Friday, 15 November 2019

Tropes and Pressors - Part 2 of a 3 part series.


Tropes and Pressors  -A 3 part series.
Part 2 of 3  # KYJ (Knowing your jargon)
This episode – The Pressors
Recap from yesterday …
Vasopressors are drugs we give to squeeze arteries (and veins) to increase SVR (Afterload and Blood pressure, and subsequently MAP.

Inoptopes :more correctly – positive inotropes, are drugs we give to increase the force of the cardiac contraction. This increases SV, and CO which of course increases MAP.  Its all about that MAP!!.
So when are each indicated?
God I wish it was that simple, but it comes down to etiology (cause) and type of shock occurring in the patient.
If you didn’t already view the post on shock, or watch my Video on shock;  then perhaps that might be a good place to refresh.
Remembering there are 4 main types of shock: hypovolemic, distributive, cardiogenic, and obstructive. Vasopressors and inotropes may be indicated for all types, and though most of the medications can be used in each type, we do need to tackle the specifics of each one.

So….here goes.
The major vasopressors include phenylephrine, norepinephrine, vasopressin and Metaraminol.
Drugs like Adrenaline and Dopamine are vasopressors, but they also exert inotrope properties.

Then  out on a limb (good choice of words really) Dobutamine and Milrinone are obligate inotropes.

So Last bit of FIZZ (physiology before we dive into the drugs)
Receptors to consider for this post :
Adrenergic - Alpha 1 – Cause Vasoconstriction
Adrenergic - Beta 1  - Causes increase Chronotropy and Inotropy
Vasopressin Receptors – V1 = vasoconstriction, V2= reduced urine output.

The Vasopressors
By redistributing blood back to the heart, vasopressors help increase CO directly with an increase in blood return to the heart (Preload), and  and increase in SVR. through arterial vasoconstriction peripherally. There are  main groups are catecholamines, Smooth Muscle and dopaminergic receptors
The Vasopressors are ‘Boss of the Pit’ when distributive shock (Sepsis, Neurogenic disruption or anaphylaxis) is the dominant cause of drop in Cardiac output.  The goal of vasopressors is to increase the SVR by direct constriction of the vessels.
Two distinct physiologies are happening in distributive shock.  
First a loss of nerve messages to blood vessel walls  causes them to relax – dilate, and blood pools in the peripheries.  With the maldistribution of volume between central and peripheral circulation, (blood stuck out in the veins of Arms and legs), there is little perfusing the core vital organs.  Remember at any given moment in time your 5.5 litres of blood is parked 30% in your arteries, and 70% in your veins.  Increases in that venous pooling causes a dramatic drop in arterial flow/volume and of course, pressure (SVR and MAP).
Secondly, as blood in peripheral areas pools, and causes congestion, this vasodilation extends to the capillaries, and these little guys are super leaky.   As they congest, and spill their plasma into the peripheral tissues, you see oedema forming and drop in blood volume, which is now becoming thick and viscous as plasma leaves, the haemoconcentrated blood now has a tenacious sticky vibe going on.  Bad bad bad.   You can see why we fluid resuscitate these people.  In fact, a fluid load, is frequently the First line treatment; and only after some sauce is given to we then squeeze the pie – ok bad visual.
Note to Americans – in Australia we eat real pies with meat inside – sauce “dead horse”  or what you mob call “ketchup” is a must have.

Right Back to it…

Remembering that that Magic MAP of 60 to 65 mm Hg is required to perfuse organs (American College of Critical Care Medicine (ACCM) guidelines). If fluid resuscitation doesn’t get that MAP up to 60 mm Hg, it is recommended that vasopressors be next in line.

So what do we select? 
Norad (Noradrenaline) / Norepinephrine
The first of our Catecholamines, and a favourite in the Sepsis world (Surviving Sepsis Campaign recommendation).

