ORGANOPHOSPHATE POISONING

By: Nandinii Ramasenderan

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

in both domestic and industrial settings.

• Examples of organophosphates include insecticides (malathion, parathion, dichlorvos, and diazinon)

• Worldwide mortality studies report mortality rates from 3-25 %

• Mortality rates depend on the type of compound used, amount ingested, general health of the patient, delay in discovery and transport, insufficient respiratory management, delay in intubation, and failure in weaning off ventilatory support.

-OPs are esters of phosphoric acid and its derivates. -Comprises a central phosphorus atom (P) and the characteristic phosphoric (P=O) or thiophosphoric (P=S) bond. -The symbol X represents the leaving group, which is replaced (by nucleophilic substitution) by the oxygen of serine in the AcHE active site. The rate of AcHE inhibition depends on the leaving group; higher tendency of leaving results in higher affinity of the inhibitor to the enzyme.

Chemical structure:

Route of entry:

Acetylcholinesterase (AChE)

AChE is an enzyme that degrades the neurotransmitter acetylcholine

↗AChE

Pathogenesis:

Clinical features

Mnemonic for muscarinic signs & symptoms:

• S – Salivation D – Diaphoresis & diarrhoea

• L- Lacrimation U - Urination

• U – Urinary incontinence M - Miosis

• D – Diarrhoea + diaphoresis B – Bradycardia, bronchospasm

• G – GI upset E – Excess

• E –Emesis L – Lacrimation &

S - Salivation

Clinical phases:

1.Initial life-threatening acute cholinergic crisis

2.Intermediate syndrome (IMS)

3.Organophosphate induced delayed polyneuropathy (OPIDN)

INTERMEDIATE SYNDROME

• Characterized by absent muscarinic symptoms with continued nicotinic symptoms and persistent AChE inhibition

• Onset = 24 – 72 hrs after acute cholinergic crisis

• Pathophysiology – inadequate oxime dosing

-Most likely due to lesions in post synaptic striated muscle regions

- Myonecrosis due to oxidative cellular damage

Later studies – down regulation or desensitization of nicotinic ACh receptors at post junctionalmembrane

Patients at risk

• Poisoning due to OPs with delayed metabolism

• Severe poisoning

• Elevated muscle enzymes

• Delayed or inadequate oxime therapy

Clinical features – NICOTINIC SYMPTOMS

• Paralysis of proximal limb muscles, neck flexors, cranial nerves, respiratory muscles, decreased DTR

• Rapid onset of difficulty in breathing

Treatment of IMS

• Mainly supportive treatment

• Complete recovery in 4-18 days if adequate ventilatory support is provided

• Oximes - preventive

OP INDUCED POLYNEUROPATHY (OPIDN)

Delayed mixed sensorimotor peripheral neuropathies

• 7-14 days after exposure

• Pathophysiology : Inhibition of neuropathy target esterase(NTE )

• C/o: Symmetric, peripheral neuropathies

Motor > sensory

Ataxia, gait disturbances

• Fate – self-resolution / persistent deficits

Investigations

ECG

Oxygen saturation

Blood gas analysis

Renal and hepatic function

Electrolytes

Glucose

Amylase

Urine toxicology

Grading of severity of poisoning

Biochemical Grading:

Red cell cholinesterase activity (% normal) Grade

• 20-50% Mild

• 10-20% Moderate

• <10% Severe

Assessment of severity of OP poisoning GRADES CNS Secretions Fasciculations Hypotension

0 Awake, alert - - - Only history

1 Awake, alert + + -

2 Drowsy ++ ++ + (SBP <90)

3 Drowsy/ Comatose

++ ++ + Inc FiO2

4 Comatose +++ +++ + PaO2 < 60 on FiO2 >40, PaCo2 >45Mechanical ventilation reqdAbnormal CXR

ICU admission if grade ≥ 2

Brent I., Wallace K., Burkhart O. & et al. Organophosphorus and carbamate insecticides, Methanol poisoning. Critical care Toxicology.Diagnosis and management of the critically poisoned patient. Philadelphia, Elsevier Mosby, 2005 : pp 937-947.

Management of OP Poisoning

Hospitalization/ ICU

1. Initial stabilization

2. Reduction of exposure

3. Administration of specific antidote

4. Supportive treatment

Initial Stabilization of the patient

• Clear airway and

• Adequate ventilation because the patient with acute organophosphate poisoning (ACC) commonly presents with respiratory distress.

• Oxygen- Circulation- iv access

Decontamination

• Dermal spills—wash pesticide spills from the patient

with soap and water and remove and discard contaminated clothes, shoes and any other material made from leather

• Gastric lavage—consider for presentations within 1 or 2 hours, when the airway is protected. A single aspiration of the gastric contents may be as useful as lavage

• Activated charcoal —50 g may be given orally or nasogastrically to patients who are cooperative or intubated, particularly if they are admitted within one or two hours or have severe toxicity

Antidotes in the treatment of OP poisoning

• Atropine- Reverses the muscarinic features.

• Oxime- Reactivate cholinesterase and reverses the nicotinic features.

Atropine

• Initial dose: 0.5-2 mg IV every 5-10min until atropinization

• Continuous infusion (8mg atropine in 100ml NS) at rate of 0.02-0.08mg/kg/hr (0.25-1.0 ml/kg/hr) with additional 1-5mg bolus

• May require about 40-1500mg/day

• For at least 5-7days

• Watch out for OVER ATROPINIZATION

Target end points for atropine therapy

• Clear chest on auscultation with no wheeze

• Heart rate> 80/min

• Pupils no longer pin point (does not imply that pupils must be dilated)

• Dry axilla

• Systolic BP > 80 mm Hg

Dilated pupils is not a reliable sign of initial atropinisation or end point for atropine therapy

Pralidoxime

• An oxime that reactivates phosphorylated cholinesterase

• Effects: skeletal-neuromuscular junctions (counteracts weakness, fasciculation and respiratory depression)

• Administration within 48 hours of poison ingestion

• IV 1-2gm in 100cc of NS over 30min (at a rate not exceeding 200mg/min), repeat in 1 hour if muscle weakness persist, then at 8-12 hours interval if cholinergic signs recur

• Severe case: IV infusion 500mg/hr (max 12gm in 24hours)

• Started after maximal atropinization

OXIMES IN OP POISONING