OPC

OPC

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Introduction

Organophosphorus compounds (OPC) are widely used as pesticides, especially in developing countries. Often they are used for deliberate self harm.

Epidemiology

The case fatality rate following deliberate ingestion of OP pesticides in developing countries of Asia is 5–20%.

Pathophysiology

  • OP compounds phosphonylate the active site of acetylcholinesterase (AChE), inactivating the enzyme and leading to the accumulation of acetylcholine (ACh) in cholinergic synapses.
  • Spontaneous hydrolysis of the OPC–enzyme complex allows reactivation of the enzyme.
  • However, loss of a chemical group from the OPC–enzyme complex prevents further enzyme reactivation, a process termed ‘ageing’.
  • After ageing has taken place, new enzyme needs to be synthesised before function can be restored.
  • The rate of ageing is an important determinant of toxicity and is more rapid with dimethyl compounds (3.7 hours) than diethyl (31 hours), and especially rapid after exposure to nerve agents (soman in particular), which cause ageing within minutes.

Clinical features

Acute cholinergic syndrome

The acute cholinergic syndrome usually starts within a few minutes of exposure.
Nicotinic or muscarinic features may be present.
Muscarinic features:
  1. Gastrointestinal: Nausea, vomiting, abdominal cramps, diarrhoea, faecal incontinence
  2. Respiratory: Pulmonary oedema, hypotension
  3. Cardiovascular: Bradycardia, hypotension.
  4. Pupils: Blurring of vision, miosis (small pupil)
  5. Urinary: Frequency, incontinence
  6. Others: increase sweating, salivation and lacrimation.
Nicotinic features:
  1. Skeletal muscles: Muscle twitching, fasciculation, cramps, weakness
  2. Sympathetic ganglion: Pallor, tachycardia, hypertension.
CNS:
Giddiness, tension, anxiety, restlessness, difficulty in concentration, confusion, slurred apeech, insomnia, headache, tremor, apathy, coma, convulsion, respiratory depression.
The intermediate syndrome
  • It develops in 20% of patients with OPC poisoning.
  • quite rapidly between 1 and 4 days after exposure
  • often after resolution of the acute cholinergic syndrome, and
  • may last 2–3 weeks.
  • Weakness spreads rapidly from the ocular muscles
  • Muscles of the head and neck,
  • Proximal limbs and
  • the muscles of respiration,
  • Resulting in ventilatory failure.
Organophosphate-induced delayed polyneuropathy (OPIDN)
  • It is a rare complication that usually occurs 2–3 weeks after acute exposure.
  • It is a mixed sensory/ motor polyneuropathy, long myelinated neurons, and
  • appears to result from inhibition of enzymes other than AChE.
  • It is a feature of poisoning with some OPCs such as trichlorocresylphosphate,
Early clinical features
  • muscle cramps followed by numbness and paraesthesiae,
  • flaccid paralysis of the lower then the upper limbs.
  • Foot drop and a high-stepping gait, progressing to paraplegia.
  • Wrist drop.
  • Sensory loss is variable.
  • Initially, tendon reflexes are reduced or lost
  • but mild spasticity may develop later.

Investigations

Routine Investigastions
  1. CBC: Leucocytosis
  2. RBS: Hypoglycaemia
  3. LFT: increased PT
  4. Electrolytes: Hypokalaemia
  5. Urine: Proteinuria
  6. Amylase: raised
  7. ECG: Arrhythmia
  8. CXR: Pulmonary oedema
Other tests can be done:
  1. Direct measurement of OPC
  2. Indirect estimation of plasma (butyrylcholinesterase) & red cell cholinesterases

Management

  1. Acute Cholinergic Syndrome:
    1. Hospitalization
    2. Resuscitation of patient by maintaining respiration and other vital signs
      1. High flow oxygen inhalation
      2. IV access
    3. Reduction of exposure.
      1. contaminated clothing and contact lenses removed,
      2. The skin washed with soap and water, and
      3. The eyes irrigated.
      4. Gastric lavage or activated charcoal may be considered if the patient presents within 1 hour of ingestion.
    4. Administration of specific antidote.
There are two antidotes
      1. Atropine: it reverse muscarinic features
      2. Oximes: reactivates cholinesterases and reverses nicotinic features.
Atropine:
      • Test dose 1mg or 0.01 mg/kg in children i.v. then look for sign of atropinization.
      • Moderate to severe cases: 2mg to 5mg i.v. repeated every 10 to 30 min and observe.
      • Most severe cases: atropine i.v. infusion 0.02 to 0.08 mg/kg/hr
      • Atropine should be maintained for at least 24 to 48 hours.
      • Target of atropine therapy
All of below
      1. Clear chest on auscultation with no wheeze
      2. Heart rate > 80 bpm
      3. Pupil no longer pin point
      4. Dry axillae
      5. Systolic BP > 80 mmHg
      • Atropine toxicity: excess atropine causes agitation, confusion, urinary retention, hypothermia, bowel ileus and tachy cardia.
Management of atropine toxicity: stop atropine infusion and check every 30 min for reappearance of OPC toxicity, sedation and urinary catheterization may be required.
Oximes:
      1. Pralidoximes: should be given as early as possible but not before atropine,
      2. 30 mg/kg loading dose i.v. over 10-20 in followed by continuous infusion of 8-10 mg/kg per hour, continued 12-24 hours after atropine is no longer required or 7 days ( whichever later).
      3. Obidoxime: 250 mg loading dose followed by i.v. infusion giving 750 mg every 24 hours.
Caution:
      • Oximes are not recommended in carbamate poisoning.
      • Side effects: vomiting, tachycardia, diastolic hypertension.
Supportive treatment.
      • Management of respiratory insufficiency
      • Maintenance of circulation
      • Treatment of convulsion
      • Fluid and electrolyte balance
      • Control of infection
      • Maintenance of nutrition
      • Control of body temperature
  1. Management of Intermediate syndrome:
    • There is no specific treatment but supportive care,
    • Including maintenance of airway and ventilation, should be provided if necessary.
  1. Management of OPIDN
    • There is no specific therapy for OPIDN.
    • Regular physiotherapy may limit deformity caused by muscle wasting.
    • Recovery is often incomplete and may be limited to the hands and feet,
although substantial functional recovery after 1–2 years may occur, especially in younger patients.

Complication

Early complications of OPC poisoning include
  • extrapyramidal features
  • pancreatitis
  • hepatic dysfunction
  • pyrexia
Cause of death:
  1. Immediate death
    1. Seizures
    2. Complex ventricular arrhythmias
  2. Death within 24 hours
    1. Acute cholinergic syndrome if untreated
    2. Respiratory failure
  3. Death within 10 days
    1. Respiratory failure due to intermediate syndrome
  4. Late death
    1. Ventricular arrhythmia including Torsades de Pointes

Further reading

  1. Davidson’s Principles & Practice of Medicine 22nd
  2. Kumar & Clark’s Clinical Medicine 8th
  3. Harrison’s Principles of Internal Medicine 18th
  4. Management of Poisoning guidelines 2007

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