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History
14-year-old Thai girl
CC : Ingested more than 20 tablets of
paracetamol 3 hr ago
PI
: 3 hr PTA, patient took approximately 20
tablets of paracetamol after she argued with
her boyfriend.
30 min PTA, She developed nausea and
vomiting with clear fluid, then her mother
took her to Siriraj hospital.
PH : No underlying disease
History of suicidal attempt by softly cut her wrist few months ago
Personal history : No smoking, no alcoholic drinking, no drug addiction,
cheerful, sensitive, tantrum
Drug history
: no other drugs used, no history of drug allergy
Family history :

Father is a noodle vendor, alcohol drinker and smoker.

Mother is a healthy seamstress, does not smoke and drink.

12 years old healthy brother
Development
: normal development, fair school performance (GPA 2.9)
Physical examination
V/S : T 36.4, P 100/min, RR 24/min, BP 120/80
mmHg, Ht 158 cm (P50-75), Wt 58 Kg (>P97)
GA
: 14 years old Thai girl on NG tube, good
consciousness, no pallor, no jaundice, no
dyspnea, no dry lips, capillary refill < 2 sec,
no diaphoresis
HEENT
: no icteric sclera
RS
: normal breath sounds, no adventitious
sounds
CVS : normal S1,S2, no murmur
Abd : soft, no tenderness, liver not palpable &
not tender, liver span 9 cm, normal bowel
sound
GU
: no CVA tenderness
NS
: E4V5M6, good consciousness
Pupils 4 mm BRTL on both sides
CN – grossly intact
Motor – normal tone, motor power grade
5/5 all extremities
Sensory – no impairment
DTR 2+ all
Problem lists
1.
Overdose paracetamol ingestion
(180 mg/kg) 3 hr prior to presentation
2. Nausea and vomiting for 30 min
3. Probable suicidal attempt
Diagnosis
Acute paracetamol overdose
Investigation
3.7
3.8
Management
Paracetamol Poisoning
Acute paracetamol overdose
Ingestion of 7.5 grams (150
mg/kg) or more of paracetamol within 4
hours in one dose
Chronic paracetamol overdose
Ingestion of 4 grams or more of
paracetamol per 24 hours
Pharmacokinetic
Therapeutic
dose is 10 to 15 mg/kg/dose
in children given every 4-6 hours
Maximum recommended dose is 80
mg/kg/day in children
Acetaminophen is rapidly and completely
absorbed from GI tract
Toxicity is likely occur with single
ingestion greater than 150-200 mg/kg in
children
Michael J Burns,Scott L Firedman,Anne M Larson. Pathophysiology and Diagnosis of
acetaminophen(Paracetamol) intoxication : Uptodate ver14.2
Pharmacokinetic
Therapeutic
serum concentrations range
from 10-20 mcg/ml
Serum
concentration peak between ½ to 1
hour after an oral therapeutic dose and 4
hours following overdose ingestion
Elimination half-life range from 2-4 hours
but greater in patient with hepatotoxicity
Michael J Burns,Scott L Firedman,Anne M Larson. Pathophysiology and Diagnosis of
acetaminophen(Paracetamol) intoxication : Uptodate ver14.2
Metabolism
Modified from: Mitchell JR,
Thorgeirsson SS, Potter WZ,
et al: Acetaminophen-induced hepatic
injury: Protective role of glutathione in
man and rationale for
therapy. Clin Pharmacol Ther 1974;
16:678–684.
High risk for hepatotoxicity
Acute
febrile illness
Pre-existing liver diseases
Excessive cytochrome P450 activity due to
induction by other drug use (such as ethanol,
isoniazid (INH), rifampin, phenytoin,
phenobarbital, barbiturates, and
carbamazepine)
Decreased capacity for glucuronidation or
sulfation
Depletion of glutathione stores due to
malnutrition (or chronic alcohol ingestion)
Anker Anthony , Acetaminophen : Ford:Clinical Toxicology, 1st ed. 2001 ; 29
Clinical presentation
 Phase
1
: 0.5-24 hours
Anorexia, nausea, vomiting,
malaise, pallor, diaphoresis

Phase 2 : 24-48 hours
‘Onset of Toxicity’
Less pronounce phase 1 manifestations,
RUQ pain, elevation of liver enzymes,
bilirubin, INR
Phase 3 : 72-96 hours
‘Time of Maximal Toxicity’
Sequelae of hepatic necrosis. Hepatic failure,
coagulopathy, hepatic encephalopathy, Renal
failure
 Phase 4 : 96 hours - 2 weeks
Death may occur in patients with
fulminant hepatic failure or multiorgan
failure, If the damage reversible, complete
resolution ,

