Salbutamol – When to give the next dose?

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Salbutamol is one of the most frequently used medicines in the paediatric pharmacopeia. Most of us can say that it’s a short acting beta agonist delivered by nebuliser or more commonly via an MDI with spacer. Some might recall that the half life is between 2.7 and 5.5hrs.

And, most perplexing of all, once we’ve used it in the acute situation, how best to use it next? I’m talking here about the post-burst, pre-discharge phase of asthma or an exacerbation of a reactive airway picture.

Pierce is 5yo, he presents at 2300 to your ED. His Mum says he can’t sleep due to the coughing and she thinks his asthma is playing up. He receives a burst and another dose an hour later; he looks like he’s coping another hour later. He takes a 2mg/kg dose of Prednisolone. You come to review Pierce and his mum asks “So, what happens next?”

We’re talking here about the frequency of salbutamol usage. If you had asked me this question a month ago, I’d have been certain of my answer. My mental model for how to manage a presentation like this (especially out of hours) was rock solid with experience, but light on evidence.

I’ve had a suspicion I’ve been doing things differently and hence decided to review my practice, first by talking to peers, then looking at some guidelines and finally my reviewing the literature.

My practice, overnight, had been to be quite prescriptive with salbutamol – a slow, regular, wean and then not less than q2h until the sun came up (0500 in the Queensland summer), before aiming for q3h, consultant review if indicated, education and discharge during the morning ward/short-stay round.

This is not the practice of my peers; “You just wean them and then send them home.” Or, “Just review them regularly and give it as you need to.”, were the common answers – hopefully what most folk reading this are thinking –  and certainly what I aim to do before the sun goes down.

The RCH Melbourne guidelines suggest only dosing salbutamol when symptoms return.

The experimental literature around this question and reducing the frequency of salbutamol dosing is surprisingly sparse, but here are a few of the highlights:

Chandra, 2005

Chandra undertook a small study of 62 adults with the aim compare regular (q4h) salbutamol plus symptomatic vs symptomatic treatment alone. Patients in the pro re nata only arm used less salbutamol and had less use of salbutamol overall but there was no significant difference in the length of stay or rate of improvement. Patients were randomised 6 hours into their treatment, which seems to expunge most of the external validity for this paper to our clinical question.

Karpel et al., Chest 1997

Karpel et al. performed an elegant study with 100 adults presenting to NY emergency departments in which the patients were dosed every 30 minutes with salbutamol or placebo inhaler such that the groups essentially became dosed at q30mins or q60mins or q90mins or q120minutes – all after an initial load of 6 puffs of salbutamol. At each time point, FEV1 was recorded. They concluded that q60mins was the optimal dose, with minimal side effects.

This study didn’t utilise a ‘burst’ / salbutamol load, which is now standard (and first described in 1988), and may alter the conclusions, as the outcomes seemed to identifying number of patients who responded well initial dosing, and noted that these early responders benefitted comparably from q30,60 and 120 minutely dosing.

Admittedly, the frequent, regular dosing of salbutamol, once loaded, doesn’t make pharmacological sense; although it’s worth noting that only 15% of the dose makes it to the lung surface, whilst the other 85% is swallowed and undergoes first-pass metabolism, there are negligible levels of salbutamol in serum. These of course, are pharmacologic parameters, rather than clinical ones.

On reflection, my prescriptive style required minimal reviews and developed from working jobs as a solo Paeds Reg on nights. The perceived benefits were that with a high patient load and variable nursing experience, I was able to reduce decision making and cognitively offload all whilst keeping patients safe (I’ve not seen salbutamol toxicity from q2h dosing.) I’ve previously suggested other arguments for this, including the predictability for parents, although I’m not so sure about this part.

There are some merits in this shape of care, but it’s not “evidence based” nor “what most doctors would do.” So, is it safe? Is it wrong? How best to change practice?

 

References:

Product Information Salbutamol CFC-free MDI – http://au.gsk.com/media/223609/ventolin_cfc_free_inhaler_pi_004_approved.pdf

Acute Asthma – RCH Melbourne Guidelines –  http://www.rch.org.au/clinicalguide/guideline_index/asthma_acute/

Karpel JP, Aldrich TK, Prezant DJ, et al. Emergency treatment of acute asthma with albuterol metered-dose inhaler plus holding chamber: how often should treatments be administered? Chest. 1997 Aug;112(2):348-56. – http://www.ncbi.nlm.nih.gov/pubmed/9266868

Chandra A1, Shim C, Cohen HW, et al. Regular vs ad-lib albuterol for patients hospitalized with acute asthma. Chest. 2005 Sep;128(3):1115-20.

