Organophosphate Poisoning
By the end of this lecture, learners will be able to:
Describe pathophysiology of organophosphate
poisoning
Discuss the signs and symptoms of
Learning organophosphate toxicity.
Outline the evaluation of a patient with suspected
Objectives organophosphate toxicity.
Summarize the evaluation and treatment of
organophosphate toxicity and the role of the inter
professional team in managing this condition.
“Organophosphates are used in at least 50% of
the world’s pesticides and cause poisoning
THAT can rapidly BE fatal.
Organophosphorus (OP) compounds which are in
use world wide as insecticides have been a source
Suicidal rate of poisoning and continue to pose management
problems.
with OPP is
Easily accessible, hence associated with self
21- 56% poisoning and mortality associated self-poisoning
Resuscitation, Decontamination, Specific antidote,
and supportive measures continue to be the main
stay of therapy.
Organophosphates (OP) form the basis of
many insecticides, herbicides and also
nerve agents.
OP in the UK exposure is mainly from
Patients can die as crop spraying and sheep dips.
a result of acute
Malathion is an OP which is used to treat
cholinergic head lice and scabies in adults.
syndrome
Sarin and VX are examples of OP nerve
agents.
OP irreversibly inactivates acetyl-
Cholinesterase (AChE).
The first organophosphate insecticide
was created in the mid-1800s but was
not widely used until after World War
II.
The onset of Organophosphates are used as
symptoms is often medications, insecticides, and nerve
within minutes, and it agents as a weapon.
can take weeks to
disappear Symptoms include; increased saliva
and tear production, diarrhea, nausea,
vomiting, small pupils, sweating,
muscle tremors, and confusion.
It has been calculated by the WHO that 3
million people are poisoned with OP, and
250,000 are killed every year, particularly in
Asian countries.
In the United States, there are around 8000
Epidemiology exposures per year with very few deaths.
While most often the exposure occurs from
an agricultural pesticide, there are
household items, such as ant and roach
spray, that also contain organophosphate
compounds.
Organophosphate pesticide exposure may
occur through inhalation, ingestion, or dermal
contact.
Crops that farmworkers come into contact
with that also may include organophosphates
such as apples, celery, bell peppers, peaches,
Exposure strawberries, nectarines, grapes, spinach,
lettuce, cucumbers, domestic blueberries,
and potatoes.
The severity of the symptoms depends on the
amount ingested, route of absorption, and
rate of metabolic breakdown of the
insecticide.
The key feature of organophosphate
insecticides is the inhibition of carboxyl ester
hydrolases, chiefly inhibition of
acetylcholinesterase.
Patho- The organophosphate insecticide inactivates
physiology AChE by phosphorylating the serine hydroxyl
group on the enzyme.
This is followed by the accumulation of
acetylcholine which then overstimulates the
nicotinic and muscarinic receptors.
For nicotinic signs of acetylcholinesterase inhibitor toxicity, think of
the days of the week:
Monday = Mydriasis
Tuesday = Tachycardia
Wednesday = Weakness
Thursday = Hypertension
Friday = Fasciculations
Clinical The more common mnemonic that captures the muscarinic effects of
Features
organophosphate poisonings is DUMBELS:
D = Defecation/diaphoresis
U = Urination
M = Miosis
B = Bronchospasm/bronchorrhea
E = Emesis
L = Lacrimation
S = Salivation
Eye: Miosis, blurred vision, pin point pupil, red
tears.
Cardiovascular: Bradycardia, hypotension.
Glands: Extreme salivation, lacrimation, sweating.
Symptoms Gastrointestinal: Anorexia, nausea, vomiting,
associated with diarrhea.
Autonomic Respiratory: Bronchoconstriction, bronchial
Nervous System secretion.
Skeletal Muscle: Fasciculations, weakness,
paralysis.
CNS: Ataxia, confusion, convulsions, coma,
paralysis & tremor.
Death
Respiratory depression due to,
Bronchoconstriction.
Increased secretions.
Paralysis of diaphragm & Intercostal
muscles.
Symptoms Central respiratory depression.
associated with Those who survive may also develop the
Autonomic following neuropsychiatric deficits:
Nervous System Confusion
Impairment in memory
Lethargy
Psychosis
Irritability
Parkinson like symptoms
If the patient survives the acute poisoning,
there are other long-term complications.
Intermediate neurologic symptoms typically
occur 24 to 96 hours after exposure.
Symptoms include neck flexions, weakness,
Complications decreased deep tendon reflexes, cranial
nerve abnormalities, proximal muscle
weakness, and respiratory insufficiency.
With supportive care, these patients can have
a complete return to normal neurologic
function within 2 to 3 weeks.
Polyneuropathy is linked to very
specific organophosphate compounds
that contain chlorpyrifos.
