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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

- Chronic intermittent exposure, nonspecific symptoms: - Weakness - Fatigue - Malaise - Anorexia

- Mild exposure: - CNS: - Headache - Dizziness - Tremors of tongue and eyelids - Weakness

- Cardiovascular: - GI: - Nausea/vomiting - Abdominal cramps

- 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

- 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

- 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

- 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

- 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

  • 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 musclesBronchorrhea and bronchoconstrictionCentral 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:

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/diaphoresisUrinationMiosis/muscle fasciculationsBradycardia, bronchorrhea, bronchospasmEmesisLacrimationSalivationMay have garlic odor
  • Chronic intermittent exposure, nonspecific symptoms:WeaknessFatigueMalaiseAnorexia
  • Mild exposure:CNS:HeadacheDizzinessTremors of tongue and eyelidsWeaknessGI:
  • Moderate exposure:CNS:Muscle fasciculation then flaccid paralysisRespiratory muscle weaknessIncoordination and ataxiaAgitationTremorsConfusionVisual:Pinpoint nonreactive pupilsRespiratory:Respiratory muscle weaknessBronchorrheaCardiovascular:GI:Nausea/vomitingAbdominal crampsExocrine glands:
  • Severe exposure:CNS:ConvulsionsComaCentrally mediated respiratory depressionRespiratory:BronchoconstrictionWheezingDyspneaIncreased bronchial secretionsCardiovascular:Bradycardia (tachycardia may follow pulmonary edema and hypoxia)Heart blockCyanosisGI:Nausea, vomitingAbdominal painDiarrhea, fecal incontinenceExocrine glands:DiaphoresisSalivationLacrimationBladder:FrequencyUrinary incontinenceNicotinic 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 poisoningDepending on the agent and the patient, these levels may varyCholinesterase levels:Latent exposure: >50% of normal valueMild exposure: 20 " “50% of normal valueModerate exposure: 10 " “20% of normal valueSevere exposure: <10% of normal valueDo 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)BradycardiaHeart blockST " “T-wave abnormalities
  • CT scan of head for altered mental status when diagnosis is uncertain

Differential Diagnosis

  • Mild to moderate exposure:GastroenteritisAsthmaVenomous arthropod bite (black widow, scorpion)Progressive peripheral neuropathy (Guillain " “Barre syndrome)Carbon monoxide
  • Severe exposure:Narcotic overdoseComa and miosis:PCP, meprobamate, phenothiazine, clonidineMuscarinic-containing mushrooms " ”cholinergic crisis without nicotinic symptomsNicotine poisoningMetabolic and infectious:Ketoacidosis, sepsis, meningitis, encephalitisHypoglycemiaReye syndromeNeurologic:Cerebrovascular accidentSubdural or epidural hematomaPostictal 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 staffMaintain 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 receptorsOnset of action is 1 " “4 min, peaks at 8 min.Goal of therapy/end point:Drying secretions of tracheobronchial treeAdminister test dose 1 " “2 mg IV/IM:No clinical response: Double dose q5min until muscarinic findings subsideDose: 1 " “4 mg IV q5min (peds: 0.05 " “0.2 mg/kg)Common pitfalls in therapy:Not giving enough atropineUsing pupillary findings (mydriasis) as end point of treatmentMistaking 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 productsNo restriction to its use even if 24 " “48 hr have passed
  • Supportive care:Dermal decontamination: Remove clothes and flush skin with waterGastric 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 suctionTreat 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)