Intranasal Ketamine: Mum “Nose” Best at St Emlyn’s

 

St Emlyn’s in Virchester is a place full of talent, only a small cross-section of which is showcased here. Now and then, the opportunity to highlight the work of other Emergency Physicians arises.

Such an opportunity has come about in the last few weeks; Dr. Alison Robinson, an ED Registrar and mum to two girls, has been thinking about the opportunities for intranasal delivery of ketamine in the ED to kids needing procedural sedation. If you’re a regular reader of twitter you’d be forgiven for thinking ketamine cures all manner of ailments – it’s certainly a frequent topic of debate, and the subject of intranasal use has come up more than once.

 

So what does Alison think? Find out below, and remember: Mum “nose” best :-)

 

Trying to balance life as a working Mother is tough, but when your two worlds collide you find knowledge of one increases the horrors of the other.  Such is where I found myself, pinning my 20-month-old daughter down, whilst an eager Paeds trainee stuck needles in her.  Holding her, watching her petechial rash increase across the SVC distribution as she screamed, I knew that the bloods being obtained were necessary, and the antibiotics needed – the possibility of the humbling meningococcal septicaemia not a risk any of us would be prepared to take.  However, my thoughts drifted to the children that I do this, or worse, to… 

What about the children getting IM injections; in my practice most commonly IM ketamine? 

These kids are the hurt ones, the scared ones, the systemically well ones; 100% aware of what you are doing – and it is awful!  Don’t get me wrong, I believe in ketamine sedation.  For the right patient it’s brilliant, but it can be a total disaster – some children getting not one but two IM injections, then being listed for a GA once the procedure has failed. 

So is there a better way?  Is swapping a painful IM injection for an IV cannula better?  Maybe, but in the chubby, no-veins-to-be-found age group probably not.  So where does that leave us?  I have heard tales of intranasal ketamine being used prehospitally, seen publications examining its use in dental sedation that excited me – could this be the answer?  Can we throw away the needles? 

Happily, it seems I am not the only one pondering this thought.  A paper recently published in Pediatric Emergency Care examined the effectiveness of intranasal ketamine for paediatric procedural sedation in the ED.  Its bottom line: IN ketamine achieved adequate sedation in only 3 put of 12 children.  Not great, but I’m not sure IN ketamine should throw in the towel quite yet…

Call me an optimist (you may be the only ones who ever will), but I feel there are several reasons to not banish intranasal ketamine but to keep the painless sedation hope alive.  Let’s have a look at the paper: see if you agree with me.

Click the image above to go to the PubMed abstract.

 The authors conducted a pilot study looking at ASA grade I and II children between 1 and 7 years who needed suturing for simple laceration repair.  Inclusion and exclusion criteria seem appropriate and consistent with the patients that I would consider ketamine for – great

Patients were then randomised by age group (12-36 months, 36-60 months and 60-84 months), to receive either 3mg/kg, 6mg/kg or 9mg/kg IN ketamine by atomiser device (0.5ml per nostril).  The groups therefore are not comparable  not  so great.

All children had local anaesthetic gel applied to the wounds and a Ramsay sedation score was assigned by a blinded assessor every 15 seconds until a sedation score of 4 (“patient exhibits brisk response to light glabellar tap or loud auditory stimulus”) or more was achieved.  I may be at risk of opening a can of worms regarding the depth of procedural sedation required (already much has been blogged about procedural sedation), however a child with a RSS of 3 (“patient responds to commands only”), or even 2 (patient is co-operative, orientated and tranquil), may let you stitch up their leg.  A child scoring RSS 6 (“patient exhibits no response”) is likely to be over sedated in this context and I would be concerned. 

There is also no control group to compare sedation scores to.  I wonder how their sedation practice would compare to the study protocol, do they really only perform procedures on children achieving RSS of 4 or more?  I suspect not, hence their study protocol is not “true to life”.   I wonder how many of our IV/IM sedations would “fail” according to this protocol.

The children were also all cannulated and had multiple blood samples taken to measure serum ketamine and norketamine.  These levels did not correlate well with clinical effects, and the process of obtaining IV access and repeated sampling may have adversely effected sedation by excess stimulation.

As so few children reached the defined criteria for adequate sedation, the study was abandoned prematurely, only recruiting 12 subjects.  Entirely reasonable given that they were failing to do the procedures on these children, but I am sceptical…  It would have been nice to see the individual scores, and that the investigators had performed any procedures that they felt could be undertaken appropriately.

I am a huge fan of IN diamorphine, which comes as a powder, easy to dissolve and give at very high concentrations minimising runoff into the oropharynx.  It is quick, easy and it works so well, so why should nasal ED delivery stop there?  Ketamine, at a maximum concentration of 100mg/ml is not so concentrated, so swallowing some may become a problem in achieving predictable sedation effects.  Simple things, however – like suctioning snotty noses, warming the drug slightly to prevent vasoconstriction, dividing the dose between the nostrils to maximise the surface area to absorb it and delivering the drug by atomiser – will all improve its absorption.

So can we throw away the needles?  Not yet I fear… But I for one would love to see IN ketamine given another chance to prove itself, so if (or perhaps knowing my daughter, when) I find myself waiting for her to be sutured a squirt up the nose is all that’s needed.  Or if it’s not, at least I will be confident in the knowledge that that needle really is necessary…

 

Dr Alison Robinson 

 

And now over to you – have you used intranasal ketamine? Did it work? Thoughts and views are very welcome!

