1. ACETAMINOPHEN
POISONING
DR.SAHAR MIRZA
Resident peads

2.  Introduction
 Acetaminophen metabolism and toxicity
 Toxic dose
 Signs symptoms
 Stages
 Workup
 Management
 prevention

3. Acetaminophin
 Nsaid with potent anti pyretic, analgesic action
 Unintentionally ingested by young children
 Intentional overdose by adults
 Inappropriately dosed in all ages

4. Acetaminophen toxicity
 Results from the formation of a
HIGHLY REACTIVE INTERMEDIATE
METABOLITE
N-acetyl-p-benzoquinone imine (NAPQI)

5. NAPQI
 In therapeutic use:
 Small percentage of dose, 5% is metabolized
by hepatic cytochrome P450 enzyme to
NAPQI
 Which is immediately conjugated with
glutathione
 Form a nontoxic mercapturic acid conjugate

6. NAPQI
 In overdose :
 Glutathione stores are overwhelmed, and free
NAPQI is able to combine with hepatic
macromolecules to produce
HEPATOCELLULAR DAMAGE

7. Acute toxic dose of
acetaminophen
 The single acute toxic dose >200mg /kg in
children
 Supratherapeutic dose>75mg/kg/d can lead
to hepatic injury in some children,especially
in the setting of
Fever
Dehydration
Poor nutrition
Dec glutathione stores

8. Clinical and laboratory
manifestations

9. Investigations
 Serum APAP level should be measured 4hr
after reported time of ingestion
 Level obtained <4hr after ingestion cannot be
used to estimate potential toxicity
 Check levels 6-8 hours if it is co ingested with
other substance that slows GI motility ,
diphenhydramine
 Other BLI lfts, rfts, coagulation prrofile

10. RUMACK –MATTHEW nomogram
foa acetaminophen poisoning
 Any patient with serum acetamiophen level in
possible or probable hepatotoxicity range per
RM nomogram should be treated with
 N-ACETYLCYSTEINE

11. N=acetylcysteine
 Start NAC
 If acetaminophen level is above the treatment
line on Rumack-matthew nomogram
 If levels are low but LFTS dearrange
 If level is > 10microg/ml even with normal lfts

12. Treatment
 Initial treatment:
 Basic life support (ABCs)
 Decontamination with activated
charcaol(Within 1-2 hr of ingestion)
 The antidote for acetaminophen is N-
acetylcysteine
 MOA replenish hepatic glutathione stores

13. NAC
 Most effective when initiated within 8 hr of
ingestion
 NAC available both oral and iv
 DOSE ]ORAL :140mgKG loading,followed by
70mgkg every 4hr for 17 doses
 (MUCOMYST)
 DOSE IV:150mg/kg iv over 1 hr, followed by
50mg kg over 4 hours, followed by 100mg/kg
over 16 hrs

14. What is next
 A patient who is being on NAC , the following
lab test , lfts and rfts should be followed daily
 Patients who develop hepatic failure in spite o
NAC therapy may be candidates for liver
transplant

15. King’’s college criteria
 Are used to determine which patients should
be referred for consideration of liver transplant
1. Acidosis (Ph <7.3) after adequate fluid
resuscitation
2. Coagulopathy if Pt is more than 100 sec
3. Renal dysfunction (creatinine >3.4mg/dl
4. Hepatic encephalopathy grade 3/4

16. Prevention
 Inform and educate parents and caregivers
proper dosing and danger associated with
misusing varioius formulations
 Parents should always be given clear dose
and formulation instructions
 Based on age and weight

17. References
 Nelson
 Osama naga
 Webmd.com