So you have a patient who is acidotic and hypotensive and you need to resuscitate them. Your agency/hospital has no care about their budget and doesn’t mind blowing money left right and center so you have access to the following vasopressors:
- Norepinephrine (Loveophed)
Which of these would be most ideal for your hypotensive acidotic patient? If you say Vasopressin you would be correct. Now lets get into the WHY this happens and we start by understanding these medications more. Vasopressin is also known as antidiuretic hormone (ADH) which is naturally synthesized by the hypothalamus and released from the posterior pituitary gland until the body notices it is hypotensive. This medication acts on V1 receptors on the vasculature causing vasoconstriction. It also acts on V2 receptors on in the renal collecting ducts which causes water reabsorption which increases blood volume. Epinephrine and norepinephrine are catecholamines and act on various adrenergic receptors. Dopamine is a catecholamine precursor. And phenylephrine is a selective alpha 1 adrenergic agonist (Phenylephrine is not as inhibited in acidotic patients in comparison to the other medications). So how does the acid-base of our patient impact these patients?
How pH impacts receptors
I have a whole post on how adrenergic receptors work which you can read here: https://scopeducation.training/implementing-beta-blockers-and-hemodynamic-dosing-for-cardiac-arrest/
There are four main ways that pH impact Adrenergic receptors:
- Amino acids like histidine, aspartate, and glutamate have ionizable side chains that are sensitive to changes in pH. When pH levels shift, these amino acid chains can gain or lose protons, altering their charge and overall structure. This can directly impact the receptor’s binding site, changing its affinity for a ligand (a molecule that binds to a receptor) and potentially affecting receptor activation.
- As amino acids gain or lose protons (hydrogen ions H+), the hydrogen bond network, salt bridges, and electrostatic interactions within the receptor can be disrupted. This leads to changes in the protein’s three-dimensional structure, which can directly impact the binding site and its interaction with the ligand.
- Allosteric sites on a receptor protein are separate from the primary ligand-binding site but can still influence the receptor’s activity. An allosteric site is just a place on an enzyme that causes a change in shape or change in function of a receptor. As pH changes, these allosteric sites can undergo conformational changes, which in turn can affect the primary binding site and how it interacts with the ligand. This is another way pH changes can subtly modulate receptor function.
- Changes in pH can also influence the rate at which a ligand binds to or dissociates from a receptor. As a receptor gains or loses a proton (H+) the receptor and the ligand change and how they bind also changes. This can lead to differences in receptor activation and how the receptor signals (this in-depth process is talked about in the blog post mentioned above).
A lot of the catecholamine derived medications that we administer perform best in our alkalotic patients as adrenergic receptors have a higher affinity to allow these medications to bind to. Vasopressin is best used in acidotic patients due to its greater efficacy in vasoconstriction and less impact on myocardial demand.
Let us say we have our same acidotic and hypotensive patient but you don’t have Vasopressin to administer to this patient, what do you do? Acidosis causes catecholamine resistance and in patients who are critically ill, they might have adrenal insufficiency or critical illness related corticosteroid insufficiency (CIRCI). There are three big ways steroids help these patients:
- Steroids can enhance the sensitivity of blood vessels to catecholamines by upregulating the expression of adrenergic receptors found on the cell wall. Upregulation occurs when there is a low amount of catecholamine/hormone present and cells create more receptors for it to bind to. Downregulation is when there is too many catecholamines/hormones in the serum and cells naturally decrease the receptor sites found on the cell membrane.
- In our septic patients, they can reduce systemic inflammation. Inflammation causes vasodilation, decreased perfusion to organs, and capillary leakage.
- CIRCI patients may have inadequate cortisol production so administering steroids can indirectly regulate catecholamine production and functions.
Cortisol is a glucocorticoid hormone produced in the adrenal cortex (epinephrine and norepinephrine are released in the adrenal medulla).
Cortisol can increase the expression and activity of tyrosine hydroxylase (used in synthesis of epinephrine and norepinephrine). Cortisol is also able to cause upregulation of adrenergic receptors on bloood vessel walls which allows catecholamines to more easily bind to which will help with vasoconstriction. We also rely on cortisol to help stimulate our SNS (flight or fight) so the more that we have in our body, the more hightened the response. And the final way cortisol can help indirectly regulate our catecholamine production is to remember everything our body does requries energy and cortisol helps maintain adequate levels of glucose in our body by promoting gluconeogenesis and glycogenolysis.
In the end, it is important to know that the various causes of acidosis and alkalosis can impact your treatment plan and not all medications are created equal in every situation. For example, epinephrine is a potent alpha and beta adrenergic receptor agonist which results in vasoconstriction, increased cardiac ouput, and bronchodilation but it also causes tachycardia and subsequently increased myocardial oxygen demand. Corticosteroids have supported use in septic shock patients who don’t respond well to fluid resuscitation and are catecholamine resistant but that doesn’t mean that they are perfect for every type of shock.
This site is meant to be used for educational use only. We strive to push evidence-based medicine with no bias to help you obtain all of the important information. You should always follow your protocols that have been set in place.
-Scopeducation Team (Matt)