By Lara Silverman, MD/MPH
Emergency Medicine PGY3

Pressors are used in hypotension. Per Scott Weingart, there are three main reasons we use pressors: 

  1. Maintain critical perfusion pressors, especially to the brain, heart, and kidneys. Below a MAP of ~50, a person will begin to have altered mental status and below ~40, the brain starts to become ischemic. The coronary arteries have a critical perfusion pressure of ~65 and below that, the heart might not pump at peak performance due to inadequate oxygenation. Finally, the kidneys will shut off in an effort to preserve volume somewhere around a MAP of 65-70. 
  2. Increase venous return, pushing reserved (“unstressed”) volume out of the venous system and into circulation in order to create preload and increase flow. 
  3. Avoid gut ischemia. The gut is a “non-essential” organ and blood flow to the gut will become restricted in times of stress, as during a catecholamine surge while in a shock state. This can lead to gut ischemia and translocation of bacteria, causing or worsening sepsis. Also beware of this with excessive exogenous catecholamine. 

Pressors, by and large, attempt to improve blood pressure by altering the cardiac output and/or the systemic vascular resistance (BP = CO x SVR). Be aware, however, that perfusion is not as straightforward as a simple math problem. When we increase the systemic vascular resistance, we do not guarantee that the cardiac output will remain constant — if we are asking a weak heart to pump against greater resistance without augmenting cardiac function, we might inadvertently decrease the cardiac output and tank perfusion. However, the counterpoint to that is that vasoconstriction likely also increases preload, which could improve cardiac output. Think of choosing a pressors as a balancing act and consider the underlying pathophysiology of hypoperfusion. Monitor the MAP, but also monitor clinical factors such as urine output, cap refill, and mental status to guide  your resuscitation.

  Classically, we think of pressors as acting on the adrenergic receptors (α1, α2, β1, β2, and β3), which are the main receptors on which endogenous epinephrine and norepinephrine act when the body mounts a fight-or-flight response. Specifically, the α receptors stimulate vasoconstriction and the β receptors stimulate vasodilation, promote bronchial smooth muscle relaxation, and increase the heart rate. 

      However, some pressors act on cAMP, dopamine, or the vasopressin receptors, resulting in slightly different effects. Rather than focusing on the nuances of the receptors, keep the equation BP = CO x SVR in mind and think of three main categories of pressors:

  • Inopressors: increase CO and SVR
  • Pure vasopressors: Increase SVR
  • Inodilators: Increase CO, decrease SVR

Receptors and Terms:

  • α1 receptor: vasoconstriction (receptors are on vascular smooth muscle)
  • β1 receptor: inotropy and chronotropy (receptors are on the heart)
  • β2 receptor: vasodilation (decreased vascular resistance, makes it easier for the heart to push blood into the vascular system. Receptors are on smooth muscles)
  • V1 receptor: vasoconstriction (receptors are on vascular smooth muscle)
  • V2 receptor: increase water reabsorption (receptors on renal tubules)
  • Dopamine: dose-dependent responses (on selective vascular beds)
  • cAMP: inotropy, chronotropy, vasodilation (second messenger that stimulates beta receptors)
  • Catecholamines: epinephrine, norepinephrine, dopamine 
  • Inotropy: strengthens the force of muscular contraction
  • Chronotropy: increases heart rate

Inopressors (aka inotropes / catecholamines): Increase CO and SVR

The inopressors are generally considered the workhorses of all the pressors, as they both increase inotropy / chronotropy and also the systemic vascular resistance, increasing BP from all angles. Scott Weingart says that he always starts with Norepi and adds a second drug once he determines if the primary issue is cardiac function or a need for more preload. If the issue is cardiac function, his second drug of choice is epinephrine, which he often uses at a low dose.

Norepinephrine: aka levophed, noradrenaline
Uses: First line in undifferentiated shock
Dose: 0-40+ mcg/min
Receptors: αααβ

In the surviving sepsis guidelines, norepi is the first line pressor and is very good in undifferentiated shock. It is primarily a vasoconstrictor, with arterial dilation leading to increased coronary blood flow and increased afterload and venous dilation leading to increased preload. However, it also has modest inotropic and chronotropic effects (primarily at higher doses), helping to improve cardiac function, and likely improves renal perfusion. It can be run peripherally for short periods of time (a few hours). 

