185 Pesticides and Herbicides
General Principles of Management
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.
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.
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.
Insecticides
Organophosphates
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
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.9–12
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.13–15
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.18,19–21
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.
N-Methyl Carbamates
In cases of serious poisoning, patients demonstrate CNS depression with coma, seizures, and hypotonicity. Nicotinic effects including hypertension and cardiorespiratory depression are also common. Respiratory effects such as dyspnea, bronchospasm, bronchorrhea, and pulmonary edema are also likely to be present.24