Herbicide Poisoning

By Lewis Nelson, MD

One hour after intentionally ingesting two cups of an unidentified herbicide, a young woman presents to the emergency department complaining of vomiting, diarrhea, and throat pain. On physical examination, her initial vital signs are normal, as are her chest and abdomen, but her oropharynx is erythematous. Neither drooling nor stridor is present.

Because the patient has upper airway symptoms and signs of irritation, clearly the first priority must be to maintain airway patency. The decision to perform endotracheal intubation after a patient has ingested a caustic or irritating agent is often difficult. In addition to the obvious signs of airway compromise, the exact nature of the exposure may be the most important factor to consider. Patients who ingest highly caustic agents such as sodium hydroxide require aggressive airway management, since intubation may be extremely difficult once the airway becomes compromised. Identification of the specific exposure is therefore critical.

THE USUAL SUSPECTS
Although no longer available in the United States, paraquat carries the greatest morbidity and mortality among ingested herbicides. Paraquat is still a major cause of death and disability in some countries, such as Australia, and it was responsible for at least four deaths from acute poisoning in the United States in 1996. These consequences occur despite the fact that the chemical has been rendered technically "nontoxic" through the addition of emetic or malodorous agents, such as valeric acid.

Paraquat has an affinity for the lung, in which it is selectively absorbed and accumulates within type I and type II alveolar epithelial cells. Within these cells, paraquat generates oxygen free radicals that ultimately damage lipid membranes and cause cell death. The initial acute lung injury may progress to acute respiratory distress syndrome (ARDS); death occurs in more than 50% of patients after an intentional ingestion. Those patients who do survive enter a proliferative phase characterized by loss of alveolar integrity, proliferation of fibroblasts, and deposition of collagen, leading to pulmonary fibrosis.

Aggressive support is a must for patients who ingest paraquat. Ironically, oxygen supplementation may have a deleterious effect because it increases the number of toxic radicals. Oxygen should therefore be given only to prevent hypoxemia. Because paraquat is also corrosive, examination of the oropharynx and gastrointestinal system is critical. Gastrointestinal decontamination can be achieved with activated charcoal, bentonite, or fuller's earth, any of which will adsorb and inactivate the herbicide. Hemoperfusion may be effective in clearing systemic paraquat in patients who present soon after ingestion.

Diquat, a related agent, is readily available in the U.S. Although its herbicidal and toxic activity is similar to that of paraquat, it is not selectively concentrated in the lung and therefore is less toxic to the pulmonary system. However, diquat appears to be considerably nephrotoxic, an effect that may be related to its accumulation in the kidneys.

Chlorophenoxy derivatives such as 2,4-dichlorophenoxyacetic acid (2,4-D) are widely used by the general population as broadleaf weed herbicides. In fact, an estimated 60 million pounds are used in the U.S. annually by both homeowners and professional landscapers. Although 2,4-D is known as a component of the infamous herbicide Agent Orange, the chlorophenoxy herbicides are usually minimally toxic when ingested unintentionally in small quantities. Large ingestions, however, produce acute poisoning characterized by compromised mental status, seizures, cardiac arrhythmias, and rhabdomyolysis. Because these agents can uncouple oxidative phosphorylation and thereby cause cellular energy failure, death may occur.

Perhaps the most widely used garden herbicide in the U.S. today is glyphosate (brand name, Roundup). Although less toxic than the herbicides described above, glyphosate has been used in hundreds of deliberate self-poisonings worldwide. As an inhibitor of plant-specific amino acid biosynthesis, glyphosate should be minimally toxic to humans. In fact, its toxic effects may be related largely to the nonionic surfactant with which glyphosate is formulated.

The most pronounced effects include gastrointestinal irritation and erosion, although the oropharynx is also often affected. The involvement of the oropharynx may explain the relatively high incidence of pulmonary aspiration cited in many studies; however, acute lung injury may be induced through systemic effects as well. Profound hypovolemia may account for the hemodynamic abnormalities, although animal studies have also found that the surfactant may produce these effects directly. Supportive treatment should be given. Long-term adverse effects have not been noted among survivors of such glyphosate poisoning.

PARAQUAT OR GLYPHOSATE?
In countries such as China where both paraquat and glyphosate are used frequently, empiric therapy for both agents is often initiated. The epidemiology of the two agents, however, suggests that in the United States, glyphosate should be suspected whenever a patient presents with herbicide ingestion, since paraquat is virtually unavailable in this country. In some countries, the rapid urine screening test for paraquat is used routinely. The test involves the addition of dithionate to a urine sample, but the results may be negative for patients with sublethal ingestions. Nonetheless, it is important to make the differentiation between the two herbicides, either statistically or scientifically, since the therapies that may be considered for paraquat poisoning, such as hemoperfusion, are neither benign nor wise when administered to patients who are actually suffering from glyphosate poisoning.

In this case, the patient had ingested glyphosate. After undergoing endoscopy, which yielded normal results, she remained clinically stable and was discharged home after an overnight observation period.

 

Suggested Reading Hung DZ, et al.: Laryngeal survey in glyphosate intoxication: a pathophysiological investigation. Hum Exp Toxicol 16:596, 1997. Sawada Y, et al.: Probable toxicity of surface-active agent in commercial herbicide containing glyphosate. Lancet 1:299, 1988. Tominack RL, et al.: Taiwan National Poison Center survey of glyphosate-surfactant herbicide ingestions. J Toxicol Clin Toxicol 29:91, 1991.