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Massive paracetamol overdose

In Journal Club today we discussed ATOM-2, aka “Massive paracetamol overdose: an observational study of the effect of activated charcoal and increased acetylcysteine dose” Chiew A, Isbister G, Kirby K, Page C, Chan B and Buckley N Clinical Toxicology 2017

This was an observational study examining prospective and retrospective data gathered by Poisons Information Centres in NSW and Queensland.

The study looked at patients 14 years and older reporting massive paracetamol overdose (“massive” was defined by these researchers as >40g), ingested over a period of time not exceeding 8 hours. They asked the questions:

  1. Is the use of activated charcoal associated with reduced hepatotoxicity?
  2. Is increased N-acetyl cysteine (NAC) dosage associated with reduced hepatotoxicity?

As a bit of background, charcoal used to be given to a much larger proportion of deliberate self poisoning patients than we give it to currently. Its use then fell out of favour due to concerns over aspiration-related pneumonitis and the belief that early NAC will be liver & life saving, thereby making any benefits of charcoal unnecessary. Recently however, “massive” paracetamol overdose is becoming more common and the risks of aspiration of activated charcoal have also been questioned by some researchers.

Data from 200 patients were examined, all of whom had taken more than 40g paracetamol within an 8 hour period.

Outcomes included:

  1. Initial paracetamol ratio (this is the paracetamol level divided by the treatment paracetamol level on the nomogram that that time)
  2. Hepatotoxicity (ALT > 1000)
  3. Liver transplant
  4. Death

The study found that patients who had activated charcoal within 4h had significantly lower paracetamol ratios than those who did not have charcoal and a lower risk of hepatotoxicity (although this is difficult to separate from the effect of NAC in those patients who received it). An increased dose of NAC (usually doubling the dose in the 3rd bag) was associated with significantly lower risk of hepatotoxicity.

Interestingly, just over 25% patients who developed hepatotoxicity had NAC commenced within 8 hours of ingestion. These patients all had paracetamol ratios greater than 2. One patient required a liver transplant despite NAC commencing within 2.5 hours. There was 1 death but it was unrelated to paracetamol.

Conclusions

  • None of the patients receiving activated charcoal within 4 hours developed severe liver injury.
  • Increasing the dose of NAC significantly decreased the odds of developing hepatotoxicity in those with an initial paracetamol ratio of more than 2.
  • Several patients who received NAC within 8 hours had severe liver injury which supplies evidence against our preconception that NAC within 8 hours is 100% effective.

Limitations

  • Some definitions are not universally accepted eg “massive” overdose and “hepatotoxicity”
  • The dose of activated charcoal given was not specified
  • Treatments were not randomly allocated
  • Influence of reporting bias to Poisons service
  • Statistical power limited (only a small number of patients develop hepatotoxicity despite NAC)

Take-homes

  • Think about activated charcoal in pxs with massive OD (this series looked at >40g but there is little evidence for what defines “massive”)
  • Discuss patients with a high paracetamol ratio with Poisons Information, regarding indications for increased dose NAC

More work needs to be done to look at the time before which charcoal is beneficial, as well as which dose of NAC is ideal and at what time.

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Why cricoid pressure doesn’t work (probably)

by Josh Holden FACEM CCPU

Ever wondered why we don’t use cricoid pressure in ED? After all, compressing the oesophagus between the larynx and C5 vertebral body should stop any breakfast from coming up the wrong way quite nicely?


Check out the ultrasound video below to see the whereabouts of Jonathon Au’s foodpipe, and what might happen (other than ruining your intubation view) if you give his larynx a choke hold:

As you can see his oesophagus lies lateral to the trachea, not below it as commonly assumed. 


This seems to be completely normal. Dynamic MRI studies demonstrate that application of pressure to the cricoid cartilage displaces the oesophagus laterally instead of occluding it (Smith 2003Boet 2012). An ultrasound study demonstrated similar findings: in 60% of patients the oesophagus was lateral to the airway and cricoid pressure led to displacement rather than occlusion in all patients. (Tsung 2012). Old news then…

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Paediatric Appendicitis Risk Calculator

Journal Club Summary 21/03/2019

Today we talked about paediatric appendicitis scores, appendicitis scores and clinical decision scores and rules in general.

The article we looked at was Development and Validation of a Novel Paediatric Appendicitis Risk Calculator (pARC) Kharbanda AB, Vazquez-Benitez G, Ballard DW, et al. PEDIATRICS. 2018 Apr;141(4):e20172699.  (if you would like a copy please let me know.)

In summary, this study developed a Paediatric Appendicitis Risk Calculator (pARC) using clinical findings in a cohort of normally well children presenting to ED with abdominal pain and then validated it using a separate cohort of patients, as well as comparing it to the existing Paediatric Appendicitis Score. The conclusions we reached from our discussion of the article were:

  • The description of the methodology was confusing and we did not feel we would be able to replicate it based on what was described in the article (one of the “acid tests” for an article.)
  • The article did not tell us what the components of the calculator they derived actually were! This is probably the biggest frustration with this article. It states: “The pARC is not intuitive and requires sophisticated calculations… The pARC can be easily programmed and integrated within the electronic health record.” Not terribly useful to staff outside of the hospitals the author plans to implement his calculator in!

We entered into some interesting discussion around clinical decision rules, summarized below:

  • Most clinical decision rules (think PECARN/CHALICE/HEART…. almost anything) condense findings on history and examination that we would all obtain during a routine assessment into a list and allocate a quantitative value to the presence or absence of those findings.
  • Most clinical decision rules are too hard to remember in full. Yes you can plug them into an app but still….
  • We usually know who has appendicitis (or a severe head injury, or ischaemic chest pain) after performing an adequate clinical assessment.
  • Possibly more importantly, we usually know who doesn’t have these conditions after assessing them.
  • The difficult patients are:
    • The “maybes” ie the intermediate scoring patients
      • Many clinical decision rules are NOT useful for this intermediate group of patients.
  • So if clinical decision rules confirm what we already know and don’t help us when we don’t know, do they have any use at all?
    • Potentially.
      • They are sometimes helpful to convey information to other teams
        • Eg convincing the surgeon they have appendicitis because they score highly on the Alvarado/PAS score
      • They can be useful in rationalizing imaging and investigations
        • Eg deciding NOT to image low risk patients (and in some cases, eg high risk appendicitis patients if admission & OT is more appropriate)
    • They can be useful for developing a standardised guideline for conditions in which there is a large variation in practice within and between departments (ie calculate score then admit/investigate/discharge based on score)
  • They can be useful in reassuring ourselves when our gut feeling is “this is not appendicitis” that a patient is, in fact, low risk and ok to go home!

Any other thoughts on these issues or suggestions for Journal Club articles, please let me know.

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