Organophosphorous poisoning
Dr. S. Parthasarathy
MD., DA., DNB, MD (Acu),
Dip. Diab.DCA, Dip. Software statistics,
Phd (physio)
Mahatma Gandhi Medical college and research
institute , puducherry , India
Out of 5 lakh self inflicted deaths
• Organophosphorus pesticide self-poisoning is
a major clinical and public-health problem
across much of rural Asia.
• OPC – responsible for 2 lakh death a year in
ASIA
• Intentional only !!
• Readily available …. Any body can buy !!
• 75000 /year – India – estimation ??
Source ??
• Organophosphorus compounds are chemical
agents in wide-spread use throughout the
world, mainly in agriculture.
• They are also used as nerve agents in
chemical warfare (e.g. Sarin gas),
• therapeutic agents, such as ecothiopate used
in the treatment of glaucoma.
Types
Most organophosphates can be divided into
two types:
• diethyl (e.g. chlorpyrifos, diazinon, parathion,
phorate and dichlofenthion)
• dimethyl (e.g. dimethoate, dichlorvos,
fenitrothion, malathion and fenthion).
Another
classification
Classification
Malathion
Normal physiology
• Acetylcholine (ACh) is the neurotransmitter released at
all postganglionic parasympathetic nerve endings and
at
the
synapses
of
both
sympathetic
and
parasympathetic ganglia. It is also released at the
skeletal muscle myoneural junction, and serves as a
neurotransmitter in the central nervous system.
• ACh is hydrolyzed by acetylcholinesterase into two
fragments: acetic acid and choline.
Acetylcholinesterase
• Two forms
• True acetylcholinesterase which is found
primarily in the tissues and erythrocytes,
• pseudocholinesterase which is found in the
serum
Mechanism of action
Instead of 60 seconds – may take hours to weeks
What is anaesthetic drug which works like this ??
Acetyl choline is pouring in all places – not getting metabolized
• Usually ingestion,
• inhalation and skin absorption also
Clinical features
Five important features
• There are five important features assessed
for cholinergic syndrome• Miosis--- local ??
• excessive sweating
• bronchorrhea and bronchospasm
• bradycardia and hypotension.
• OP compounds can be absorbed through skin,
conjunctiva, oral mucosa, GI tract, respiratory
tract, by direct contact, ingestion, inhalation
and injection
• Lipid soluble --- CNS
• Resecretion
• Bronchorrhea is the usual mechanism of early morbidity and
mortality in OPP.
• The origin of this excess fluid is from the airway secretions and not
exudation of fluid across the alveolar-capillary membrane.
•
The obstruction of upper and lower airways and the potential
intrusion of these bronchial secretions into the alveolar sacs
produces hypoxia that is the primary concern
Cardiovascular
• Phase I: A brief period of increased sympathetic
tone
• Phase II: A prolonged period of parasympathetic
activity including AV node blockade
• Phase III: Q-T prolongation followed by torsade
de
pointes,
ventricular
ventricular fibrillation.
tachycardia
and
Respiration
• Secretions may choke
• Nicotinic effects – weakness
• CNS depression
Neurological
• Type I paralysis or acute paralysis- cholinergic crisis
• Type II paralysis or Intermediate syndrome
• 24 – 48 hours later ,proximal , head lift ?? Respiration OK
?? Extraocular muscles, VII and X – 4 – 18 days persist
• Type III paralysis or Organophosphate- induced delayed
polyneuropathy
• 4 weeks later, weakness of hand and feet , calf pain
• Rarely seizures and coma
Diagnosis
• Clinical features ,History ,Suspicion Unconsciuos ??
• Smell ( vomitus ?? Breath, sweat) alcohol ??
• Cholinesterase levels – true and pseudo
• Normal serum acetylcholinesterase level is 3,500 - 8,500 U/L
•
< 1700 , < 700
< 100 – should improve with treatment
• electro diagnostic abnormalities, the 30 Hz rapid nerve
stimulation decremental response correlates best with
clinically detectable weakness and hence it is the most useful
diagnostic test for IMS
Red cell cholinesterase
• These assays measure acetylcholinesterase expressed on
the surface of red cells.
• Red-cell acetylcholinesterase inhibition is a good marker
of such inhibition in synapses and of poisoning severity.
• Atropine ??
• P2 AM stoppage ??
GOALS OF TREATMENT
• Reduce absorption of the toxin
• Enhance elimination
• Neutralize toxin.
• ABC remains
Reduce absorption of the toxin
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Removal from surface of skin, eyes and hair
• Emesis induction
• Gastric lavage
• Activated charcoal administration and cathartics
• Dilution—milk/other drinks for corrosives
• Whole bowel irrigation
• Endoscopic removal of ingested chemical
• Skin decontamination—important aspect—not to be
neglected:
• – Remove contaminated clothing
• – Wash with soap and water
Wash, wash and wash
• Skin folds and underside of fingernails and long hairs
require particular attention.
• Ocular decontamination is to be carried out by washing
eyes with water/normal saline
• Contaminated leather articles should be discarded as the
leather absorbs the chemical and cannot effectively be
cleaned - document in notes and explain necessity to the
family.
• Gastric lavage
• Activated charcoal 25 g 2 hourly
• Sorbitol as cathartic.
