Paracetamol Poisoning

Introduction

Poisons are chemical or physical agents that produce adverse responses in biological systems.
Poisoning on the other hand is the ingestion by, or exposure of a patient to excessive doses of a medicine or other substances that may cause harm.
In paracetamol Poisoning or toxicity often occurs following an acute ingestion (within 24 hours) of 7.5-10 g (15-20 tablets of 500 mh) in adults or 150 mg/kg in children.
In patients with certain risk factors, dose of up to 5g can cause liver damage.

Risk factors for paracetamol poisoning

The following are the risk factors for

  1. Concurrent treatment with drug that induces hepatic CYP450 activity
    (rifampicin, carbamazepines, St. John’s wort etc).
  2. Decrease glutathione reserve due to
    • Acute starvation
    • Alcoholism
    • Chronic malnutrition:
    • HIV

Clinical features of paracetamol poisoning

Acute poisoning:

Often divided into 4 overlapping phases with varying physical signs:

Phase 1

  • (0.5-24 hours after ingestion)
  • May be asymptomatic
  • May present with anorexia, nausea, vomiting and malaise
  • Examination may show palor ± diaphoresis

Phase 2

  • (18-72 hours after ingestion)
  • Anorexia, nausea and vomiting ± right upper quadrant abdominal pain
  • Right upper quadrant tenderness
  • ± Tachycardia and hypotension (ongoing volume loss)
  • ± Decrease urinary volume

Phase 3 (Hepatic phase):

  • 72-92 hours after ingestion)
  • Anorexia, nausea, vomiting,
    abdominal pain ± tender hepatic edge
  • Jaundice, coagulopathy, hypoglycemia and hepatic encephalopathy may develop
  • Acute renal failure may develop.
  • Multi-organ failure and death

Phase 4 (recovery phase):

  • 4 days-3 weeks after ingestion
  • Patient who survives phase 3 have complete resolution of symptoms and organ failure

Poor prognostic factors:

  • Encephalopathy or hepatic failure
  • Greater than two fold prolongation of  Prothrombin time
  • Serum bilirubin 68 micromol/L (4mg/dL)
  • Serum creatinine>3.3 mg/L

Chronic poisoning:

This is usually similar but alcoholics may present with a syndrome of severe combined hepatic & renal insufficiency.

Investigations:

  • Liver function tests including prothrombin time and serum proteins
  • Urea, Electrolytes and Creatinine
  • Blood sugar estimation
  • Blood levels of paracetamol at least 4 hours post-ingestion (where facility is available).
  • Paracetamol levels done before earlier than this may be misleading.

Treatment for paracetamol poisoning

Treatment objectives

The treatment objectives of paracetamol poisoning are:

  1. To prevent or reduce damage to organs
  2. To restore normal metabolic functions

Drug treatment

Activated charcoal, especially within 4 hours of ingestion

  • Adult: 50 g orally, repeated if necessary
  • Child: under 12 years, 25 g (50g in severe poisoning)

Acetylcysteine
Adult and child: initially 50 mg/kg by intravenous infusion over 15 minutes, then 50 mg/kg over 4 hours and then 100 mg/kg over 16 hours
Diluted 3:1 with a non-alcoholic, non dairy beverage
Loading dose is 140 mg/kg; maintenancedose 70 mg/kg every 4 hours for 17 doses
Treatment is effective if started within 8 10 hours
Alternatively:
Methionine
Adult and child over 6years: 2.5 g orally followed by a further dose of 2.5 g every 4 hours
Child under 6 years: initially 1 g followed by 3 further doses of 1g every 4 hours

Supportive measures

  • As for all cases of acute poisonings

Notable adverse drug reactions

Acetylcysteine may cause:

  • Nausea
  • Vomiting and
  • Epigastric discomfort.
    • Antiemetics (metoclopramide) may berequired.

Methionine may cause:

  • Nausea,
  • Vomiting.
  • Drowsiness,
  • Irritability: