Paracetamol overdose: an evidence based flowchart to guide management

C I Wallace; P I Dargan; A L Jones

doi:10.1136/emj.19.3.202

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Correction - July 01, 2002

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Paracetamol overdose: an evidence based flowchart to guide management

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Apparant incompatibility between the flow chart provided and Medicines for Children
Pushkar Kumar Srivastava
Published on: 29 April 2016
Re: Caution: printing error and reply to previous eLetters
Andrew B Rowlands
Published on: 29 April 2016
Paracetamol Overdose Guidance
Michelle F Jacobs
Published on: 29 April 2016
Caution: printing error and reply to previous eLetters
Alison L Jones
Published on: 29 April 2016
Weaknesses in the flowchart
Andrew B Rowlands
Published on: 29 April 2016
Re: Psychiatric evaluation in acute poisoning
Gavin Lloyd
Published on: 29 April 2016
Re: Paracetamol overdose
Alan G Jones
Published on: 29 April 2016
Psychiatric evaluation in acute poisoning
Alan E O'Connor
Published on: 29 April 2016

Published on: 29 April 2016
Apparant incompatibility between the flow chart provided and Medicines for Children
- Pushkar Kumar Srivastava, SHO in Paediatrics
Dear Editors,
I must congratulate the authors for coming up with such a simple flow chart which is very clear regarding how should the junior doctors manage Paracetamol overdose. However,if I go by this flow chart then SHOs in Paediatrics prescribe potentially hepatotoxic dose of Paracetamol to probably all the " high risk groups". Consider the case of a child...
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Dear Editors,
I must congratulate the authors for coming up with such a simple flow chart which is very clear regarding how should the junior doctors manage Paracetamol overdose. However,if I go by this flow chart then SHOs in Paediatrics prescribe potentially hepatotoxic dose of Paracetamol to probably all the " high risk groups". Consider the case of a child with cystic fibrosis (or say epilepsy on carbamazepine)who is reviewed for a viral fever and is prescribed Paracetamol ( which in accordance with " Medicines for Children" would be ) 15 mg/kg/dose, 4-6 hourly ( max 90mg/kg/day for kids >3 months ). If we go by this flow chart ,then, if the child recieves 5 0r 6 doses over 24 hours then he is at risk of hepatotoxicity ( Iatrogenic !!!). This apparant incompatibility between guidelines issued on behalf of NPIS and " Medicines for Children" needs sorting out or further clarification.
References
1)Wallace CI, Dargan PI, Jones AL. Paracetamol overdose : an evidence based flow chart to guide management. Emerg Med J 2002;19:202-5.
2)The Medicines Committee of The Royal College of Paediatrics and Child Health and Neonatal and Paediatric Pharmacists Group. Medicines for Children 2003, page 470.London : Royal College of Paediatrics and Child Health Publications 2003.
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Conflict of Interest:
None declared.
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Published on: 29 April 2016
Re: Caution: printing error and reply to previous eLetters
- Andrew B Rowlands, Specialist Registrar in Accident & Emergency
- Other Contributors:
  John Thomson
Dear Editors,
I wonder if we may make further comment in light of the reply of Jones et al. to our initial concerns over perceived weaknesses of their flowchart on the management of paracetamol poisoning.
Our ongoing major concern is that, in their reply, Jones et al. appear to be holding to the position that INR is the best prognostic indicator in paracetamol poisoning. Studying the r...
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Dear Editors,
I wonder if we may make further comment in light of the reply of Jones et al. to our initial concerns over perceived weaknesses of their flowchart on the management of paracetamol poisoning.
Our ongoing major concern is that, in their reply, Jones et al. appear to be holding to the position that INR is the best prognostic indicator in paracetamol poisoning. Studying the reference they give to back this position [1] one finds two clear statements: Firstly, that "The most sensitive prognostic marker is prothrombin time"; and secondly that "In (their) clinical experience, when PT starts to improve full recovery follows". Where INR is mentioned is when the article itself refers to another article [2] which, on closer scrutiny, does not in fact make any reference to INR but does include prothrombin time amongst the data collected and presented .
We should be most grateful for final confirmation as to which marker to monitor because if the answer is prothrombin time, as we suspect, then further important amendments will need to be made to the flowchart and it's legend before reprinting.
Finally, and with all due respect to Jones et al.. can we say that rather than misreading the 8-24hr pathway, we evidently did not interpret it in the way which was intended. Perhaps this in itself is justification for reviewing the flowchart.
References
[1] Dargan PI, Jones AL. Acetaminophen poisoning: an update for the intensivist. Critical Care 2002;6:108-10.
[2] Gyamlani GG, Parikh CR: Acetaminophen toxicity: suicidal vs accidental. Critical Care 2002;6:155-9.
