General Principles
Within developed countries, regulatory and engineering controls have largely limited the population’s exposure to many fatal pesticides and industrial toxins; however, worldwide, poisoning accounts for substantial morbidity and mortality. Global medicine presents the challenge of providing care to unique poisonings with limited resources. Fortunately, most poisonings are successfully managed using basic principles.
Activated charcoal: For exposures occurring because of the ingestion of a poison, gastrointestinal decontamination may provide benefit. Activated charcoal adsorbs some poisons; however, this therapy is not without risk. Given the high frequency of vomiting with toxic ingestions there is the potential for aspiration of activated charcoal resulting in significant pulmonary damage and death. Therefore, activated charcoal should not be given to patients who are sedated or have the potential to become sedated, unless their airway is protected via endotracheal intubation. Activated charcoal should also not be given for ingestions for which no significant toxicity is anticipated. Although some clinicians report that activated charcoal provides no benefit if given over an hour after the overdose, there is evidence clearly demonstrating that overdose may result in delayed gastric emptying and increase the duration from ingestion that activated charcoal is potentially beneficial. Activated charcoal is not expected to provide significant adsorption of most caustics, hydrocarbons, metals, or alcohols.
Syrup of ipecac: Syrup of ipecac has not demonstrated benefit, can cause significant harm, and is not recommended in the treatment of overdose.
The majority of toxicology deaths can be prevented through standard supportive care. This includes airway management, ventilator support, intravenous (IV) fluids and vasopressors for hypotension, and benzodiazepines for seizures and agitation. Of note, benzodiazepines are the preferred medication for poison-induced seizures and are preferred over phenytoin and other anticonvulsants.
Pesticides
Eliminating exposure is the most effective means of decreasing poisoning morbidity and mortality. When possible, clinicians should advocate for eliminating access to these toxins while maintaining balance with the potential benefits pesticides may provide (e.g., controlling disease vectors, decreasing malnutrition by increasing crop production).
Insecticides
Organic Phosphorus Compounds and Carbamates
Worldwide, anticholinesterase insecticides are one of the leading causes of acute poisoning deaths. Organic phosphorous compounds (OPs) inhibit the enzyme acetylcholinesterase, resulting in excessive stimulation of the postsynaptic cholinergic and nicotinic receptors.
The excessive stimulation of cholinergic receptors results in a toxidrome of symptoms that can be memorized using the acronym SLUDGE and the killer “B”s:
Salivation
Lacrimation
Urination
Defecation
Increased Gastric motility
Emesis
Bradycardia
Bronchospasm
Bronchorrhea
Seizure
Symptoms resulting from the excessive stimulation of nicotinic receptors include muscle fasciculation, weakness, and paralysis.
Death results from excessive bronchorrhea and decreased respiratory muscle strength, resulting in respiratory failure.
Treatment consists of the administration of intramuscular (IM) or IV atropine. Atropine blocks the postsynaptic acetylcholine receptors thereby decreasing the SLUDGE and the symptoms of the killer “B”s, but has no effect upon the nicotinic receptors. Doses for inhalational exposure typically range from 1 to 6 mg IV/IM in adults. For ingestions or organophosphates, patients may require significantly higher doses.
Pralidoxime and other oximes are used to chemically remove the OP from acetylcholinesterase. Of note, some organophosphates (particularly chemical warfare agents) undergo “aging,” which is the development of a permanent covalent bond between the organophosphate and acetylcholine. Therefore, for pralidoxime to have an effect, it must be administered before aging. Although pralidoxime use is widely accepted for exposure to chemical warfare organophosphates, studies have demonstrated conflicting evidence regarding its use for pesticide exposures. There is therefore no consensus on whether pralidoxime should be used for organophosphate ingestion.
For respiratory depression resulting from excessive stimulation of the nicotinic muscle receptors, endotracheal intubation and mechanical ventilation is the treatment of choice.
Intermediate syndrome: Approximately 2 to 4 days following exposure, patients may develop proximal motor weakness. Early recognition is necessary to avoid the potentially fatal rapid onset of respiratory muscle weakness. These symptoms last for 1 to 3 weeks and do not respond to atropine or oximes. Treatment consists of mechanical ventilation support.
