Organophosphate

Poisoning
By Usman Ali Akbar & Ammar Yasir Dab

What are Organophosphates?

Organophosphate (OP) compounds are a diverse group of chemicals used

in both domestic and industrial settings. Examples of organophosphates
include insecticides (malathion, parathion, fenthion ethion), nerve
gases (soman, sarin, VX), ophthalmic agents (echothiophate etc)

In the developing world, OP and other pesticide poisonings represent

the most common cause of overdose deaths .

OPs are also potent chemical terrorism and warfare agents (nerve gas
agents) ,(e.g., sarin in the Tokyo subway attack, tabun in the IraqIran
war)

Pathophysiology

The primary mechanism of action of organophosphate pesticides is inhibition

of carboxyl ester hydrolases, 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).

Organophosphates inactivate AChE by phosphorylating the serine hydroxyl

group located at the active site of AChE. The phosphorylation occurs by loss
of an organophosphate leaving group and establishment of a covalent bond
with AChE.

Pathophysiology

Once AChE has been inactivated, ACh accumulates throughout the

nervous system, resulting in overstimulation 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.

Once an organophosphate binds to AChE, the enzyme can undergo one

of the following:

Endogenous hydrolysis of the phosphorylated enzyme by esterases or

paraoxonases

Reactivation by a strong nucleophile such as pralidoxime (2-PAM)

Irreversible binding and permanent enzyme inactivation (aging)

What are the signs & symptoms of OP

poisoning ?

Signs and symptoms of organophosphate poisoning can be divided into

three broad categories:

(1) Muscarinic effects

(2) Nicotinic effects
(3) CNS effects.

Muscarinic effects

Cardiovascular - Bradycardia, hypotension

Respiratory - Rhinorrhea, bronchorrhea, bronchospasm, cough,

severe respiratory distress

Gastrointestinal - Hypersalivation, nausea and vomiting, abdominal

pain diarrhea, fecal incontinence

Genitourinary - Incontinence

Ocular - Blurred vision, miosis

Glands - Increased lacrimation, diaphoresis

Nicotinic effects
Nicotinic signs and symptoms include

Ganglionic: Tachycardia, hypertension, diaphoresis, mydriasis.

Neuromuscular: Neuromuscular depolarization, fasciculations, motor
weakness, paralysis with respiratory failure.

CNS Effects
CNS effects include the following:

Anxiety

Emotional lability

Restlessness

Confusion

Ataxia

Tremors

Seizures

Coma

OP Poisoning is a Triphasic Illnes

Three types of paralysis may result from organophosphate poisoning.

Acute

Cholinergic Crisis :

Type I is described as acute paralysis secondary to continued

depolarization at the neuromuscular junction.It occurs within few
minutes of exposure. Vomiting and Profuse Diarrhea are typical
following ingestion. Miosis is charteristic and presence of muscle
fasiculations strongly suggest the diagnosis.

Type II (intermediate syndrome)

Type

II (intermediate syndrome) is reported to develop

24-96 hours after resolution of acute organophosphate
poisoning symptoms and to manifest commonly as paralysis and
respiratory distress. This syndrome involves weakness of
proximal muscle groups, neck, and trunk, with relative sparing of
distal muscle groups. Cranial nerve palsies can also be observed.

Organophosphate-induced delayed
polyneuropathy (OPIDP)

Type III paralysis, or organophosphate-induced delayed

polyneuropathy (OPIDP) occurs 2-3 weeks after exposure to large
doses of certain organophosphates and is due to 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

Investigations

Organophosphate (OP) toxicity is a clinical diagnosis.

Confirmation of organophosphate poisoning is based on the
measurement of cholinesterase activity; typically, these results are
not readily available. Although red blood cell (RBC) and
plasma (pseudo) cholinesterase (PChE) levels can both be
used, RBC cholinesterase correlates better with central nervous
system (CNS) acetylcholinesterase (AChE) and is, therefore, a more

useful marker of organophosphate poisoning.

Other laboratory findings include the following:

Leukocytosis

Hemoconcentration

Metabolic and/or respiratory acidosis

Hyperglycemia

Hypokalemia

Elevated troponin levels

Elevated amylase levels

Elevated liver function test results

ECG Findings

ECG findings include prolonged QTc interval, elevated ST segments,

and inverted T waves. Although sinus tachycardia is the most common
finding in the poisoned patient, sinus bradycardia with PR
prolongation can develop with increasing toxicity due to excessive
parasympathetic activation.

Management

First step for the physician is to put on protective clothing as OP are

absorbed by the skin.

Then remove all clothing from the patient and gently cleanse patients
suspected of organophosphate exposure with soap and water because
organophosphates are hydrolyzed readily in aqueous solutions with a
high pH.

The airway should be cleared of excessive secretions, breathing and

circulation assessed

High flow O2 administered and IV Access should be obtained.

Gastric Lavage or Activated Charcoal may be considered if the patient

presents within 1 hour of ingestion

Management

Convulsions should be treated with proper anti-convulsant.

The ECG, oxygen saturation, blood gases, temperature, urea and

electrolytes, amylase and glucose should be monitored closely

Atropinization
Atropine Use :

Early use of sufficient doses of atropine is potentially life-saving in

patients with severe toxicity. Atropine reverses ACh-induced
bronchospasm, bronchorrhoea,bradycardia and hypotension.

GOAL: Atropinization (i.e., drying of bronchial secretions with

normalized oxygen saturation, Dry axilla, Pupil size more than 5mm,
chest secretions clear,systolic BP more than 90 mmHg, Pulse rate 80-100
bpm)

The initial adult dose is 1 to 3 mg IV bolus. Then titrate according to

persistence of bronchorrhea by giving the double of the previously used
dose every 5 minutes until atropinization is achieved.

The initial pediatric dose is 0.02 mg/kg IV. Titrate as in adults Once
the patient is stabilized, an infusion of atropine should be started
with 10% to 20% of the i.nitial atropinization dose per hour and should
be held once anticholinergic effects occur (absent bowel sounds,
urinary retention, agitation)

Pralidoxime (2-PAM): Pralidoxime forms a complex with OPs that are

bound to AChE. The pralidoximeOP complex is then released from the
enzyme and thus regenerates AChE function. Once the AChE bound
OPs start aging, pralidoxime is rendered ineffective. Therefore, it is
crucial to start pralidoxime therapy early.Pralidoxime also binds to
some degree to free OPs and so prevents further AChE binding.

Adult dosing used to be administered as boluses given over time.

New evidence,however, is favoring an infusion regimen 1 to 2g of
pralidoxime in 100 mL NS IV over 20 minutes, then infusion of 500
mg/hr.

Benzodiazepines are the first-line agents for OP-induced

seizures

Further Patient Care

Because of risks of respiratory compromise or recurrent symptoms,

hospitalizing all symptomatic patients for at least 48 hours in a high
acuity setting is recommended. Patients who are asymptomatic 12
hours after organophosphate exposure can be discharged since
symptom onset should usually occur within this time frame.

Thankyou!
Any Questions ?