Felipe M.

Replying to scott@vtx-cpd.com 07/04/2024 - 18:52

Hi Scott

Very fair point. And not very straightforward to tackle, because for me the approach is definitely quite diffuse in my choice-making:

– By increasing SVR we do increase MAP, but we are likely decreasing cardiac output -we are also decreasing perfusion in general due to the vasoconstriction- which in turn decreases the overall oxygen delivery to the tissues. It sounds like an overall bad idea, but it is not so. When we give isoflurane to our patients we are causing excessive vasodilation -compared to normal- of the vessels, and we see hypotension. In these animals, which usually show a slightly high to high heart rate -actually is a big proportion of our patients if they did not have alpha-2 agonists on board- a bit of vasoconstriction is not a bad thing. So noradrenaline is then a good idea. However it is difficult to know how much vasoconstriction is the right amount to return the vasomotor tone to wherever it was and should be for optimal fluid dynamics -we can get this information with a cardiac output monitor and a peripheral tissue saturation monitor, but otherwise we are guessing-. So for this reason, unless heart rate is high or there is a specific reason for accurate targeting, I tend to go with a beta agonist (dobutamine, moderate doses of dopamine) first, as they will surely increase cardiac output and oxygen delivery to the tissues. This is all a bit of personal view, and there are many nuances to this that make it a very complex subject, that I am not accounting for actually!.

– However, when would I actively avoid noradrenaline? I don’t think it’s necessarily wrong having norad as a first line drug for blood pressure control, and we do use it very frequently too. I would try to avoid it in animals where an increase in SVR can be detrimental (mitral valve disease, heart failure, low contractility, DCM…) or with ongoing kidney injury (so as to not decrease perfusion). But it all depends on the complete macrovascular (and microvascular too!) picture, so not definite contraindications in my opinion.
To illustrate this, in my experience animals with mitral valve disease on pimobendan and then going on isoflurane, especially if they had some acepromazine, do not respond very well to dobutamine (they get tachycardic and the blood pressure never goes to acceptable values), and do benefit from low doses of noradrenaline (to compensate the compounding vasodilatory effects, which yields a lower heart rate and good blood pressure – but this obviously depends on many cardiac variables). So as you can see, far from straight forward!

Hope it makes sense!

Felipe

Hi all

Great, so let’s go one by one in a summarised manner:

Noradrenaline: as mainly an alpha-1 agonist, with a bit of beta-1 (and 2) agonism too, it increases SVR and a bit of contractility and rate. So mainly a vasoconstrictor with some inotropic effects too. This is the absolute go-to for animals in sepsis as it has been shown to have better outcomes. I also use it in animals needing higher blood pressure but with a high heart rate (due to vasodilation, for example). Heart rate tends to decrease and MAP to increase when giving noradrenaline. Very predictable in its effects, however bear in mind that increasing BP by mostly vasoconstriction gives a lovely MAP with poor peripheral perfusion, and that’s why I do not use it as first instance.

Ephedrine: it works mainly through the release of endogenous noradrenaline, so it does mainly what noradrenaline does. However it is usually given as a bolus (although an infusion can be also administered). It tends to be handy for animals just needing 10-20 minutes worth of effect, having low MAP with a normal to high heart rate. Heart rate tends to decrease, MAP to increase, and sometimes depth of anaesthesia can lighten (as in itself ephedrine is a sympathomimetic). After a couple of doses, ephedrine may not work any more (it shows what we call tachyphylaxis) as its effect depends on endogenous reserves of NA. Some animals actually show tachycardia when given ephedrine, if the sympathomimetic effect overcomes the baroreceptor activation).

Dobutamine: mainly a beta-1 agonist with some b-2 agonism too. So it causes an increase in contractility and rate, with some vasodilation. It is the one of choice in animals with low contractility, or in which increasing contractility will improve cardiac performance (like mitral valve disease or geriatric animals). It tends to increase heart rate and blood pressure, however it can also cause tachycardia. In animals with several vasodilators on board (pimobendan, acepromazine, isoflurane…), it can cause a moderate to severe tachycardia with almost no improvement in MAP, due to the compounding vasodilatory effect. It can cause arrhythmia.

