Organo phosphate poisoning
Dr.Gireesh kumar.K.P
OP s
Nerve agents Tabun (GA), sarin (GB), soman (GD), cyclosarin (GF),
and VX. VR
Insecticides Dimethyl compounds Diethyl compounds
Dichlorvos Chlorpyrifos
Fenthion Malathion Diazinon
Methamidophos Parathion-ethyl
Quinalphos
Action
• OPs irreversibly inactivate Acetylcholinesterase (AChE)
• This will lead to accumulation of acetylcholine (Ach) at
cholinergic synapses
Stages
• Acute cholinergic phase
• Intermediate syndrome
• Delayed polyneuropathy
• Acute
– Starts in minutes, usually within one hour
– It lasts up to 48-72 hours
– OPs produce muscarinic, nicotinic and CNS effects
Muscarinic
• All secretions increased
– Sweating, Salivation, Lacrimation,Increased urination
– Increased bronchial secretion, Pulmonary oedema
• Miosis – constricted pupil
• Bradycardia (tachycardia in 20 % cases)
• Heart blocks, hypotension
• Bradycardia and hypotension are usually present in
moderate to severe poisonings. However, tachycardia or
hypertension may transiently occur due to direct
sympathetic stimulation.
Muscarinic signs
• The muscarinic signs can be remembered by use of one
of two mnemonics:
– SLUDGE/BBB – Salivation, Lacrimation, Urination, Defecation,
Gastric Emesis, Bronchorrhea, Bronchospasm, Bradycardia
– DUMBELS – Defecation, Urination, Miosis,
Bronchorrhea/Bronchospasm/Bradycardia, Emesis,
Lacrimation, Salivation
Nicotinic
• Nicotinic: The nicotinic effects occurs via acetylcholine
stimulation of receptors at the neuromuscular junction.
• Muscle twitching, fasciculation, weakness, respiratory
paralysis
• Hypertension, tachycardia
Systemic effects
• CNS: Nicotinic and muscarinic receptors also have been
identified in the brain, and may contribute to
– central respiratory depression
– Anxiety, restlessness, weakness
– Confusion, Convulsions, Coma
• Cardiac issues :Cardiac arrhythmias, including heart block and
QTc prolongation, are occasionally observed in
organophosphorus agent poisoning
• Respiratory issues — Fatalities from acute organophosphorus
agent poisoning generally result from respiratory failure due to a
combination of depression of the CNS respiratory center,
neuromuscular weakness, excessive respiratory secretions,
and bronchoconstriction.
Intermediate syndrome
• It begins after 48 hours ( in 20% cases ),it may be delayed up to
72 - 96 hours
• Patient will have muscle weakness due to receptor dysfunction at
neuromuscular junction
• Risk factors for the development of intermediate syndrome appear
to include exposure to a highly fat-soluble organophosphorus
agent, and may be related to inadequate doses of oximes. The
intermediate syndrome has rarely been described following
carbamate poisoning.
• Muscles involved are – Ocular muscles, neck muscles, proximal
limb muscles, respiratory muscles
• Patient also have anxiety, sweating, cyanosis and may develop
coma
Delayed polyneuropathy
• This occurs after 1 to 3 weeks of exposure due to
degeneration of myelinated nerve fibres
• Clinical features
– Symmetrical, flaccid, distal muscle weakness and foot drop
– Absent deep tendon reflexes
– Sensory loss – All starts in distal parts of lower limb; then upper
limb also
Diagnosis
• Pungent garlic like smell
• Toxicology analysis for OPs in blood, gastric secretions,
urine
• Serum (or pseudo) cholinesterase levels reduced
General management
• Remove the cloths and clean the body
• Gastric lavage (consider gastric lavage for oral poisonings
if presentation is within 1 hour of ingestion) – send the
sample for toxicology screen
• Induction of emesis is contraindicated.
• Activated charcoal - 50–100 g initially, followed by 50 g 4-
hourly until charcoal appears in the faeces or recovery
occurs.
Atropine
• Atropine reverses Ach induced bronchospasm,
bronchorrhoea, bradycardia and hypotension
• Atropine competes with acetylcholine at muscarinic receptors,
preventing cholinergic activation.
• Initial dose 1 mg IV, if no adverse effects give 2 mg every 15
minutes till the patient develops atropinization ( drying of
secretions, tachycardia, dry mouth, and dilated pupil)
• Injection(Vial) - 1 mL contains: atropine 1 mg, (Ampule – 1ml =
0.6mg), Atropine also can be used as infusion ( The average
patient requires approximately 40 mg/d )
• Monitor the patient – heart rate, pupil size, fasciculations,
secretions, lung crepitation
Glycopyrrolate
• Glycopyrrolate is a medication of the muscarinic
anticholinergic group. It does not cross the blood brain
barrier and consequently has no to few central effects.
• It is used as an alternative to atropine when atropine
produces psychological adverse effects
• Injection - Each 1 mL contains: Glycopyrrolate 0.2
mg
Pralidoxime
• Oximes – They reactivates phosphorylated AChE
• Since atropine does not bind to nicotinic receptors, it is ineffective in treating neuromuscular
dysfunction. Pralidoxime (2-PAM) and other oximes, such as HI-6 and obidoxime, are
cholinesterase reactivating agents that are effective in treating both muscarinic and nicotinic
symptoms
• Pralidoxime should NOT be administered without concurrent atropine in order to prevent
worsening symptoms due to transient oxime-induced acetylcholinesterase inhibition
• Pralidoxime 1 gm (at least 30 mg/kg in adults, and 25 to 50 mg/kg for
children in 100 ml normal saline IV over 30 minutes) 8th hourly for 1st 24-48
hours
• Pralidoxime should be administered slowly over 30 minutes, since rapid administration has
occasionally been associated with cardiac arrest, and slow administration prevents the
muscle weakness that results from the transient inhibition of acetylcholinesterase as
pralidoxime binds to the enzyme
• After the bolus dose, it appears that superior antidotal effects occur with pralidoxime given as
a continuous infusion of at least 8 mg/kg per hour in adults and 10 to 20 mg/kg per hour for
children
Carbamate intoxications
• Carbamate compounds : Aldicarb, Carbofuran, Methomyl
• They are very short acting (half life is only 30 to 40 minutes): carbamates
are rapidly absorbed via all routes of exposure. Unlike organophosphates,
these agents are transient cholinesterase inhibitors, which spontaneously
hydrolyze from the cholinesterase enzymatic site within 48 hours. Carbamate
toxicity tends to be of shorter duration than that caused by equivalent doses
of organophosphates
• Their clinical features are same as OPs, but less severe and short acting
• They reversibly inactivate Acetylcholinesterase
• They can also produce Pancreatitis
• Treatment – Atropine Infusion
• Unlike organophosphates, carbamate intoxications do not irreversibly inhibit
cholinesterase, and thus pralidoxime is not usually required and may worsen
symptoms.
