Insecticide Poisoning

Definition

Insecticides are substances used to kill insects or prevent them from destructive behaviors.

• Insecticides are classified as pesticides, defined by the U.S. Environmental Protection Agency (EPA) as any substance intended for preventing, destroying, or repelling any pest. 
• The term “pesticides” also applies to fungicides, rodenticides, bactericides, and herbicides.
• Insecticides work by interfering with biologic mechanisms in insects. 
• Many organisms share similar biologic mechanisms, so effects of pesticides are often nonspecific to organism type.

Dichlorodiphenyltrichloroethane (DDT)

Etiology

Dichlorodiphenyltrichloroethane:

• Commonly known as DDT
• Colorless, tasteless, crystalline organochlorine
• Uses:
  • Treat insect spread of malaria, yellow fever, and insect-vectored diseases
  • Insect control in crop and livestock production and buildings
• 1st of the modern synthetic insecticides in the 1940s but use was stopped by EPA in 1972 because of its adverse effects on wildlife and the environment
• Still used where malaria remains a major health problem with high mortality
• Highly persistent chemical:
  • Soil half-life: 2–15 years
  • Human half-life: 3–6 years

Pathogenesis

• DDT exposure:
  • Humans are exposed usually through ingestion of meat, fish, and dairy products.
  • Can also be absorbed from direct contact and inhalation
• DDT is converted to metabolites including dichlorodiphenyldichloroethane (DDE) → DDT and DDE are stored in adipose tissues
• Effects:
  • Associations of DDT and tumor development are seen in laboratory animals, but there is no clear evidence that it causes cancer in humans. 
  • Oxidative stress could be a key factor in hepatocarcinogenesis.
  • Produces neurotoxicity by causing delays in the closing of the Na⁺ channel
• Considered an endocrine-disrupting chemical (EDC), causing reproductive toxicity by affecting estrogenic activity

Clinical presentation

• Neurotoxicity:
  • Paresthesias around the mouth
  • Dizziness
  • Confusion
  • Incoordination/ataxia
  • Tremors
  • Seizures
• Nausea/vomiting
• Lethargy
• May be related to hepatotoxicity and carcinogenicity (chronic)

Diagnosis and management

• Diagnosis is clinical and based mainly on a history of exposure and symptoms. 
• Levels can be measured in blood, urine, semen, fat, and breast milk.
• Management:
  • Decontamination
  • Supportive care, observation, and symptomatic treatment/relief are the mainstays of therapy. 
  • No antidote

Organophosphate Toxicity

Etiology

Organophosphates:

• Irreversible cholinesterase inhibitors
• Examples of organophosphate (OP) chemicals:
  • Insecticides: malathion, parathion, diazinon, fenthion, dichlorvos, chlorpyrifos, ethion
  • Herbicides: tribufos (DEF), merphos
  • Nerve gases: soman, sarin, tabun, VX
  • Ophthalmic agents: echothiophate, isoflurophate
  • Anthelminthics: trichlorfon
  • Industrial chemical (plasticizer): tricresyl phosphate

Pathophysiology

• Inhibit the cholinesterase enzyme in the synaptic cleft
• Irreversible phosphorylation of acetylcholinesterase (AChE) by inhibition of the AChE enzyme, which is present in:
  • Parasympathetic and sympathetic ganglia
  • Parasympathetic muscarinic terminal junctions
  • Sympathetic fibers located in sweat glands
  • Nicotinic receptors at the skeletal neuromuscular junction
• Persistently ↑ acetylcholine levels due to AChE inhibition leads to ↑ neurotransmitter signaling.

Clinical presentation

• Presents as a cholinergic toxidrome
• Pinpoint pupils
• Sweating, salivation
• Bronchoconstriction
• Vomiting 
• Diarrhea
• CNS stimulation then depression
• Muscle fasciculations, weakness, paralysis
• Death from respiratory failure

Diagnosis

• Primarily a clinical diagnosis based on history and examination. 
• Some organophosphorus agents have a distinct petroleum or garlic-like odor.
• Confirmation can be confirmed by measurement of cholinesterase activity:
  • RBC AChE and plasma cholinesterase (PChE) or butyrylcholinesterase (BuChE) levels can both be used.
  • RBC AChE correlates with degree of toxicity.

