ACETAMINOPHEN TOXICITY

Question 1

Approach to the Critically Ill Acetaminophen Toxicity

Answer 1

ABC(MOVIE)DDDDDS

Monitor
Oxygen if required
IV Access
Vitals
ECG / Airway Equipment

AIRWAY / BREATHING
Generally no concern unless AMS as a late finding of hepatic encephalopathy

CIRCULATION

DISABILITY
GCS
Pupils
Lateralizing sigs
Generally no concern unless AMS as a late finding of hepatic encephalopathy OR if co-formulation with other medications

DETAILED PHYSICAL EXAM(Secondary Survey)
There are no reliable early signs or symptoms suggestive of toxicity

DRUGS
Universal Antidotes - none unless indicated

DECONTAMINATION
Activated charcoal 1 g / kg if ingested within 1 hr

DRAW LABS

serum acetaminophen levels
VBG
Lactate
CBC
Electrolytes
AST / ALT
INR / aPTT

Single potentially toxic doses are >150 mg/kg or >10 g in adults.

Increased risk of hepatotoxicity with massive ingestion (>30 g)

4 hours post ingestion
if the time of single acute ingestion is known OR
Immediately if the time of ingestion is unknown
AND
Plot on Rumack-Matthew nonogram.

SPECIFIC ANTEDOTES

150 mg / kg loading dose N-acetylcysteine within 8 hours of ingestion:

4 hour levels are above the treatment line (>1000 umol / L in the US)

OR

Elevated AST / ALT with any detectable acetaminophen concentration in the setting of unknown or chronic ingestion

Pregnant patients are treated as non-pregnant patients

Question 2

History & Physical

Answer 2

There are no reliable early signs or symptoms suggestive of toxicity

Things to ask:

What was taken

When was it taken (TIME)

How much was taken (DOSE AND NUMBER OF TABLETS)

Type of preparation (IMMEDIATE OR SUSTAINED RELEASE)

How it was taken (ROUTE)

What else was taken (CO-INGESTIONS?)

Why was it taken (INTENTIONAL VS ACCIDENTAL)

COLLATERAL INFORMATION: medication containers, EMS

ONSET OF SYMPTOMS

There are no reliable signs or symptoms of acute acetaminophen toxicity

Question 3

Investigations

Answer 3

Serum Acetaminophen level
CBC
Liver Function Tests (AST / ALT, bilirubin, INR / aPTT)
VBG
Lactate Level
Electrolytes
Renal Function

ECG

Question 4

Management

Answer 4

Activated charcoal 1 g / kg if ingested within 1 hr

N-acetylcysteine within 8 hours of ingestion if:

4 hour levels are above the treatment line (>1000 umol / L in the US)

OR

Elevated AST / ALT with any Detectable acetaminophen concentration in the setting of unknown or chronic ingestion

N-acetylcysteine 3-bag protocol:

Bag 1:
150 mg/kg added to 200 mL of 5% dextrose in water (D5W) or sterile water for infusion
Infuse at 150 mg/kg/hour over 1 hour

Bag 2:
50 mg/kg added to 500 mL of D5W or sterile water for infusion
Infuse at 12.5 mg/kg/hour over 4 hours

Bag 3:
100 mg/kg added to 1,000 mL of D5W or sterile water for infusion
Infuse at 6.25 mg/kg/hour over 16 hours

OR

N-acetylcysteine 1-bag intravenous protocol:

30 g in 1 L of D5W (30 mg/mL)

Bolus from bag 150 mg/kg over 1 hour

Infuse at 12.5 mg/kg/hour over the next 20 hours

Repeat labs before completion 21-hour infusion or 24 hours after overdose.

Continue N-acetylcysteine if acetaminophen concentration is detectable or with rising AST/ALT and PT/INR.

Discontinue if acetaminophen concentration is undetectable and AST, ALT, and PT/INR are normalizing.

Pregnant patients are treated as non-pregnant patients

Question 5

Disposition: Discharge or Admission

Answer 5

Discharge:
APAP concentration <150 μg/mL (1,000 μmol/L) at 4 hours or below Rumack-Matthew nomogram treatment line after 4 hours following a single acute poisoning.

Admission:
All patients receiving N-acetylcysteine go to floor

Consider ICU if:
Hemodynamic Instability
Signs of acute liver failure
Clinical Deterioration

Question 6

King’s College Criteria indicated probable need for liver transplant

Answer 6

Any of the following: lactate >3.0 mmol/L, pH <7.3, or recalcitrant hypotension despite adequate resuscitation

OR

All of the following: creatinine >3.3 mg/dL (>300 µmol/L), PT >100 s (INR >6.5), and grade III or IV encephalopathy