Adapted from books and internet sources For education purpose

1. Dr Shahana

2. Used as insecticides worldwide for more than 50 years
Worldwide, an estimated 3,000,000 people are exposed
each year, with up to 300,000 fatalities

3. Malathion, Parathion, Octam ethyl pyrophosphoramide
(OMPA), Hexaethyltetraphosphate (HETP), Diazinon, Tik20,
Methyl Parathion, Metacide and TEPP
 HETP-least toxic
 TEPP-most toxic and fastest acting OP compound
 The noxious odor and taste of OP ensures that accidental
ingestion is minimal and therefore nonlethal
 On the contrary, homicidal administration is usually lethal.

4. OP compounds can be absorbed through skin, conjunctiva,
oral mucosa, GI tract, respiratory tract
By direct contact, ingestion, inhalation and injection.
The onset and severity of symptoms depend on the nature of
the compound, amount, route of exposure and rate of
metabolic degradation.
Rapidly distributed in all body tissues
Lipid solubility makes easy access to CNS and fat stores.
Intermittently released from fat stores to circulation/secreted
to stomach

5. OPC binds irreversibly to enzyme acetylcholinesterase,
preventing the breakdown of acetylcholine
Acetylcholine accumulates resulting in muscarinic, nicotinic
and parasympathetic stimulation of the central nervous
system
After some period of time, the acetylcholinesterase-
organophosphorus compound undergoes a conformational
change, known as "aging," which renders the
enzyme irreversibly resistant to reactivation by an antidotal
oxime

6. Muscarinic effects: (seen more commonly in adults)
SLUDGE—Salivation, Lacrimation, Urination, Defecation,
Gastrointestinal cramping and Emesis
DUMBBELS—Diarrhea, Urinary incontinence, Miosis,
Muscle fasciculation, Bronchorrhea, Bronchospasm,
Bradycardia, Emesis, Lacrimation, Salivation
Nicotinic effect initially results in stimulation followed by
paralysis of the preganglionic and somatic nerve fibers
leading to twitching of eyelids, tongue and facial muscles.
This is followed by neuromuscular blockade and paralysis.
Secretions, altered mental status and miosis are the
commonest presentations in children.

7.  Direct measurement of RBC acetylcholinesterase (RBC AChE)
activity-measure of the degree of toxicity.
 Sequential measurement of RBC AChE activity (if rapidly
available) may also be used to determine the effectiveness of
oxime therapy in regeneration of the enzyme. Determination of
RBC AChE activity can also be helpful in evaluating chronic or
occupational exposure. However, most hospital laboratories are
unable to perform this test.
 An assay for plasma (or pseudo-) cholinesterase activity is more
easily performed, but does not correlate well with severity of
poisoning and should not be used to guide therapy

8.  Due to significant variability in toxicityidentify if dimethyl or
diethyl
 Dimethyl compounds undergo rapid aging, making early initiation of
oxime therapy critical; diethyl compounds may exhibit delayed
toxicity, and may require prolonged treatment
 In case of doubt, a therapeutic challenge of atropine may be
attempted:
 Administer 0.01 mg/kg Atropine in children < 12 year (minimum
dose of 0.1 mg).
 2 mg in children > 12 years and adults
 This dose will relieve symptoms in a child with OPP, but cause side
effects of atropinization in a normal child

9.  Aggressive decontamination with complete removal of the patient's
clothes and vigorous irrigation of the affected areas
 If a large quantity of poison has been ingested and the child has
been brought within 1 hour of ingestion gastric lavage may be
helpful*
 Activated charcoal 1 g/kg (maximum dose 50 g)
 Substantial risk of aspiration in patients with increased secretions
and decreased mental status
*Interventions for acute Organophosphate poison South Asian Cochrane Network and Centre
(SASIANCC) 2012

10. Airway and Breathing
 Profuse secretions and respiratory failure could occur due to
overwhelming bronchorrhea. Mechanical ventilation may be required in
up to 25% of patients.
 Correction of hypoxia is mandatory prior to atropinization to avoid the
risk of ventricular fibrillation.
 Oropharyngeal suctioning.
 Provide oxygen using a JR circuit.
 Intubate using the pharmacologically assisted intubation (PAI)
technique.
 Avoid Succinylcholine since it increases secretions and can prolong
muscle paralysis in OPP

11. Circulation
 Two IV lines be secured and blood samples for haematological and
biochemical and ChE be collected.ECG be recorded.
 Administer NS 10 mL/kg (max 20–30 mL/kg may be needed to
correct shock). Inotrope may be needed if hypotensive or hypoxia has
caused cardiogenic shock.
Disability
 Manage convulsions using the standard protocol for status
epilepticus.

