General

Vasopressors and Inotropes are a powerful class of drugs that have become the therapeutic cornorstone for the management of shock. These medications enhance vasoconstriction and/or contractility with the end goal to elevate mean arterial pressure (MAP). 

 

Although many of these agents have been used since the 1940s, there are very few clinical trials that have actually compared these agents to each other. In all, the use of these agents largely reflect expert opinion, animal data, physician preference and the use of surrogate end points (eg. tissue oxygenation) as a proxy for decreased morbidity and mortality. 

 

Physiology / Biochemistry

Endogenously, catecholamines are synthesized from the amino acid tyrosine and are secreted from either the brain stem, locus ceruleus or adrenal medulla during flight or fight response.

 

Catecholamine synthesis

 

Catecholamines act mainly on adrenergic receptors as well as dopamine receptors.  

  • rate-limiting step

  • THB (hydroxylates)

  • NADPH

Found in:

  • locus coeruleus

  • sympathetic nerve

  • adrenal medulla

Found in:

  • nucleus succubus

  • substantia nigra

Found in:

  • adrenal medulla

Alpha-1 Receptors

  • located in vascular walls

  • induce vasoconstriction

  • also present in the heart and can increase duration of contraction without chronotropy

Beta-1 Receptors

  • most common in the heart

  • increase inotropy and chronotropy

  • minimal vasoconstriction

 

Bet-2 Receptors

  • found in blood vessels and cause vasodilation

Extravasation

Heat

  • apply proximal to site of extravasation (causes vasodilation which increases blood flow to the area and helps distribute the vesicant)

Elevation

Nitroglycerin 2% Ointment

  • apply 1" strip to outer border of extravasation

Terbutaline 1mg subQ

  • dilute 1:10 with 0.9% NaCl for larger affected areas or 1:1 for localized ischemia

  • inject 10mL of terbutaline solution as five separate injections subQ into the edge of extravasation using a 25G needle (change the needle with each injection)

Phentolamine

  • reversible nonselective alpha-adrenergic antagonist

  • used for extravasation of vasoactive agents

    • dopamine​

    • norepinephrine

    • epinephrine

    • dobutamine

    • phenylephrine

    • vasopressin

Na/K ATPase

Glycogen

Glucose

Glucose 6-P

Fructose 6-P

PEP

Fructose 1,6-biphosphate

phosphofructokinase

citrate

Cori

Cycle

Lactic Acidosis: "existance?"

  • increased aerobic respiration (glycolysis) as part of the stress response (release of epinephrine) causes increase in lactic acid formation

  • possibly important adaptive survival response during critical illness

  • marker of disease severity

  • not an indication of anaerobic metabolism

  • titrating therapy to a blood lactate level may be harmful

Pyruvate

Lactate

NADH

NAD+

lactate dehydrogenase

muscles

skin

brain

RBC

intestine

pyruvate

carboxylase

alanine

oxaloacetate

ATP

NADH

Reference

 

UpToDate, Use of Vasopressors and Inotropes

 

Overgaard, Inotropes and Vasopressors: Review of Physiology and Clinical use in Cardiovascular Disease

... but I would more especially commend the clinician who, in acute diseases, by which the bulk of mankind are cutoff, conducts the treatment better than others.
 
Hippocrates, 400 BC