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Conflict of Interest:
None declared.
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Published on: 29 April 2016
Paracetamol Overdose Guidance
- Michelle F Jacobs, Specialist Registrar
Dear Editor
While the paracetamol overdose flowchart proposed by Wallace et al. [1] puts forward a generally helpful approach to this common problem, I would like to raise two points which could be of concern.
First, the authors do not recommend measurement of paracetamol levels after a staggered overdose. Since a staggered overdose relies entirely on the patient's history, a blood paracetamol level...
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Dear Editor
While the paracetamol overdose flowchart proposed by Wallace et al. [1] puts forward a generally helpful approach to this common problem, I would like to raise two points which could be of concern.
First, the authors do not recommend measurement of paracetamol levels after a staggered overdose. Since a staggered overdose relies entirely on the patient's history, a blood paracetamol level will at least help to confirm the most recent ingestion and guide treatment.
Secondly, there is no mention of mental state assessment or psychiatric liaison before discharging the patient. If junior doctors are to use the flowchart as their guide for management, a reminder of the inportance of mental state evaluation and,in particular,risk of further suicide attempts is vital.
Michelle Jacobs
Reference
(1) Wallace CI,Dargan PI,Jones AL. Paracetamol overdose:an evidence based flowchart to guide management. Emerg Med J2002;19:202-5.
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Conflict of Interest:
None declared.
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Published on: 29 April 2016
Caution: printing error and reply to previous eLetters
- Alison L Jones, Consultant Physician and Clinical Toxicologist
- Other Contributors:
  Dr Paul I Dargan
Dear Editors
We are grateful to Lloyd et al.[1] and Rowlands et al.[2] for correctly pointing out the typographical errors in our flowchart. These were production errors, and did not reflect the original version supplied to the journal. Patients who present after a paracetamol overdose with an unknown quantity of paracetamol should definitely be treated as though they may have taken a potentiall...
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Dear Editors
We are grateful to Lloyd et al.[1] and Rowlands et al.[2] for correctly pointing out the typographical errors in our flowchart. These were production errors, and did not reflect the original version supplied to the journal. Patients who present after a paracetamol overdose with an unknown quantity of paracetamol should definitely be treated as though they may have taken a potentially hepatotoxic dose. Similarly, along the staggered overdose pathway, all doses should be described on a dose/kg/day and not a dose/kg basis. These errors are of sufficient importance that we have asked the editor to reprint the flowchart with these corrected.
Rowlands et al.[2] ask for more detail on the management of at risk patients who present with a staggered overdose of >= 75mg/kg/day or unknown. The management of these patients is controversial and, we feel, needs to be discussed on an individual case basis once the result of baseline blood tests are available.
Patients who are treated with N-acetylcysteine within 8 hours of a single paracetamol ingestion have a less than 1% risk of developing hepatotoxicity [3] and for this reason do not require liver function tests, INR, creatinine to be checked until after the course of N-acetylcysteine has been completed.
Rowlands et al[2] have misread the 8-24 hour pathway, the second box refers to checking the blood results rather than taking a second blood test.
We agree with Rowlands that there is minor interference by N- acetylcysteine with certain paracetamol assays and doctors should check with their local laboratory which assay is used in their hospital. However, it is paramount that N-acetylcysteine is started as soon as possible in late presenting patients as delayed treatment will result in decreased efficacy. [3]
Late presenting patients and those with staggered overdose who have abnormal blood tests carry a high mortality and management is complex and ever changing.[4] Thus, it is critical both in terms of decisions on management and criteria for transfer to liver units that discussion takes place with a clinical toxicologist at a poisons centre.
INR is the best prognostic indicator in paracetamol poisoning.[4]
We agree with O’Connor et al.[5] that all patients who present after paracetamol overdose require psychiatric evaluation and this is our every day practice.
References
(1) Lloyd G, O'Sullivan I. Re: Psychiatric evaluation in acute poisoning [electronic response to Wallace et al. Paracetamol overdose: an evidence based flowchart to guide management. emjonline.com http://emj.bmjjournals.com/cgi/eletters/19/3/202#66
(2) Rowlands AB, Thomson J. Weaknesses in the flowchart in acute poisoning [electronic response to Wallace et al. Paracetamol overdose: an evidence based flowchart to guide management. emjonline.com http://emj.bmjjournals.com/cgi/eletters/19/3/202#65
(3) Prescott LF, Illingworth RN, Critchley JA et al. Intravenous N- acetylcysteine: the treatment of choice for paracetamol poisoning. BMJ 1979;2:1097-100.