Organophosphate-induced delayed neuropathy (OPIDN): Some cholinesterase inhibitors may cause a delayed peripheral neuropathy causing a frequently permanent dysfunction of the long nerves of the legs.
Carbamate pesticides produce toxicity via the same mechanism as organophosphates; however, carbamates are less toxic because of decreased penetration into the central nervous system and a shorter duration of effect (<24 hours). Carbamates do not undergo aging and pralidoxime should not be used for carbamate poisonings.
Additional insecticides are shown in Table 8.1 .
| Agent | Mechanism of Action | Clinical Manifestations | Management |
|---|---|---|---|
| Organic chlorine pesticides | Hyperexcitability of the central nervous system via multiple mechanisms. | Nausea, vomiting, headache, parasthesias, tremor, seizures, hyperthermia, respiratory failure, death. | Airway management, skin decontamination with soap and water, benzodiazepines for seizures. |
| Pyrethrins and pyrethroids | Bind to voltage-sensitive sodium channels in the open state, causing prolonged depolarization. | Paresthesias, vomiting, fasciculations, altered mental status, seizures, acute lung injury. | Skin decontamination with soap and water, consider activated charcoal for ingestions, benzodiazepines for tremor and seizures. |
| N,N-deithyl-3-methylbenzamide (DEET) | Unknown. | Although rare, severe exposure may result in encephalopathy, ataxia, convulsions, respiratory failure, hypotension, and death. | Skin decontamination with soap and water, consider activated charcoal for ingestions, benzodiazepines for tremor and seizures. |
Herbicides
Paraquat and Diquat
Paraquat and diquat are dipyridiyl herbicides, used worldwide given their efficacy and low cost. They are extremely potent toxins that may result in multisystem organ damage when absorbed through the skin, inhaled, or ingested. Ingestion of 10 to 20 mL of 20% paraquat solution may result in death.
Dipyridyls produce reactive free radicals via nicotinamide adenosine dinucleotide phosphate (NAPDH)-dependent reduction and oxidation cycling, resulting in lipid peroxidation inducing cell death. Paraquat is concentrated in the pulmonary alveolar cells, resulting in significant and frequently fatal pulmonary damage. Diquat is not taken up into pulmonary alveolar cells and does not cause pulmonary toxicity. Both paraquat and diquat cause renal, hepatic, and cardiovascular failure.
Symptoms of dipyridyl ingestion include oral pain/swelling, nausea, vomiting, and abdominal pain. Ingestion of 20 to 40 mg/kg of paraquat leads to death days to weeks after the ingestion via progressive pulmonary fibrosis. Larger ingestions of 20 to 40 mg/kg of paraquat lead to gastrointestinal injury, myonecrosis, shock, and death within hours to days. Diquat ingestion results in similar symptoms without the pulmonary fibrosis.
Treatment: Symptomatic and supportive care should be employed. Given the potential for supplemental oxygen to increase redox cycling in pulmonary alveolar cells, it should only be used for clinically significant hypoxia. There is no specific antidote for dipyridyl exposure. Skin should be washed thoroughly with soap and water. Activated charcoal (100 g in adults; 1.5 g/kg in children) should be administered as soon as possible followed by a second dose 1 to 2 hours later. If activated charcoal is unavailable, fuller’s earth (a superabsorbent form of aluminum silicate) can be used as an alternative. Although multiple other therapies have been used, none have proven effective.
Additional herbicides are shown in Table 8.2 .