 

 

Comments

  1. Dave says

    Interesting stuff Alison. I certainly agree with that this is an area that this is an area that we could do with improving. Sticking needles in kids is always distressing for patient/parent and doctor!

    I do worry about the unpredictability of the uptake of the nasal route. Dosing these kids safely will be extremely difficult. At least with the (marginally more predictable) im route – you can use some emla/ametop first.

    Good Luck getting ethics approval for the study!

    • Alison Robinson says

      Thanks Dave, I think there is still a lot of work to be done on the intranasal route. There are a lot of methods that if used religiously I feel would increase the predictability of the dosing.

  2. Janos Baombe says

    Interesting concept indeed!
    A few myths about ketamine were dropped in the past years (atropine to prevent bradycardia in the paediatric population or midazolam preemptively for potential emergence phenomenon) and I am convinced that ketamine has more than a surprise left up its sleeve.
    It is an extremely safe agent which has been in use in the prehospital and rural settings for years but got a bad reputation for reasons I do not quite understand well (street drug association?).
    I think it’s a viable option as the route of administration is easy and the delivery repeatable without major effect on the CVS (unlike propofol and the other agents)!

    Can we expect a short cut review of the literature on this soon?

  3. says

    It seems like IN ketamine could be a very useful agent. During our recent research rounds, there was talk of a study looking at IN ketamine to be given at the triage desk for immediate pain relief, but I really like the idea of IN ketamine for pediatric procedures.
    Part of the problem with using this will be delivery systems, particularly in North America where drug restrictions seem to be more extreme – I was stunned by your use of IN diamorphine, only because it would never occur to me to try to use it as the regulatory hurdles would be crushing.

  4. Gareth Roberts says

    I think its worth a mention that the use of intranasal diamorphine is off licence still (i think??) . It is a brilliant method of analgesia.

  5. says

    Hi folks
    great discussion and article

    Here is a Military DOD memo, declassified on prehospital IN ketamine analgesia on the battlefield
    http://www.vighter.com/wp-content/uploads/2012/08/DHB-Memo-120308-Ketamine.pdf

    Sedation and analgesia should go hand in hand. even if all you do is get an analgesic dose of IN ketamine administered, thats worthwhile Once you make them comfortable then getting an IV or IO is easier.
    I think the notion of being able to conduct adequate procedural sedation via IN is a bit of a stretch. IMI ketamine sedation can be effective if its for a brief procedure.

  6. says

    hi Natalie
    yes I have used it, in remote clinics, ED and aeromedical.
    you need to give a decent dose..6mg/kg, divide between both nostrils, use adequate atomiser device or setup. this is for procedural sedation
    if you just want analgesia, then 3mg/kg is a decent IN anaglesic dose.

    one thing to remember. with the higher dosing needed for IN and IM there is more vomiting. pre procedural antiemetic is handy. ondansetron wafers are my usual choice.

    to be honest, I trained with IMI ketamine a lot and that to me is still more effective for certain situations. Having said that IN is handy option to get quick analgesia for kiddies.
    but dont expect it to be the magic sedation trick.
    but for paeds burns, limb fractures, foreign bodies, it can quickly help settle pain and distress without needing to IMI the kid.

    • Alison Robinson says

      Thanks Minh, your experience is really interesting. I have mainly used IM and have had really good experiences, but of late some nasty experiences where it failed. Maybe our increased use of off license IN diamorphine has increased professional expectations, or maybe other pressures are to blame, but I have also found our nursing staff increasingly less supportive of IM ketamine hence more children are being admitted for relatively minor procedures. (I also may have become very soft and overly empathetic now I’m a Mummy as I dislike the tears!)

      • says

        I must admit that I have moved away from IM to IV in all but exceptional circumstances. Much better control with more rapid onset and offset.

        The key is whether you have the skills, help, environment, help and help to obtain IV access. In a Paeds ED we have fabulous support so we can, but in other environments I might well go back to IM…..and that is when IN starts to look really attractive as an option.

        S

  7. says

    I was thinking about IN ketamine more for the very short procedure, such as pulling out a splinter or removing an ear foreign body, but I could see it being useful pre-iv for kids who need procedures done or who may have to wait for a while before an iv is started.

  8. says

    So….interesting discussion. The paper has flaws…but it is presented as a preliminary study (not the 3CPO of IN ketamine) so we should expect it to leave us with questions. Maybe if we approached it more as a proof of concept level publication?

    I know that IN ketamine can achieve extremely good sedation – anyone who’s worked in Virchester ED on a Saturday night can tell you about the patients with the tell-tale yellow powder at the nares who have demonstrated that without any medical assistance. The question is, can it be achieved reliably and safely enough to be useful to us?

    So, where does the paper leave us? I wonder reading it if they were planning to set up a randomisation system stratified by age ie to use all doses in all age groups and see if the dissociative threshold varied by age – it’s hard to tell from their description. I think it’s reasonable to conclude from their findings that 3mg/kg and 6mg/kg aren’t likely to cut it for our purposes. However, I have to agree with Ali’s comments regarding oversedation and the choice of outcome measures – I’d much prefer my daughter to be “undersedated” at Ramsay 2 with her lac safely sutured than have a practitioner determined to achieve Ramsay 4 at all costs…… I have data on a 2000+ prospective series of kids in dental practice where 97% had successful completion of treatment with Ramsay scores of 3 or less.

    9mg/kg though – this paper leaves good clinical equipoise on that – it did work for 3 of 4 of their patients (although the numbers leave you a confidence interval of 30-94%!). So yet again the conclusion is that we need a proper trial……….

Thanks so much for following. Viva la #FOAMed