Epinephrine: aka adrenaline
Uses: Bradycardia, second line to augment cardiac function in shock, push-dose pressor in peri-arrest bradycardia, anaphylaxis
Dose: 2-5mcg/min for isotropy; 10-20+mcg/min for isotropy and vasoconstriction; 5-20mcg q2-5min as push dose
Receptors: αββββ

At low doses, epi works as an inotrope, increasing cardiac contractility and heart rate. This makes it an ideal agent for bradycardia in a multitude of settings (including sepsis with normal-low HR) and can be used to augment cardiac function in a patient who has already established a baseline increase in afterload with a first-line agent. At higher doses, epi will also have vasoconstrictive effects.  Epi can be used as a push-dose pressor in a patient with peri-arrest bradycardia.       Beware that epi can cause an increase in lactate production (not a decrease in tissue perfusion) which can make lactate an unreliable marker of successful resuscitation when using epi at moderate to higher doses.  It has been shown to be very safe peripherally –even subQ injections don’t seem tto cause ischemia.

Uses: EMS, or if it’s the only pressor you have access to
Dose: 1-5mcg/kg/min (low); 4-10mcg/kg/min (medium); 10-20 mcg/kg/min (high)

The team at the Internet Book of Critical Care calls this the “devil’s drug” and recommends that we never use it. Dopamine has different effects at different doses, but it is almost impossible to titrate. Trials show that use of dopamine actually leads to increased mortality. Scott Weingart adds that it makes patients produce urine regardless of their kidney perfusion, making urine output an unreliable marker. The experts seem to agree: don’t use dopamine.

Pure Vasopressors: Increase SVR

Vasopressors are straightforward — they act only to constrict the vasculature. These are great in septic shock, neurogenic, and anaphylactic shock, though remember that epinephrine is the mainstay for the latter. Vasopressin is Scott Weingart’s recommended second drug if we have determined that the patient needs more preload.

Use: Distributive shock (okay as first line if good cardiac function
Dose: 0.01-0.06 u/min; fixed dose 0.03 u/min
Receptors: V1 and V2

Vasopressin acts specifically on the vasopressor receptor causing pure vasoconstriction without additional catecholamine effects. It is also believed that vasopressin causes selective vasodilation in the pulmonary system, brain, and coronary arteries and can help postpone the need for hemodialysis by constricting arteries in the renal tubules. It can be used in septic shock, but should be used in patients with good cardiac output (as there are no chronotropic effects from this drug) or as a second line agent if additional preload is needed. 

     This drug is difficult to titrate as it has a long half life. Notably, there are a limited number of endogenous receptors and a fixed dose of vasopressin is more common to use than a titratable dose. Some patients are hypotensive not because they need more catecholamines (epi/norepi), but because they are vasopressin deficient. Scott Weingart recommends adding a background fixed dose once patients are on ~20 of norepi if they are persistently hypotensive. At this dose, it will do nothing if a patient is not vasopressin deficient, but it will improve BP if the patient is actually hypotensive due to a lack of vasopressin. 

     A downside to this drug is that it should be given peripherally with extreme caution, as it can cause digital/ peripheral ischemia if it extravasates. This risk seems especially high when given in combination with epi.

Use: Push-dose pressor (esp during intubation, a-fib provoked by too much beta stimulation, Carcinoid syndrome, Neurogenic shock (second agent), Aortic stenosis
Dose: 40-180 mcg/min (initiate at high dose ~100-180 and titrate back; 50-200mcg q1-5 min as push dose
Receptors: αααα

Phenylephrine works as a pure vasoconstrictor by acting exclusively on α1 receptors, affecting primarily large arterioles. Classically, the fear with phenylephrine (especially compared to norepinephrine) is that it will decrease cardiac output by increasing systemic vascular resistance without augmenting the cardiac function at all. Thus, overall perfusion would decrease even if the BP on the monitor looks improved.

     However, Josh Farkas did a lit review looking at phenylephrine vs norepi and says that there clinically isn’t much of a difference between the two. He hypothesizes that in practice, venoconstriction improves preload, which helps augment and ultimately maintain the CO. Josh Farkas said that he will often use phenylephrine in the septic patient with a good CO who just needs a little bit of BP augmentation to get him through initial hypotension. 