Managing acute asthma in children – Australian Asthma Handbook (Accessed 1/8/1016) – http://www.asthmahandbook.org.au/figure/show/67

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About 

A Paediatric Trainee based in Queensland, Australia, Henry is passionate about Adolescent Medicine & General Paediatrics, with a strong interest in Medical Education & Clinical Teaching. An admitted nerd & ironman with a penchant for Rubik's Cubes & 'Dad jokes'.

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10 Responses to "Salbutamol – When to give the next dose?"

  1. Annie
    Annie 1 year ago .Reply

    I agree that salbutamol dosing decisions is directed by a whole host of factors – I’ve also been prescriptive about intervals at smaller hospitals without on site paediatric support, so as to ensure patients aren’t ‘stretched’ too quickly. Nursing skills make a big difference even if paediatric staff are on site, as on a busy shift it’s not always possible to have a medical review at frequent enough intervals to appropriately adjust doses. Often there is a reverse issue in that salbutamol is given too frequently by less experienced staff simply for a minor wheeze, or even for slightly low SpO2 (which is more likely in this case to be due to V/Q mismatch than bronchospasm per se) without any work of breathing or other evidence of significant bronchospasm. Ensuring adequate training for nursing staff can be extremely helpful so as to allow the nursing team to determine appropriate salbutamol intervals independently. If the child is going home, the level of prescriptiveness is also dependent on the experience of the parents, but my practice is to only send children home if confident they can manage at lease 3 hours between doses, and so I provide a weaning schedule over a few days starting from Q3 or 4 hourly dosing for the first 12-24 hours (explaining to parents that this is a guide only and if confident to do so they may wean faster or slower, and/or see their GP daily for additional guidance).

    • Henry Goldstein
      Henry Goldstein 1 year ago .Reply

      Hi Annie, thanks for your comments!

      I think your point about nursing skills and experience is really important, as is the relevance of an overall nursing load. With this in mind, one of the other reasons I held to the q2h frequency overnight was that I felt the “accidental wean” from 2 to 3 hours is safer than q3h inadvertently extending to 4 or 5 hours. (I’m not entirely naive that an increased frequency means an increased nursing workload).

      I agree that most clinicians use the q3hrly threshold for discharge; again, I’m unsure about the evidence base looking at deterioration/rate of return or other outcomes for this frequency.

  2. Jan
    Jan 1 year ago .Reply

    Agree that nursing experience makes a big difference – I tend to be more prescriptive in places with less paediatric experience (I suspect Annie and I may be thinking of the same places!). It’s also an opportunity to give asthma ed to parents (and nurses) regarding how to give, what to give for, what *not* to give for…

    The RCH guidelines assume you’re somewhere with 24/7 onsite paeds as well as v experienced paed nurses, such as RCH (with possible bed pressure therefore emphasis on not admitting well kids, allegedly 😉) so nil wean/nurse criteria-led d/c is a good option. However, there is life outside Flemington…

  3. Brad Sobolewski
    Brad Sobolewski 1 year ago .Reply

    Just a quick question based on The way the little case interlude was written. Are you giving 2mg/kg prednisolone when 1mg/kg is just as good? And why give prednisone/prednisolone when dex for 2 days is just as good

    • Henry Goldstein
      Henry Goldstein 1 year ago .Reply

      Hi Brad, thanks for your comment & well spotted.

      I find the first dose of steroid is an evolving discussion, although most of the dosing I see is still 2mg/kg Prednisolone. The Australian Asthma Handbook was rewritten in 2015 and uses the Pred 2mg/kg as first dose only; previous editions suggested 1mg/kg (http://www.asthmahandbook.org.au/acute-asthma/clinical/corticosteroids).

      It looks like there’s a newly published Cochrane Review on the question of Prednisolone dosing (http://www.ncbi.nlm.nih.gov/pubmed/27176676), although it hasn’t made it to the top of my reading list as yet! The use of dexamethasone is yet to permeate Australian practice, although there is an increasing awareness of it’s use and the Cronin paper ( http://www.ncbi.nlm.nih.gov/pubmed/26460983 )

      Thanks again!

