Official reprint from UpToDate®

www.uptodate.com ©2018 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Use of vasopressors and inotropes

Author: Scott Manaker, MD, PhD

Section Editor: Polly E Parsons, MD
Deputy Editor: Geraldine Finlay, MD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2018. | This topic last updated: Feb 08, 2018.

INTRODUCTION — Vasopressors are a powerful class of drugs that induce vasoconstriction and thereby elevate
mean arterial pressure (MAP). Vasopressors differ from inotropes, which increase cardiac contractility; however,
many drugs have both vasopressor and inotropic effects. Although many vasopressors have been used since the
1940s, few controlled clinical trials have directly compared these agents or documented improved outcomes due
to their use [1]. Thus, the manner in which these agents are commonly used largely reflects expert opinion,
animal data, and the use of surrogate end points, such as tissue oxygenation, as a proxy for decreased morbidity
and mortality.

Basic adrenergic receptor physiology and the principles, complications, and controversies surrounding use of
vasopressors and inotropes for treatment of shock are presented here. Issues related to the differential
diagnosis of shock and the use of vasopressors in patients with septic shock are discussed separately. (See
"Definition, classification, etiology, and pathophysiology of shock in adults" and "Evaluation and management of
suspected sepsis and septic shock in adults".)

PHYSIOLOGIC MECHANISMS OF VASOCONSTRICTION — The main categories of adrenergic receptors relevant

to vasopressor activity are the alpha-1, beta-1, and beta-2 adrenergic receptors, as well as the dopamine
receptors [2,3].

Alpha adrenergic — Activation of alpha-1 adrenergic receptors, located in vascular walls, induces significant
vasoconstriction. Alpha-1 adrenergic receptors are also present in the heart and can increase the duration of
contraction without increased chronotropy. However, clinical significance of this phenomenon is unclear [4].

Beta adrenergic — Beta-1 adrenergic receptors are most common in the heart and mediate increases in inotropy
and chronotropy with minimal vasoconstriction. Stimulation of beta-2 adrenergic receptors in blood vessels
induces vasodilation.

Dopamine — Dopamine receptors are present in the renal, splanchnic (mesenteric), coronary, and cerebral
vascular beds; stimulation of these receptors leads to vasodilation. A second subtype of dopamine receptors
causes vasoconstriction by inducing norepinephrine release.

Calcium sensitizers — Some agents increase the sensitivity of the myocardial contractile apparatus to calcium,
causing an increase in myofilament tension development and myocardial contractility (eg, pimobendan,
levosimendan). These agents have additional pharmacologic properties, such as phosphodiesterase inhibition,
which may increase inotropy and vasodilation and contribute significantly to their clinical profile, the details of
which are discussed separately.
Angiotensin — Angiotensin receptors (AT1 and AT2) are G-coupled protein receptors with angiotensin II as their
ligand. Angiotensin II is a vasoconstrictor that is part of the renin-aldosterone-angiotensin (RAAS) system. When
receptors are stimulated, cytosolic calcium concentration increases to mediate vasoconstrictive effects as well
as aldosterone and vasopressin secretion [5].

PRINCIPLES — Hypotension may result from hypovolemia (eg, exsanguination), pump failure (eg, severe
medically refractory heart failure or shock complicating myocardial infarction), or a pathologic maldistribution of
blood flow (eg, septic shock, anaphylaxis). (See "Definition, classification, etiology, and pathophysiology of shock
in adults" and "Inotropic agents in heart failure with reduced ejection fraction".)

Vasopressors are indicated for a decrease of >30 mmHg from baseline systolic blood pressure, or a mean
arterial pressure <60 mmHg when either condition results in end-organ dysfunction due to hypoperfusion.
Hypovolemia should be corrected prior to the institution of vasopressor therapy [6]. (See "Treatment of severe
hypovolemia or hypovolemic shock in adults".)