     In practice, the main way we’ll see phenylephrine is as a push-dose pressor (the “phenyl stick”). This is a safe and effective pre-made tool when you run into trouble, especially during intubation or in the situation of afib or dysrhythmia provoked by beta simulation from other pressors. Our phenyl sticks are typically 100mcg / mL and you can give 0.5 – 2mL every 1-5 min. Note that it is very safe peripherally. There are essentially no reports of skin necrosis.

Inodilators: Increase CO (Positive inotropes / chronotropes, increase HR, cardiac contractility) and decrease SVR (vasodilators)

   Inodilators cause the heart to pump “better” (positive inotropy / chronotropy) and cause there to be less vascular resistance (due to vasodilation), making it easier for the heart to get blood out to the rest of the body. This class of pressors are valuable when the primary problem is pump failure (ie, cardiogenic shock, sepsis complicated by cardiomyopathy) and will not be helpful in pure distributive shock.

    Importantly, inodilators have variability in the effects on blood pressure and should always be used after adequate fluid resuscitation and preload augmentation (with an inopressor, etc). This is because if the heart doesn’t have recruitable (ie, live / healthy) myocardium or was already working at peak performance, the inodilators will just vasodilate, causing BP to tank.  Additionally, inodilators have historically caused concern about increasing myocyte oxygen demand leading to myocardial ischemia.

Use: Cardiogenic shock
Dose: 2-20 mcg/kg/min
Receptors: αββββ

Dobutamine is a synthetic catecholamine derivative. It primarily causes inotropy and vasodilation, however at high doses (>15mcg/kg/min), it has some alpha agonism, causing vasoconstriction. There is some concern that the inotropy increases oxygen demand, leading to increased mortality, and it can cause tachycardia and dysrhythmias. The half life is only ~2 minutes. After ~72 hours, the body develops resistance and dobutamine will “auto-titrate” off.

Use: Cardiogenic shock (esp in patient with daily beta blocker use)
Dose: 0.375 – 0.75 mcg/kg/min
Receptors/Mechanism: cAMP

Milrinone augments inotropy, diastolic relaxation, and peripheral vasodilation. The overall effect is reduced preload, afterload, and vascular resistance, carrying the risk of hypotension. However, milrinone can be especially helpful for patients on daily beta-blockers. Milrinone is renally excreted and shouldn’t be used in patients with CrCl <50. It has a long half life (1-2 hours) that can lead to accumulation in renal failure and cause BP to tank.

Use: Cardiogenic shock with bradycardia
Dose: 2-10 mcg/min
Receptors: ββββ

Isoproterenol is very expensive, but awesome in bradycardia. It can be a great second line option if a patient’s heart rate has not responded to epi.

Oral Vasopressors:

Occasionally, we have the patients who are recovering from sepsis and are persistently requiring 2-3 mcg of norepi intermittently. Often, we just dump liters of fluids into these people, however this usually leads to third-spacing and causes more harm than good. In these patients, we can consider given oral pressors temporarily in order to wean them off of the drips.

Use: Septic shock, hepatorenal syndrome, cirrhosis
Dose: 10-40 mg q8h
Receptors: αααα

Midodrine is an oral vasoconstrictor that works well on patients who have been on pressors for a prolonged period of time and have developed some level of beta insensitivity. It can cause some reflexive bradycardia, which is something to beware of, and should only be used in the short term, and ultimately titrated off (once out of the ICU / SDU).


Methylene blue
Use: Refractory septic shock, anaphylaxis
Dose: start with a test loading dose of 2mg/kg over 15min. If good BP response, infusion at 0.25 – 2mg/kg/hr

Methylene blue causes vasoconstriction by reducing nitric oxide levels and inhibiting the creation of the vasodilator cGMP. It can also bypass the electron transport chain to produce ATP and thus can be very beneficial in patients with mitochondrial toxicity, as in the setting of metformin toxicity, for example. Dosing should be more aggressive in patients recovering from cardiothoracic surgery and less aggressive in patients with septic shock or mitochondrial toxicity. 

