St t wave abnormalities in paracetamol [acetaminophen] overdose

1. ST/T wave abnormalities in
paracetamol [acetaminophen]
overdose.
B Y S I M O N M A R K D A L E Y ( 2 0 1 9 )
A 'quick-lit-review'.

2. I was asked twice in the space of a week to look at the ECGs of 2
patients with paracetamol overdose.
Both were otherwise well, but showed T wave inversion across the
anterior-lateral territories (ECG otherwise unremarkable).
I began to wonder whether there was some clinical significance that
I may be overlooking & decided to look at the literature.
BACKGROUND

3. QUESTION POSED;
Are ST and/or T wave abnormalities a common or
normal & perhaps more importantly benign ECG
finding in a patient with paracetamol overdose?

4. 2016 & 2019
2 RECENT STUDIES
(LAST 5YRS)
2011 & 1993
2 LESS RECENT
STUDIES
My quick-lit-search
identified;
I extended this & found;
(We'll look at these first) (We'll look at these in
greater detail)

5. "10-12 tablets of paracetamol ingestion revealed ST depression &
T wave inversion in 2/3 of cases."
"In patients with severe paracetamol poisoning, the ECG often
reveals minor nonspecific ST change & T wave flattening with U
waves during the first 48hrs which is likely to be related to
hyperkalaemia, but not due to direct cardiotoxicity".
Ralapanawa, U., Jayawickreme, KP., Ekanayake, EMM., & Dhammika Menike Dissssanayake, AMS. (2016)
Rahman, A., Chowdhury, A. & Jabeen, S. (2019)

6. "A 29yr old man with significant paracetamol overdose was found to have an abnormal ECG which in the
absence of hepatic encephalopathy was considered due to a direct cardiotoxic effect of the drug. A
functional coronary insufficiency resulting from inhibition of endothelium-derived relaxing factor
secondary to depletion of sulphydryl groups is postulated."
Armour, A. & Slater SD. (1993)
"It is suggested that in paracetamol poisoning evidence of cardiotoxicity alone may be sufficient justification
for treatment with acetylcysteine."
Suggested ECG on admission, & daily for patients with “significant overdose”. If there are ST/T wave changes
then treatment with acetylcysteine should be considered, irrespective of plasma paracetamol concentration
levels or time lapse from ingestion.

7. "Dysrhythmias & abnormalities of the ST-segment or T wave frequently occur in paracetamol poisoning in
comatose encephalopathic patients, with the cause at least partly related to severe metabolic changes.
However, ST/T wave changes in non-encephalopathic patients have been documented, with case studies
describing ST segment changes in the absence of hepatotoxicity, metabolic derangement or encephalopathy."
Contractor, H., Gauge, V., Nabi, S., Titu, H., Arya, S. & Naqvi, N. (2011)
"This presentation appears to be rare, although there has not been a systematic investigation of
cardiotoxicity in patients presenting with paracetamol overdose. It has been suggested that unexpected deaths
associated with paracetamol overdose may be due to cardiac arrhythmmias, which have been documented in
conjunction with ST/T wave changes."
"Although clinically apparent cardiotoxicity in paracetamol poisoning is rare, the cardiotoxic potential should
not be overlooked. Routine ECGs on poisoning victims may suffice to risk stratify individuals & guide
clinicians."

8. These earlier two studies appear to
contradict the latter two, stating clearly &
overtly that ST/T wave changes in this
context should prompt consideration of
treatment in the absence of any other
indications.
None of these 4 studies are high quality
evidence, but the older studies & the '93
study in particular appear more robust &
reliable.

9. RCEM 'Guideline for
Paracetamol Overdose'
doesn't indicate any risk
stratification or treatment
based upon ECG
abnormalities; their treatment
algorithm does not even
suggest an ECG be performed.
Royal College of
Emergency Medicine.
I looked for guidelines that might offer further insight..
'Paracetamol overdose; an
evidence based flowchart to
guide management' also
makes no reference to
consideration of a routine
ECG or how ECG
abnormalities should be
interpreted.
Emergency Medical
Journal.
UpToDate.
A search on the clinical
database "UpToDate" for
"paracetamol overdose" and a
further search within the
results for "ECG",
"electrocardiography" or
"electrocardiogram" rendered
no results.
Cochrane published a review
of interventions for
paracetamol overdose. This
reviewed 11 RCTs & failed to
reference ECG use once,
either in risk stratification or
as a modality to direct
onward management.
Cochrane
Collaboration.
NO MENTION OF ECG! NO MENTION OF ECG! NO MENTION OF ECG! NO MENTION OF ECG!

10. 4 TAKE HOME POINTS
It would appear - if only anecdotally -
that ST-segment & T wave abnormalities
are a relatively common phenomenon in
paracetamol overdose.
ST/T wave changes should be sufficient
to consider treatment with acetylcysteine
irrespective of paracetamol levels or
time since ingestion.
There is a gap in the evidence regarding
cardiotoxicity in paracetamol overdose.
The most robust evidence on the topic suggests that;
There is currently no guideline that
suggests an ECG in the context of
paracetamol overdose.

11. Chiew, AL., Gluud, C., Brok, J. and Buckley, NA. (2018) Interventions for paracetamol (acetaminophen) overdose (Review). Cochrane Library, Cochrane Database of Systematic
Reviews. 2018, issue 2, art no. CD003328. John Wiley & Sons, Ltd.
Armour, A. and Slater SD. (1993) Paracetamol cardiotoxicity. Postgraduate Medical Journal. 69, 52-54.
Contractor, H., Gauge, V., Nabi, S., Titu, H., Arya, S. and Naqvi, N. (2011) ST segment elevation secondary to paracetamol overdose. Therapeutic Advances in Cardiovascular
Disease. 2011, 4(1) 83-85.
Rahman, A., Chowdhury, A. and Jabeen, S. (2019) Changes in ECG among patients with drug induced poisoning in a tertiary care hospital. Bangladesh Medical Research Council
Bulletin 44(3), 160-167.
Ralapanawa, U., Jayawickreme, KP., Ekanayake, EMM., and Dhammika Menike Dissssanayake, AMS. (2016) A study on paracetamol cardiotoxicity. Pharmacology and
Toxicology 2016, 17:30.
Royal College of Emergency Medicine (2017) “Paracetamol overdose: new guidance on the use of intravenous acetylcysteine” and “paracetamol poisoning proforma to guide
ED management of oral ingestion in adults”. Both available at https://www.rcem.ac.uk/RCEM/Quality-Policy/Clinical_Standards_Guidance/RCEM_Guidance.aspx?
WebsiteKey=b3d6bb2a-abba-44ed-b758-467776a958cd&hkey=862bd964-0363-4f7f-bdab-89e4a68c9de4&RCEM_Guidance=6
UpToDate (2019) https://www.uptodate.com/home, Wolters Kluwer.
Wallace, C., Dargan , P. and Jones AL (2002) Paracetamol overdose: an evidence based flowchart to guide management https://emj.bmj.com/content/19/3/202
References.