ORGANOPHOSPHORUS

POISONING

Introduction

OPCs are used as pesticides in most developing countries
750,000 to 3,000,000 cases annually (globally)
Exposure Accidental, Occupational, Intentional Exposure


Mechanism of Toxicity

Irreversible binding and inhibition of the enzyme Acetyl Choline Esterase that leads to
excessive accumulation of Ach at synapses resulting in overstimulation of muscuranic and
nicotinic receptors.

Commonly used OP insecticides:
Acephate, anilophos, chlorpyrifos, dichlorvos, diazinon, dimethoate, fenitrothion, methyl
parathion, monocrotophos, phenthoate, pirimiphos, quinalphos

Ageing: Permanent and irreversible binding of the OP compound to the cholinesterase. Time to
aging is highly variable ranging from minutes to a days. Once aging occurs, the enzymatic
activity of cholinesterase is permanently destroyed, and new enzyme must be resynthesized.
Therefore Oximes must be given before aging occurs to be work.


Clinical Presentation

Muscuranic
Nicotinic
CNS


CVS: Bradycardia, Hypotension
Muscle Fasciculations, Cramping,
RS: Bronchorrhea, Bronchospasm Neuromuscular weakness
GI: N&V, Salivation, Diarrhea
GU: Urinary Incontinence
Eye: Blurred Vision, Miosis
Glands: Lacrimation, Sweating

Anxiety, Restlessness, Tremors,
Ataxia, Confusion, Seizures,
Coma

Look at the respiratory pattern, Single breath count, proximal muscle weakness, neck
muscles power, pupils, HR, BP, SpO2, Lungs.

Remember they key features as:

SLUDGE: Salivation, Lacrimation, Urination, Defecation, GI Distress, Emesis

Killer Bs: Bradycardia, Bronchorrhea, Bronchospasm

DUMBBELLS: Defecation, Urination, Muscle weakness, Miosis, Killer Bs, Emesis, Lacrimation,
Salivation

Three classical phases:

1. Acute Cholinergic crisis (often seen in the ED)

Due to excessive Ach, Watch for SLUDGE symptoms
May proceed quickly to respiratory muscle weakness and paralysis
May need ventilation
Check neck muscle power and single breath count

2. Intermediate Syndrome (IMS)

Develops within 24-96 hours after the event
Manifests as paralysis and respiratory distress
More of proximal muscle involvement, sparing of distal muscles
May persist upto 2-3 weeks
Rx: Respiratory support, good supportive care (Prevent infections)

3. OP induced delayed polyneuropathy (OPIDN)

Sensory motor neuropathy
Seen after 2-3 weeks of exposure
Distal muscle weakness
Recover may take upto 6-12 months


Delayed OP Encephalopathy (DOPE)

AMS/ Coma 4-7 days after presentation
No pupillary reaction or brainstem activity!!
Recover completely within 7-10 days with supportive therapy
Excellent Prognosis


Labs

Serum Pseudocholine esterase (Send repeat sample after 12 hrs if high
suspicion and first one turns out to be within the normal range)
CBC
Creat, Urea, Electrolytes (HypoK)
ECG
CXR
Blood Gas


Don't wait for lab tests Treat on the basis of suspicion
Clinical diagnosis with the toxidrome + Garlic like odour

Management (Use PPE)

1. ABC (O2, Intubate/IV Fluids)
Avoid succinyl choline for RSI Use non-depolarising agents (Rocoronium)
Manage seizures with benzosphenobarb (No phenytoin)

2. Reduce absorption
Remove from skin/eyes not to be neglected
Gastric lavage (questionable benefit)
Activated Charcoal (questionable benefit)

3. Medications

Atropine: Antidote of choice, anticholinergic effect reverses the toxidrome

Adequate atropinisation with HR>110/min, mid dilated pupils, clear lungs,
BS+
Atropine does not reverse muscle weakness
Dose: 1-2mg bolus IV, double every 5 min and start infusion (may require upto
100mg/hr atropine)
Look at the overall picture for administering atropine
Risk of atropine toxicity, replace with glycopyrolate (does not cross BBB)


Oximes (Pralidoxime): Reactivates Ach esterase if given early enough

If using this, give ASAP before aging occurs
Research: No change in survival
Overall no effect some studies suggest possible harm!
WHO recommends it, Dose: 30mg/Kg bolus the 8mg/kg/hr infusion
Continue for 24-48 hours

Adrenaline
Gives adrenergic stimulus
Used to supplement atropine when bradycardia is refractory
Low dose infusion

4. Supportive Care
Mechanical Ventilation for IMS
Prevent Infections (VAP, CRBSI)
Early feeding (improved outcomes)

5. Other potential therapies (follow local protocols)
Clonidine
IV MgSO4 (associated with decreased hospital days)
Blood alkalization (possible benefit)
Antioxidants
FFP (Bioscavenger therapy Not ready for prime time)

Take Home:

Atropine is the antidote of choice for OP poisoning
Avoid succinyl choline for RSI
OP induced Seizures BZD, Phenobarbitone (No Phenytoin)
Know DOPE Supportive care, Excellent prognosis


Thank You

Questions/Comments/Feedback

Lakshay Chanana
drlakshay_em@yahoo.com
Twitter @EMDidactic
EM Academy @ Facebook


Further Reading:

1. Pichamuthu K, Jerobin J, Nair A, et al. Bioscavenger therapy for organophosphate
poisoning - an open-labeled pilot randomized trial comparing fresh frozen plasma or
albumin with saline in acute organophosphate poisoning in humans. Clin Toxicol (Phila).
2010;48(8):813-9.
2. Blain PG. (2011). Organophosphorus poisoning (acute). Clin Evid. [Online] Available
from www.ncbi.nlm.nih.gov/pubmed/21575287.
3. Perera PM, Jayamanna SF, Hettiarachchi R, et al. A phase II clinical trial to assess the
safety of clonidine in acute organophosphorus pesticide poisoning. Trials. 2009;10:73.
4. Eddleston M, Juszczak E, Buckley NA, et al. Multiple-dose activated charcoal in acute self-
poisoning: a randomised controlled trial. Lancet. 2008;371(9612):579-87.
5. Roberts DM, Buckley N. (2012). Alkalinisation for organo-phosphorus pesticide
poisoning.
[online]
Available
from
www.onlinelibrary.wiley.
com/doi/10.1002/14651858.CD004897.pub2/abstract.
6. Blain PG. (2011). Organophosphorus poisoning (acute). Clin Evid. [Online] Available
from www.ncbi.nlm.nih.gov/pubmed/21575287.