pathway which is present in plants but absent in humans.[1] The exact mechanism of toxicity of this herbicide to humans is unknown and it is thought that it may be due to uncoupling of oxidative phosphorylation[2] and the surfactant POEA mediated cardiotoxicity.[3] Although its structure is similar to organophosphates (OP) it does not show any anticholinesterase activity and the OP like syndromes.

Poisoning could be via ingestion, inhalation, and skin or eye exposure. Clinical features of this herbicide poisoning are varied, ranging from asymptomatic to even death. The manifestations can be transient gastrointestinal disturbance, oral ulceration, esophagitis, lactic acidosis, gastrointestinal hemorrhage, hypotension requiring vasopressor support, renal failure requiring replacement therapy, respiratory failure requiring mechanical ventilation, arrhythmias, cardiac arrest, and death.[145] Case fatality rate is from 3.2-29.3%. Factors like advanced age, amount ingested >100 mL, X-ray abnormalities, respiratory distress needing intubation, hypotension needing vasopressor support, lactic acidosis, prolonged QT interval, elevated creatinine, elevated alanine aminotransferase (ALT), hyperkalemia are associated with poor outcome and mortality.[6789]

There is no definitive treatment or antidote and supportive treatment is the mainstay for glyphosate poisoning. When ingested gastric lavage may be done within one hour provided if there is no evidence of burns. Early upper gastrointestinal endoscopy in patients with gastric involvement is recommended. Removal from the area for inhalational exposure and decontamination for skin and eye exposure is recommended. Early renal replacement therapy may be helpful but the risk-benefit ratio should be taken into consideration. The use of an intravenous lipid/fat emulsion in patients with refractory hypotension was shown to be effective according to some case reports. Intravenous fat emulsion (IFE) acts by lowering the serum concentration of free POEA thereby reducing its cardiotoxicity.[11011]

Our patient had multiple poor prognostic factors like advanced age, amount ingested 500 mL, X-ray abnormalities, respiratory distress needing intubation, hypotension needing vasopressor support, lactic acidosis, and prolonged QT interval. Most patients with these poor prognostic factors would have a poor outcome. But with timely supportive management, the patient recovered.

In conclusion, this case report emphasizes that glyphosate poisoning could be life-threatening. There is no antidote for this herbicide poisoning. By aggressive supportive therapy and careful monitoring of complications, even critically ill patients with multiple poor prognostic factors can be saved.

Declaration of patient consent

The authors certify that appropriate patient consent was obtained.

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Conflicts of interest

There are no conflicts of interest.