The rational use of vasopressors and inotropes is guided by three fundamental concepts:

● One drug, many receptors – A given drug often has multiple effects because of actions upon more than one
receptor. As an example, dobutamine increases cardiac output by beta-1 adrenergic receptor activation;
however, it also acts upon beta-2 adrenergic receptors and thus induces vasodilation and can cause
hypotension.

● Dose-response curve – Many agents have dose-response curves, such that the primary adrenergic receptor
subtype activated by the drug is dose-dependent. As an example, dopamine stimulates beta-1 adrenergic
receptors at doses of 2 to 10 mcg/kg per minute, and alpha adrenergic receptors when doses exceed 10
mcg/kg per minute.

● Direct versus reflex actions – A given agent can affect mean arterial pressure (MAP) both by direct actions
on adrenergic receptors and by reflex actions triggered by the pharmacologic response. Norepinephrine-
induced beta-1 adrenergic stimulation alone normally would cause tachycardia. However, the elevated MAP
from norepinephrine's alpha-adrenergic receptor-induced vasoconstriction results in a reflex decrease in
heart rate. The net result may be a stable or slightly reduced heart rate when the drug is used.

PRACTICAL ISSUES — Use of vasopressors and inotropic agents requires attention to a number of issues:

Volume resuscitation — Repletion of adequate intravascular volume, when time permits, is crucial prior to the
initiation of vasopressors. As an example, most patients with septic shock require at least 2 liters of intravenous
fluid in order for vasopressors to be maximally effective [7]. Vasopressors will be ineffective or only partially
effective in the setting of coexistent hypovolemia.

Fluids may be withheld in patients with significant pulmonary edema due to the acute respiratory distress
syndrome (ARDS) or heart failure (HF). In patients with a pulmonary artery catheter, pulmonary capillary wedge
pressures (PCWP) of 18 to 24 mmHg are recommended for cardiogenic shock [8], and 12 to 14 mmHg for septic
or hypovolemic shock [9]. (See "Pulmonary artery catheterization: Interpretation of hemodynamic values and
waveforms in adults".)

Selection and titration — Choice of an initial agent should be based upon the suspected underlying etiology of
shock (eg, dobutamine in cases of cardiac failure without significant hypotension, epinephrine for anaphylactic
shock). The dose should be titrated up to achieve effective blood pressure or end-organ perfusion as evidenced
by such criteria as urine output or mentation. If maximal doses of a first agent are inadequate, then a second
drug should be added to the first. In situations where this is ineffective, such as refractory septic shock,
anecdotal reports describe adding a third agent, although no controlled trials have demonstrated the utility of this
approach.

Route of administration — Vasopressors and inotropic agents should be administered through an appropriately

positioned central venous catheter, if available. This facilitates more rapid delivery of the agent to the heart for
systemic distribution and eliminates the risk of peripheral extravasation. When a patient does not have a central
venous catheter, vasopressors and inotropic agents can be administered through an appropriately positioned
peripheral intravenous catheter temporarily, until a central venous catheter is inserted. (See "Complications of
central venous catheters and their prevention" and "Overview of central venous access".)

Tachyphylaxis — Responsiveness to these drugs can decrease over time due to tachyphylaxis. Doses must be
constantly titrated to adjust for this phenomenon and for changes in the patient's clinical condition [10,11].

Hemodynamic effects — Mean arterial pressure (MAP) is influenced by systemic vascular resistance (SVR) and
cardiac output (CO). In situations such as cardiogenic shock, elevating SVR increases afterload and the work of
an already failing heart, thus potentially lowering CO. Some authors recommend keeping the SVR approximately
700 to 1000 dynes x sec/cm5 to avoid excessive afterload and to minimize complications from profound
vasoconstriction (calculator 1) [12]. However, there is no consensus regarding an ideal target cardiac index (CI).
Studies that have attempted to maintain a supraphysiologic CI of >4 to 4.5 L/minute per m2 have not shown
consistent benefit [13,14]. (See "Oxygen delivery and consumption".)