We follow this with Adrenaline (epinephrine) or Vasopressin  as a back up plan
Norepinephrine is recommended as the initial pressor for  because it lights up those Alpha  receptors.  In blood vessels, these receptors act like switches that open Calcium gateways into the smooth muscle cells lining the vessel walls.   As they get turned on, Calcium rushes in, causing the muscles to contract (constrict) pushing up the pressure, and squeezing the blood out of those naughty veins, back to the heart and central core circulation.   By increasing the venous return, then you increase the Preload, and the heart now has volume it can use to pump with.  They also act on the arteries (remember that constriction here increases SVR and MAP)  … And that is the game changer.

Metaraminol
Metaraminol is trade named Aramine, and Metaramin.  It is a potent alpha 1 stimulant, with weak Beta effects.  It tends to be used in spinal cord injuries that result in distributive neurogenic shock, and to bring up BP in a perianaesthetic scenario.  RFDS in Australia use it as a first line "rescue drug" for increasing BP that can occasionally plummet when performing rapid sequence induction (emergency intubation).   Dose is usually up to 10mg diluted to 20 ml and given in a good secure IV line as a slow push over 1-2 mins

Vasopressin
Vasopressin is a natural hormone also known as ADH (Antidiuretic Hormone) normally secreted from the Pituitary gland.
It fires up specific Vasopressin 1 and 2 receptors.  Remember V-1 receptors to stimulate smooth muscle contraction of the vessels , and the V-2 receptors in the kidneys stop urine production hence increased blood volume, and increased CO and MAP.
It wont cause the patient to increase heart rate, or increase force of contraction.

Phenylephrine
This is another pressor that occasionally gets bandied around, but caution in use is advised because it tends to cause a reflex bradycardia.
Ironically, as much as it fires off those alpha receptors to cause vasoconstriction, The sudden increase in BP can trigger off the vagus nerve (Parasympathetic) which is actually the nerve that tells the heart to “Go Slow – this is a school zone”.  So BP goed up, parasympathetic response kicks in and a reflex bradycardia loses the ground you gain.  Some docs love it- Im not convinced.  Many of you will know of Phenylephrine as the why bother replacement for pseudoephedrine in the old cold and flu tablets.
Phenylephrine is a pure alpha-1 agonist, inducing peripheral arterial vasoconstriction. Reflex bradycardia may occur due to selective vasoconstriction and elevation of blood pressure.

Adrenaline
Also known as Epinephrine, this hormone has essentially equivocal activity on alpha-1 and beta -1 receptors. So Epinephrine increases SVR through the Alpha 1, and the Beta effects on increasing Inotropy and  HR, boost cardiac output on both sides of the equation (CO=SVxHR).

Dopamine is a precursor of norepinephrine and epinephrine (catecholamines).  So it essentially does the same thing.  All good pies need a reliable base, so as a precursor to the catecholamines, the effects are both vasopressor and inotropic.
Controversy exists around whether differing doses of Dopamine affect different tissues. Many readers will recall that low doses increase renal perfusion(5 to 15 micrograms/kg/min), and higher doses (>15 micrograms/kg per minute), are more peripherally vasopressor.
Giving Pressors
IV.   Say it out loud.  IV.   These drugs are for intravenous (IV) use only.   They are fast acting, short duration, and epically destructive if an IV cannula through which these drugs are given, should extravasate (tissue).
It’s a brave clinician that will settle for a peripheral IV line, so as soon as possible these patients should have a central access (either CVL or PICC).  Doses are dependent on presentation but always via a pump, and the patient should be very closely monitored – especially heart rate and BP, but also Sats, JVP and breath sounds.  As BP can rise dramatically with pressors, complications like heart failure can declare itself with a surprise ankle swelling, pulmonary oedema, and breathlessness.
Next part of our series will tackle the other class of drugs, looking deeper at the Beta 1 receptor meds  - the inotropes.

Now the physiology and Jargon is out the way, stay tuned for Part 2 as we dive into the deep dark world of the "Tropes and Pressors"
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