Most commonly this starts as stocking-
Complications glove paresthesia and progresses to
symmetric polyneuropathy with flaccid
weakness that starts in the lower
extremities and progresses to include
the upper extremities.
Grading Severity of AchE Poisoning
Normal AChE
levels:
8-18 units/L
Diagnosis of acute or chronic organophosphate
poisoning is strictly clinical.
You must have a high clinical suspicion for OP when
no history of exposure or ingestion is known.
If OP is on the differential but not confirmed, a trial
of atropine may be employed.
Diagnosis If symptoms resolve after atropine, this increases the
likelihood of an acetylcholinesterase inhibitor
poisoning.
Some labs can directly measure RBC
acetylcholinesterase activity.
Some organophosphates have a distinct garlic or
petroleum odor that may help in diagnosis.
The first step in the management of patients with
organophosphate poisoning is putting on personal
protective equipment.
Secondly, you must decontaminate the patient.
This means removing and destroying all clothing
because it may be contaminated even after
Treatment & washing.
Management The patient’s skin needs to be flushed with water.
Dry agents such as flour, sand, or bentonite also can
be used to decontaminate the skin.
In the case of ingestion, vomiting and diarrhea may
limit the amount of substance absorbed but should
never be induced.
Activated charcoal can be given if the patient
presents within 1 hour of ingestion, but studies
have not shown a benefit.
Airway control is vital. In some patients,
intubation may be required due to bronchospasm,
seizures, or bronchorrhea.
Treatment & During intubation, succinylcholine must be
Management avoided as it may prolong the paralysis.
The reason is that succinylcholine is also
degraded by acetylcholine esterase.
Good intravenous access, cardiac monitoring, and
pulse oximetry are the standard of care.
The definitive treatment for organophosphate
poisoning is Atropine, which competes with
acetylcholine at the muscarinic receptors.
The initial dose for adults is 2 to 5 mg IV or 0.05
mg/kg IV for children until reaching the adult
dose.
Treatment If the patient does not respond to the treatment,
double the dose every 3 to 5 minutes until
respiratory secretions have cleared and there is
no bronchoconstriction.
In patients with severe poisoning, it may take
hundreds of milligrams of atropine given in
bolus or continuous infusion over several days
before the patient improves.
Treatment
Algorithm
Pralidoxime works by reactivating the phosphorylated
AChE by binding to the organophosphate.
Pralidoxime (2-PAM) also should be given to affect the
nicotinic receptors since atropine only works on
muscarinic receptors.
Treatment However, to work, it has to be given within 48 hours of
with Oxime the poisoning.
The agent does not depress the respiratory center and
can be combined with atropine.
Evidence about the use of oximes is inconsistent, and
interpretation is difficult.
However, all patients poisoned with organophosphorus
agents should be treated with an oxime.
Atropine must be given before 2-PAM to avoid
worsening of muscarinic-mediated symptoms.
A bolus of at least 30 mg/kg in adults or 20 to
50 mg/kg for children should be given over 30
minutes.
Rapid ATROPINE administration can cause
Atropine cardiac arrest.
After the bolus, a continuous infusion of at least
8 mg/kg/hr for adults and 10 to 20 mg/kg/hr
for children should be started and may be
needed for several days.
Patients with seizures may benefit from
benzodiazepines.
Globally, organophosphate insecticides have
mortality rates that vary from 2 to 25%.
The most common insecticides involved in
death are fenitrothion, dichlorvos, malathion,
Prognosis, and trichlorfon.
Postoperative The most common cause of death is
and respiratory failure.
Rehabilitation Because of the risk of recurrent symptoms
Care and respiratory distress, patients should be
hospitalized and observed for at least 48
hours in an intensive care setting.
Those who remain asymptomatic after 12
hours may be discharged.
The diagnosis and management of
organophosphate poisoning are done with
an inter professional team that consists of
an emergency department physician,
poison control, nurse practitioner,
Enhancing anesthesiologist, intensivist, and other
Healthcare specialists depending on organ system
Team involvement.
Outcomes The key is to prevent further absorption via
the skin, eyes, or lungs.
The pharmacist must ensure that the patient
is on no other medication that can
exacerbate the cholinergic crises.
In addition, the pharmacist should be aware
that in organophosphate toxicity, hundreds
of milligrams of atropine may be required.
The treatment should follow the trauma
Enhancing protocol with the first emphasis on the
Healthcare airways.
Team Symptomatic patients need to be
Outcomes monitored in the ICU.
Both atropine and pralidoxime can be used
in symptomatic patients but close
monitoring is necessary. The outlook for
most patients is excellent.
References:
• Sundaray, N. K., and R. Kumar.
"Organophosphorus poisoning:
THANK current management
guidelines." Medicine update 20.5
YOU! (2010): 420-425.
• patient.info/doctor/organophosp
hate-poisoning