(4) Dargan PI, Jones AL. Acetaminophen poisoning: an update for the intensivist. Critical Care 2002;6:108-10.
(5) O'Connor AE, Lockney AL. Psychiatric evaluation in acute poisoning [electronic response to Wallace et al. Paracetamol overdose: an evidence based flowchart to guide management. emjonline.com http://emj.bmjjournals.com/cgi/eletters/19/3/202#58
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Conflict of Interest:
None declared.
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Published on: 29 April 2016
Weaknesses in the flowchart
- Andrew B Rowlands, Specialist Registrar in Accident & Emergency
- Other Contributors:
  John Thomson
Dear Sir,
The flowchart to guide management in paracetamol overdose, by Wallace, Dargan and Jones (EMJ Vol 19 No.3 p202) was presented at our weekly Journal Club and generated some thoughts and observations.
Along the "Single" overdose pathway for "Low risk" patients the guideline suggests that if the ingested dose of "< 150mg paracetamol per kg or UNKNOWN" the patient can be discharged. Presumab...
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Dear Sir,
The flowchart to guide management in paracetamol overdose, by Wallace, Dargan and Jones (EMJ Vol 19 No.3 p202) was presented at our weekly Journal Club and generated some thoughts and observations.
Along the "Single" overdose pathway for "Low risk" patients the guideline suggests that if the ingested dose of "< 150mg paracetamol per kg or UNKNOWN" the patient can be discharged. Presumably this is a typographical error, as it would make greater sense for the box immediately below to read ">= 150mg paracetamol per kg or UNKNOWN" as this path leads to treatments.
Along the "Staggered" overdose pathway one route, is taken based on an ingested dose of "< 75mg paracetamol per kg PER DAY" whereas the other 3 routes are taken based on simply a dose per kg. It is impossible to know what the message is here.
We also wondered what advice NPIS offers when a staggered overdose of ">= 75 mg paracetamol per kg or unknown" has been taken by an "At risk" patient - other than: take LFT’s, INR, creatinine and bicarbonate; start NAC and recheck bloods at a specified interval if the first set are abnormal. Surely that advice, whatever it may be, could be incorporated into the flowchart.
Along the pathways for "Single" ingestions <= 8hrs we found ourselves uncomfortable at the prospect of leaving checks of LFT’s, INR*, creatinine and bicarbonate until the end of the NAC course. Twenty hours is a long time to wait to discover that NAC has failed to prevent coagulopathy.
Along the 8-24 hour pathway the guideline suggests commencing treatment with NAC; taking bloods for paracetamol etc; plotting the paracetamol; then checking the bloods again before starting treatment. This seems convoluted and illogical:
Firstly, with regard to the testing for paracetamol , our understanding from local laboratory services and Toxbase is that paracetamol levels taken while on NAC are unreliable (because of the direct effect of NAC on the paracetamol assay). It would therefore seem more sensible to ensure the first set of bloods are taken off before commencing the NAC.
Also, in this part of the flowchart, the blood tests are repeated back to back with no obvious justification. Perhaps it is intended that these should be rechecked after a certain period of treatment with NAC, but this is not stated and might well lead to confusion for those unused to managing paracetamol overdose and relying on the flowchart.
Similarly, for "Late" presentation or "Staggered" overdose patients on NAC but with abnormal blood results it would be useful to have some advice as to when to recheck bloods rather than simply being directed to the National Poisons Information Service. We feel that monitoring coagulopathy is appropriate even if the patient is already on treatment with NAC since ongoing deterioration may demand consideration of patient transfer to another unit (e.g. liver transplant unit) which may be distant from the initial treating hospital.
Finally, considering coagulopathy further, *we would question the use of INR as a measure of coagulopathy in paracetamol overdose. Our understanding is that this test is reserved for guiding Warfarin dosage and that Prothrombin time itself is more appropriate.
Overall, we approve of the idea of the flowchart but feel that with the weaknesses detailed above it is perhaps not quite ready for use, particularly by clinicians unfamiliar with this common clinical problem.
Yours faithfully
Mr. Andrew Rowlands (SpR in Accident & Emergency) Dr. John Thompson (SHO in Accident & Emergency)
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Conflict of Interest:
None declared.
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Published on: 29 April 2016
Re: Psychiatric evaluation in acute poisoning
- Gavin Lloyd
- Other Contributors:
  Iomhar O'Sullivan
Dear Editor
We congratulate Wallace et al on producing a useful paracetemol overdose flowchart. It does appear to have a typographical error. Unknown quantaties of ingested paracetemol should be boxed with > not <150 mg paracetemol. If the pdf file could be amended we will gladly update our on-line departmental handbook. The point regarding psychiatric assessment has already been made.

