Vasoactive is an umbrella term for any drug that makes your heart rate and/or blood pressure go up or down. Vasopressor, on the other hand, is a term for a drug that makes your blood pressure goes up by the process of vasoconstriction (squeeze).
A positive inotrope is different from a vasopressor in that an inotrope affects cardiac contractility in a positive way- e.g. it makes your heart pump stronger. So a positive inotrope increases the strength of the muscular contraction and a negative inotrope weakens the strength of the muscular contraction. Some drugs act as both a vasopressor and an inotrope. Drugs can also effect chronotropy which simply means a change in heart rate. Positive chronotropy means an increase in heart rate and negative chronotropy means a decrease in heart rate.
You should be slightly familiar with the idea of drug receptors if you want to understand how our ICU vasoactive drugs work. The drugs we give our patients have neurotransmitters that land on receptor sites and act as either agonists or antagonists. Agonists stimulate the response and antagonists block the response.
Cholinergic nerves release acetylcholine and are part of the parasympathetic nervous system. The parasympathetic system is our “rest and digest” system. Activation makes blood vessels dilate, heart rate slow, pupils constrict and makes you secrete more saliva. Anticholinergics block vasodilation and decrease saliva secretion. Atropine is a good example of an anticholinergic- it competes for receptor sites to blocks the effect of the parasympathetic nervous system and the vagal nerve. The vagal nerve can be responsible for bradycardia. This is why you sometimes hear a nurse or health care provider say the patient has vagal’d down or brady’d down when the patient drops their heart rate suddenly.
Adrenergic nerves release epinephrine, norepinephrine and dopamine and are part of the sympathetic nervous system, our “fight or flight” system. Norepinephrine primarily actives alpha 1 receptors in vascular walls, which causes increased vasoconstriction. Epinephrine primarily activates beta receptors but sometimes activates alpha receptors as well. Beta 1 receptors are most commonly found in your heart and beta 2 receptors are most commonly found in your lungs.
An easy way to remember this is to remember that you have 1 heart (beta 1) and you have 2 lungs (beta 2). Activation of beta 1 receptors increases contractility (a positive inotropic effect) and also increases heart rate (a positive chronotropic effect). Beta 2 receptor activation causes bronchodilation in the lungs and causes vasodilation in the vascular smooth muscule. When epinephrine activates alpha receptors, we get local vasoconstriction. Adrenergic blocking agents are in the anti-hypertensive drug category because they block the alpha and beta effects, thereby causing relaxation of smooth muscle and preventing the fight or flight response from taking over.
Dopamine receptors are found in renal, mesenteric, coronary, and cerebral vascular beds. When dopamine receptors are stimulated, the result is vasodilation.
It is important to understand the mechanism of action for the vasoactive drugs we use in the ICU. As we mentioned earlier, some drugs may activate multiple receptors and have varied responses. Also, some drugs activate certain receptors at a lower dose and additional receptors at a higher dose. The prescriber does not randomly choose a vasoactive medication. Careful thought should go into determining why the patient is hypotensive before choosing the best vasoactive medication to reverse the hypotension. Does the patient need an increase in vasoconstriction or an increase in heart muscle strength? Vasoactive medications are dangerous drugs with many side effects and are therefore only used in a monitored unit for patients who are in shock.
Neosynephrine may also be referred to as “Neo” in the ICU. It is a pure alpha adrenergic so it causes vasoconstriction. The vasoconstriction increases systemic vascular resistance (SVR), which in turn increases the mean arterial pressure (MAP). If you were giving Neosynephrine to a patient with a pulmonary artery catheter, you should see an increase in your SVR values. An increase in SVR can sometimes mean a decrease in cardiac output because an increase an SVR makes the heart work a little harder to pump blood out against the squeezing/vasoconstricting vessels. Therefore, this drug may not be the best choice for a patient with heart dysfunction.
In addition to being a vasoconstrictor, Neosynephrine has some positive inotropic and chronotropic action. This means Neosynephrine may slightly increase cardiac contractility and slightly increase the patient’s heart rate.
Norepinephrine may also be referred to as “Norepi” or “Levo.” It is an alpha and beta adrenergic agonist as well as a sympathomimetic drug. Sympathomimetic drugs mimic the sympathetic nervous system, so we get a fight or flight type response.
Norepinephrine causes potent vasoconstriction and has a small positive inotrope effect so you may see a small increase in your patient’s cardiac output. In addition, Norepinephrine dilates the coronary arteries to help deliver more oxygen and nutrients to the heart muscle. This is a result of the beta adrenergic agonist response.
With Norepinephrine, the MAP is elevated by severe vasoconstriction. Fluid resuscitation is important for patients on pressors so you’ll often given a fluid bolus before starting a pressor and start a maintenance fluid like Normal Saline 0.9% or Lactated Ringers. If the patient is in hemorrhagic shock, where the problem is loss of blood, you should replace blood products and give fluid before hanging a pressor. You can’t squeeze a dry tank! If you squeeze a dry tank, you may see renal failure (decreased urine output), tissue hypoxia/ischemia and lactic acidosis and meanwhile your monitor is telling you the blood pressure is adequate. Why? Because it is measuring the amount of squeeze in the vessels, not delivery of oxygen and nutrients to the tissues. That’s why we look at the entire patient, not just the monitor. Signs of poor cardiac output are dusky skin, cold and clammy skin, and decreased urine output.
Norepinephrine also has a small positive chronotropic effect that gets cancelled out by reflex bradycardia (caused by the increase in MAP). As a result, your patient’s heart rate usually stays the same or decreases slightly.
Norepinephrine is used as a first line treatment for septic shock.
Epinephrine may also be referred to as “Epi” in the ICU. Epinephrine is a potent beta 1 agonist and a moderate beta 2 (vasodilation) and alpha 1 (vasoconstriction) agonist.
The beta 1 agonist effects include increased inotropy and chronotropy and unfortunately the beta 1 activation puts the patient at risk for cardiac dysrhythmias due to the beta 1 stimulation in the heart. So when you’re giving Epinephrine, you may start to see ectopy on the cardiac monitor. We will talk about this more in Part 2 where we go over complications of vasoactive medications.
Epinephrine is a dose dependent drug, so at lower doses you see different effects than you would in higher doses. At low doses, there is more vasodilation as a result of beta 2 receptor stimulation in the muscles and the liver. At low to moderate doses, Epinephrine should give your patient an increased cardiac output and a decreased SVR but you may not see much of a change in your MAP. At higher doses of Epinephrine, there is more vasoconstriction secondary to alpha 1 activation.
Epinephrine is second line treatment for septic shock and first line treatment for anaphylactic shock. Post operative cardiac surgery patients are usually on Epinephrine drips as well because of the positive inotropy and positive chronotropy.
See Part II for information on Dopamine, Dobutamine, Vasopressin, and a discussion of complications and tips for ICU drips.