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Dr. Ajith Kumar J MD
Dept. of Emergency Medicne
KIMS, Kollam
India
editor
It is the one of the most commonest toxic exposures reported to poison centre.
Pharmacology
It is primarily metabolized by liver through sulfation (20 – 46%) & glucoronidation (40 – 67%) with <5% undergoing renal elimination.
Normally a small percentage is also oxidised by the cytochrome P-450 system to a reactive metabolite N- acetyl-p-benzoquinoneimine (NAQPI) which is detoxified by hepatic glutathione to a non toxic acetaminophen-mercapturate compund that is renally eliminated.
Acetaminophen overdose, hepatic metabolism through glucorindation & sulfation may be saturated & a large proportion of acetominophen is metabolised by cytochrome P-450 to NAQPI depleting intracellular glutathione.
When hepatic stores of glutathione decrease to <30% of normal ,NAPQI binds to other hepatic macromolecule and hepatic necrosis ensues.
DOSE : Max: Adult dose :4grams/day; Childrens : 75mg/kg.
CLINICAL FEATURE
Stage1 (24h) | Stage 2 (2-3 days) | Stage 3(3-4days) | Stage 4 (after 5 days) |
Anorexia Nausea Vomiting Malaise | Right upper quadrant abdominal pain & tenderness. Other symptoms improves | Recurrence of anorexia, nausea & vomiting. Encephalopathy Anuria Jaundice | Clinical improvement & recovery
or Deterioration to MODS |
Hypokalemia | Elevated AST/ALT levels Elevated bilirubin & prolonged prothrombin time if severe. | Hepatic failure Metabolic acidosis Coagulopathy Renal failure Pancreatitis | Improvement & resolution
or
continued deterioration. |
DIAGNOSIS
A toxic exposure is suggested when an adult ingest >10gm or 200mg/kg as a single ingestion or over a period of 24hrs.
>6grms or >150mg/kg per 24hrs for a period of atleast two consecutive days.
Rumack- Mathew Normogram
This normogram was derived from a retrospective analysis of acetominophen overdose patients & their clinical outcome.
Here the acetominophen drug levels in plasma is plotted against time duration of post ingestion.
Original normogram line separating possible toxicity from unlikely toxicity was based on a 4hr acetominophen level of 200mcg/ml but was modified by US FDA by moving the line to 150mcg/ml to increase the safety margin.
The normogram applies to an acetominophen level obtained after a single exposure & during the window between 4 hrs & 24hrs post ingestion.
TREATMENT
Activated charcoal PO or through NG tube.
Acetyl Cysteine
MOA
In early stage (<8hrs) acetylcysteine averts toxicity by preventing the binding of NAPQI to hepatic macromolecules. It may act as glutathione precurosor or a substitute, a sulfate precursor or it may directly reduce NAPQI back to acetaminophen.
In established acetaminophen toxicity or >24 h it acts an antioxidant, decreasing neutrophil infiltration , improving microcirculatory blood flow or increasing tissue oxygen delivery & extraction.
If treatment is initiated within 8hrs following acute ingestion it is considered 100% effective.
Availability & compatibility
Oral preparation :It is available as 10% or 20% at is diluted to a strength of 5% in a fruit juice or soft drinks.
Parenteral preparation is available as a 20% solution & is given as 2% dilution through peripheral vein. Compatible with 5% D or NS.
Administration
| Oral | IV adult | IV pediatric |
Loading dose | 140mg/kg | 150mg/kg in 200ml 5% dextrose in water infused over 15-60min | 150mg/kg (7.5ml/kg) over 15-60/min |
Maintenance dose | 70mg/kg every4h for 17 doses | 50 mg/kg in 500ml 5% dextrose in water infused over 4h
followed by100mg/kg in 1L 5%D infused over 16h | 50mg/kg (2.5ml/kg) infused over 4h followed by 100mg/kg (5ml/kg infused over 16h) |
Duration of therapy | 72h | 20h | 20h |
Comments | Dilute with juice, soft drinks Serve chilled Drink through straw to reduce disagreeable smell. |
| Dilute 20% solution in 450ml of dextrose. This enough for a child with 33kg for a20h course. |
Adverse effect | Nausea & vomiting | Anaphylotoid reaction. | Anaphylotoid reaction. |
Fulminant Hepatic failure
Acetaminophen toxicity is the no. one cause for liver failure in 39 -46% of cases.
Kings college criteria for liver transplantation.
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emmedonline
Dr. Ajith Kumar J MD
Dept. of Emergency Medicne
KIMS, Kollam
India
editor