Organophosphate toxicity

7/28/2019 Organophosphate toxicity

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MCHENRY WESTERN LAKE COUNTY EMS SYSTEM

OPTIONAL CE

MARCH 2012

ORGANOPHOSPHATE POISONING

Organophosphate (OP) compounds are a diverse group of chemicals used in both domestic and

industrial settings. Examples of organophosphates include insecticides, nerve gases, ophthalmic

agents (to treat glaucoma), and antihelmintics (a substance that expels or destroys gastro-intestinal worms).

Organophosphate compounds were first synthesized in the early 1800s. Shortly thereafter in

1854, Philip de Clermount described the synthesis of tetraethyl pyrophosphate at a meeting of

the French Academy of Sciences. Around 1934, a chemists in Germany, investigated the use oforganophosphates as insecticides. However, the German military prevented the use of

organophosphates as insecticides and instead developed an arsenal of chemical warfare agents

(i.e., tabun, sarin, soman). A fourth agent, VX, was synthesized in England a decade later.During World War II, in 1941, organophosphates were reintroduced worldwide for pesticide use,

as originally intended.

Massive organophosphate intoxication from suicidal and accidental events, such as the Jamaican

ginger palsy incident in 1930, led to the discovery of the mechanism of action of

organophosphates. In 1995, a religious sect, Aum Shinrikyo, used sarin to poison people on aTokyo subway. Mass poisonings still occur today; in 2005, 15 victims were poisoned after

accidentally ingesting ethion-contaminated food in a social ceremony in Magrawa, India.

Nerve agents have also been used in battle, notably in Iraq in the 1980s. Additionally, chemical

weapons still pose a very real concern in this age of terrorist activity.

Pathophysiology

The primary mechanism of action of organophosphate pesticides is inhibition of carboxyl esterhydrolases, particularly acetylcholinesterase (AChE). AChE is an enzyme that degrades the

neurotransmitter acetylcholine (ACh) into choline and acetic acid. ACh is found in the central

and peripheral nervous system, neuromuscular junctions, and red blood cells (RBCs).

Once AChE has been inactivated, ACh accumulates throughout the nervous system, resulting inoverstimulation of muscarinic and nicotinic receptors. Clinical effects are manifested via

activation of the autonomic and central nervous systems and at nicotinic receptors on skeletal

muscle.

Organophosphates can be absorbed cutaneously, ingested, inhaled, or injected. Although most

patients rapidly become symptomatic, the onset and severity of symptoms depend on the specificcompound, amount, route of exposure, and rate of metabolic degradation.


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Epidemiology

United States

In 2007, The American Association of Poison Control Centers' received 96,307 calls (3.4% of all

human exposures) related to pesticide exposures, many of which involved organophosphate (OP)agents and 80 uses of 2-PAM. However, poison center recorded exposures to

organophosphates (OPs) from 1995 to 2004 have declined because of the United States

Environmental Protection Agency phasing out commonly used household and agriculturalorganophosphate (OP) agents.

Mortality/Morbidity

Worldwide mortality studies report mortality rates from 3-25%. Mortality rates depend on the type of compound used, amount ingested, general health of

the patient, delay in discovery and transport, insufficient respiratory management, delay

in intubation, and failure in weaning off ventilatory support. Complications include severe bronchorrhea, seizures, weakness, and neuropathy.

Respiratory failure is the most common cause of death.

Signs and Symptoms

Signs and symptoms of organophosphate poisoning can be divided into 3 broad categories,

including (1) muscarinic effects, (2) nicotinic effects, and (3) CNS effects.

Mnemonic devices used to remember the muscarinic effects of organophosphates areSLUDGE (salivation, lacrimation, urination, diarrhea, GI upset, emesis) and DUMBELS

(diaphoresis and diarrhea; urination; miosis; bradycardia, bronchospasm, bronchorrhea;

emesis; excess lacrimation; and salivation). Muscarinic effects by organ systems includethe following:

o Cardiovascular - Bradycardia, hypotensiono Respiratory - Rhinorrhea, bronchorrhea, bronchospasm, cough, severe respiratory

distress

o Gastrointestinal - Hypersalivation, nausea and vomiting, abdominalpain,diarrhea, fecal incontinence

o Genitourinary - Incontinenceo Ocular - Blurred vision, miosiso Glands - Increased lacrimation, diaphoresis

Nicotinic signs and symptoms include muscle fasciculations, cramping, weakness, anddiaphragmatic failure. Autonomic nicotinic effects include hypertension, tachycardia,mydriasis, and pallor.

CNS effects include anxiety, emotional lability, restlessness, confusion, ataxia, tremors,seizures and coma.
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Note that clinical presentation may vary, depending on the specific agent, exposure route,

and amount. Symptoms are due to both muscarinic and nicotinic effects. Interestingly, a

review of 31 children with organophosphate (OP) poisoning described that, in contrast toadults, the most common presentations were seizure and coma with relatively less muscarinic

or nicotinic findings. The authors hypothesized the difference may be due to difficulty in

detecting muscarinic findings in infants (e.g., crying) and ingestion of contaminated produceinstead of organophosphate (OP) directly.

Vital signs: Depressed respirations, bradycardia, and hypotension are possible symptoms.Alternatively, tachypnea, hypertension, and tachycardia are possible. Hypoxia should be

monitored for with continuous pulse oximetry.

Paralysiso Type I: This condition is described as acute paralysis secondary to continued

depolarization at the neuromuscular junction.

o Type II (intermediate syndrome): Intermediate syndrome was described in 1974and is reported to develop 24-96 hours after resolution of acute organophosphate

poisoning symptoms and manifests commonly as paralysis and respiratorydistress. This syndrome involves weakness of proximal muscle groups, neck, and

trunk, with relative sparing of distal muscle groups. Cranial nerve palsies can alsobe observed. Intermediate syndrome persists for 4-18 days, may require

mechanical ventilation, and may be complicated by infections or cardiac

arrhythmias. Although neuromuscular transmission defect and toxin-induced

muscular instability were once thought to play a role, this syndrome may be dueto suboptimal treatment.

o Type III: Organophosphate-induced delayed polyneuropathy (OPIDP) occurs 2-3weeks after exposure to large doses of certain organophosphates (OPs) and is dueto inhibition of neuropathy target esterase. Distal muscle weakness with relative

sparing of the neck muscles, cranial nerves, and proximal muscle groups

characterizes OPIDP. Recovery can take up to 12 months.

Neuropsychiatric effects: Impaired memory, confusion, irritability, lethargy, psychosis,and chronic organophosphate-induced neuropsychiatric disorders have been reported.

The mechanism is not proven.

Extrapyramidal effects: These are characterized by dystonia, cogwheel rigidity, andparkinsonianfeatures (basal ganglia impairment after recovery from acute toxicity).

Other neurological and/or psychological effects: Guillain-Barrlike syndrome andisolated bilateral recurrent laryngeal nerve palsy are possible.

Ophthalmic effects: Optic neuropathy, retinal degeneration, defective vertical smoothpursuit, myopia, and miosis (due to direct ocular exposure to organophosphates) are

possible.

Ears: Ototoxicity is possible. Respiratory effects: Muscarinic, nicotinic, and central effects contribute to respiratory

distress in acute and delayed organophosphate toxicity.

Muscarinic effects: Bronchorrhea, bronchospasm, and laryngeal spasm, for instance, canlead to airway compromise.Respiratory failureis the most life-threatening effect and

requires immediate intervention.
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Nicotinic effects: These effects lead to weakness and paralysis of respiratoryoropharyngeal muscles.

Central effects: These effects can lead to respiratory paralysis. Rhythm abnormalities: Sinus tachycardia, sinus bradycardia, extrasystoles, atrial

fibrillation, ventricular tachycardia, and ventricular fibrillation (often a result of, or

complicated by, severe hypoxia from respiratory distress) are possible. Other cardiovascular effects: Hypotension, hypertension, and noncardiogenic pulmonary

edema are possible.

