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Welcome back to the tasty morsels of critical care podcast.
Condensing all of “inotropes and vasopressors” into a single 5 minute podcast is of course doomed to fail but that’s never stopped me before. The main reference for this is Oh’s Manual Chapter 92 by John Myburg who is known to me for describing adrenaline as “God’s own inotrope” and in the same lecture describing dobutamine as “the Devil’s semen”. i have also heard him say with regards to fluid choice in the ICU that you can give any cat’s piss if you like as long as you do it carefully.
The chapter begins with a brief discourse on some of the physiology noting that ~ 20% of blood volume is held in the large conducting arterial vessels, meaning that the majority is held in the smaller vessels and venous structures. This larger venous proportion is often referred to as the unstressed volume. I think of it like the lazy river in a swimming pool, slowly meandering it’s way back to the RV while the arterial side is the flumes that you weren’t allowed on till you were 7 years old and you always had some unconscious fear that you’d enter in and never leave again. But that’s enough about my childhood.
Blood in this lazy river of unstressed volume returns on the venous side along a gradient from something called the mean systemic filling pressure (MSFP) to the lower right atrial pressure (RAP). Maintenance of a lowish CVP will therefore aid venous return.
In terms of improving cardiac output, autotransfusion of this unstressed volume (and increasing preload to LV) is the easiest and quickest and most effective way of improving CO.
Altering vascular tone and cardiac output can be done through a variety of systems:
- the adrenergic system
- renin angiotensin, aldosterone system (RAAS)
- Vassopressinergic
- Glucocorticoid
- Local systems such as nitric oxide and endothelin
Finally the determinants of cardiac output are stroke volume and heart rate. Heart rate in particular is easy to measure and causes issues at either end of the spectrum. When it’s too low the oveerall CO is too low, at some point it’s too fast, impairing cardiac and coronary filling and hence impairing stroke volume.
Pretty much all vasoactive medications have the same end point – that is the release, utilisation or sequestration of intracellular calcium. There are various methods to get there, many of which are cAMP dependant, but calcium is the end point.
First off our beloved catecholamines. There are typically our first line in the fight against MAP<65. We have a fairly bewildering range of options available to us all with their own nuances.The nuances stem from the variety of catecholamine receptor biology we have evolved over the millenia. We know the basics of α and β but these can be extensively sub divided further in forms that only reinforces how little I understand about medicine despite over 20 years studying it.
For exam purposes I find having a rudimentary understanding of the differences between α and β stimuli is useful. Following a β receptor stimulus, there is increased cAMP while following an α receptor stimulus something called phospholipase C is engaged.
Tachyphylaxis is a common clinical phenomenon with the adrenergic drugs and reduced receptor density, sequestration and enzymatic uncoupling are all part of down regulation. Of note steroids act as pressors probably by increasing receptor sensitivity to catecholamines.
Both adrenaline and noradrenaline are predominantly β in action at lower doses with the α effect coming in at higher doses. Pretty much all the synthetic catechols are β in action with the obvious exception being phenylephrine as a pure α.
Myburgh is keen to make the point that at the doses we use, the catecholamines have no effect on arterial tone and CABG or vascular grafts, which is a frequent concern of our surgical colleagues who are understandably somewhat precious about their grafts and anastamoses. However it seems that when they go iscahemic it’s not the use of catecholamines is to blame but rather the severity of illness that requires the use of catecholamines. It is acknowledged that necrosis is common but more likely due to microthrombosis from sepsis rather than vasoconstriction from pressors.
Next let’s look at the phosphodiesterase inhibitors. Milrinone, enoxamone and levosimendan are all in this bucket. They work by non-receptor mediated inhibition of PDE, ultimately resulting in increased cAMP. They are thought to be unique in that they may improve lusitropy (ability of heart to relax). All come with potent vasodilation so expect to have to crank up your pressor to compensate. They do not seem to suffer from tolerance and tachyphylaxis. It’s reported that they can inhibit platelet aggregation but unclear how significant this is in real life. A major downside is their prolonged half life and dependance on working kidneys for excretion.
Vasopressin is another obvious category to discuss but I’ll save that for its own entry.
References
Ashley Miller’s short video on MacroCirculation physiology