Modified from Linden CH, Rumack BH: Acetaminophen overdose. Emerg Med Clin North
Am 1984; 2:103.
Management
ER Management
 Primary



survey
Airway
Breathing
Circulation
 Admit
 Consult
Pediatric toxicologist and
psychiatrist
Specific Management
 Activated
charcoal (AC)
 Useful to remove unabsorbed drug up
to 4 hour after the ingestion
 1 g/Kg p.o. or feed via NG tube
 Not useful in paracetamol syrup
ingestion (absorb in 30 min)
 Antidote = NAC (N-Acetylcysteine)
Anker Anthony , Acetaminophen : Ford:Clinical Toxicology, 1st ed. 2001 ; 29
Antidote = N-Acetylcysteine
(NAC)
Mechanism of NAC
 NAC
increases the synthesis and
availability of glutathione. (NAC is
converted to cysteine, which is then
converted to glutathione within
hepatocytes)
 NAC
increases the fraction of the initial
sulfation product of acetaminophen and
reducing the amount of NAPQI
Anker Anthony , Acetaminophen : Ford:Clinical Toxicology, 1st ed. 2001 ; 29
NAC

In patients with hepatic failure,
NAC decreases the development of
cerebral edema, prevents the
progression of hepatic encephalopathy,
and improves survival rate.
Anker Anthony , Acetaminophen : Ford:Clinical Toxicology, 1st ed. 2001 ; 29
Mechanism of NAC
NAC
NAC

If the time of ingestion is known, take serum
paracetamol level at 4 hr after ingestion, start
NAC within 8 hr after ingestion when
concentration is above the lower line of
Rumack-Matthew nomogram

If the time of ingestion is uncertain. The most
conservative(earliest) estimate of the time of
ingestion should be used to determine the
likelihood of toxicity. Empirical treatment of
NAC is safe and reasonable
NAC
The first doses should be administered
empirically when diagnostic acetaminophen
levels cannot be obtained within this 8-hour
window.
 NAC therapy can be discontinued if the
awaited serum acetaminophen level falls below
the nomogram treatment line.

NAC therapy : PO vs IV

Oral:
st choice
 1
 Low risk of anaphylactoid
 S.E. = Vomiting (any dose vomited in 1 h
of administration should be repeated)

Intravenous:
 Useful in intractable vomiting despite NG
tube instillation & adequate antiemetics
therapy
 Can use in Pregnancy, hepatic failure
 Use only under consultation
 S.E. = Urticaria, Anaphylactoid reaction
(rarely death)
Dose of NAC
Maintenance dose
Course
FDA
appro
val
Oral
140
mg/kg
70 mg/kg every 4 h
17 doses
72 h
Yes
Intravenous
150
mg/kg
over 15
min
50 mg/kg over 4 h
followed by
100mg/kg
over 16 h
20 h
Yes
Route
Rakel
Loading
dose
, Conn's Current Therapy 2006, 58th ed. ,2006 Saunders, An Imprint of Elsevier
Monitor
Clinical sign & Symptom
RUQ pain, Jaundice, Conscious, Urine output,
Abnormal bleeding
 Paracetamol Level
: at 24 hr after
ingestion

Liver function test
 Coagulogram

: SGOT daily
: PT, INR daily
Behrman, Kliegman, Jenson , Acetaminophen Poisoning : Nelson 17ed. ,704 : 2366
When to stop NAC
Acetaminophen level is nondetectable
and the absence of evidence of liver injury
at 24 hours is documented
 Patients with evidence of liver injury are
treated for the full 72-hour course.

Anker Anthony , Acetaminophen : Ford:Clinical Toxicology, 1st ed. 2001 ; 29
Treatment
-
(in this patient)
Primary survey was done
Activated charcoal 56 mg
at ER
NPO and retain NG tube
NAC (150 mg/kg) 6,300 mg + 5%D/W 200 ml
IV drip in 1 hr
then NAC (50 mg/kg) 2,100 mg + 5%D/W 200
ml IV drip in 4 hr
then NAC (100 mg/kg) 4,200 mg + 5%D/W 200
ml IV drip in 16 hr
- Consult pediatric psychiatry
Progression
Day 1
 no N/V, no abdominal pain, no malaise, no jaundice
No depressive symptoms
 V/S BP 120/80 mmHg, P 80/min
 Abd : soft, not tender, no hepatospenomegaly,
active bowel sound
 Paracetmol level at 24 hr after ingestion = 1.9
 LFT : normal
 I/O = 1492 cc / 810 cc(0.6 cc/kg/hr)
 Urine pregnancy test = negative
Day 2
 active ,no N/V , no jaundice ,no abnormal
bleeding
 V/S : stable , no RUQ pain,
 no hepatosplenomegaly
 LFT : normal
 I/O = 2950 cc / 2280 cc( 1.6 cc/kg/hr)
Day 3
 Alert, good consciousness, no jaundice ,
no abnormal bleeding
 I/O = 2500 cc / 2300 cc(1.6 cc/kg/hr)
 Plan D/C
Psychiatric assessment
 Dx
: Anxiety disorder, NOS
Depression, NOS
 HM : fluoxetine (20 mg) sig ½ tab oral
OD 1 week then 1 tab OD 1 wk
Reference

Anker Anthony , Acetaminophen : Ford:Clinical
Toxicology, 1st ed. 2001 ; 29
 Rakel , Conn's Current Therapy 2006, 58th ed.
,2006 Saunders, An Imprint of Elsevier
 Behrman, Kliegman, Jenson , Acetaminophen
Poisoning : Nelson 17ed. ,704 : 2366
 Michael J Burns,Scott L Firedman,Anne M
Larson. Pathophysiology and Diagnosis of
acetaminophen(Paracetamol) intoxication :
Uptodate ver14.2
Thank you