Tag Archive: asthma


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

I caught this audio last week at about 4 AM when the ambos rushed this 3 1/2 year old boy in with his mother to ED.  The story was classical croup – a day of URTI sxs, coryza, low grade fever followed by the early AM wake up with stridor, the “seal barking” cough and marked dyspnoea.  So it was a slam dunk for diagnosis.  Also the medical students never get to hear a good croup bark – because they are always safely tucked up in bed at 4 AM – so I produce this video to share….Croup (click to view)

Now this kid was sick:  RR 60, marked chest wall recession, biphasic stridor and looking very scared.  Of course his SpO2 was 99% – as it often is in early, severe upper airway obstruction.  The Ambo team had given 2 x salbutamol nebs in transit without any change in his dyspnoea.

On examination his chest was ‘clear’ aside from transmitted stridor.  No wheeze, creps etc.  So it had to be croup.

Given how severe his dyspnea, we went in with an adrenaline neb immediately – which worked really well – he lost the stridor after 5 minutes and his work of breathing improved dramatically.  We got an IV access and gave a dose of oral dexamethasone. Yes, I use dexamethasone – not prednisolone.  I guess you could argue for IV hydrocortisone – no problem with that.  I do not use prednisolone for the following reasons:

  1. It tastes terrible, whereas dex is sweet and kids tend to swallow it better
  2. The trials done right here in WA used dexamethasone – see Geelhoed et al these trials showed in summary -
    1. Paed Pulmonology 2005:  0.15 mg/kg of oral dex was as good as 0.3 mg, and 0.6 mg in treating croup
    2. BMJ 1996.  A single dose of 0.15 mg/kg dramatically reduced recurrence / representation in mild outpatient croup
    3. Arch of Dis in Childhood 2006.  Dexamethasone as above was superior to prednisolone in preventing recurrence and other markers of severity for managing mild – moderate outpatient croup.
  3. Prednisolone has some mineralocorticoid activity which is just unecessary in this clinical context – dex is a bit cleaner.
So anyway back to our kid in ED.  He settles with the adrenaline, the dex has time to kick in and he looks like a mild croup and hour later – the sun is coming up, so the paraflu is running back to cover!  We admit him to the ward and ask the friendly Paeds to review him on their round.  I head off to bed…
Around 10 AM I stumble out of the on-call room and pop onto the ward to check on the little guy.  The Paediatrician says:  ”Oh that kid isn’t croup -he has asthma!  He has a good going wheeze and is responding to salbutamol…”
So I say: “Nah, mate.  He was croup – classic!” and I show her the video clip above. We agree that we are both right.
Back the truck up and look at the previous history – there was a strong family history of asthma / atopy, smoke exposure and one possible previous episode of asthma after a viral illness. So – he probably has another bout of viral-induced asthma, the virus [maybe paraflu]also caused the croup.  Of course the adrenaline neb did a great job of masking any wheeze / bronchospasm signs he might have had.
1. There can be 2 disease processes taking place in the same patient.      2. Examine, then re-examine kids before and after interventions      3. After an emergency – you still have to go back and take a thorough history

 

The winter in Australia is at an end, which means we hope we have seen the last of those wheezy, crackly, sick looking babies for the moment.  Bronchiolitis is the bread and butter of a lot of Paeds wards and EDs over the winter, we all know how to diagnose it and what the normal course is.  But I think we are mostly treatment nihlists.  My teaching to the JMOS and students has always been simple – keep them in if they are small, sick or have unreliable carers; keep them hydrated;  and give ‘em oxygen to relieve their dyspnoea and try to normalise hypoxia.  However – I fear I am a bit outdated – maybe too simple…

There have been a heap of trials and reviews in the last 5 years looking at what might work in bronchiolitis - and what doesn’t.  So I thought I would do a quick review of the literature and find out the evidence circa 2011….

So what works?

Nope.  Cochrane review basically showed no consistent benefit in important outcomes – admission, length of stay..  There was a possible mild improvement in clinical severity scores in children treated as outpatients in some studies – not sure how this translates into practice.  There is a risk:benefit[side effect vs. mild improvement with B2agonists] trade-off, so bronchodilators are at best unhelpful on balance.

Yes, it does according to recent studies and the Cochrane analysis of the studies which all agree – it works.  If you would like a well thought out and detailed review of the literature – go to WA’s own EMPEM website and listen to Colin Parker (no relation) and his team go over the numbers. In practice this is an inpatient intervention, though you could use it in the ED.  The studies showed a decrease in the length of admission as the main outcome of benefit.  Check out the NNT review on the topic for more info

For me this is the big new thing in bronchiolitis – so cheap and easy, the evidence looks good and I think this is practice changing for our hospital – any comments?

