Toxicology 18: Organophosphates Toxicity Portal
Pharmacology
Organophosphates inhibit the enzyme acetylcholinesterase
resulting in the accumulation of acetylcholine at muscarinic and
nicotinic receptors.
Pharmacokinetics
Most organophosphates are well absorbed from all routes of
exposure. Many are water soluble, but a few have higher partition
coefficients leading to delayed and prolonged signs and symptoms (eg,
dichlofenthion, leptophos). The liver metabolizes organophosphates.
Some organophosphates having metabolites that are more toxic than the
parent compound (eg, malathion, parathion).
Range of Toxicity
A range of toxicity for organophosphates has not been well
established. An ingestion of an estimated 60 grams of malathion would
be fatal for a 70 kg man.
Clinical Effects
Presenting symptoms may occur from within just a few minutes
to 12 hours post exposure. Organophosphates are lipid soluble so
patients will develop muscarinic symptoms first and then progress to
nicotinic and CNS symptoms. Hypersecretion occurs due to hyperactivity
of the gut and the bronchial muscles. Patients secrete copious amounts
of fluids from every orifice. (See mnemonic DUMBBBELS
under Symptom Recognition.) Effects on
the brain may produce staggering gait, severe tremor, and a psychosis
that may be mistaken for alcohol intoxication.
Quick recognition of symptoms is necessary to reverse
cholinergic effects. Sudden unconsciousness may be
attributable to heat exhaustion, but may potentially be a result of
organophosphate exposure. Miosis and muscle twitching are symptoms not
seen with heat exhaustion but seen with organophosphate exposure.
Symptom Recognition for Organophosphate Toxicity
Acute (Cholinergic effects predominate.)
GI: diarrhea, vomiting, nausea, abdominal cramps, fecal
incontinence
CV: bradycardia, hypotension, hypertension, tachycardia, VT
RESP: bronchospasms, increased bronchial secretions, dyspnea, cyanosis
NEURO: muscle twitching, fasciculations, weakness, ataxia, seizures
OTHER: miosis, sweating, salivation, urinary incontinence
To recognize symptoms, use the following mnemonics to remember symptoms:
|
Muscarinic—DUMBBBELS
|
Nicotinic (note the Monday - Friday memory trigger)
As the chemical gets deeper into the tissue, the patient
will develop nicotinic symptoms. |
CNS – Headaches, Ataxia, Confusion, Seizures, Coma
Subacute
An intermediate paralytic syndrome may occur 24 to 96 hours
after exposure and after cholinergic effects have resolved.
Chronic
Polyneuropathy (developing 1 to 2 weeks post exposure) as well
as behavioral changes have occurred, even in cases where no cholinergic
effects were initially observed.
Decontamination
Skin exposure. All types of
clothing absorb organophosphates, so remove and decontaminate clothing
to prevent further exposure. Wash the patient thoroughly with soap and
water 3 times. The nursing staff and personnel should wear protective
gowns and rubber gloves to avoid contamination.
Ocular exposure. Irrigate eyes with a
copious amount of tap water at room temperature for 15 minutes. If
redness, irritation, or swelling develops, refer patient to an
ophthalmologist for an eye examination.
Oral exposure. Syrup
of ipecac is contraindicated. Perform gastric lavage followed by
activated charcoal. Because some organophosphates are carried in
hydrocarbon-based solvents, use a cuffed ET tube to prevent aspiration.
Inhalation exposure. Monitor for
respiratory distress. Suctioning of secretions may be necessary (via
any route of exposure). Give 100% humidified oxygen with assisted
ventilation if respiratory distress occurs. If respiratory irritation
such as bronchitis or pneumonitis occurs, monitor ABCs, PaCO2, FiO2,
pH, oxygen saturation, and FEV/FVC ratio. Order a chest x-ray. If the
patient has decreased LOC or is comatose, suction oral secretions and
begin atropinization immediately.
Treatment
Initial Treatment
- Protect yourself
- Remove the patient’s clothes.
- Decontaminate the patient.
- Intubate the patient, if needed.
- Obtain IV access.
- Obtain an ECG.
- Medications. Atropine blocks the action of acetylcholine. 2-PAM treats the muscle weakness and blocks the action of acetylcholine but atropine is cheaper and more readily available to start treatment. Atropine may be given up to 1 to 2 grams in severe cases. Give until mucus membranes are dry.
Atropinization. Consider for all patients with significant cholinergic symptoms. Adult Dose: 1 to 2 mg slow IV push and PEDS Dose: 0.015 to 0.05 mg/kg slow IV push. Doses may be repeated every 15 minutes as needed, and doses can be doubled (2 to 4 mg). Atropine drips may also be used at 0.5 to 2.4 mg/kg/hour.
The endpoint of therapy is drying of secretions (nasal, oral). Atropine may also be given via subcutaneous, ET, and intraosseous routes. For severe poisonings, therapy may be required for 48 hours. Note: Atropine does not reverse muscle weakness or respiratory failure.
Pralidoxime (2-PAM). 2-PAM reverses the phosphorylation of the cholinesterase molecule. It should be given within 24 hours but may be effective up to 36 to 48 hours. If use of atropine indicates an organophosphate exposure, administer 2-PAM concurrently. Adult Dose: 1 gram IV and PEDS Dose: 25 to 50 mg/kg in 200 mL D5W or NS over 15 minutes. Too rapid exposure can result in tachycardia, muscle rigidity, and neuromuscular blockade. The dose may be repeated in 1 hour and every 6 to 12 hours for 24 to 48 hours if symptoms are still present.
The endpoint of therapy is resolution of coma and fasciculations. Note: Highly fat-soluble compounds may require longer therapy. Continuous infusion of 500 mg/hour or 10 to 25 mg/kg every 8 hours may be used.
Other
For seizures, diazepam (Valium) is the preferred drug;
phenobarbital and/or phenytoin may also be used. Avoid use of
parasympathomimetics, which may increase cholinergic activity. Avoid
also phenothiazines/antihistamines. These may potentiate toxicity.
Monitoring
Measure erythrocyte acetylcholinesterase and plasma
pseudocholinesterase levels in all patients suspected of
organophosphate toxicity.
The erythrocyte test is a more accurate indication of toxicity, although the plasma test is more readily available. Interpretation of these tests may be difficult, but the following guidelines are helpful:
Erythrocyte Acetylcholinesterase Level |
Toxicity |
20% to 50% baseline |
mild exposure |
10% to 20% baseline |
mod exposure |
10% baseline |
severe exposure |
Collect and evaluate serial levels as baseline values usually will not be available.
The erythrocyte acetylcholinesterase represents acetylcholinesterase (ACh) in nerve tissue, brain, and RBCs. This value gives a more accurate reflection of nervous system ACh.
If no baseline values are available, use laboratory normals with caution due to their high variability. Small repeated exposures may lead to gradual decreases in ACh without signs and symptoms developing.
Obtain blood for samples prior to 2-PAM use, since these can serve as markers for regeneration of erythrocyte ACh.
Place patient on continuous cardiac monitor and monitor chest
radiograph;
obtain baseline electrolytes.
Observe patient for 48 hours after last atropine dose. Consult with your poison control center and consider need for transfer.