Pesticides and Herbicides

Published on 22/03/2015 by admin

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Last modified 22/03/2015

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185 Pesticides and Herbicides

The U.S. Environmental Protection Agency (EPA) broadly defines a pesticide as any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest. These agents are typically further classified according to their chemical, physical, or biological class, or they may also be categorized as acting on either animal or insect pests or undesirable plants. In the context of intended use, the categories of insecticide, herbicide, or rodenticide are also commonly used and often useful for reviewing toxicity profiles of agents most likely to be encountered in critical care medicine.

image General Principles of Management

As with a variety of other toxic exposures, the general principles of management for many of the pesticides have changed in recent years. Most notably, these changes have related to gastric decontamination, but there also have been emerging controversies regarding the use of antidotes intended to aid in the treatment of pesticide poisonings, especially those cases involving organophosphate (OP) insecticides.

Methods of gastric decontamination that have been reexamined over the last decade include the use of gastric lavage, activated charcoal, syrup of ipecac, and whole-bowel irrigation.1 Ipecac largely has been abandoned for routine use in either the prehospital or hospital care setting.2,3 Its slow onset of action, incomplete return of toxin, and ability to cause emesis in an unconscious or seizing patient render it unacceptable in most cases in which gastric decontamination might be considered a therapeutic option. Furthermore, many of the pesticide products are liquid formulations with hydrocarbon solvents, and this fact further precludes the use of an emetic owing to the risk of aspiration.

Gastric lavage is still a preferred method of decontamination in those substantial ingestion exposures where patients present within 60 minutes of ingestion.4 Care must be taken to ensure that the patient’s airway is protected with a cuffed endotracheal tube. Lavage should be carried out using a large-bore tube with adequate aliquots of water or saline. Since recovery rates may be small, clinicians should evaluate the risk-to-benefit ratio of use for each patient.

Although single-dose administration of activated charcoal has become the empirical treatment of choice for most significant toxic ingestions, its use and ability to improve patient outcomes in pesticide poisoning has not been systematically studied or proven.5 Furthermore, unless it is administered within the first hour after exposure, even its theoretical benefit may be questioned. Still, potential benefit may warrant its early use, especially with extremely toxic substances such as paraquat and diquat or substantial ingestions of long-acting anticoagulant rodenticides.

Multiple-dose activated charcoal also has been a therapeutic intervention intended to decrease absorption of toxins but, more importantly, enhance elimination of toxins once absorbed. Despite promising results in cases involving selected toxins, there are no data to document effectiveness in poisoning cases involving pesticides.

For those patients in whom activated charcoal may offer potential therapeutic benefit, active bowel sounds must be present, and an appropriate dose must be determined. Adults typically receive 25 to 100 g of charcoal as a mixed aqueous slurry with or without sorbitol as an added cathartic. Children and infants should receive 25 to 50 g or 1 g/kg body weight. Although the addition of sorbitol or other cathartics to activated charcoal has been shown to enhance elimination of certain toxins, their ability to reduce bioavailability or improve patient outcomes after pesticide poisoning has not been demonstrated. Thus, use of a sorbitol-containing activated charcoal preparation is neither indicated nor contraindicated.

Whole-bowel irrigation (WBI) involving the use of large volumes of a polyethylene glycol (PEG)-containing isosmotic solution has also been anecdotally reported to produce positive results in the treatment of poisoning. It is purported to cleanse the gut of toxins by inducing liquid stooling. In dog models, it has been shown to increase the mean total body elimination of paraquat.6 There have been no systematic controlled clinical studies to demonstrate its effectiveness in humans, and side effects frequently complicate its use and can mask emerging toxin-induced side effects that can confuse the clinical picture.

As many pesticides have hydrocarbon diluents or vehicles, any method of gastric decontamination must be cautiously attempted in only those patients likely to receive the greatest benefit. Hydrocarbon aspiration remains a real concern, and attempts at most forms of gastric decontamination will likely increase the risk of aspiration by either direct or indirect means, including the induction of spontaneous emesis.

Skin decontamination in all substantial dermal exposures remains indicated and should be carried out concomitantly with other life-saving measures. Care should be taken to remove and discard contaminated clothing, consider and avoid contamination of emergency and healthcare personnel, and perform full decontamination of all exposed tissue with copious amounts of soap and water. Note that some agents such as the fungicide, chlorothalonil, or concentrated versions of the herbicide, glyphosate, are corrosive and in cases of ocular exposure may require extensive eye washing and evaluation by an ophthalmologist.

image Specific Agents

There are more than 3000 different formulations and 25,000 brand names of pesticides registered with the EPA.7 A brief list of those categories of agents most likely to be encountered in critical care medicine include the OPs, N-methyl carbamates, solid organochlorines, pyrethroids and pyrethrins, chlorophenoxy herbicides, paraquat, diquat, and a limited variety of commonly encountered agents with unique toxicology profiles.