Gastric lavage
• Gastric lavage decreases absorption by 42% if done at
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20 minutes and by 16% if performed at 60 minutes
Performed by first aspirating the stomach and then
repetitively instilling and aspirating fluid
Left lateral position delays spontaneous absorption
No evidence that a larger tube is better
Simplest, quickest and least expensive way—funnel
Choice of fluid - tap water: 5–10 mL/kg (sodium ?)
Preferably done on awake patients
More will – vomit or push into the small bowel
For our staff
• Charcoal mask and impermeable gown are to
be worn in the isolation room.
• • When caring for the patient, rubber gloves
are to be worn (as per chemotherapeutic
precautions).
• • In severe poisoning, industrial goggles for
eye protection/comfort should be worn.
• Rotate staff frequently
• Hypochlorite solution on transfer
Atropine
• The recommended starting dose of atropine is
2 mg IV bolus.
• Subsequent doses of 2-5mg every 5-15
minutes should be for adequate atropinization
• increased heart rate (>100 beats/min.),
moderately dilated pupils,
• a reduction in bowel sounds, a dry mouth
(axillae) and a decrease in bronchial
secretions.
• The drying of pulmonary secretions is the
most important and most reliable endpoint
and not tachycardia or mydriasis.
• Double the dose in 15 minutes if no effect
• Prefer atropine if oxygen is NA
• Rate increase by more than 25 + flushing ??
• Table maintain
To note
• Genaral wheezing decreased ??
• Localised wheezing ?? Aspiration
• Miosis ?? Indicator
• Some use atropine to maintain consciousness!!
How to continue
• Shots of atropine every 5 minutes
• Atropinised in one hour
• Then every hour he/ she may need 10- 20 % of
the dose received in the first hour as one hour
infusion
• Inbetween atropinisation lost– one more
bolus and increase the infusion rate by 10 %
Atropine
• Continuous atropine infusions are used in
some centres in doses of 0.02-0.08mg/kg/hr.
• Day 1 maximum
• Usually weaned off in around 7 days
• Nebulised atropine may improve respiratory
distress and oxygenation by decreasing
bronchial secretions
• Hyoscine was used successfully to treat a
patient with severe extra-pyramidal features
Glycopyrrolate- (Dose-0.05mg/kg)
• The main advantages of glycopyrrolate over atropine are –
• nil central toxicity (central antichoilinergic syndrome) as it is a
quaternary ammonium compound and hence has
penetration,
no CNS
NO DELIRIUM
• lesser tachycardia, better control of tracheobronchial secretions
lower incidence of respiratory tract infection.
• Atropine glyco combinations
• First day – atropine
High atropine
• Excess atropine causes agitation, confusion,
urinary retention, hyperthermia, bowel ileus
and tachycardia
• Stop , watch for 30 minutes – restart at 70 %
dose
• Catheterize for agitation
Oximes
To quote a few
• obidoxime, diacetyl monoxime, bisaldoxime,
• pralidoxime (2-PAM or P2AM –2hydroxy
iminomethyl-1-methyl pyridinium chloride) is
most often used, world wide
• Reversal of Nicotinic effects
How do oximes act ??
• These agents reactivate acetyl cholinesterase
by removing the phosphoryl group
P2AM
Now acetyl cholinesterse is ready to destroy acetyl choline
P2AM
• The WHO recommendation is a loading dose of 30mg/kg
followed by an infusion of >8mg/kg/hr.
• The therapeutic endpoint for P2AM therapy is the
resolution of muscle fasciculations and weakness,
reactivation and permanent
clinical improvement and
incremental SChE levels
• Nicotinic
• Usually anticholinergics a few days later – stop
P2AM
• Serum levels of P2AM >4mg/lit is necessary for
effectively treating OP toxicity
• Less IMS
• Lipid solubility low – CNS penetration is less
• diethyl compounds (OPCs) reactivate and “age” at a
significantly slower rate than dimethyl compounds.
More effective in diethyl poisons
WHO tells what??
• WHO recommends that oximes be given to all
symptomatic patients who need atropine
• Effectiveness after 2 hours ??
• The loading dose of oxime should not be given
rapidly as a bolus because this method causes
vomiting
(risking
aspiration),
diastolic hypertension.
tachycardia,
and
Other options
• HupA has been proven to be a powerful, highly specific,
and reversible inhibitor of Acetyl cholinesterase
• Butane - 2, 3-dionethiosemicarbazone is an oxime with
antioxidant properties
• detoxification routes of OPs (both insecticides and nerve
agents)
is
hydrolysis
‘phosphotriesterases’ (PTEs).
by
esterases
called
Other options
• The alpha2-adrenergic receptor agonist clonidine
also reduces acetylcholine synthesis
• Soda bicarb to increase pH
• toxic
molecules
can
be
counteracted
by
antioxidants such as vitamins C and E, melatonin
• Circulation –Give 500–1000 ml (10–20 ml/kg) of
normal saline over 10–20 min and assess
• cautious use of noradrenaline
• Fits – atropine and benzodiazepines
Other options
• Benzodiazepines
• No opioids
• No deriphyllin
• No scoline
• Mechanical ventilation
• FFP
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Organo carbamates
Reversible
Atropine ‘’Ok
but no oximes
• Organochlorides
Organochlorides
• endosulfan, chlordane, aldrin, dieldrin, endrin,
• isoflurane.??
• Pesticides
• Decontamination and supportive therapy
• No atropine and no pralidoxime
Summary
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OPC
Clinical features
Mechanism
Treatment
Atropine
P2AM
Newer things
Thank you all