  4. Derek Louey
    Derek Louey 1 year ago .Reply

    Here is the challenge:

    1) Acute asthma is a heterogenous disease. It depends whether wheeze is predominantly due to bronchospasm or mucosal inflammation. Salbutamol only works on the former
    2) Mucosal inflammation takes from hours and days to resolve following systemtic steroid treatment
    3) The systemic kinetics of salbutamol might be known but what of the local kinetics of absorption and distribution in an acutely well patient. Do serum levels correlate with peak effect? Or before? Or after? Is there wide individual variation?
    4) ‘Weaning’ and ‘stretching’ suggests there is some adaptation of body physiology that responds different to rate of drug withdrawal, and that an incorrect regime can adversely affect that adaption. Is there evidence for this?
    5) There is no absolutely reliable means of evaluating the degree of untreated or relapsing bronchospasm versus slow-to-resolve inflammation. Clinical assessment for clinicians and some degree of astuteness from parents. Spirometry is difficult acutely and unavailable at home.
    4) Lactic acidosis from salbutamol toxicity is of theoretical concern is there a definite level that predicts adverse consequences or whether further treatment should be withheld before levels rise.

    More art than science?

  5. Mike South
    Mike South 12 months ago .Reply

    Thanks Henry.

    lots of great points made here

    Variation in practice is interesting for such a common condition.

    We work on the understanding that salbutamol is a short acting drug for relieving bronchospasm and if the patient has no signs of airway obstruction then no further doses are needed unless/until those signs return. That way we can more quickly judge how frequently these doses are actually needed. Some kids will get intensive treatment for an hour and then need no further doses, some will have ongoing bronchospasm over hours or days and need ongoing therapy with salbutamol. If you are giving it regularly when the child has no signs then you may do this for longer than is needed.

    ONGOING TREATMENT
    Salbutamol dose: 6 puffs if 6 years old
    The next dose of salbutamol should be given only when signs of asthma return. It does not need to be weaned.
    Do not give just for wheeze without other features of airway obstruction (tachypnoea, retractions, accessory muscle use).
    Seek review if doses are needed more often than every hour.

    This is also what we teach the parents in regard to “When to give the Ventolin”. We don’t teach them to gradually wean off the Ventolin when they treat their child for exacerbations at home so it seems inconsistent / confusing to do that in hospital. It is hard to teach them the signs of airway obstruction and the indications for doses of salbutamol if you give doses when the child has none of these signs in hospital.

    This approach is also that recommended in the Australian Asthma Handbook See the “after the first hour” box at http://www.asthmahandbook.org.au/figure/show/67.

    There is indeed “life outside Flemington” but I suspect the pharmacology is much the same 😉

    Good to debate

    Cheers

    Mike

  6. Jan
    Jan 12 months ago .Reply

    I’m sure research on the elusive “Frankston receptor” is continuing, though…

    https://www.etsy.com/au/listing/61642384/melbourne-greeting-card-id-go-to-zone?ref=shop_home_active_14

  7. Phil Coote
    Phil Coote 9 months ago .Reply

    Hi Henry,

    I agree that there’s huge variation in practice – probably because of the overwhelming lack of evidence. I tend to follow the RCH pathway of “give only when required”, but I think the alternative of slow weaning (or give sometimes when asymptomatic) is more plausible than we are acknowledging. The trigger for the exacerbation, namely, the virus, is still present.

    This recent paper (details below) used a severity score to be more objective about when to give bronchodilator, and were able to demonstrate a reduced length of stay and reduced variability. Their protocol is a little different from what we Australians are used to, but I like the idea of standardising practice in this way.

    Improving the Efficiency of Care for Pediatric Patients Hospitalized With Asthma
    Kathleen W. Bartlett, Victoria M. Parente, Vanessa Morales, Jillian Hauser, Heather S. McLean
    Hospital Pediatrics Jan 2017, 7 (1) 31-38; DOI: 10.1542/hpeds.2016-0108

    Phil

  8. Henry Goldstein
    Henry Goldstein 8 months ago .Reply

    Hi Phil,

    Thanks for the thought, it certainly is an interesting paper. The idea of reducing practice variability is really important. I agree that protocolised dosing, “asthma scores” and a regimented increase of dose frequency permits a kind of objectivity, (potentially aided in the study by the Respiratory Therapist as an additional objective agent.)

    I suspect that one of the real challenges is the interaction between the “data collector” and “decision maker”. That is, finding the sweet spot whereby those two entities can objectively negotiate the best outcome.

    As a ward/unit/hospital increases in size, this has the effect of diffusing decision-making (and reducing flexibility), from one or two key people to an entire team or set of processes. I suppose that’s the beautiful tension of knowing “What is best for patients with … ?” vs “What is best for this patient?”

    (And that the answer is – more often than not – the same!)

    Henry

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