The primary toxicologic effects of OP insecticides relate to their ability to phosphorylate acetylcholinesterase (AChE), thereby forming an irreversible covalent phosphate linkage with a serine residue at the active site. This inhibition effectively allows unopposed action of acetylcholine at the nerve synapse, resulting in sustained depolarization of the postsynaptic neuron. This action occurs both in the central nervous system (CNS) and at muscarinic sites in the peripheral nervous system, nicotinic sites in the sympathetic and parasympathetic ganglia, and nicotinic sites at the neuromuscular junction. Although OP insecticides registered by the EPA are relatively more selective in acting on insect cholinesterase, they also affect mammalian AChE in the event of excessive exposure.

The rate of spontaneous reactivation of AChE is dependent on the chemical structure of the agent involved. The most commonly encountered agents carry either two methyl or two ethyl ester groups attached to the phosphorus atom. The significance of this structural finding relates to the fact that poisoning with dimethyl agents (e.g., demeton-S-methyl, dichlorvos, dimethoate, or malathion) results in rapid and spontaneous reactivation of AChE, whereas poisoning with diethyl agents (e.g., chlorpyrifos, diazinon, or parathion) is associated with slower reactivation of AChE. The differences among the OP insecticides can create therapeutic dilemmas in determining appropriate courses of treatment.8

Patients acutely poisoned with OP insecticides present with a range of signs and symptoms, depending on the dose and potency of the agent involved. Significant poisoning exposures result in respiratory failure due to muscle weakness, excessive mucous secretion, and noncardiogenic pulmonary edema, which may be an immediate cause of death. Severe poisoning also can cause neurologic effects including seizures, coma, or delirium, which result from cholinergic input in the midbrain and medulla. Dystonias, choreoathetoid movements, and fasciculations also can be noted.

Varieties of arrhythmias have been reported, including tachyarrhythmias, bradyarrhythmias, and torsades de pointes ventricular tachycardia. Diarrhea and vomiting are almost universally seen in severe poisoning, along with excessive secretions of tears, saliva, and sweat. This constellation of symptoms has given rise to a number of mnemonics to describe the cholinergic excesses, such as DUMBELS (diarrhea, urination, miosis, bronchospasm, emesis, lacrimation, salivation) and SLUDGE (salivation, lacrimation, urination, defecation, emesis).

An intermediate syndrome or type II toxicity also has been described. In this syndrome, patients exhibit paralysis of proximal limb muscles, neck flexor muscles, motor cranial nerves, and respiratory muscles, without significant muscarinic symptoms. These effects are noted 24 to 96 hours after initial signs and symptoms and are thought by some to be a result of initial underdosing with the antidote.912

Some OPs such as the triaryl phosphates can produce a delayed peripheral neuropathy known as organophosphate-induced delayed neuropathy (OPIDN), which manifests 2 to 3 weeks after a single acute poisoning. After abatement of acute cholinergic effects and symptoms associated with the intermediate syndrome (see later), patients with OPIDN develop signs and symptoms including tingling of the extremities, sensory loss, progressive muscle weakness and flaccidity of the distal skeletal muscles of the lower and upper extremities, and ataxia. The mechanisms leading to OPIDN are not fully understood and may not be directly related to inhibition of AChE, since some of the agents involved are poor AChE inhibitors.1315

Diagnosis of OP poisoning typically requires a clinical picture of cholinergic symptoms, onset of symptoms within 12 hours of exposure, a 50% or more reduction of plasma and red blood cell (RBC) cholinesterase below baseline, and clinical improvement of muscarinic signs and symptoms with the administration of atropine.

The most severe cases of poisoning can be rapidly fatal if not aggressively treated. Atropine is the mainstay of treatment, and in some cases extremely large doses (>100 mg/d) may be required to reverse muscarinic symptoms. Critical care clinicians often will be faced with the decision to administer an oxime such as pralidoxime (2-PAM), which regenerates AChE by reversing phosphorylation of the active site on the enzyme before the phosphorylated AChE has undergone aging. Although animal data consistently have shown a positive effect of oxime therapy, a number of authors have questioned their utility, and reviews of the clinical effectiveness of oxime therapy have produced mixed results.16,17 Still other work has demonstrated a more convincing benefit associated with the use of 2-PAM and provides a rationale for appropriate dosing that includes continuous pralidoxime infusion, as compared to repeated bolus injection.18 Although various studies have lead the World Health Organization to recommend standard doses of 2-PAM, including an intravenous (IV) bolus of 30 mg/kg as a loading dose followed by infusion of at least 8 mg/kg/h, a modified administration schedule of a 2-g IV bolus dose followed by a continuous infusion of 1 g over an hour for 48 hours demonstrated reduction in both morbidity and mortality of moderately severe cases of acute OP poisoning.18,1921

As such, 2-PAM administration is warranted in moderate to severe poisoning in patients with respiratory compromise, seizures, or coma. Furthermore, 2-PAM is typically used in combination with atropine, as atropine blocks only the effects of acetylcholine at the postsynaptic neuron but does not regenerate AChE.

Animal studies suggest that other new treatment approaches such as alkalinization hold promise in the effective management of OP intoxication, but there is insufficient evidence supporting their role in the routine care of these patients.22,23 If the patient receives appropriate treatment and survives the first few hours, prognosis is good, even in severe cases of poisoning.