This document discusses acetaminophen poisoning, including its metabolism, toxicity, signs and symptoms, treatment with N-acetylcysteine, and prevention. Acetaminophen toxicity results from formation of a reactive intermediate metabolite, NAPQI, which can cause hepatocellular damage in overdose by overwhelming glutathione stores. A toxic dose is above 200mg/kg in children or supratherapeutic doses above 75mg/kg/day. Treatment involves decontamination, monitoring acetaminophen levels, and administering N-acetylcysteine to replenish glutathione if levels are above the toxic range or if liver enzymes are elevated. Education is needed to prevent misuse and overdose.

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