PaperChase4 - Intranasal Ketamine for Analgesia

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Gary A., M.D. -

Sanjay, Mike (and Mel): Thanks for the great presentation as always but 1 correction to make -- I believe I may have told you that I was one who was hallucinating -- actually, none of the patients we treated had any. In terms of adverse effects, the main thing was that about half the patients had transient "dizziness" and about 1 in 3 felt "stoned" ... no vital signs changes and all of these spontaneously resolved within 40 minutes or less. Preliminary for sure and we'll see what the future holds. I also like the name but I've since been informed that "INKA" is actually a Polish roasted grain beverage used as a coffee substitute -- so there goes my claim to originality. Keep up the good work and thanks.

Michelle O., M.D. -

I like the information presented, but please Mike and Sanjay, a little less banter and more info. You are beginning to sound like Bukata and Hoffman!

Brian D., M.D. -

Is the enthusiasm exceeding the science?

There is nothing wrong with adequate and appropriate doses of opiates.

Intransasal fentanyl has been studied much more extensively and has a proven track record. Just stick with this. Fentanyl is very potent and lipophilic and an ideal drug for intranasal administration. Ketamine is just the opposite and is poorly absorbed via mucosa. Drug finding studies have shown that up to 9mg/kg need to be administered in order to get appropriate sedation for ED procedures (very small studies). This is very similar to the dose of oral ketamine when given as a premed for anaesthesia i.e. 10mg/kg.

Let's settle down a bit regarding ketamine outside of IV or IM procedural sedation until we get a bit more science.

Timothy R. W., M.D. -

Having spent the last 20 years immersed in product development and research relating to the clinical applications of nasal drug delivery in the ER and EMS setting I have some thoughts regarding intranasal ketamine for acute pain and on the above comment. Intranasal ketamine for acute pain is indeed not as well sorted out by our specialty as intranasal fentanyl. However, the recent study discussed here on EMRAP does not stand alone. There are a dozen or more studies investigating sub-dissociative doses (0.5 to 1 mg/kg) intranasal ketamine for acute pain published in the last decade (see this link I wrote specifically discussing those studies- It exists on a web site my colleagues and I have written on intranasal drug delivery):
http://www.intranasal.net/PainControl/INpaincontroldefault.htm#Intranasal_Ketamine_for_acute_pain
All three of the studies examining intranasal ketamine in the ER and EMS setting were published in 2013. They are all small proof of concept designs: One in children with acute limb trauma – VAS pain reductions of 44 mm at 30 minutes, one in EMS setting of ski trauma with 50 mm VAS pain reduction and the final one reviewed by Paper chase in adults with acute pain showing 34 mm VAS reductions in 30 minutes.
I hope soon we will have some larger studies to validate this effect (I believe both authors of the peds and adults studies are now doing larger trials). Never the less, despite Brian D’s comments I do think that there are clinical situations today that it may be more appropriate to just try this therapy first (very little downside) in the patient who you prefer to avoid an opiate.
However, I agree with Dr. Brian D. comment that intranasal synthetic opiates such as fentanyl should be first line intranasal therapy for many severe pain situations we see where an IV is not clearly needed (or even if it is but will be delayed). Intranasal fentanyl for acute pain in the ED is fairly well studied – especially in children. It is as effective as IV morphine for long bone fractures, yet no pain (no IV) and very little delays in treatment occur. Furthermore due to the absorptive pharmacokinetics and concentration of generic intranasal fentanyl, there are no reports of respiratory depression. For adults (who tend to have higher opiate tolerances) the generic concentrations of fentanyl can be a bit too dilute to be reliably effective, in which case our department has been using generic intranasal sufentanil (8-10 times the potency of fentanyl) for years. (This more potent drug can cause respiratory depression so monitoring is mandatory.) These synthetic opiates are so effective (for burns, fractures, I&D abscess, etc.) and titratable and require very little nursing support (no IV) that despite my penchant for trying new things, I have very rarely used nasal ketamine.
So, while many of us get excited about new ideas for pain control I see nasal ketamine as an adjunct to the extremely effective and well studied nasal synthetic opiates. If you have little experience with intranasal drug delivery I strongly recommend your first use be for severe pain (burn or fracture) in a child using the appropriate dose of nasal fentanyl (2 micrograms/kg) atomized half up each nostril. It is highly likely the treatment will be successful (if not, give another half dose in 10-15 minutes) and you can then move on to other less well documented therapies (such as ketamine) with that successful experience under your belt.

Tim Wolfe, MD
Emergency physician
Inventor of the MAD (no financial conflict of interest – the company was sold in 2010 and I have no shares in the new corporate owners).

Pål AW -

Tim: Do you have dosing examples for sufentanil? We use Fentanyl with great effect intranasal. Had some xp in adults that amount is to much,

KJ, MD -

I was hoping someone could help direct me to a ketamine as analgesia protocol used in your hospital system or another one that you’re familiar with. I’m an ER doc in pacific NW and I’m on the P&T committee and am fighting about/collegially debating over the safety of ketamine for analgesia at low doses (0.15-0.3 mg/kg) with the anesthesiologist chair of the committee.

As it currently stands, ketamine use of any kind is defined as a sedation, when it is clearly non dissociative at such doses and I’d imagine much less likely to cause airway compromise, apnea etc.

Our local EMS providers are about to start using it pre-hospital (not sure exactly what context), so I figure that in a more controlled environment it’ll be very helpful for the many opioid tolerant patients and patients with neuropathic pain etc.

Any protocols/resources that I could use as ammunition would be very, very helpful. Thanks for your help and keep up the good and important work!

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Episode 149 Full episode audio for MD edition 234:03 min - 111 MB - M4AEM:RAP 2014 Febrero - Resumen Español Español 89:51 min - 123 MB - MP3EM:RAP 2014 Février Résumé en Français Français 44:28 min - 61 MB - MP3EM:RAP 2014 February - Aussie Edition Australian 63:41 min - 87 MB - MP3EM:RAP 2014 February MP3 297 MB - ZIPEM:RAP 2014 February - Summary 710 KB - PDFEM:RAP 2014 February - Board Review Questions 696 KB - PDFEM:RAP 2014 February - Board Review Answers 456 KB - PDF