Transcript College tutorial for trainees 2013

HKCEM College Tutorial
Acute
Paracetamol
Overdose
AUTHOR
Dr Chan Yiu Cheung
AUGUST 2013
Case Scenario
▪ F/25
▪ Good past health
▪ DO 20 tablets of “Panadol®” at 1200
▪ Arrived at AED at 1330
▪ Normal vitals
▪ Normal examination
Is the dose toxic?
Paracetamol – Acute Toxic Dose
▪ Potential Acute Toxic Dose
>7.5g
>150mg/kg
▪ Toxicity may occur at lower level in those malnourished and those with induced
cytochrome P450 activity (e.g. chronic alcoholic and those on cytochrome P450 2E1
inducers such as isoniazid or ethanol).
▪ Paracetamol Content in
different Panadol®
▪ Tab Form
▪ 250-665mg
▪ Remedy Form
▪ 600mg – 1000mg
Her panadol® preparation contains
500mg paracetamol per tablet
20 X 500mg = 10g
( A potential toxic dose)
Severity of Acute Poisoning
What is the expected clinical toxicity?
Acute Paracetamol Overdose
Clinical Features
Stage
Hours post-ingestion
I
2 – 24 hr
II
24 – 96hr
III
96hr – weeks
Clinical Features
•
•
•
•
•
•
•
None
Non-specific symptom (mainly GI)
Nausea, vomiting and malaise
Progressive elevation of liver enzymes (AST, ALT),
bilirubin, PT
Clinical features of hepatitis
Renal injury possible
May progress to liver failure
•
Recovery
Acute Poisoning - Management
Specific Treatment
Antidote
Decontamination
Supportive Management
GI Decontamination
▪ Single dose AC in toxic ingestion within 1-2
hours
▪ Gastric lavage reserved for massive
paracetamol overdose (>1g/kg) or
significant co-ingestion
She was given a dose of AC
What next?
The Antidote : N-Acetylcystecine (NAC)
▪ Mechanism of action in early phase
▪ Major
▪ Increases non-toxic sulfation
▪ Precursor for glutathione
▪ Minor …..
▪ The benefit of NAC declines with time; it can effectively
prevents toxicity if given within 8 hours of ingestion and
may significantly reduce hepatotoxicity if given within 24
hours
To give or Not to give
▪ Give NAC
▪ Paracetamol level above the treatment line in
Nomogram OR
▪ Nomogram is not applicable
▪ Nomogram is applicable
▪ Single ingestion
▪ Known time of ingestion
▪ Blood Paracetamol level within 4-24 hours post
ingestion
Rummack Matthew Nomogram
US, Australia, HKPIC
Lines in Nomogram
▪ There are 3 lines in nomogram used as treatment line; 100 line (red line) , 150 line (black
broken line) and 200 line (green line)
▪ In USA, Australia, the 150 line (black broken line) is used as the treatment line
▪ In UK, the 200 line and 100 line are used as treatment line for low risk or high risk
individuals respectively. Recently, the 100 line (red line) is also recommended for both
low and high risk individual.
▪ In Hong Kong, HKPIC recommends using the 150 line (black broken line) as treatment line
based on current data and local experience
▪ it eliminates the need of considering “high risk” factors which are either unavailable or unreliable in
emergency setting.
Time of Presentation
Paracetamol level available < 8 hours
▪
▪
Wait for level
NAC if above nomogram
Paracetamol level not available < 8 hours post ingestion
▪
▪
NAC first
Make decision to continue or stop therapy based on level
Her progress
Paracetamol level taken at 1600 (4 hour level)
NAC not started empirically
Paracetamol level is 1,200 umol/L
▪ 1,200 umol/L = 182 mg/L (conversion factor 6.6)
*
NAC Dose
▪ 150mg/kg in 200ml D5 over 1 hour or 15 min*
then
▪ 50mg/kg in 500ml D5 over 4 hours
then
▪ 100mg/kg in 1000ml D5 over 16 hours
(Total dose 300mg/kg in 21 hours)
*For presentation > 8 hours and without history of asthma
Efficacy of NAC
▪ Early
▪ <8 hours - no morbidity nor mortality
▪ In-between
▪ 8- 24 hours, 10-30% had AST>1000
Smilkstein: N Engl J Med 1988;319:1557-62
▪ Late
▪ 10-36 hours, reduce mortality in FHF (58% Vs 37%)
Harrison: Lancet. 1990 Jun 30;335(8705):1572-3
▪ 36-80 hours, reduce mortality in FHF (48% Vs 20%)
Keays: Brit Med J 1991;303:1026
Progress
▪ The patient give further history that she is
pregnant (10 weeks gestation)
▪ Quarrel with her boyfriend
▪ Impulsive act of DO
▪ Regret now
▪ A wanted pregnancy
Would you still start the NAC?
Pregnancy
▪ Paracetamol can cross placenta
▪ Lack of fetal P450
▪ Overdose in pregnancy
▪ Seem to have associated with abortion & labor
Riggs BS. Obstet Gynecol 1989;74:247-253
▪ NAC (Pregnancy Cat B)
▪ Both Paracetamol / NAC – not shown to be
teratogenic
Practical Suggestion
▪ Treat as non-pregnant patient
▪ Do NOT withhold NAC if indicated
▪ Paracetamol overdose is NOT an indication
for Termination of Pregnancy (TOP) per se
NAC started
30 minutes after the NAC
▪ Nurse informed you that there is rash over
her face and chest
What would you do?
NAC Allergy?
▪ NAC is associated with anaphylactoid reaction
▪ 6%-23%
▪ Most within the 1st hour
▪ Unlikely to be life threatening (except Hx of asthma)
▪ May associate with lower blood APAP level
▪ Management
▪ Stop the infusion
▪ Treat with antihistamine +/- steroid
▪ Restart at lower rate
Progress
▪ Managed as NAC anaphylactoid reaction
▪ Given piriton / hydrocortisone
▪ Restart NAC at slower rate
▪ No more rash
▪ Finished the NAC
▪ Remained asymptomatic
Is she ready to go home?
After Full Dose NAC
▪ In general, if the NAC started within 8 hours
after ingestion and the patient is clinically
well after the full course NAC – she can be
considered as toxicologically clear
▪ Recheck of paracetamol level or LFT is not
essential
▪ Assessed by Psychiatric doctor
▪ Fit for discharge
She is ready to go home now
+/- refer to Gyn X assessment
Q&A
The End