ST/T wave abnormalities in paracetamol [acetaminophen] overdose; A quick lit review.

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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.