| Agent | Mechanism of Action | Clinical Manifestations | Management |
|---|---|---|---|
| Glyphosate | Toxicity is frequently attributed to the surfactant the glyphosate is dissolved in. | Gastrointestinal symptoms, respiratory distress, hypotension, altered mental status, and oliguria. | Symptomatic and supportive care, skin decontamination with soap and water. |
| 2,4-D and chlorophenoxy herbicides | Cell membrane damage, uncoupling of oxidative phosphorylation, and disruption of acetyl coenzyme A. | Vomiting, abdominal pain, diarrhea, tachycardia, muscle weakness, rhabdomyolysis, hepatitis, renal failure, metabolic acidosis, seizure, coma. | Skin decontamination with soap and water, consider activated charcoal for ingestions, benzodiazepines for tremor and seizures. Monitor the patient for at least 6–12 h after ingestion owing to the potential for delayed symptom onset. |
| Glufosinate and bialaphos | Inhibits glutamate decarboxylase resulting in decreased gamma-aminobutyric acid (GABA). | Initially nausea and vomiting with delayed central nervous system (CNS) symptoms 4–8 h after ingestion. CNS symptoms include sedation, confusion, respiratory depression, seizure, and coma. | Symptomatic and supportive care, consider activated charcoal for ingestions, endotracheal intubation for sedation and respiratory depression, benzodiazepines for tremor and seizures. Monitor the patient for at least 12 h after ingestion. |
| Nitrophenolic herbicides (dinitrophenol and substituted nitrophenolic compounds) | Uncoupling of oxidative phosphorylation. | Malaise, rash, headache, dyspnea, diaphoresis, hyperthermia, death, delayed onset cataracts. | No specific antidote, paralysis using a nondepolarizing neuromuscular blocker may decrease hyperthermia, sedation with benzodiazepines or barbiturates. |
Other Pesticides
See Table 8.3 for descriptions of other pesticides.
| Agent | Mechanism of Action | Clinical Manifestations | Management |
|---|---|---|---|
| Barium | Competitive blocking of cellular potassium channels leading to intracellular potassium sequestration and severe hypokalemia. | Vomiting, abdominal pain, diarrhea, tachycardia, muscle weakness resulting in respiratory depression, lactic acidosis, seizure, ventricular dysrhythmias, death. | Symptomatic and supportive care. Endotracheal intubation for sedation and respiratory depression. Administer potassium chloride for hypokalemia (large doses may be required). Magnesium sulfate or sodium sulfate (adults, 30 g; pediatrics, 250 mg/kg) orally to precipitate ingested barium. Monitor the patient for cardiac dysrhythmias for at least 6–8 h. |
| Sodium mono-fluoroacetate and fluoroacetamide | Metabolized to fluorocitrate which blocks the Krebs cycle resulting in systemic cellular poisoning. | Vomiting, diarrhea, tachycardia, renal failure, hypocalcemia, lactic acidosis, confusion, seizure, coma, respiratory arrest, ventricular dysrhythmias, death. | Symptomatic and supportive care. Given the time necessary for the body to convert the pesticide into fluorocitrate, patients should be monitored for 36–48 h. Ethanol may theoretically provide benefit by increasing blood acetate levels which decreases the conversion to fluorocitrate (recommend two standard alcoholic drinks per hour or IV ethanol infusion with a blood alcohol concentration target of 100 g/dL). |
| Yellow phosphorus | Highly corrosive and a general cellular poison. Causes cardiovascular collapse following ingestion. Spontaneously combusts in air at room temperature to a highly irritating fume. | Inhalation: Mucous membrane irritation, cough, wheezing, chemical pneumonitis, pulmonary edema. Ingestion: Gastrointestinal burns and hemorrhage, vomiting, abdominal pain, diarrhea, “smoking stools,” headache, delirium, shock, seizures, coma, arrhythmias, metabolic derangements, hepatic failure, renal failure, death. | Symptomatic and supportive care. Whole bowel irrigation for ingestions. DO NOT INDUCE VOMITING. Aggressive IV fluid replacement. Rescuers must wear appropriate protective gear and the patient’s stool should be placed in a sealed container to avoid exposure to toxic fumes. Contaminated skin should be irrigated with soap and water and covered with moist dressing to prevent spontaneous combustion of yellow phosphorus. |
| Strychnine | Competitively antagonizes the inhibitory neurotransmitter glycine in the spinal cord. | Muscular stiffness and painful cramps; generalized muscle contractions leading to rhabdomyolysis, renal failure, and respiratory arrest. Muscle contractions exacerbated by noise, touch, and other sensations. | Benzodiazepines and analgesics for mild muscle contractions. Paralysis with a nondepolarizing neuromuscular blocker and mechanical ventilation for more severe symptoms. |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
