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
- Concurrent treatment with drug that induces hepatic CYP450 activity
(rifampicin, carbamazepines, St. John’s wort etc). - 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:
- To prevent or reduce damage to organs
- 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: