Felipe M.

Hi Jo

It’s fantastic to hear you are enjoying your experience. Hospital settings can be lots of fun.

Great question, and one that does not have a straightforward answer.

The reality is we do not have much evidence in terms of the effects of SQ or IM single doses of ketamine for pain relief. SQ pulse ketamine therapy is a fairly popular choice, where the patient gets an injection of around 0.5mg/kg SQ every so often (it can be days, weeks or even months) as part of a chronic pain plan. It would be wishful to think the ketamine hangs around for such a long time to help our patients, as realistically it will be gone in no more than a couple of hours. What we hypothesise is that the transient effect in down-regulating the wind-up part of chronic pain (through NMDA receptor antagonism) helps get control of pain, yielding relief for some time (until the wind-up gets set in again). I do use it regularly and find it works, as so do many colleagues. However there are no studies on this. It would be very difficult to replicate in an uniform and reliable way to get trustworthy results. When we are in need of proper control of chronic pain though, a ketamine infusion for some hours, or even days, is definitely the way to go. Hope you find this useful!

Interestingly, there is a paper which documents the absorption and pharmacokinetics of SQ ketamine (albeit delivered constantly through an insulin pump) in dogs (DOI https://doi.org/10.1111/jvp.13440) and another one in the positive effects of SQ ketamine given on postoperative pain in humans (DOI https://doi.org/10.1007/s12630-017-0914-0).

Great topic

Felipe

Hello everyone
Hope you all are doing great.
I’d like to take the chance to join Scott in thanking everyone for choosing Vtx and myself for this journey.
Anaesthesia, like many other disciplines, includes different techniques as well as the management of many different types of patients. In this course I have tried to put together some of the hottest topics I am frequently asked about, which build up on the basic principles of anaesthesia but go beyond them. Although these are more advanced concepts, I will still maintain a solid grounding with all the foundations which now become ever so important.
At the end of every section I will upload a video as a form of catch up, where I will reflect on some of the concepts explored or expand on them.
It is frankly very difficult to include every aspect of anaesthesia, and thus I have tried to include the ones I considered most helpful for everyone, but please do feel free to ask away in the forum if there is something you would like me to comment, or if you need some clarification on any concepts.
I sincerely hope you find this course helpful and that you enjoy it as much as I enjoyed producing it.
Very excited to start this journey with you all!
Felipe

Hi Scott (and delegate!)

What a fantastic question.

Well done to our delegate, the approach is already very sensible indeed. However I cannot refrain from taking the chance to chip in to a couple of concepts.

When wanting to avoid or decrease the dose of sedatives to avoid their side effects, using higher doses of opioids is a great option. I would go as high as 0.5mg/kg butorphanol/methadone, or start with a similar 0.3mg/kg dose and top up at any given time with 0.1mg/kg up to twice, to deepen the sedation.

I will many times introduce some acepromazine at low doses (5-10mcg/kg) 20 min before the opiod to have some background sedation and additive/drug sparing effects. Obviously we don’t want to go much higher as lowering the blood pressure too much with a long-lasting agent in a hypertensive patient with an up-regulated organ perfusion auto-regulation is not desirable either.

There is some value in having a very dilute low dose of medetomidine/dexmedetomidine (1-2mcg/kg in 5-10mL of saline) and administering over 5-10 minutes to get sedation with much less pronounced vasoconstriction. This is very much case and blood pressure values dependent, but in the cases where the animal is fit for them, the quality of the sedation is better than in any other combination. Introducing a benzodiazepine with this technique, to spare the dose given is a very good way forward too, more on that below!

Using alfaxalone (or propofol) at subanaesthetic doses to achieve a sedation can be very helpful in these scenarios, but caution must be exercised as anaesthesia can be induced inadvertently and airway compromise may happen (due to obstruction, hypoventilation or aspiration). I would say that personally I find these drugs, compared to alpha-2 agonists at equivalent sedation levels, cause more respiratory depression and loss of airway protective reflexes, which I am not a fan of. I always recommend to have means to intubate and ventilate at the ready next to any sedated animal, much more so if these drugs are used.

Introducing a benzodiazepine (especially after a low dose of alfaxalone/propofol, so as to avoid hyperexcitability) can be very helpful to deepen the sedation with less side effects than if we continued with the anaesthetic agent. I do this many times in cats (or even in cases where I used opioid and some alpha-2 agonist, to spare the alpha-2 agonist dose) and usually it works great. I have to say I personally do not do this in dogs as often, given they are more prone to hyperexcitability and even display of aggressive behaviour.

In some cases I do use more complex combinations to spare drug dosing and side effects. As an example, I may start with 5mcg/kg acepromazine 20 minutes before the rest, then give butorphanol, then a very dilute alpha-2 agonist, and when I do not want to go any higher with alpha-2 agonists, deepen with alfaxalone or midazolam (or even both) at lower doses.

Hope this helps! Please let me know if you would like me to elaborate further.

