Vasopressors and Inotropes

Pharmacy and Therapeutics

Definitions of Vasopressors and Inotropes

  • Inotropes are drugs that increase myocardial contractility (inotropy) — e.g. Epinephrine, Dobutamine, Isoproterenol, Ephedrine
  • Vasopressors cause vasoconstriction resulting increased systemic and/or pulmonary vascular resistance (SVR, PVR) — e.g. Norepinephrine, vasopressin, vasopressin.
  • Inodilators are agents with inotropic effects that also cause vasodilation leading to decreased systemic and/or pulmonary vascular resistance (SVR, PVR) — e.g. milrinone

Dosing and Titrating Vasopressors and Inotropes

Dosing and Titration of Vasopressors and inotropes.

How to Choose Pressors and Inotropes

When choosing pressors, you look at two key things:
1) Heart Rate
2) Blood pressure
You want to choose a drug that gives you the effect you want on your blood vessels without raising the heart rate if your heart rate is already high. For example, we had an ICU pt on Norepinephrine drip with a heart rate of 136 and SBP of 90 and a MAP of about 60. We gave a liter of LR first to try to raise the blood pressure. [FYI: A good way to check for likely response to fluids is to lift the patient’s legs up (make sure pt doesn’t have any potential trauma to hips). If the BP or MAP rises, then it will likely respond to fluids.] When the patient didn’t respond to fluids, we wanted to choose a second pressor. Heart rate was already 136 and so we didn’t want to choose anything that had inotropic activity. Patient’s PH was also 7.2. In such low PH, the adrenergic agonists that are used as pressors wouldn’t work. So we went for Vasopressin which doesn’t work through alpha or beta adrenergic receptors. In fact in this patient, because NE has inotropic effects, even though it is usually the first line drug, our goal was to start vasopressin and then try to wean off NE since he was tachycardic.
That’s an example of how you chose a pressor or inotrope. If you want to improve heart function, then chose one that mainly has beta receptor activity. If you want to improve BP without affecting heart function much, you chose one with mostly alpha receptor activity. That’s it.
Vasopressors and inotropes in treatment of acute hypotensive states and shock: Adult dose and selected characteristics (adapted from uptodate.com)
**Epinephrine, dobutamine and Isoproterenol also have (β-2) effects on the lungs.
Most pressors are adrenergic receptor agonists. Their use exploits our understanding of the sympathetic nervous system.
Agent IEffect on blood vessels (α-1) Effect on Heart
(β-1)		 Uses and important properties
Vasopressors (mainly alpha-1 adrenergic)
Norepinephrine (noradrenaline)  +++ ++ Initial vasopressor of choice in septic, cardiogenic, and hypovolemic shock.
 Epinephrine (adrenaline)  +++  +++
  • Initial vasopressor of choice in anaphylactic shock.
  • Typically an add-on agent to norepinephrine in septic shock when an additional agent is required and occasionally an alternative first-line agent if norepinephrine is contraindicated.
  • Increases heart rate; may induce tachyarrhythmias and ischemia.
  • Elevates lactate concentrations during initial administration (ie, may preclude use of lactate clearance goal); may decrease mesenteric perfusion.
  • Note that epinephrine has an equally strong effect on both heart and blood vessels. It doesn’t favor any one side. It’s 50-50, as Dr. Beinstein put it to me.
 Phenylephrine   +++  0
  • Pure alpha-adrenergic vasoconstrictor.
  • Initial vasopressor when tachyarrhythmias preclude use of norepinephrine.
  • Alternative vasopressor for patients with septic shock who: (1) develop tachyarrhythmias on norepinephrine, (2) have persistent shock despite use of two or more vasopressor/inotropic agents including vasopressin (salvage therapy), or (3) high cardiac output with persistent hypotension.
  • May decrease stroke volume and cardiac output in patients with cardiac dysfunction.
 Dopamine (5-10mcg/kg/min)
  •  A second-line agent to norepinephrine in highly selected patients (ie, low risk of tachyarrhythmias or bradycardia induced hypotension).
  • More adverse effects (eg, tachycardia, arrhythmias particularly at doses ≥20 mcg/kg/minute) and failed therapy than norepinephrine.
  • May be useful in selected patients (eg, with compromised systolic function or bradycardia at low risk for tachyarrhythmias).
  • Dose dependent effects
 Dopamine (10-20mcg/kg/min)
Antidiuretic Hormone (Vassopressor)
 Vasopressin (arginine-vasopressin)
  • Add-on to another vasopressor (eg, norepinephrine) to augment efficacy and decrease initial vasopressor requirement. Not recommended as a replacement for a first-line vasopressor.
  • Pure vasoconstrictor; may decrease stroke volume and cardiac output in myocardial dysfunction or precipitate ischemia in coronary artery disease.
Inotrope (Beta-1 Adrenergic)
 Dobutamine 0/+ +++
  • Initial agent of choice in cardiogenic shock with low cardiac output and maintained blood pressure.
  • Add-on to norepinephrine for cardiac output augmentation in septic shock with myocardial dysfunction (eg, in elevated left ventricular filling pressures and adequate MAP) or ongoing hypoperfusion despite adequate intravascular volume and MAP.
  • Increases cardiac contractility and rate; may cause hypotension and tachyarrhythmias.
  • Dobutamine also has ++ effects on Beta-2 adrenergic receptors (in the lungs).
Isoproterenol 0  +++ It also has +++ effects on Beta-2 adrenergic receptors.
Inotrope (nonadrenergic, PDE3 inhibitor)
Milrinone
  • Alternative for short-term cardiac output augmentation to maintain organ perfusion in cardiogenic shock refractory to other agents.
  • Increases cardiac contractility and modestly increases heart rate at high doses; may cause peripheral vasodilation, hypotension, and/or ventricular arrhythmia.
  • Renally cleared; dose adjustment in renal impairment needed.
 * All the drugs with mainly inotropic effects on the heart (dopamine, dobutamine, isoproterenol) can cause tachyarrhythmias.