Dopamine: a bit of an odd one. Low to moderate doses clinically cause mostly beta agonism (up to 10mcg/kg/min), making it behave like dobutamine, and when doses go beyond 10mcg/kg/min alpha effects become more evident, causing vasoconstriction on top. It makes it handy for the average healthy animal as increasing doses if necessary will give an additional different effect to increase BP, when accurate targeting is not necessary. However it can cause tachycardia, bradycardia and arrhythmia. And as I said above, it does a bit of everything in a not-so-clear-cut manner, so not adequate when we want to target how we increase MAP (or cardiac output).

Hope this helps!

Excellent!

Felipe

Replying to Natalie Niven 28/03/2024 - 22:09

Hi there Natalie

Thanks a lot for your thoughts! Very interesting points there.

– In terms of the timing, there is no consensus to my knowledge. Obviously giving it beforehand follows the principles of preventive analgesia and maximises its effects by being in the tissues before surgical manipulation happens. However by decreasing the production of PGE2, we are taking away one of the autoregulation mechanisms of the kidney. Given that general anaesthesia can cause hypotension, I am of the opinion of having all the protection mechanisms we can. For this reason I prefer to give the NSAID in recovery, when I know the blood pressure is fine and will not drop. Alternatively, if the animal has been cardiovascularly very stable I may choose to give it towards the end of the procedure. I think the key point is to ensure renal perfusion whichever way we want to go with the NSAIDs (and in any situation, really!).

– In terms of which one to use peri-operatively, robenacoxib, meloxicam and carprofen are licensed for intraoperative use (so we can be confident they will not tamper with the coagulation to a point that will be clinically relevant). I tend to reach for meloxicam due to having more experience with it. However if the animals are on a different one I will continue with the same. Studies in general show similar enough outcomes to not have a strong preference for one or the other, so experience plays a big part.

– When it gets to chronic use, the main factor is how well the animals tolerate the drug and side effects. Both meloxicam and robenacoxib have been tested in cats with renal disease, with good results (10.1177/1098612X20935750) (10.1177/1098612X15590870). So I tend to favour one or the other for OA, depending which one gives less side effects, and always at the lowest dose that gives a benefit. Anecdotally, I seem to find some cats which will get GI side effects with meloxicam but tolerate robenacoxib very well.

– In terms of orthopaedic vs soft tissue cases, I do not treat them differently given I cannot find enough evidence to favour one or the other.

– When treating osteoarthritis, I do also find many animals respond nicely to anti-NGF antibodies. However it is important to not forget that those antibodies block pain, but do not do much for inflammation. For this reason I would still assess case by case, and always keep NSAIDs as an option even if as a pulse therapy (a week’s worth of treatment when weather is worse or the animal has done a bit too much exercise) as they will still yield the best results for OA pain, and help towards slowing the progression. Physiotherapy, either in clinic or at home, still plays an essential part of ensuring the muscle stays in shape and provides the support the joint is unable to do by itself.

Hope this helps!

Great stuff!

Felipe

Hi all

Hope you are well and had a lovely Easter!

So, my personal take is that they are very much comparable at equipotent doses. And this is a very important point. We know that dexmedetomidine is the isolated isomer that is active. Racemic mixtures have 50% of each isomer, and for this reason dexmedetomidine is twice as potent as medetomidine (which is 50% dexmedetomidine and 50% levomedetomidine -inactive-). This is why medetomidine is 1mg/mL whilst dexmedetomidine is 500mcg/mL, as the volumes given by the charts will yield equipotent dosing. Levomedetomidine has cardiovascular effects similar to dexmedetomidine, and actually reduces its sedative effects, however only at very high doses (10.2460/ajvr.2001.62.616).

In my opinion, this is pretty much where it ends for dexmedetomidine. This paper actually shows they are very similar (10.3390/ani10071240).

The only instance where I may favour dexmedetomidine is in animals where liver metabolism is not fully competent. By giving half the number of molecules per kilogram, I assume I am giving less metabolic load for the liver to deal with. However, I have serious doubts this makes any difference given the low doses commonly used, and the non-activity of levomedetomidine at normal clinical doses. Potentially in long-term infusions dexmedetomidine could be favoured as we would be giving less molecules for the liver metabolise as a constant infusion. But again, I cannot say I see a clinical difference.

Hope this helps!

Excellent!