     Be aware that methylene blue can potentially increase pulmonary vascular resistance, so should be avoided in patients with pulmonary hypertension, hypoxia, or right ventricular dysfunction. It can also cause methemoglobinemia at high doses or hemolytic anemia in patients with G6PD deficiency. Consider intermittently checking methemoglobinemia levels and monitoring patients with a blood gas, as a patient will start to become blue-ish and the pulse-ox will stop working after ~10 minutes of the infusion.  Methylene blue is contraindicated in pregnancy as it decreases placental blood flow.

Use: Control tachycardia in the setting of exogenous beta stimulation
Dose: gtt at 25-50
Receptor: β1 blockade

This is a cool tool to add if we’re worried that tachycardia is iatrogenic and secondary to exogenous catecholamine administration. The example Dr. Weathers gives is: your patient is tachy to the 130-140s on 20 of levo (aka norepi). You echo their heart and see that they’re not in concomitant cardiogenic shock (thus, you feel good that the tachycardia isn’t compensatory). You can consider adding esmolol gtt at 25 – 50 and titrate to a HR of 80-95. In a patient who has been adequately resuscitated, slowing the heart can allow for proper ventricular filling and cardiac perfusion. Check out the full pearl here.

TL;DR Summary:

Receptors and terms:

  • α1 receptor: vasoconstriction 
  • β1 receptor: inotropy and chronotropy 
  • β2 receptor: vasodilation 
  • V1 receptor: vasoconstriction 
  • V2 receptor: increase water reabsorption
  • Dopamine: dose-dependent responses 
  • cAMP: inotropy, chronotropy, vasodilation
  • Catecholamines: epinephrine, norepinephrine, dopamine 
  • Inotropy: strengthens the force of muscular contraction
  • Chronotropy: increases heart rate
  • Pressors are used in hypotension in order to: 
    • Maintain critical perfusion pressures 
      • AMS at MAP <50, Brain ischemia at MAP <40
      • Coronary artery and kidney perfusion decreases at MAP <65
    • Increase venous return
    • Avoid gut ischemia
  • Pressors alter inotropy/chronotropy and/or the systemic vascular resistance (BP = CO x SVR)

Pressors generally fall into one of three categories: 

  • Inopressors: increase chronotropy/inotropy, vasoconstrict
    • Norepi aka levophed: First line in undifferentiated sepsis
      • αααβ, increases SVR with some CO augmentation
      • Dose: 0 – 40+ mcg/min
    • Epi: Good second drug to augment cardiac output, good in bradycardia
      • αββββ, primarily an inotrope / chronotrope at low dose
      • Inotrope dose: 2-5 mcg/min 
      • Inotrope and vasoconstriction dose: 10-20+ mcg/min
      • Push dose: 5-20 mcg q2-5min
      • Increases lactate production, makes trending lactate unreliable 
    • Dopamine: don’t use this unless you absolutely have nothing else available 
  • Pure vasopressors: Increase SVR
    • Vasopressin: Good second agent if increased preload is needed; consider background dose if vasopressin deficientV1 and V2
      • Dose: fixed, 0.03 u/min
    • Phenylephrine: Good push-dose pressor, or to get a patient through a transient period of hypotension, αααα
      • Dose: 40-180 mcg/min (initiate at high dose ~100-180 and titrat back)
      • Push dose: 50-200mcg q1-5 min
  • Inodilators: Increase CO, decrease SVR
    • Dobutamine: Good in cardiogenic shock, αββββ
      • Dose: 2 – 20 mcg/kg/min
    • Milrinone: Good in cardiogenic shock, especially if on a daily beta blocker, cAMP 
      • Dose: 0.375 – 0.75 mcg/kg/min
    • Isoproterenol: Very expensive, but good in cardiogenic shock with bradycardia, ββββ
      • Dose: 2 – 10 mcg/min 
  • Oral Vasopressors
    • Midodrine: Good when transitioning septic shock patients off of IV pressors, αααα
      • Dose: 10-40 mg q8h
  • Troubleshooting: 
    • Methylene blue: Good in refractory septic shock, anaphylaxis
      • Dose: start with a test loading dose of 2mg/kg over 15 min
      • If good BP response, c/w infusion at 0.25 – 2 mg/kg/hr
      • Will make pulse ox unreliable, can cause methemoglobinemia, hemolytic anemia
    • Consider giving esmolol to counteract iatrogenic tachycardia from exogenous beta 1 stimulation


June 2024