HArd to say, the NEJM published this study in 2009 looking at inhaled adrenaline and high doses of Dexamethasone orally – the jury is still out.  I have heard a number of doctors interpret this study in a number of ways – it looks promising, but then the fine print taketh away.  The dose of dex was 1mg/kg (big), and the use of inhaled adrenaline is not always a fun intervention – so big guns were used and the benefits were mild if there.  Don’t tink this is going to change my practice.  If used – I think it is in the ED, the goal being to prevent admission – I cannot imagine the ward staff being happy to do this outside of a well monitored bed.

Well – not a lot of data. Only one true RCT to look at it. In my experience a lot of kids get them – but no good improvement. So – no, I never have used them in the straight bronchiolitic, and I still won’t.

Well – not a lot to go on – it did improve PaCO2 in this study, but not really a patient oriented-outcome sort of way.  This seems to be the cool new thing for the little ones with bad bronchiolitis.  I have little experience with it, so we will see…

This has been shown to help in asthma. But in bronchiolitis – this large international study was clearly negative

Well – we saw the mixed results from the dex/adrenaline trial out of NEJM in 2009. Was there any other evidence for roids? The Cochrane group looked at the big trails and found no benefit.

So those are the interventions we as Docs have looked at and tried.  Traditionally there are few interventions that help other than a tincture of time and watchful waiting.  My review has shown me one possible addition to the armament – super salty nebs seem to be helpful.

Anyone out there got any other tricks they use in the bronchiolitics?

Casey

 

All of these recent posts and commentary on severe COPD has lead to a few discussions about the management of the Acute Severe Asthmatic around my workplace.  It is fair to say that this is an area where tradition and long-held beliefs have a grip, but there is a bit of recent evidence to suggest we have some options with good efficacy which we should use in this nasty disease of largely young people.  So I have had a look at the evidence and reviews and come up with my usual super-summarised version for the simple folk like me to read…

Oxygen is good. Give it. No evidence, just do it.

In Australia this is salbutamol [albuterol in the US]. This is proven to be effective and reduces hospital admission / physiological parameters etc. There is a Cochrane review looking at continuous vs. intermittent nebs which showed a modest benefit to continuous vs intermittent nebs.  So how does this change my practice?  In reality we give nebs, and give a lot, so just give as many as you can probably no downside to continuous and in practice you will have gaps, ce la vie.  I think you need to be aware of the side effects – watch the K+ and heart rate, try and keep it as normal as you can.

In Oz this is ipratropium.  The evidence here is less convincing.  The summary from the Cochrane review – adding anticholinergics to B2-A in severe asthma is as follows:  A single dose of an anticholinergic agent is not effective for the treatment of mild and moderate exacerbations and is insufficient for the treatment of severe exacerbations. Adding multiple doses of anticholinergics to beta2 agonists appears safe, improves lung function and would avoid hospital admission in 1 of 12 such treated patients.   

So I say – go for it, give multiple doses of ipratropium to the severe asthmatics. Anecdotally it causes less tachcardia, and appears to have little downside.  But don’t settle for just one neb – I have been guilty of this I fear.

Steroids are well proven and part of the woodwork when it comes to asthma of all severity it seems.  In severe asthma they are given IV usually – hydrocortisone or methylpred.  The NNT is about 8, so well worthwhile I reckon.  Most of these patients get a guernsey on the ward – so how much steroids becomes a question for the ward team to ponder.  Turns out some is as good as a lot according to the Cochrane folks:  equivalent of 400 mg hydrocortisone per day was adequate with no benefit to higher doses.

Also some evidence to say early steroids might reduce admission – so give them early (first hour) and you might save a bed’s occupancy (not my favourite end-point)

There are 2 Cochrane reviews on this – one for kids and one for adults and the data turns out to be about the same. In practical terms aminophylline seems to have some effect on bronchodilation but no difference in the patient-oriented outcomes of – intubation, mortality or symptom reduction. Aminophylline has a narrow therapeutic index and high rate of side effects- eg, vomiting [which is even less fun when you are in respiratory failure and you might inhale a carrot] So the jury is tied but not moving anywhere – I think I will give it a miss unless everything else has failed, even then, not a good drug to give to an already super-sick patient.

Magnesim keeps popping up everywhere it seems. So in severe asthma – what is the deal? Well magnesium looks very good for severe asthma – the NNT is 2 – 3 for “admission”! Nothing is that good in our day-day work.  Once again – this end-point is a bit shaky – I am going to admit them anyway if they are severe enough to need Mg, however there was no documented harm – so I think I will keep doing it. How much do you need?  I used the same dose we do for eclampsia – are there any guidelines out there?  This recent Brit study also showed Mg (thanks resus.me) was good at limiting tachycardia in these patient – which is a bonus given how much B2-agonist we are using – has to help the CO a bit to keep the HR down?

However beware – no benefit found for less severe asthma – so this is easy – if they are not sick enough to get a drip, don’t give IV mag.