Vasopressors can cause life-threatening hypotension and hypertension, dysrhythmias, and myocardial ischemia. They should be administered by use of an infusion pump adjusted by clinicians trained and experienced in dose titration of intravenous vasopressors using continuous noninvasive electronic monitoring of blood pressure, heart rate, rhythm, and function. Hypovolemia should be corrected prior to the institution of vasopressor therapy. Reduce infusion rate gradually; avoid sudden discontinuation.

Vasopressors can cause severe local tissue ischemia; central line administration is preferred. When a patient does not have a central venous catheter, vasopressors can be temporarily administered in a low concentration through an appropriately positioned peripheral venous catheter (ie, in a large vein) until a central venous catheter is inserted. The examples of concentrations shown in this table are useful for peripheral (short-term) or central line administration. Closely monitor catheter site throughout infusion to avoid extravasation injury. In the event of extravasation, prompt local infiltration of an antidote (eg, phentolamine, if available) may be useful for limiting tissue ischemia. Stop infusion and refer to extravasation management protocol.

All vasopressors and inotropes come in forms that must be diluted before administration. Pharmacy takes care of that.

Vasoactive medication receptor activity and clinical effects
Drug Receptor activity Predominant clinical effects
Alpha-1 Beta-1 Beta-2 Dopaminergic
Phenylephrine +++ 0 0 0 SVR ↑ ↑, CO ↔/↑
Norepinephrine +++ ++ 0 0 SVR ↑ ↑, CO ↔/↑
Epinephrine +++ +++ ++ 0 CO ↑ ↑, SVR ↓ (low dose) SVR/↑ (higher dose)
Dopamine (mcg/kg/min)*
0.5 to 2. 0 + 0 ++ CO
5. to 10. + ++ 0 ++ CO ↑, SVR ↑
10. to 20. ++ ++ 0 ++ SVR ↑ ↑
Dobutamine 0/+ +++ ++ 0 CO ↑, SVR ↓
Isoproterenol 0 +++ +++ 0 CO ↑, SVR ↓

Vasopressin is not listed above.

+++: Very strong effect; ++: Moderate effect; +: Weak effect; 0: No effect.
* Doses between 2. and 5. mcg/kg/min have variable effects.

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