Subcutaneous delivery of medications — Critically ill patients often receive subcutaneously injected

medications, such as heparin and insulin. The bioavailability of these medications can be reduced during
treatment with vasopressors due to cutaneous vasoconstriction.

This was demonstrated in a study that monitored plasma factor Xa levels in three groups of hospitalized patients
following the initiation of prophylactic low molecular weight heparin [15]. Patients who required vasopressor
support (dopamine >10 mcg/kg per minute, norepinephrine >0.25 mcg/kg per minute, or phenylephrine >2
mcg/kg per minute) had decreased factor Xa activity compared to both intensive care unit (ICU) patients who did
not require vasopressors and routine postoperative control patients. The clinical significance of the decrease in
plasma factor Xa levels was not determined.

The authors of the study suggested that patients might need higher doses of LMW heparin to attain adequate
thrombosis prophylaxis. Another approach is to change subcutaneous medications to an intravenous form
whenever a patient is receiving vasopressor therapy.

Frequent re-evaluation — Critically ill patients may undergo a second hemodynamic insult which necessitates a
change in vasopressor or inotrope management. The dosage of a given agent should not simply be increased
because of persistent or worsening hypotension without reconsideration of the patient's clinical situation and the
appropriateness of the current strategy.

ADRENERGIC AGENTS — Adrenergic agents, such as phenylephrine, norepinephrine, dopamine, and dobutamine,

are the most commonly used vasopressor and inotropic drugs in critically ill patients (table 1). These agents
manifest different receptor selectivity and clinical effects (table 2).

Norepinephrine — Norepinephrine (Levophed) acts on both alpha-1 and beta-1 adrenergic receptors, thus
producing potent vasoconstriction as well as a modest increase in cardiac output [6]. A reflex bradycardia usually
occurs in response to the increased mean arterial pressure (MAP), such that the mild chronotropic effect is
canceled out and the heart rate remains unchanged or even decreases slightly. Norepinephrine is the preferred
vasopressor for the treatment of septic shock. (See 'Choice of agent in septic shock' below and "Evaluation and
management of suspected sepsis and septic shock in adults".)
Phenylephrine — Phenylephrine (Neo-Synephrine) has purely alpha-adrenergic agonist activity and therefore
results in vasoconstriction with minimal cardiac inotropy or chronotropy. MAP is augmented by raising systemic
vascular resistance (SVR) [16]. The drug is useful in the setting of hypotension with an SVR <700 dynes x
sec/cm5 (eg, hyperdynamic sepsis, neurologic disorders, anesthesia-induced hypotension). A potential
disadvantage of phenylephrine is that it may decrease stroke volume, so it is reserved for patients in whom
norepinephrine is contraindicated due to arrhythmias or who have failed other therapies.

Although SVR elevation increases cardiac afterload, most studies document that cardiac output (CO) is either
maintained or actually increased among patients without pre-existing cardiac dysfunction [4,17]. The drug is
contraindicated if the SVR is >1200 dynes x sec/cm5.

Epinephrine — Epinephrine (Adrenalin) has potent beta-1 adrenergic receptor activity and moderate beta-2 and
alpha-1 adrenergic receptor effects. Clinically, low doses of epinephrine increase CO because of the beta-1
adrenergic receptor inotropic and chronotropic effects, while the alpha adrenergic receptor-induced
vasoconstriction is often offset by the beta-2 adrenergic receptor vasodilation. The result is an increased CO,
with decreased SVR and variable effects on the MAP [3].However, at higher epinephrine doses the alpha-
adrenergic receptor effect predominates, producing increased SVR in addition to an increased CO. Epinephrine is
most often used for the treatment of anaphylaxis, as a second line agent (after norepinephrine) in septic shock,
and for management of hypotension following coronary artery bypass grafting.

Other disadvantages of epinephrine include dysrhythmias (due to beta-1 adrenergic receptor stimulation) and
splanchnic vasoconstriction. The degree of splanchnic vasoconstriction appears to be greater with epinephrine
than with equipotent doses of norepinephrine or dopamine in patients with severe shock [18], although the
clinical importance of this is unclear.

Ephedrine — Similar to epinephrine, ephedrine acts primarily on alpha- and beta-adrenergic receptors, but with
less potency. It also has an effect by leading to release of endogenous norepinephrine. Ephedrine is rarely used
except in the setting of post-anesthesia-induced hypotension.

Dopamine — Dopamine (Intropin) has a variety of effects depending upon the dose range administered. It is most
often used as a second-line alternative to norepinephrine in patients with absolute or relative bradycardia and a
low risk of tachyarrhythmias. Weight-based administration of dopamine can achieve quite different serum drug
concentrations in different individuals [19], but the following provides an approximate description of effects:

● At doses of 1 to 2 mcg/kg per minute, dopamine acts predominantly on dopamine-1 receptors in the renal,
mesenteric, cerebral, and coronary beds, resulting in selective vasodilation. Some reports suggest that
dopamine increases urine output by augmenting renal blood flow and glomerular filtration rate, and
natriuresis by inhibiting aldosterone and renal tubular sodium transport [20-22]. These effects may be
blunted by haloperidol and other butyrophenones [22]. However, the clinical significance of these
phenomena is unclear, and some patients may develop hypotension at these low doses [23]. (See "Renal
actions of dopamine".)

● At 5 to 10 mcg/kg per minute, dopamine also stimulates beta-1 adrenergic receptors and increases cardiac
output, predominantly by increasing stroke volume with variable effects on heart rate [24]. Doses between 2
and 5 mcg/kg per minute have variable effects on hemodynamics in individual patients: vasodilation is often
balanced by increased stroke volume, producing little net effect upon systemic blood pressure. Some mild
alpha adrenergic receptor activation increases SVR, and the sum of these effects is an increase in MAP.

● At doses >10 mcg/kg per minute, the predominant effect of dopamine is to stimulate alpha-adrenergic
receptors and produce vasoconstriction with an increased SVR [24,25]. However, the overall alpha-adrenergic
 receptor effect of dopamine is weaker than that of norepinephrine, and the beta-1 adrenergic receptor
stimulation of dopamine at doses >2 mcg/kg per minute can result in dose-limiting dysrhythmias.

In practical terms, the dose-dependent effects of dopamine mean that changing the dose of the drug is akin to
switching vasopressors. Conversely, simply increasing the dose of dopamine without being cognizant of the
different receptor populations activated can cause untoward results.

The usual dose range for dopamine is 2 to 20 mcg/kg per minute, although doses as high as 130 mcg/kg per
minute have been employed [26]. When used for cardiac failure, dopamine should be started at 2 mcg/kg per
minute and then titrated to a desired physiologic effect rather than depending on the predicted pharmacologic
ranges described above.

Dobutamine — Dobutamine (Dobutrex) is not a vasopressor but rather is an inotrope that causes vasodilation.
Dobutamine's predominant beta-1 adrenergic receptor effect increases inotropy and chronotropy and reduces left
ventricular filling pressure. In patients with heart failure this results in a reduction in cardiac sympathetic activity
[27]. However, minimal alpha- and beta-2 adrenergic receptor effects result in overall vasodilation, complemented
by reflex vasodilation to the increased CO. The net effect is increased CO, with decreased SVR with or without a
small reduction in blood pressure.

Dobutamine is most frequently used in severe, medically refractory heart failure and cardiogenic shock and
should not be routinely used in sepsis because of the risk of hypotension. Dobutamine does not selectively
vasodilate the renal vascular bed, as dopamine does at low doses. (See "Inotropic agents in heart failure with
reduced ejection fraction".)

Isoproterenol — Isoproterenol (Isuprel) also is primarily an inotropic and chronotropic agent rather than a
vasopressor. It acts upon beta-1 adrenergic receptors and, unlike dobutamine, has a prominent chronotropic
effect. The drug's high affinity for the beta-2 adrenergic receptor causes vasodilation and a decrease in MAP.
Therefore, its utility in hypotensive patients is limited to situations in which hypotension results from bradycardia.

