Transcript EVIDENCE- BASED PRACTICE

MELBOURNE HEALTH
Evidence into Practice:
Paracetamol toxicity.
(a focus on the process)
Kirstie Galbraith
Clinical Senior Lecturer, Victorian College of Pharmacy, Monash University
Senior Pharmacist, Research & Education, RMH
What do we know?
• Paracetamol perceived to be a “safe” drug
in normal therapeutic doses
• Known to be dangerous in overdose
– Fulminant hepatic failure
• Many forms of oral paracetamol available
– Potential for accidental overdose
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What do we know?
• Intravenous paracetamol relatively new
on market
– Approved for restricted use at MH in Nov 2004
– Maybe exposing a new populations of patients
who are “nil orally” & potentially at risk of toxicity
– Significantly more expensive than oral/rectal
• Quantities of IV paracetamol being
dispensed indicates significant usage
without approval from Pain Service
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What do we know?
• 2004: 2 deaths at RMH due to liver toxicity
associated with therapeutic doses of
paracetamol
– Both malnourished & underweight
– Prescribed paracetamol up to 4g/d but no accurate
record of doses administered (not at MH)
• Presented at Medications Safety Week Dec
2005, Grand Round 2006, InphaRMHation Jan
2007
• Presentation at SHPA by Paul Gow (Austin)
– Publication of paper in MJA 2007
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What do we know?
• Suggested risk factors for paracetamol toxicity (where
reduced dosing should be considered):
– Prolonged fasting or “nil oral” patients
– Malnourished patients
– Prolonged duration with risk of accumulation
– Elderly patients with renal & cardiopulmonary insufficiency
– Acute hepatitis of any cause
– Chronic liver disease including cirrhosis
– Regular alcohol intake of >3 standard drinks per day
(>30g/day)
– Concurrent use of drugs that induce CYP450 eg isoniazid,
carbamazepine
– Small body mass
– Sepsis
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Lubel JS, Angus PW, Gow PJ. Accidental paracetamol
poisoning. Med J Aust 2007; 186(7): 371-2
A. Normal healthy patient
•
Most conjugated & excreted
•
Small amount metabolised by CYP450 to
NAPQI (liver toxin)
•
Conjugated & excreted
B. Prolonged starvation
•
•
Co-substrates for conjugation depleted
•
Glutathione stores depleted
•
NAPQI accumulates
Alcohol & other CYP450 inducers
•
Increase production of NAPQI
•
Chronic alcohol depletes glutathione
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What don’t we know? (Our knowledge gaps)
• In patients admitted to The Royal
Melbourne Hospital, is paracetamol being
prescribed appropriately taking into
account potential risk factors for
hepatotoxicity?
• Are doctors at The Royal Melbourne
Hospital seeking appropriate approval to
prescribe intravenous paracetamol
according to DTC restrictions?
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Filling our knowledge gaps
• In patients admitted to The Royal
Melbourne Hospital, is paracetamol being
prescribed appropriately taking into
account potential risk factors for
hepatotoxicity?
– Audit undertaken recently (1 day, n=389)
> Paracetamol dose ordered & administered
> Risk factors
> Liver function tests
> Data currently being analysed
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Initial data on risk factors (n=389)
Risk Factor
Number at
risk
Number
ordered at
least 4g/d
Number
administered
at least 4g/d
Weight <50kg
19
18
2
Malnourished
9
9
1
Acute
hepatitis
5
5
2
Nil orally > 3
days
8
7
4
>3 drinks per
day
11
9
5
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What don’t we know? (Our knowledge gaps)
• Are doctors at The Royal Melbourne
Hospital seeking appropriate approval to
prescribe intravenous paracetamol
according to DTC restrictions?
– Anecdotally NO!
– Being included in iApprove to streamline use
according to approved indications &
durations
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Not the whole answer!
• Experience dictates leakage from system
due to borrowing
• Won’t stop inappropriate oral dosing
– Important role for education by ward
pharmacists
• Medication safety requires approaches
from a number of angles
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MELBOURNE HEALTH
Evidence into Practice:
Paracetamol toxicity.
(a focus on the process)
Kirstie Galbraith
Clinical Senior Lecturer, Victorian College of Pharmacy, Monash University
Senior Pharmacist, Research & Education, RMH