Paracetamol Toxicity - BHS Education Resource

Paracetamol Toxicity

Mark HartnellDec 2009

Last updated: 14 Dec 2012 Ballarat Grampians Emergency Medicine Training Hub

Session aims

Understand a few important numbers Difference between acute overdose, delayed

presentation and repeated supratherapeuticingestion

Rationalise use of blood tests Understand use of nomogram Some possible traps and controversies


Why important?

Common, cheap drug and overdose May be unrecognised clinically

(asymptomatic early presentation) A simple and safe antidote is available Managed properly no one should die Emergency doctors are the “specialists” at

managing this!


Crucial numbers

Ingestion > 150mg/kg potential harm Level done <4H after ingestion useless If starting NAC <8H survival is 100%


Risk assessment

Based firstly on stated time of ingestion, amount ingested and paracetamol level

Aminotransferases (ALT/AST) limited use Other bloods only in pts who have toxicity


Clinical phases of overdose

Phase 1 (<24H) Usually no symptoms

Phase 2 (1-3 days) RUQ tender, raised aminotransferases

Phase 3 (3-4 days) fulminant hepatotoxicity Coagulopathy, encephalopathy, jaundice, multi-organ

failure, acidosis

Phase 4 (4days – 2 weeks) = recovery


decontamination

Charcoal is NOT life saving Only possible use in cooperative pt if given

<1H post ingestion IF that leads to level at 4H below Rx line This is very rare

NOT used in children


nomogram

Used to identify patients needing NAC Start prior to level if: unknown time of ingestion If won’t get level back and Rx started < 8H Patient is unwell

Several different versions, seem to work Original based on small no.s, 1970’s!



Nomogram issues (CRUCIAL!)

“Time anchoring” is a strategy to use when ingestion time is unclear: Plot the level & identify the “at risk time” Ask if prior ingestion possible cf. to that time?

In repeated / staggered ingestion: assume ‘worst case scenario’ = all taken at the

earliest possible time Consider rpt level re ? all taken eg <4H


Bloods – general points

Only screening test = paracetamol & ECG Same for ANY poisoning, if NOT toxic

Specific tests = level & aminotransferases Next slide for indications

Other bloods ONLY need to be added if patient is unwell / estabished toxicity: clotting / FBE (for plt.) / U&Es / acid-base Same for ANY really sick patient


Bloods - when

If known time ingestion can wait until >4H Then start NAC or discharge

If NAC gets started in <8H only a single first paracetamol level needed

If NAC >8H do ‘baseline’ ALT/AST along with level for serial testing

“All the bloods”: ALT/AST up / rising / unwell


Repeated supratherapeutic OD

Definition = >4g/day in adult or >60mg/kg/day in children

Dangerous responsible for 1/8 adult paracetamol deaths and

all children < 6 yrs Nomograms do not work! ‘biochemical’ risk assessment


RSI continued

Paracetamol levels v. low (<10mg/L) and low ALT/AST (<50 IU/L) good prognosis Don’t continue treatment

If not start NAC and rpt levels at 8H If rapid rise continue Rx until falling Serial monitoring of INR / ALT


NAC (a very ‘benign’ antidote)

150 mg/kg in 200mL 5% D over 15/60 Occas anaphylactoid reactions, slow rate down

Then 50 mg/kg in 500mL over 4H Then 100mg/kg in 1000mL over 16H Standard Rx duration is 20 hours Beyond 20H if late presentation, rpt supraRx

dosing, or hepatotoxic Until ALT/AST falling or pt. improving


Transfer indications…(same as transplant!)

INR > 3 @ 24H, or >4.5 any time Creatinine >200 or oliguria Acidosis, pH <7.3 after resuscitation BP < 80 Hypoglycaemia Severe thrombocytopaenia encephalopathy


Very sick pt.s (= fulminant liver F)

Look for and Rx hypoglycaemia Minimise fluids, consider early inotropes Be wary coagulopathy (eg. Line insertion) Get help: ED consultant, toxicologist, ICU,

liver transplant centre Coordinating transport difficult Some good outcomes with ‘heroic’ Rx


controversies

Which nomogram to use?... Probably the “local one”

More important is checking units, plotting correct time, starting NAC at right time

Extrapolation past 15 H not validated No evidence to support “high risk” line Extended release preparations…

Start if >150mg/kg and check level @ 4 & 8 hours


Final points

Nb 150mg/kg, 4H and 8H Look the rest up when they are needed

Be careful when using nomograms Be aware of and look for RSI Patients can generally be believed We do far too many blood tests but don’t ever

think twice about ordering a level

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Paracetamol Toxicity - BHS Education Resource

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