Acute Paracetamol Overdose
3/11/10
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PY ICU Drug Book
- most common OD in the west
- hepatic metabolism
- following overdose glucuronidation and sulphation pathways are rapidly saturated ->
increased metabolism to NAPQI (N-acetyl-P-benzoquineimine)
- glutathione is required to inactivate NAPQI and when levels depleted -> hepatocellular
death takes place
CLINICAL FEATURES
- overdose of > 10g or > 200mg/kg
- doses of > 250mg/kg associated with massive hepatic necrosis and liver faillure
- be aware of the late presenters (> 8 hours since OD and start NAC empirically)
Stage 1 (0-24hrs)
- asymptomatic or GI upset only
Stage 2 (24-48 hrs)
- resolution or nausea and vomiting
- RUQ pain and tenderness
- progressive elevation of transaminases, bilirubin, PT
Stage 3 (48-96 hrs)
- hepatic failure (jaundice, coagulopathy, encephalopathy)
Stage 4
- death from hepatic failure
- normalisation of LFT’s and complete resolution of hepatic architecture by 3 months
Risk Factors
Underlying hepatic impairment
- viral hepatitis
- alcoholic liver disease
Microsomal enzyme induction
- phenobarbitone
- carbamazepine
- phenytoin
Jeremy Fernando (2011)
-
rifampicin
OCP
chronic alcohol ingestion
starvation
Acute glutathione depletion states
-
acute illness with decreased nutrient intake
anorexia/bulimia/malnutrition
chronic alcoholism
HIV
INVESTIGATIONS
- paracetamol levels:
-> compare to Rumack-Matthews nomogram
-> no role in chronic toxicity
-> treat if above threshold @ 4 hrs
-> a level of > 153mg/L is above treatment threshold regardless of time of ingestion
-> NAC must be given within 8 hours of OD (if level going to take longer than 8
hours start NAC empirically)
- transaminases: peak @ 72 hrs
- PT: if >180 seconds on day 4 will need transplantation
- renal failure
- metabolic acidosis = poor prognostic marker
MANAGEMENT
Resuscitation
A: may require intubation and intubation if polypharmacy overdose and unrousable
B: lung protective ventilation
C: volume resuscitation
D: dextrose for hypoglycaemia
Evaluation
History
-
timing
quantity
dose
other meds
psychiatric history
Examination
Jeremy Fernando (2011)
- fuliminant hepatic failure signs
- signs of other drug toxicity
Investigations
-
LFTs
paractamol level
urine tox
coag’s
ECG
lactate
amylase
blood alcohol
pregnancy test
ECG: check QTc
Treatment
Specific
- decrease absorption: activated charcoal if presented within 4 hours (controversial as if NAC
given then this is a benign OD)
- N-acetyl cystine in D5W (based on 4 hour level or empirically if > 8 hours since OD):
-> 150mg/kg LD
-> 50mg/kg over 4 hours
-> 100mg/kg over 16 hours
- can be administered at any time of presentation (up to 72 hours post ingestion with some
improvement in outcome)
- can be administered orally but efficacy reduced by 40% if given with activated charcoal
- provides a substrate of glutathione and acts as an alternative substrate for NAPQI
metabolism via the cytochrome P450 pathway
- watch for adverse effects: rash, bronchospasm, hypotension, angioedema (antihistamines
helpful and also slowing of infusion)
Liver failure management
-
don’t correct coagulopathy unless bleeding (vitamin K IV, blood products)
arterial ammonia (aids in prognostication: absolute level and failure to fall)
glucose monitoring
avoid hypothermia
reverse jugular venous saturation monitoring
ICP monitoring (controversial)
avoid hyponatraemia
ventilate to normocapnia
thiopentone and indomethacin infusions (consult with liver unit)
renal failure management
MARS therapy: some benefit shown in paracetamol OD as a bridge to transplantation
General
- don’t give FFP until discussed with transplant unit as indicated or liver function (unless
bleeding)
Jeremy Fernando (2011)
-
metabolic acidosis from hepatic and renal failure -> supportive care
withhold any renal or hepatotoxic medications
intubation and ventilation if indicated
GI prophylaxis
attention to pressure areas
feed
airway toilet
Disposition
- discuss early with transplantation team (develop liver failure within 48 hours)
- admit to medical/gastro unless requires ICU
- will require psychiatric assessment if was an intentional overdose
Prognostication
- can use the O’Grady criteria:
- acidaemia (pH < 7.3)
- renal impairment (creatinine > 300micromoles/L)
- hepatic encephalopathy (grade III or IV)
- PT > 100 seconds (INR > 6.5)
- factor V level < 10%
Jeremy Fernando (2011)