Conflict of Interest:
None declared.
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Published on: 29 April 2016
Re: Paracetamol overdose
- Alan G Jones, Cons A&E
Dear Editor
Good article but for wrinkly, rheumy old gits like me I cannot read the [I'm sure ] excellent flowchart. The main thrust of an article is to have it read. Do you supply free magnifiers for the 'aged ' ?!! this also goes for the splendid algorithm om page 207 on salycilates.

Conflict of Interest:
None declared.
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Published on: 29 April 2016
Psychiatric evaluation in acute poisoning
- Alan E O'Connor, Emergency Physician
- Other Contributors:
  Amanda Louise Lockney
Dear Editor
I would like to complement Wallace et al. for there production of a useful and user friendly algorithm for the management of paracetamol poisoning.[1] However, I would like to suggest that the addition of an acute psychiatric evaluation in patients who present with intentional overdose would greatly enhance the usefulness of the algorithm in the emergency department environment. This evaluation sh...
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Dear Editor
I would like to complement Wallace et al. for there production of a useful and user friendly algorithm for the management of paracetamol poisoning.[1] However, I would like to suggest that the addition of an acute psychiatric evaluation in patients who present with intentional overdose would greatly enhance the usefulness of the algorithm in the emergency department environment. This evaluation should be carried out either by the attending emergency physician or a psychiatrist and will aid in planning patient disposition from the emergency department. Such an evaluation should be an essential part of management of all intentional acute poisoning.[2]
References
(1) CI Wallace, PI Dargan, AL Jones Paracetamol overdose: an evidence based flowchart to guide management Emerg Med J 2002; 19: 202-205.
(2) JM Bostwick, F Pochard, Robin M, et al. Treatment of Suicidal Patients N Engl J Med 1998;338:261- 262.
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Conflict of Interest:
None declared.
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