There is some evidence for nebulised MgSO4 – in this review it improved pulmonary function but not clinically important outcomes – admission, symptoms etc

Giving iV salbutamol is one of hose things we do in bad asthma, but is it a good idea?  Well, maybe not.  The best review I could find was 10 years old and showed no benefit, some worse physiology and lets face it – it makes you feel pretty crappy.  Positive chronotropy plus increased O2 demand seem like bad things in asthma.  So I think I will leave this out until further review.  Kane from LITFL has reminded me that an adrenaline infusion is worth a try in the severe asthmatic not getting better on all the rest – probably OK in place of salbutamol – works on the same receptors – any evidence – not sure….

Now we get to the meat of the matter. This seems to divide ED folk.  The teaching has for a while been – NIV for COPD but not for asthma.   So lets look at the evidence…  well not so easy, as there is not a lot of good quality data out there – no RCTs, only some case series and observational studies.  It seems very tricky to make a clear choice based on the available evidence as it is almost certainly biased by the fact that given the current culture only the sickest status asthmaticus patients would be getting a trial of NIV.  The Cochrane group looked into NIV and found it was proven to help with some endpoints, no different for others and negative effect – it depends which outcome you look at.  We need a good RCT on this.

In my opinion it would make sense to put a severe asthma with respiratory failure on NIV if you are planning to intubate otherwise – Scott Weingart @ Emcrit has posted on this a few times.  However, my understanding is that NIV works by assisting ventilation in the patient with respiratory muscle fatigue, and rising CO2.  So why not use it early in the severe asthmatic and prevent this from occurring as much as possible?  Is there a downside?  Sure you need to watch the preload and BP, but they are usually fitter from a cardiac POV than the average COPD patient with chronic lungs / pulm. hypertension and a bit of IHD from all the cigarettes.  So should we use it earlier – not wait until they are on the brink of intubation?

DrGDH has a new blog – he appears to be slightly obsessed with all things NIV – check out his posts on the topic – NIV in Asthma? no point right?.  Covers all the current available evidence in a page of internet – check it out.  The theme seems to be – lots of small, non-randomised trials that show a decrease in the need for intubation / IPPV in the severe asthmatics, but not enough good data to say for sure it works.  So – what to do?

I think it is worth a try, still need to do all the medical management, and I would definitely prefer a course of NIV if it were me!  In our little hospital I think this is a smart move – intubation mandates a long air transfer with significant risk.  After all – we can still tube them if the NIV fails – but once you have intubated – you have committed to a long, expensive and potentially hazardous transfer.

So once all else has failed – you have an otherwise healthy patient with respiratory failure and the end of the road if intubate and ventilate. Sounds good – but be warned – this is a tough road, ventilating a patient with this degree of obstruction is tricky. And you had better have a good plan for induction and getting the vent running – because a minute of fiddling might be the difference between a bad situation and a disaster. I am not the expert - Dr Scott Weingart at EmCrit has a great podcast on this scenario – so I direct you there for some gold! In summary:

  • Prepare, plan and plan B, C ready.
  • Have the patient on NIV for the induction – and have the vent set to go once you are in.
  • Use ketamine for your induction – it is a bronchodilator and keeps the CO up.  You might want to ensure adequate preload before switching to IPPV.

USe the “obstructive lung vent strategy” as per Dr Weingart

There are only 4 things you need to remember for an obstructive patient

  1. Vt (Tidal Volume) = 8 ml/kg, don’t mess with it
  2. Flow Rate = shorter insp times, 80-100 lpm
  3. Resp Rate = Lung protection, start at 10 work your way down if necessary
  4. FiO2/PEEP = Oxygenation, should need much O2 (40%)m I recommend PEEP of 0, but certainly keep it less than 5

The MJA has just released a review of the management of asthma in kids the review looks mainly at chronic / outpatient management and there are a few changes.  They also looked at acute management of asthma and have created a divide between young (< 5 yrs) and older children with regards to oral steroid treatment.

The guidelines are based on the division of asthmatic children into 3 groups: mild / infrequent intermittent,  frequent intermittent and chronic / persistent asthma. I use this strategy in my practice and find it useful.  The commonest errors that I see in my part of the world is over-prescription of inhaled to corticosteroids to the mild / infrequent group, and the use of combination ICS/long-acting B-agonist as 1st line (hence the title of this post).

The algorithm in the article shows the suggested guidelines for the children with indications for ongoing preventer therapy.  The leukotriene blockers get a bit of an upgrade and the older agent Intal get a guernsey…

In terms of acute therapy – the gurus have looked at the stats and feel the younger kids – they have queried the use of oral steroids in acute management of the viral-induced wheeze.  They should probably be reserved for the more severe end of the spectrum / those requiring admission.  In terms of dose – they recommend 2mg/kg of oral prednisolone on day 1 then a few more days of 1mg/kg.

Asthma is one of the bread and butter diseases of GP, however it is one where the evidence is often not well applied.  Let me know, will this change our management?