Christian A. Tomaszewski
INSECTICIDES
Pesticides include insecticides, herbicides, and rodenticides. Insecticides are responsible for over half of the poisonings and deaths.
ORGANOPHOSPHATES
EPIDEMIOLOGY
The most common organophosphates are diazinon, acephate, malathion, parathion, and chlorpyrifos. Nerve gas agents, such as sarin and VX, are organophosphates used in terrorist attacks.
PATHOPHYSIOLOGY
Organophosphates bind irreversibly to and inhibit cholinesterases in the nervous system and skeletal muscle, which leads to the accumulation of acetylcholine at synapses and neuromuscular junctions.
Aging refers to the irreversible binding of the compound to the cholinesterase; once this occurs, antidotes are ineffective.
CLINICAL FEATURES
Patients usually become symptomatic within 8 hours of dermal exposure to organophosphates; nerve gas agents (eg, VX gas) can cause immediate effects via dermal or inhalational routes. Fat-soluble agents (eg, fenthion) can cause delayed or persistent symptoms.
Muscarinic overstimulation from cholinesterase inhibition results in a classic cholinergic crisis (Table 115-1). Exposure to nerve gas agents may lead initially to blurred vision with miosis.
Nicotinic stimulation leads to muscle fasciculations and weakness, which is most pronounced in the respiratory system already compromised by excessive secretions from muscarinic effects. Nicotinic effects can also lead to paradoxical tachycardia and mydriasis.
Central nervous system (CNS) effects, which often predominate in children, include tremor, restlessness, confusion, seizures, and coma.
An intermediate syndrome, which occurs 1 to 4 days after acute poisoning, may present with paralysis or weakness of neck, facial, and respiratory muscles. Since cholinergic excess may not be evident, it can be missed and result in respiratory arrest if not treated.
Delayed organophosphate-induced neuropathy occurs 1 to 3 weeks after acute poisoning from inhibition of neuronal esterase, causing a distal motor-sensory polyneuropathy.
TABLE 115-1 SLUDGE, DUMBELS, and “Killer Bees” Mnemonics for the Muscarinic Effects of Cholinesterase Inhibition
DIAGNOSIS AND DIFFERENTIAL
The diagnosis of organophosphate poisoning is clinical and based on recognition of the classic toxidrome. An odor of garlic or hydrocarbons may suggest exposure.
Other clues to organophosphate poisoning include pulmonary edema on chest radiograph and prolonged QT, which is an independent predictor of toxicity.
Although plasma and erythrocyte cholinesterase levels can confirm exposure, they are not clinically useful in the acute setting.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Table 115-2 outlines the treatment for organophosphate poisoning.
Primary decontamination and personal protective equipment (neoprene or nitrile) for health care workers is essential to prevent secondary contamination.
Support airway and breathing with 100% oxygen, suctioning, and endotracheal intubation and mechanical ventilation when necessary; avoid succinylcholine during RSI because of prolonged paralysis in organophosphate poisoning.
Use atropine to reverse the muscarinic and central effects from parasympathetic stimulation. It is used in large amounts, titrating to drying of tracheobronchial secretions. Tachycardia is not a contraindication to its use.
Response to pralidoxime is measured by clinical improvement in muscle weakness and fasciculations. It can be used for up to 48 hours post-poisoning, but its efficacy wanes with time. Pralidoxime is not recommended in asymptomatic patients.
Watch mild asymptomatic exposures 6 to 8 hours in the ED. Contaminated clothing, especially leather, are potential sources of exposure and should be discarded.
Significant poisonings will need admission to the ICU. The first 24 to 48 hours are critical and patients usually survive if they respond to treatment during that time period.
TABLE 115-2 Treatment for Organophosphate Poisoning
CARBAMATES
EPIDEMIOLOGY
Carbamates are cholinesterase inhibitors and include the pesticides carbaryl, pirimicarb, propoxur, and trimethacarb as well as the pharmacological agents physostigmine, pyridostigmine, and neostigmine.