Management

• Airway, breathing, and circulation (ABC) assessment
• Decontamination:
  • Removal of clothes, irrigation or washing of exposed areas
  • Activated charcoal (AC; within an hour of ingestion)
  • PPE: Use neoprene gloves and gowns, as hydrocarbons can penetrate nonpolar substances such as latex and vinyl.
  • Charcoal cartridge masks for respiratory protection
  • Irrigate the eyes of patients who have had ocular exposure.
• Supportive care: 
  • IV fluids
  • Intubation:
    • Avoid succinylcholine because it is metabolized by AChE.
    • May be necessary in cases of respiratory distress due to laryngospasm, bronchospasm, bronchorrhea, or seizures
• Seizures: Give benzodiazepines.
• Antidotal therapy:
  • Atropine: 
    • Binds to muscarinic receptors, temporarily blocking them and reducing cholinergic effect(s)
    • Dosing titrated to clearance of respiratory secretions and cessation of bronchoconstriction
  • Pralidoxime (2-PAM): 
    • Effective in both muscarinic and nicotinic effects
    • Reactivates AChE but has a transient inhibitory effect on the enzyme, so should be given in conjunction with atropine

Mnemonics

SLUDGE BBB (muscarinic effects):

• Salivation
• Lacrimation (crying is key feature)
• Urination
• Defecation (diarrhea)
• GI cramping (distress)
• Emesis
• Bronchospasm
• Bronchorrhea
• Bradycardia

DUMBELS (muscarinic effects):

• Defecation
• Urination
• Miosis
• Bronchorrhea/bronchospasm/bradycardia
• Emesis
• Lacrimation
• Salivation 

Carbamate Toxicity

Etiology

Carbamates:

• Derivatives of carbamic acid
• Structurally and mechanistically similar to organophosphates (which are derivatives of phosphoric acid)
• Includes compounds such as carbaryl, methomyl, and carbofuran 
• Carbaryl is the 2nd most widely detected insecticide in surface waters in the United States:
  • Low mammalian toxicity
  • Short half-life in the environment
  • Effective against 160 harmful insects

Pathophysiology

• Toxic exposures: dermal, inhalational, and GI
• While carbamates have a similar mechanism of action to that of organophosphates, they bind to AChE reversibly. 
• Similar toxicologic presentation to OP poisonings but often with a duration of < 24 hours
• Mechanism:
  • Inhibits the AChE enzyme by carbamylation of AChE at neuronal synapses and neuromuscular junctions →  overstimulation of the nervous system 
  • Carbamate bonds are eventually hydrolyzed in 24–48 hours → AChE broken down to acetic acid + choline → cessation of neurotransmitter signaling

Clinical presentation

• Presents as a cholinergic toxidrome (mnemonics similar to OP)
• Pinpoint pupils
• Sweating, salivation
• Bronchoconstriction
• Vomiting 
• Diarrhea
• CNS stimulation then depression
• Muscle fasciculations, weakness, paralysis
• Death from respiratory failure

Diagnosis and management

• Diagnosis is clinical based on history of exposure and symptoms. 
• Laboratory testing can be done, but do not delay potentially lifesaving treatments while waiting on results.
• Confirmation can be done by measurement of cholinesterase activity:
  • BuChE and RBC AChE levels
  • RBC AChE rapidly returns to normal in carbamate poisoning.
• Management:
  • Patients who are asymptomatic 12 hours after exposure can be discharged.
  • Hospitalize all symptomatic patients for at least 48 hours in a high-acuity setting.
  • Decontamination (similar to management of OP poisoning)
  • Atropine and benzodiazepines are primary medical treatments.
  • Intubation may be necessary in cases of respiratory distress due to laryngospasm, bronchospasm, bronchorrhea, or seizures.
  • Pralidoxime can be used in carbamate poisoning but not in carbaryl poisoning (associated with poor outcomes).

Clinical Relevance

• Caustic ingestion: Acidic or alkaline substances damage tissues severely if ingested. Alkali ingestion typically damages the esophagus. Acids cause more severe gastric injury. In large amounts and high concentrations, caustic ingestion also leads to severe injuries such as shock, abdominal rigidity, respiratory distress, and/or altered mental status. Diagnosis is by laboratory tests, abdominal and chest imaging, and endoscopy. Management involves stabilizing the patient, decontamination, and supportive therapy. Severe injury may require surgery.
• Herbicides: chemical substances used to kill or control the growth of unwanted plants. Important herbicides that can affect humans include paraquat, Agent Orange, glyphosate, and organophosphates. Different types of herbicides result in different clinical manifestations and have various toxicity levels. Exposure can be dermal or by inhalation or ingestion. Management consists of stabilizing the patient and decontamination. Organophosphate toxicity has an antidote. Treatment revolves around supportive care dependent on the involved organ system. 
• Toxidrome: group of clinical signs and symptoms associated with toxic ingestion or exposure. There are 5 traditional toxidromes: anticholinergic, cholinergic, opioid, sympathomimetic, and sedative-hypnotic. Toxidromes often arise from ingestion of overdose amounts, accumulation of medications with resultant elevated serum levels, adverse drug reactions, or interactions between ≥ 2 medications.  Diagnosis is by clinical findings based on medication and exposure history and physical examination.