GI manifestations: Nausea, vomiting, diarrhea, and abdominal pain may be some of thefirst symptoms to occur after organophosphate exposure.

Genitourinary and/or endocrine effects: Urinary incontinence, hypoglycemia, orhyperglycemia is possible.

Management

Initial resuscitation Moderately to severely poisoned patients with markedly depressed mental

status require 100 percent oxygen and immediate endotracheal intubation. In addition, patientswho appear mildly poisoned may rapidly develop respiratory failure due to a combination of

CNS respiratory center depression, nicotinic receptor mediated diaphragmatic weakness,

bronchospasm, and copious secretions. Thus, patients with mild to moderate poisoning should

also be considered for early endotracheal intubation.

Bradycardia and hypotension are usually present in moderate to severe poisonings. However,

tachycardia or hypertension may transiently occur due to direct sympathetic stimulation.

Adequate volume resuscitation with isotonic crystalloid (saline) should be performed together

with other resuscitative efforts.

Atropine Atropine competes with acetylcholine at muscarinic receptors, preventing

cholinergic activation. For moderate to severe cholinergic toxicity, atropine should be

administered per protocol at 1mg rapid IVP/IM. Repeat every 3minutes until improvement.

Atropine dosing should be titrated to the therapeutic end point of the clearing of respiratory

secretions and the cessation of bronchoconstriction. Tachycardia and mydriasis are NOT

appropriate markers for therapeutic improvement, as they may indicate continued hypoxia,

hypovolemia or sympathetic stimulation. In patients with severe poisoning, much larger doses

may be required and there is no upper dose limit.

Versed Organophosphorus agent-induced seizures should be treated with a Versed in 2mg

increments every 30-60 seconds IVP/IO (0.2mg/kg IN) up to 10 mg IVP/IN/IO titrated to patient

response. If unable to establish IV and IN contraindicated IM dose 5 10 mg (0.1 - .0.2 mg/kg)

max 10mg single dose. May repeat to a total of 20mg if SBP > 90.

Decontamination In cases of topical exposure with potential dermal absorption the patient

should be removed from the contaminated area and decontaminated as much as possible before

moving patient to ambulance. Decontamination with complete removal of the patients clothes


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and vigorous irrigation of the affected areas should be performed. The patients clothes and

belonging should be discarded since they absorb organophosphorus agents, and reexposure may

occur even after washing. Prehospital providers must take precautions to avoid accidental

exposure including wearing proper PPE and providing treatment in a well ventilated area.


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MCHENRY WESTERN LAKE COUNTY EMS SYSTEM

OPTIONAL CE

March 2012

ORGANOPHOSPHATE POISONING

POST TEST

Name: ___________________________

Department: ______________________

Date: ___________________________

Level of Practice: __________________

1. Organophosphate compounds are found in:

A. Insecticides

B. Nerve gas

C. A & B

D. None of the above

2. Organophosphates inhibit the enzyme acetylcholinesterase causing an accumulation of the

neurotransmitter acetylcholine.

A. True

B. False

3. Signs and symptoms of organophosphate poisoning can be divided into 3 broad categories

A. ______________________

B. ______________________

C. ______________________

D. ______________________

4. The mnemonic SLUDGE stands for

S__________________

L__________________

U__________________

D__________________

G__________________

E__________________


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5. The mnemonic DUMBELS stands for

D__________________

U__________________

M__________________

B__________________

E__________________

L__________________

S__________________

6. List 4 nicotinic signs and symptoms you may see with organophosphate poisoning:

A. ____________________

B. ____________________

C. ____________________

D ____________________

7. List 3 CNS signs and symptoms you may see with organophosphate poisoning:

A. ___________________

B. ___________________

C. ___________________

8. List the 4 factors that could contribute to respiratory failure in a patient who appears mildly

poisoned with organophosphates:

A. ______________________________________

B. ______________________________________

C. ______________________________________D. ______________________________________

9. What are the therapeutic end points of Atropine dosing?

10. What drug and dose would be used to treat seizures in a patient with organophosphate

poisoning?

Organophosphate toxicity

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