12.  Atropine neutralizes the muscarinic effects of acetylcholine by competitive antagonism at
postsynaptic muscarinic receptors; not bind to nicotinic receptors, it is ineffective in
treating neuromuscular dysfunction
 Dose:
 Children < 12 years: 0.05 to 0.1 mg/kg of atropine.
 In children > 12 years and adults: 2 to 4 mg.
 If no effect is noted, the dose should be doubled every three to five minutes until pulmonary
muscarinic signs and symptoms are alleviated.
 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, HUNDREDS of milligrams of atropine by bolus and
continuous infusion may be required over the course of several days.
Eddleston M, Roberts D, Buckley N. Management of severe organophosphorus pesticide
poisoning. Crit Care 2002; 6:259.

13.  Atropine maintenance: - Infusion of atropine reduces the fluctuation in atropine
concentration associated with repeated bolus doses. The rate of infusion is set at
10 -20 % of the total atropine required to load the patient every hour. Usually it is
maintained for 24- 48 hrs or longer in severe cases, and gradually withdrawn over
3-5 days.
 Atropine toxicity: - Confusion, agitation, hyperthermia, ileus, tachycardia etc
would suggest over atropinisation which would necessitate discontinuation of the
atropine infusion, followed by frequent observation. When they settle down the
infusion is to be started at 70- 80 % of the previous rate.

14. PRALIDOXIME
 cholinesterase reactivating agents that are effective in treating both muscarinic
and nicotinic symptoms
 Reactivation of ChE is more marked in the skeletal muscle than at autonomic site
and not at all in CNS (Do not enter CNS)
 NOT be administered without concurrent atropine in order to prevent worsening
symptoms due to transient oxime-induced acetylcholinesterase inhibition
 IV bolus therapy 25 to 50 mg/kg slowly over 30 minutes for children, based upon
the severity of symptoms(WHO)*
 continuous infusion of at least 8 mg/kg per hour in adults and 10 to 20 mg/kg per
hour for children
 Evidence is inconsistent and difficult to interpret
Eddleston M, Szinicz L, Eyer P, Buckley N. Oximes in acute organophosphorus pesticide
poisoning: a systematic review of clinical trials. QJM 2002; 95:275.

15.  Magnesium Therapy: - Magnesium therapy in addition to atropine and oximes has
been found to benefit. The mechanism appears to be inhibition of AChE and OP
antagonism.
 Glycopyrolate: does not enter CNS initial muscarinic signs like coma or
drowsiness will not respond; however used when there is copious secretion as an
adjunct to atropine or when features of atropine toxicity like delirium etc are
confused with CNS effects of poison
 Furosemide: - It is recommended if pulmonary oedema persists, even after full
atropinisation
Pajoumand A,Shadnia S,Razaie A etal.Benefit of magnesium sulfate in the management of
acute human poisoning by organophosphorus insecticides. Hum Exp Toxicol. 2004;23:565-
9(Medline)

16.  Ten to 40 percent of patients
 24 to 96 hours after exposure
 characteristic neurological findings including neck flexion weakness, decreased
deep tendon reflexes, cranial nerve abnormalities, proximal muscle weakness, and
respiratory insufficiency
 Risk factors: exposure to a highly fat-soluble organophosphorus agent, and may be
related to inadequate doses of oximes
 adequate supportive care
 prolonged mechanical ventilation
 most patients have complete resolution of neurologic dysfunction within two to
three weeks

17.  one to three weeks after ingestion
 inhibition of neuropathy target esterase (NTE)
 transient, painful "stocking-glove" paresthesias followed by a symmetrical motor
polyneuropathy characterized by flaccid weakness of the lower extremities, which ascends
to involve the upper extremities. Sensory disturbances are usually mild.
 primarily affects distal muscle groups, but in severe neurotoxicity, proximal muscles groups
may also be affected
 Electromyograms and nerve conduction studies of affected patients reveal decreased firing
of motor conduction units
 Histopathologic sections of peripheral nerves reveal Wallerian (or "dying-back")
degeneration of large distal axons
 risk of developing OPIDN is independent of the severity of acute cholinergic toxicity. Some
organophosphorus agents, such as parathion, are potent cholinergic agents but are not
associated with OPIDN. Others, such as triorthocresyl phosphate (TOCP), produce few
clinical signs of cholinergic excess but are frequently implicated in OPIDN
 early oxime treatment may be of benefit