Contraindications and interactions — Several conditions or medications require avoidance of specific agents:

● In patients with cardiogenic shock, norepinephrine is preferred over dopamine as the first-line vasopressor
because a subgroup analysis from a randomized trial found that patients with cardiogenic shock who
received dopamine had a higher mortality than those who received norepinephrine [28]. In addition,
dysrhythmias were more common in the dopamine group.

● Patients with pheochromocytoma are at risk of excessive autonomic stimulation from adrenergic
vasopressors.

● Dobutamine is contraindicated in the setting of idiopathic hypertrophic subaortic stenosis.

● Patients receiving monoamine oxidase inhibitors are extremely sensitive to vasopressors and, therefore,
require much lower doses.

VASOPRESSIN AND ANALOGS — Vasopressin (antidiuretic hormone) is used in the management of diabetes

insipidus and esophageal variceal bleeding; however, it may also be helpful in the management of vasodilatory
shock (table 1). Although its precise role in vasodilatory shock remains to be defined, it is primarily used as a
second-line agent in refractory vasodilatory shock, particularly septic shock or anaphylaxis that is unresponsive
to epinephrine [29-34]. It is also used occasionally to reduce the dose of the first-line agent. Terlipressin, a
vasopressin analog, has been assessed in patients with vasodilatory shock [35-40], but it is not available in the
United States.
The effects of vasopressin and terlipressin in vasodilatory shock (mostly septic shock) were evaluated in a
systematic review that identified 10 relevant randomized trials (1134 patients) [41]. A meta-analysis of six of the
trials (512 patients) compared vasopressin or terlipressin with placebo or supportive care. There was no
significant improvement in short-term mortality among patients who received either vasopressin or terlipressin
(40.2 versus 42.9 percent, relative risk 0.91, 95% CI 0.79-1.05). However, patients who received vasopressin or
terlipressin required less norepinephrine. A second randomized trial compared vasopressin with norepinephrine
in 409 patients with septic shock. Although vasopressin did not improve mortality or the number of kidney
failure-free days, it may have been associated with a reduction in the rate of kidney failure requiring renal
replacement therapy (25 versus 35 percent) [42]. Further studies are needed before vasopressin can replace
norepinephrine as the first-choice agent for those with septic shock. (See 'Choice of agent in septic shock'
below.)

The effects of vasopressin may be dose dependent. A randomized trial compared two doses of vasopressin
(0.0333 versus 0.067 IU/min) in 50 patients with vasodilatory shock who required vasopressin as a second
pressor agent [43]. The higher dose was more effective at increasing the blood pressure without increasing the
frequency of adverse effects in these patients. However, doses of vasopressin above 0.03 units/min have been
associated with coronary and mesenteric ischemia and skin necrosis in some studies [44-47], although some of
these studies were in animals and necrosis in humans may also have been due to coexisting conditions (eg,
disseminated intravascular coagulation). However, doses higher than the therapeutic range (0.04 units/min) are
generally avoided for this reason unless an adequate mean arterial pressure (MAP) cannot be attained with other
vasopressor agents.

Rebound hypotension appears to be common following withdrawal of vasopressin. To avoid rebound

hypotension, the dose is slowly tapered by 0.01 units/min every 30 minutes.

Other potential adverse effects of vasopressin include hyponatremia and pulmonary vasoconstriction [44-48].
Terlipressin appears to have a similar side effect profile to vasopressin. In a meta-analysis of four trials (431
patients) that was conducted as part of the systematic review described above, there was no significant
difference in the frequency of adverse events among patients who received either vasopressin or terlipressin
(10.6 versus 11.8 percent, relative risk 0.90, 95% CI 0.49-1.67) [41].

NONADRENERGIC AGENTS — A number of agents produce vasoconstriction or inotropy through nonadrenergic

mechanisms, including phosphodiesterase inhibitors and nitric oxide synthase inhibitors, calcium sensitizers, or
angiotensin II.

