Tintinallis Emergency Medicine

Introduction

Acetaminophen
N-acetyl-p-aminophenol
Paracetamol
APAP

Erroneous belief
Benign
The victim was unaware that it was an

ingredient in the ingested preparation

5% of all toxic exposure

23% of reported fatalities

Pharmacology (1)

Recommended dosage
Adult
650~1000mg every 4 to 6hr, <4g/day
children
10~15mg/kg every 4 to 6hr

Peak serum level

Therapeutic doses: <30min~2hr
Overdose: <2h

Pharmacology (2)

Metabolization
Sulfation (20~46%)
Glucuronidation (40~67%)
Renal elimination (<5%)

Oxidization by cytochrome P450 ( 10%)

CYP2E1, CYP1A2, CYP3A4
NAPQI (N-acetyl-p-benzoquinoneimine)

Immediate hepatic injury (<12hr)

Prolonged hepatic damage (~2day)

Clinical Presentation (1)

Four stage
Stage 1 (the first 24hr)
anorexia, nausea, vomiting, pallor, malaise
Stage 2 (by day 2 to 3)
RUQ pain & tenderness, abnormal laboratory tests (AST,
ALT, bilirubin
recover without sequelae
Stage 3 (by day 3 to 4)
some fulminant hepatic failure (metabolic acidosis,
coagulopathy, renal failure, encephalopathy, GI symptoms
Stage 4
Recovery from fulminant hepatic failure
Complete resolution of hepatic dysfunction

Clinical Presentation (2)

Risk Factors
Insufficient glutathione stores
alcoholics, AIDS pt.
cytochrome P450 enzymatic activity
alcoholics, anticonvulsant, antituberculous mx.
Adult

Ingestion of massive doses of AAP

4-h AAP level 800/mL
Altered sensorium (coma, agitation)
Metabolic (lactic) acidosis

Etc.
isolated renal insufficiency, cardiac toxicity, pancreatitis

Diagnosis
>140mg/kg
>7.5g

single dose

within 24hr

Rumack-Matthew nomogram

Treatment (1)
GI decontamination
Timely use of the antidote
Supportive care

Treatment (2)

GI decontamination
activated charcoal
Ipecac (x) : antidote adminisration delay
Gastric lavage, whole bowel irrigation
Unnecessary except polydrug DI

Timely use of the antidote

Supportive care

Treatment (3)

GI decontamination

Timely use of the antidote

N-acetylcysteine (NAC)
Unknown mechanism
<8hr: prevent the NAPQI to hepatic macromolecules
>24hr: hepatic necrosis (antioxidant, neutrophil

infiltration, microcirculation, tissue oxygen delivery and

extraction)

Supportive care

Treatment (4)

GI decontamination

Timely use of the antidote

Standard 72-h oral NAC regimen
Loading dose: 140mg/kg
Maintenance dose: 70mg/kg every 4h x17

Supportive care

Treatment (5)

GI decontamination

Timely use of the antidote

Complications of oral NAC therapy
Nausea, vomiting

IV NAC
Less emetic

Supportive care

Fulminant Hepatic Failure

Mortality: 58~80%
Most Fatalities occur on days 3 to 5
Cereral edema, hemorrhage, shock, ARDS, sepsis,
MOF
Recovery by days 5 to 7
Prediction of poor outcome

pH<7.3 despite resuscitation

Coagulopathy (PT>100)

Creatinine(s) >3.3mg/dL
Grade III or IV encephalopathy