Organophosphate Poisoning, Emergency Medicine

Basics

Description

Organophosphates (pesticides and nerve agents) irreversibly bind and deactivate cholinesterases, including acetylcholinesterase
Acetylcholine accumulates at neural synapses, causing central and peripheral cholinergic overdrive
Predominant effects (muscarinic, nicotinic, CNS) may vary and can overlap.
Mortality is secondary to respiratory failure:
- Weakness of respiratory muscles
- Bronchorrhea and bronchoconstriction
- Central depression of respiratory drive

Symptoms are difficult to differentiate in toddlers
Common symptoms: Miosis, salivation, and muscle weakness
Seizure activity in 25% of pediatric cases:
- Only 3% in adults

Etiology

Exposure to insecticides (organophosphorus compounds)
Exposure to chemical nerve agents (sarin, soman, tabun, VX)
Extremely well absorbed from lung, GI tract, skin, mucosa, eyes

Diagnosis

Signs and Symptoms

Classic presentation: Cholinergic toxidrome:
- DUMBELS:
  - Diarrhea/diaphoresis
  - Urination
  - Miosis/muscle fasciculations
  - Bradycardia, bronchorrhea, bronchospasm
  - Emesis
  - Lacrimation
  - Salivation
- May have garlic odor
Chronic intermittent exposure, nonspecific symptoms:
- Weakness
- Fatigue
- Malaise
- Anorexia
Mild exposure:
- CNS:
  - Headache
  - Dizziness
  - Tremors of tongue and eyelids
  - Weakness
- GI:
  - Anorexia
Moderate exposure:
- CNS:
  - Muscle fasciculation then flaccid paralysis
  - Respiratory muscle weakness
  - Incoordination and ataxia
  - Agitation
  - Tremors
  - Confusion
- Visual:
  - Pinpoint nonreactive pupils
- Respiratory:
  - Respiratory muscle weakness
  - Bronchorrhea
- Cardiovascular:
  - Bradycardia
- GI:
  - Nausea/vomiting
  - Abdominal cramps
- Exocrine glands:
  - Salivation
  - Lacrimation
Severe exposure:
- CNS:
  - Convulsions
  - Coma
  - Centrally mediated respiratory depression
- Respiratory:
  - Bronchoconstriction
  - Wheezing
  - Dyspnea
  - Increased bronchial secretions
- Cardiovascular:
  - Bradycardia (tachycardia may follow pulmonary edema and hypoxia)
  - Heart block
  - Cyanosis
- GI:
  - Nausea, vomiting
  - Abdominal pain
  - Diarrhea, fecal incontinence
- Exocrine glands:
  - Diaphoresis
  - Salivation
  - Lacrimation
- Bladder:
  - Frequency
  - Urinary incontinence
  - Nicotinic manifestations

Essential Workup

Inquire about possible exposure, occupation, recent insecticide at home, mislabeled, or poorly stored insecticides: ‚

Obtain original container if suicide attempt.
Look for parasympathetic and CNS signs with muscle weakness or paralysis.

Diagnosis Tests & Interpretation

Lab

RBC and plasma cholinesterase levels to confirm diagnosis:
- RBC (true) cholinesterase level is best for synaptic inhibition (a send-out lab).
- Plasma (pseudo)cholinesterase level not as reliable but more timely:
  - These are markers for poisoning
  - Depending on the agent and the patient, these levels may vary
- Cholinesterase levels:
  - Latent exposure: >50% of normal value
  - Mild exposure: 20 " “50% of normal value
  - Moderate exposure: 10 " “20% of normal value
  - Severe exposure: <10% of normal value
- Do not wait for cholinesterase results before administering treatment.
CBC, electrolytes, glucose, BUN, creatinine
ABG when respiratory symptoms are present

Imaging

CXR if respiratory difficulty is present or suspect pulmonary edema:
- Pneumonitis from hydrocarbon aspiration
ECG:
- Dysrhythmias (atrial fibrillation, ventricular tachycardia, torsades de pointes, QT prolongation)
- Bradycardia
- Heart block
- ST " “T-wave abnormalities
CT scan of head for altered mental status when diagnosis is uncertain

Differential Diagnosis

Mild to moderate exposure:
- Gastroenteritis
- Asthma
- Venomous arthropod bite (black widow, scorpion)
- Progressive peripheral neuropathy (Guillain " “Barre syndrome)
- Carbon monoxide
Severe exposure:
- Narcotic overdose
- Coma and miosis:
  - PCP, meprobamate, phenothiazine, clonidine
  - Muscarinic-containing mushrooms " ”cholinergic crisis without nicotinic symptoms
  - Nicotine poisoning
- Metabolic and infectious:
  - Ketoacidosis, sepsis, meningitis, encephalitis
  - Hypoglycemia
  - Reye syndrome
- Neurologic:
  - Cerebrovascular accident
  - Subdural or epidural hematoma
  - Postictal state

Treatment

Pre-Hospital

Decontamination is initial priority:
- Decontaminate, airway, breathing, circulation (DABC)
- Remove all clothes and store as toxic waste (double bagged)
Protection of health care workers of utmost importance:
- Impenetrable gloves (neoprene, nitrile), gowns, eye protection
Decontaminate skin with soap and water:
- Shower or gentle scrubbing ideal if done before entrance into the ED
Maintain airway and oxygenate.
IV access and place on cardiac monitor

Initial Stabilization/Therapy

Decontaminate ABCs:
- Decontamination and protection of staff
- Maintain airway and oxygenate.
- For unstable airway, intubate, and ventilate.
- IV access with D5W 0.9% NS
Altered mental status: Administer thiamine, glucose, and naloxone (Narcan)

Ed Treatment/Procedures

Atropine:
- Blocks acetylcholine at muscarinic receptor sites.
- No effect on nicotinic receptors
- Onset of action is 1 " “4 min, peaks at 8 min.
- Goal of therapy/end point:
  - Drying secretions of tracheobronchial tree
- Administer test dose 1 " “2 mg IV/IM:
  - No clinical response: Double dose q5min until muscarinic findings subside
- Dose: 1 " “4 mg IV q5min (peds: 0.05 " “0.2 mg/kg)
- Common pitfalls in therapy:
  - Not giving enough atropine
  - Using pupillary findings (mydriasis) as end point of treatment
  - Mistaking dilated pupils or tachycardia as contraindications to atropine
Pralidoxime (2-PAM):
- Regenerates cholinesterase by reversing the phosphorylation of the enzyme.
- Synergistic with atropine " ”muscarinic signs/symptoms will start to resolve in 10 " “40 min.
- Side effects: Neuromuscular blockade with rapid infusion, respiratory arrest, HTN, nausea/vomiting, dizziness, blurred vision.
- End point is resolution of muscle weakness and fasciculations.
- Effective before enzyme aging occurs (permanent inactivation of cholinesterase)
- Onset of aging varies among products
- No restriction to its use even if 24 " “48 hr have passed
Supportive care:
- Dermal decontamination: Remove clothes and flush skin with water
- Gastric lavage (early presentation of severe ingestion):
  - Gastric emptying with continuous suction via a nasogastric tube.
  - Handle contents with care " ”avoid direct contact to prevent personal exposure.
- Respiratory difficulty:
  - Frequent oropharyngeal suction
  - Treat bronchospasm with atropine, not bronchodilators.
  - Tachycardia may result from hypoxia (pulmonary secretions and bronchospasm).
  - Atropine will dry secretions and paradoxically lower the heart rate.
  - Intubate and ventilate if necessary.
  - Avoid succinylcholine; may have prolonged duration as it is metabolized by cholinesterase.

Medication

Atropine: 1 " “2 mg (peds: 0.05 " “0.2 mg/kg) IV q5min (see the previous section for details)
Dextrose: D50W, 1 amp (25 g) of 50% dextrose (peds: 2 " “4 mL/kg D25W) IV push
Naloxone (Narcan): 2 mg (peds: 0.1 mg/kg) IV/IM
Pralidoxime: 1 " “2 g (peds: 25 " “50 mg/kg) dissolved in 0.9% NS over 30 min IV; repeat in 1 hr if necessary, then q6h as needed:
- Some propose continuous infusion (500 mg/h) for serum concentration of 4 mg/L.

Follow-Up

Disposition

Admission Criteria

ICU admission for any exposure confirmed with atropine response.
Any symptomatic patient should be admitted for monitoring.
Avoid opioids, phenothiazines, and antihistamines; these may potentiate toxicity of organophosphates.

Discharge Criteria

Asymptomatic for 6 " “12 hr after exposure
Ensure close reliable follow-up and specific instructions when to return for evaluation.

Issues for Referral
Contact toxicologist or poison center for patients with significant exposures requiring repeat atropine administration. ‚

Followup Recommendations

Psychiatry referral for intentional ingestions. ‚

Pearls and Pitfalls

Treatment failure often secondary to inadequate atropine dosing
Recognize nicotinic manifestations (tachycardia, seizures).

Additional Reading

Buckley ‚ NA, Eddleston ‚ M, Li ‚ Y, et al. Oximes for acute organophosphate pesticide poisoning. Cochrane Database Syst Rev. 2011;(2):CD005085.
Cannard ‚ K. The acute treatment of nerve agent exposure. J Neurol Sci. 2006;249:86 " “94.
Eddleston ‚ M, Clark ‚ RF. Insecticides: Organic phosphorous compounds and carbamates. In: Goldfrank ‚ LR, ed. Goldfranks Toxicologic Emergencies. New York, NY: McGraw-Hill; 2010.
Masson ‚ P. Evolution of and perspectives on therapeutic approaches to nerve agent poisoning. Toxicol Lett. 2011;206:5 " “13.
Yanagisawa ‚ N, Morita ‚ H, Nakajima ‚ T. Sarin experiences in Japan: Acute toxicity and long-term effects. J Neurol Sci. 2006;249:76 " “85.

Codes

ICD9

987.9 Toxic effect of unspecified gas, fume, or vapor
989.3 Toxic effect of organophosphate and carbamate

ICD10

T59.94XA Toxic effect of unsp gases, fumes and vapors, undet, init
T60.0X1A Toxic effect of organophos and carbamate insect, acc, init
T60.0X2A Toxic effect of organophosphate and carbamate insecticides, intentional self-harm, initial encounter

SNOMED

8260003 Organophosphate poisoning (disorder)
216700007 Accidental poisoning by insecticides of organophosphorus compounds (disorder)
243059005 Poisoning due to nerve gas (finding)

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