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Stuck at home with a temp and myalgia. 10 minute teaching session today is PHYSIOLOGY. The best reflex no one has heard of, and causes 'tourniquet pain', AKI and post op ileus. The Exercise Pressor reflex. [If I ever get my hands on the FRCA :p]
Several phenomena in medicine we see a lot and can't quite explain. e.g. one hour into a tourniquet/ischaemic event of some kind, it doesn't matter what analgesia you give, they get hypertensive, tachycardic and behave like rampantly in agony.
Anaesthesia/surgery is associated with AKI, cerebral perfusion deficits, and ileus, especially general surgery ofc (but all). yes many factors, inc hypotension, but we measure the radial perfusion or brachial perfusion. Everything is sympathetically innervated and organ level
perfusion is variable. I bet you didn't know that splanchnic perfusion decreases nearly 40% IN SPITE OF AN EPIDURAL when we cause ischaemic events in the lower limb, or that light load exercise with an epdiural affecting the lower legs, still causes 3x the sympathetic
signalling to the renal artery and activation of RAAS. Why would the epidural betray us like this. Why does anaesthesia not know about these experiments OF GIVING EPIDURALS, OPIOIDS AND LOCAL ANAESTHETICS TO CYCLISTS THIS IS SO TOTALLY OUR BAG
It's because, fundamentally, fight and flight is more important to survival than the epidural. So the physiology bit: blood flow conductance increases 5 x in exercise yet BP increases. Have you seen the Sepsis? Is that what happens when they go all vasodilatey. Je pense pas.
So how then, are we going to provide all these lovely muscules with metabolites. We ask the body nicely to up O2 delivery and washout, and cardiac output, and fluid. We want increased BP, increased HR, increased resp rate. Does this sound anything like tourniquet pain yet?
How do the muscules ask for more stuff. They write a little list for the brain in the form of acid and ATP. Small nerve fibres (Group III/IV; thin and unmyelinated respectively if you care) innervate vessels and have co-dependent signalling from ATP receptors and acid receptors.
very sensibly, any single one of protons, lactic acid, ATP does very little, as does any of them if no co-localised. But put them together and wow the ASIC3 receptor goes a bit crazy. In health this is cos that's exercise, so you need more blood flow. In muscle death/ischaemia
it still thinks the same, so, you're gunna get the same reponse. These signals go through this little afferents to the dorsal horn (mixture of 1,2 and 5, Rexed laminae for those who care) and ascend in the spinothalamic tract, where they will integrate with sympathetic input
in medulla. Outflow is mediated sympathetically from thoracolumbar chain, and can also be evoked directly by metabolites at a peripheral level, causing vasodilation on top of central increased 'pressor' response.
So. Let's give the epidural to cycling people (heh it wasn't even an anaesthetist doing these experiments). At small local anaesthetic conentrations you don't really see any effect on reducing the pressor response. (like 0.5% and 1% lignocaine without a high block).
In fact, the Central Processing Unit (the brain) decides that if it isn't getting enough feedback from the grp iii/iv afferents, then something is lying, and it just goes harder on the centrally decided sympathetic outflow.
Thwarted. So the main way to abrogate the pressor response is to ensure a high spinal blockade which gives sympathetic block. This kind of makes sense to us all, who give clonidine (antagonises noradrenaline) with mixed efficacy for this tourniquet pain.
That's probably nicer for your kidneys etc too. I do wince a bit considering all the cross clamping vascular does, that the body is interpreting this as an 8 hour run, and tried to increase cardiac output accordingly. HELP!
The good news is that when they used fentanyl in the epidurals that went high enough (and tried to account for RR and central effects), the exercise induced cardiac output was reduced by 20%. So that is nice, for these patients. In fact with decent afferent blockade
and output, the cardiovascular reponse to cycling exercise was attenuated to between 25 and 90% of the maximal oxygen consumption. I did know this deep down, but that is a profound difference!
The caution, however is that when we abrogate the pressor response like this, muscle fatigue is prfooundly enhanced. Twitch strength is reduced - the development of fatigue (objective, not subjective) is 70% steeper. So what does this mean for patients we are trying to rehab/come
off ventilators. We protect their hearts with beta blocklade etc, with consequences for their muscle strength. Notably, the biggest attenuation for the pressor reponse is with 0.5% bupiv and 2% lignocaine - that used for epidurals and surgical spinals.
BUT THEY MUST GO INTO THE SYMPATHETIC REGION. There is also a hugely variable amount of spatial and temporal summation at the level of the nociceptor, the spinal cord, and the central processing. Enhanced anxiety affects this.
Interestingly, epidurals etc didn't ever affect the quantity of metabolite production, so the signalling and reponse was all spinally or cerebrally driven. Some drugs such as paroxetine (for some mental health problems) really affects the ASIC3 acid sensing etc
I can't explain the onset of the pain at an hour, but i suspect it is to do with redistribution of the opioid or block out of thin, non insulated axons, and then need for sympathetic blockade to be maximal.
The full fascinating papers here: https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/expphysiol.2011.057679
