Paracetamol: mostly harmless?

This post was inspired by Colin Parker (the original C. Parker) and the team at EMPEM.org who did a discussion on the recent paper released by the ISAAC group (International Study of Asthma and Allergy in Childhood).  This collaborative of researchers (based in NZ, but internationally reaching – kinda like Dr C. Nickson) has been looking into the epidemiology of atopic disease and environmental influences for over 20 years.

The EMPEM podcast looked at the latest dataset out of ISAAC  it is titled ISAAC blows wheezy whistle on APAP.  This is going to be a serious debate over the coming years – does paracetamol have a causative association with asthma and other atopic disease?  Causality is nigh on impossible to prove, but this massive multinational data-set has established a statistical association that we cannot really ignore.  Unfortunately it raises a lot more questions than it answers!

So here is my summary of the papers and how I think I will integrate this stuff into my practice.

Beasley et al published this paper in the Lancet,2008. This is analysis of the 3rd phase of the ISAAC cohort, more than 200,000 kids.

• Paracetamol use in the 1st year of life was associated with increase rate of asthma at 6-7 years age.  The odds ratio was about 1.5 (with a narrow CI)
• Current use of paracetamol had a dose-related association with current symptoms of asthma
• There was also an association with other atopic conditions- rhino-conjunctivitis, eczema..

Eyers and the above-mentioned Beasley published this in Clinical & Experimental Allergy 2011

• Antenatal exposure to paracetamol also had an association with childhood asthma (OR 1.21 – just significant)
• So, now do we keep saying paracetamol is safe to expecting mums???

What about using ibuprofen in asthmatics with acute febrile illness?  The teaching has always been that Ibuprofen was bad – it might trigger asthma – but is this true?

• Lesko et al, in Pediatrics 2002 did this neat study of nearly 2000 kids and largely debunked this theory.
• The paracetamol group did worse – more asthma symptoms than the ibuprofen group.
• Unfortunately no control / placebo group to get a feel for the true effect – was paracetamol harmful or ibuprofen protecting the kids?

Peirce & Voss (Annals of Pharmacotherapy 2010) did a meta-analysis comparing paracetamol to ibuprofen in terms of safety and efficacy – fever and pain reduction.  For me this is the clincher:

• Ibuprofen was more effective than paracetamol for the symptom control – fever and pain
• There was almost no adverse events, they were equally very safe in the immediate sense.
• So ibuprofen looks like a winner here.

So how does this all fit together and what does it mean for the patient you are about to see in your practice?

1. Paracetamol might be a bit less safe than we have all been thinking – I think the data is not yet there to show a causative effect – but Vioxx was blacklisted for less heinous crimes!
2. The medical dogma that ibuprofen is bad for asthmatics and paracetamol is safe has pretty much been reversed.  I am definitely giving ibuprofen as first-line to the next atopic kid I see with an indication for it!
3. Not sure what to tell the pregnant mums:  take nothing? might be the only truly “safe” option
4. Ibuprofen does look better for fever and analgesia for kids.  It might have a protective role in atopic disease.  So I think it should be 1st line.
5. On the whole, the data is still inconclusive, therefore hard to apply to the individual.  However, I think as an institution / hospital we need to look at our policy / practice – is giving every snotty, febrile kid Panadol at triage a wise move?  I think we need to step back and be more selective with our use of these medicaines – after all they don’t really stop anything truly bad (seizures, brain-injury etc) from happening – so the risk must justify the benefits?

Ok, this I expect to cause a few ripples through the waters of common practice.  Please let me know – how will you change if at all?

Casey