PATHOPHYSIOLOGY
Like organophosphates, carbamates are absorbed through ingestion, inhalation, and dermal contact.
Unlike organophosphates, carbamates bind only transiently to cholinesterase.
CLINICAL FEATURES
Acute carbamate poisoning produces a cholinergic syndrome similar to organophosphates, but of shorter duration and less neurotoxicity.
DIAGNOSIS AND DIFFERENTIAL
The diagnosis is clinical. Cholinesterase activity is of no clinical value.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Initial treatment is the same as for organophosphates (Table 115-2).
Use atropine for muscarinic symptoms.
Pralidoxime is usually not indicated because symptoms typically resolve within 24 hours, and pralidoxime may exacerbate carbaryl poisoning.
Mild poisonings can be discharged.
Observe moderately symptomatic poisonings for up to 24 hours.
ORGANOCHLORINES
EPIDEMIOLOGY
Organochlorines include DDT (dichlorodiphenyltrichloroethane), methoxychlor, endosulfan, toxaphene, and the therapeutic agent lindane.
PATHOPHYSIOLOGY
Organochlorines are toxic via inhalation, ingestion, and dermal exposure. Through antagonism of γ-aminobutyric acid (GABA) at membranes, sodium channel permeability is decreased resulting in neuronal hyperexicitability. These agents can accumulate because of high lipid solubility.
CLINICAL FEATURES
Acute poisoning primarily produces CNS stimulation and fever.
Mild exposures can cause dizziness, ataxia, headache, tremor, and myoclonus.
Severe exposures can cause seizures, coma, respiratory distress, and death.
Exposure to concomitant hydrocarbon solvent causes cardiac sensitization to catecholamines and dysrhythmias.
DIAGNOSIS AND DIFFERENTIAL
The diagnosis is clinical.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Support airway and breathing as needed.
Remove clothing and wash skin with soap and water.
Consider activated charcoal or gastric lavage in recent, large ingestions. Cholestyramine may be useful in cases of chlordecone ingestion.
Use benzodiazepines to treat seizures.
Treat arrhythmias per Advanced Cardiac Life Support (ACLS) protocols, but avoid epinephrine due to toxic cardiac sensitization to catecholamines.
PYRETHRINS AND PYRETHROIDS
EPIDEMIOLOGY
Natural pyrethrins and synthetic pyrethroids have replaced organophosphates as home insecticides because of their relative safety.
PATHOPHYSIOLOGY
Toxicity occurs primarily through inhalation, although dermal or oral exposure can also occur.
These agents block sodium channels in neurons, leading to neuronal excitability and repetitive discharge.
CLINICAL FEATURES
The most common effect from these agents is allergic hypersensitivity, including dermatitis, bronchospasm, and anaphylaxis.
In massive ingestions, gastrointestinal (GI) distress, and rarely tremors, paresthesias, and seizures can occur.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Decontaminate eyes, skin, and GI tract.
Treat symptomatic allergic reactions.
N, N-DIETHYL-3-METHYLBENZAMIDE
N, N-diethyl-3-methylbenzamide (DEET) is an over-the-counter insect repellant toxic through dermal absorption.
Systemic toxicity includes confusion, ataxia, tremors, and seizures. Large ingestions can cause hypotension and bradycardia.
Decontaminate the skin with mild soap and water; administer activated charcoal for recent ingestions.
Treat seizures with benzodiazepines.
HERBICIDES
Herbicides are used as weed killers, and may be mixed in solvents, surfactants, and preservatives, all of which have potential toxicity.
CHLOROPHENOXY HERBICIDES
EPIDEMIOLOGY
Chlorophenoxy compounds are synthetic plant hormones that kill broadleaf weeds.
CLINICAL FEATURES
Local exposure can cause eye and mucous membrane irritation.
Inhalation can cause dyspnea and pulmonary edema.
Ingestion can lead to nausea, vomiting, and diarrhea.
With severe systemic toxicity hypotension, dysrhythmias, altered mental status, seizures, and rhabdomyolysis can occur.
DIAGNOSIS AND DIFFERENTIAL
The diagnosis is clinical.