Felipe

Replying to Bethany Deadman 09/03/2025 - 16:34

Hi Bethany

Pregabalin is regarded as a bit more predictable in its effects in humans, requiring less titration to reach a reliable clinical effect. The pharmacodynamics are quite complex because it does not work only on calcium channels, but in several other receptors, which makes it appear more advantageous. This article supports the pharmacokinetics in dogs: 10.1111/j.1467-2995.2009.00486.x

In terms of NMDA antagonists, I do use them a lot in OA or any other type of sensitisation, including visceral. At the end of the day, what we are targeting is the open and working NMDA receptor in the dorsal horn of the spinal cord, which is causing the second order neuron to depolarise more easily. I do introduce them quite early in OA, even if in pulse therapy, if NSAIDs on their own do not yield all the effects I want. It’s the same principle as giving SQ ketamine every now and then, since ketamine, amantadine and memantine work in similar ways. Amantadine did have a restriction to its use in EU due to more astringent antiviral prescription guidelines, but we did not seem to get it in UK. However, I tend to prescribe even more frequently memantine, which is another molecule that works in the same NMDA receptor, but to my knowledge not regarded as an antiviral and still fine to be dispensed in EU countries under their equivalent to the cascade.

Felipe

Replying to Bethany Deadman 02/03/2025 - 17:17

Hi Bethany (and Scott)

I agree, there is a big challenge in many cases when transitioning from an in-patient to out-patient pain management. Without any doubt.

I tend to rely a lot on gabapentin too. Although primarily used for neuropathic pain, there are reports of its use even in acute pain cases (the one that comes to mind, in a cat) with a very good result. I many times use gabapentin in a multimodal approach as soon as the animal allows tablets, to de-escalate the parenteral medication. Pregabalin is a drug I use nowadays even more than gabapentin, with superior analgesia effects in dogs due to higher bioavailability. It can cause also more sedation at times, so evaluating the effect in each patient will direct me towards changing to gabapentin in some cases.

But obviously, gabapentin/pregabalin is not the cure for everything! and many animals need stronger analgesia.

I agree with Scott, if I am against paracetamol, I will stay away from NSAIDs as well for the reasons he has nicely stated.

Another one to use, especially if there is visceral sensitisation (or any other type of sensitisation), or somatic pain, is amantadine/memantine, which are also a good option within the multimodal approach.

Although always keeping a healthy amount of skepticism due to its very large interindividual variability in effects, I do consider trialing oral tramadol as it will work in some animals. If I need more reliable analgesia than this, I will then move on to oral-transmucosal buprenorphine. This has been proven to work both in dogs and cats.

If things are beyond this, I would re-consider keeping the animal as in-patient. If the animal must be discharged but is beyond the above, a fentanyl patch (ensuring the owners are also good candidates for this) can yield very good results too, with only visits needed every 3 days.

Hope this helps!

Felipe

Hi Bethany

First of all, it seems you did already a fantastic job, well done!

Hypoalbuminaemia can make things certainly tricky. In first place it will make a higher free fraction of the drug to be present due to lower binding capacity (albumin for neutral and acid drugs, alpha 1 glycoprotein for bases, such as local anaesthetics). Additionally the lower COP and glycocalyx disturbance will cause adverse fluid shifts and make patients more likely to become hypotensive. Lastly, acid-base status can be affected by hypoproteinaemia (reflected in the Atot in Stewart’s approach).

So, with all this in hand it seems it was a great idea to infuse some albumin beforehand, even if the net effect wasn’t so impressive in the end. At that low level of serum proteins I would have done the same, more for the COP/glycocalyx than for the altered pharmacokinetics, which I can otherwise adjust the dosing for.

In terms of the dosing, I find difficult to set standardised values for dosing indexed for the protein levels. This is so because the drugs commonly used in anaesthesia have a quite wide therapeutic window, and thus many times (but certainly not always) we won’t see dramatically different effects from administering 50% to even 100% more free fraction. In the case of induction agents, they are dosed to effect so we more or less bypass the problem. Even so, I tend to estimate the percentage decrease of albumin from the normal serum levels, and decrease my doses by roughly the same. In your case, given albumin was around half the normal levels, I would have gone with 0.1mg/kg of both butorphanol and midazolam. However, you can see things went very smoothly for you, so clearly what I wrote above applies in many cases.

Administering FFP as a fluid was also a great choice to not dilute COP further and promote IV compartment retention of fluids. Certainly better than synthetic colloids!!! (dare I say their name…)

Noradrenaline would probably have been my plan B too, if the heart rate had been on the higher side (more likely than not), there was no response to fluids and there was no other contraindications.

Very complex cases with several potential complications!

Hope this is of help, but let me know if you need further information.

Felipe

Hi Bethany

Great question!

Unfortunately all the information we have so far from SQ ketamine is anecdotal. I do agree it does seem to work in many animals, yielding an improvement in comfort levels sometimes for weeks.
Pharmacokinetically the most probable way things work is that ketamine is absorbed, metabolised and excreted within a couple of hours at a maximum, however parmacodynamically, having exerted its action on the NMDA receptors does help in “resetting” to some extent the ascending pain pathways at the time, and helps other drugs be more effective. This causes a clinical effect that can be seen for weeks sometimes, but I would say caused by a short term pharmacological effect. I typically use 0.5-1mg/kg SQ.

Unfortunately a SQ dose of ketamine cannot substitute an infusion. Using a ketamine infusion will always yield more profound effects, and actually having the patients on the infusion for 24-48h will have more chances at resetting the biochemical wind up than only doing so for 4-6h. So depending on the severity of the condition I will choose from a SQ injection as an add-on, an infusion for a couple of hours, or a protracted therapy for 1-2 days.

Hope this helps!

Felipe