Laboratory findings may include metabolic acidosis, rhabdomyolysis, and hepatorenal dysfunction.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Care is primarily supportive and includes decontamination and respiratory assistance.
Consider alkalinization of the urine with intravenous sodium bicarbonate to increase elimination.
Consider hemodialysis for massive ingestions.
Observe mild exposures for 4 to 6 hours prior to discharge.
BIPYRIDYL HERBICIDES
PATHOPHYSIOLOGY
Paraquat and diquat are caustic, causing local irritation and burns, as well as systemic toxicity leading to multiorgan failure.
CLINICAL FEATURES
Paraquat is extremely caustic to skin, mucous membranes, and cornea causing ulceration. Inhalation can cause cough, dyspnea, chest pain, pulmonary edema, epistaxis, and hemoptysis that can last for weeks.
Ingestion causes mucosal and esophageal ulceration, abdominal pain, vomiting, and potential hypovolemia.
Systemic effects include acute renal, cardiac, and hepatic failure followed by multiorgan dysfunction.
Delayed effects include progressive pulmonary fibrosis with refractory hypoxemia.
DIAGNOSIS AND DIFFERENTIAL
Differential includes other corrosives and herbicides.
Qualitative and quantitative urine and blood paraquat levels are available; plasma levels >0.4 milligram/L 10 hours postingestion predict death.
Chest radiography early on may show pneumome-diastinum from esophageal perforation followed by lung parenchyma consolidation.
Additional laboratory findings include evidence of multiorgan failure.
Esophagoscopy may be indicated to define the extent of upper GI corrosive injury.
TABLE 115-3 Non-Anticoagulant Rodenticides
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Early aggressive decontamination with activated charcoal (1-2 grams/kg) should be repeated every 4 hours.
Institute charcoal hemoperfusion early for paraquat poisoning.
Use low inspired oxygen fraction (<21%) to reduce pulmonary injury.
RODENTICIDES
EPIDEMIOLOGY
Rodenticides are classified as non-anticoagulants (Table 115-3) or anticoagulants.
Warfarin rodenticides can contain simple warfarin or, due to rodent resistance, superwarfarin, which includes bordifacoum, diphenacoum, coumafuryl, and bromadoline.
CLINICAL FEATURES
Most one-time ingestions of warfarin anticoagulants do not cause bleeding problems.
Anticoagulant effects develop within 12 to 24 hours for warfarin anticoagulants and 24 to 48 hours for superwarfarins.
The duration of action is short for regular warfarin, with a half-life of 42 hours, while superwarfarins that have a half-life or 120 days.
Toxicity from anticoagulants can be manifested as ecchymosis, mucosal bleeding, hemoptysis, hematuria, and pelvic or GI bleeding.
DIAGNOSIS AND DIFFERENTIAL
The presence of an unexplained coagulopathy suggests possible anticoagulant poisoning.
Prolongation of the INR can be seen with moderate ingestions and large doses can prolong the PTT as well.
In suspected ingestions, INR should be checked postingestion at 12 to 24 hours for warfarin, and 24 to 48 hours for superwarfarin.
EMERGENCY DEPARTMENT TREATMENT AND DISPOSITION
Treat elevated INR with vitamin K1. For regular warfarin ingestions, the oral daily dose is 20 milligrams (1-5 milligrams in children) divided in two to four doses. The same starting dose can be used for superwarfarins; however, daily divided doses of up to 100 milligrams for many months may be required.
After initiating treatment with vitamin K1, follow INR regularly—at least every 24 hours. When discontinuing the therapy, a follow up INR should be obtained in 24 to 48 hours.
Active hemorrhage requires aggressive therapy with intravenous vitamin K1 and fresh frozen plasma. Consider prothrombin complex concentrate or recombinant activated factor VII for refractory bleeding.
Asymptomatic accidental ingestions of large amounts of superwarfarin can be managed as an outpatient with an INR checked 24 to 48 hours postingestion.
For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 195, “Pesticides,” by Walter C. Robey III and William J. Meggs.