PDE inhibitors — Phosphodiesterase (PDE) inhibitors, such as inamrinone (formerly known as amrinone) and
milrinone, are nonadrenergic drugs with inotropic and vasodilatory actions. In many ways, their effects are similar
to those of dobutamine but with a lower incidence of dysrhythmias. PDE inhibitors most often are used to treat
patients with impaired cardiac function and medically refractory heart failure, but their vasodilatory properties
limit their use in hypotensive patients [24]. Inamrinone is no longer available in North America and most/all other
countries so the only intravenous PDE inhibitor used in the US is milrinone. (See "Inotropic agents in heart failure
with reduced ejection fraction".)

NOS inhibitors — Nitric oxide overproduction appears to play a major role in vasodilation induced by sepsis (see
"Pathophysiology of sepsis"). Studies of nitric oxide synthase (NOS) inhibitors such as N-monomethyl-L-arginine
(L-NMMA) in sepsis demonstrate a dose-dependent increase in systemic vascular resistance (SVR) [49].
However, cardiac index (CI) and heart rate (HR) decrease, even when patients are treated concomitantly with
norepinephrine or epinephrine. The increase in SVR tends to be offset by the drop in CI, such that mean arterial
pressure (MAP) is only minimally augmented. The clinical utility of this class of drugs remains unproven.
Calcium sensitizers — Several agents increase myocardial contractility (eg, pimobendan, levosimendan) but
conclusive evidence of improved outcomes with their use is lacking [50,51].

Angiotensin II — Preliminary trials have reported an adequate vasopressor effect when angiotensin II is
exogenously administered for vasodilatory shock (eg, septic shock) [52,53]. Best supporting its role as a
vasopressor agent is a randomized trial of 344 patients with vasodilatory shock (80 percent had sepsis and
patients had a normal cardiac output) already receiving high dose norepinephrine or similar vasopressor
equivalent [54]. When compared with placebo, angiotensin II resulted in a greater proportion of patients achieving
a 10 mmHg or greater increase in the baseline mean arterial pressure (MAP) or more or an increase in the MAP
to 75 mmHg or higher (70 versus 23 percent), at three hours. There was no effect on mortality or on the
sequential organ failure assessment score. Serious adverse events were no different among the groups.
Angiotensin II resulted in less background vasopressor use and higher heart rates but did not result in life-
threatening tachyarrhythmias. Further trials will be required to compare angiotensin II with other vasopressor
agents and to examine its effects in populations other than those with vasodilatory shock before it can be
routinely used as a second line agent for the treatment of shock.

COMPLICATIONS — Vasopressors and inotropic agents have the potential to cause a number of significant
complications, including hypoperfusion, dysrhythmias, myocardial ischemia, local effects, and hyperglycemia. In
addition, a number of drug interactions exist.

Hypoperfusion — Excessive vasoconstriction in response to hypotension and vasopressors can produce

inadequate perfusion of the extremities, mesenteric organs, or kidneys. Excessive vasoconstriction with
inadequate perfusion, usually with an systemic vascular resistance (SVR) >1300 dynes x sec/cm5, commonly
occurs in the setting of inadequate cardiac output or inadequate volume resuscitation.

The initial findings are dusky skin changes at the tips of the fingers and/or toes, which may progress to frank
necrosis with autoamputation of the digits. Compromise of the renal vascular bed may produce renal
insufficiency and oliguria, while patients with underlying peripheral artery disease may develop acute limb
ischemia.

Inadequate mesenteric perfusion increases the risk of gastritis, shock liver, intestinal ischemia, or translocation
of gut flora with resultant bacteremia. Despite these concerns, maintenance of MAP with vasopressors appears
more effective in maintaining renal and mesenteric blood flow than allowing the MAP to drop, and maintenance
of MAP with vasopressors may be life-saving despite evidence of localized hypoperfusion [16,55].

Dysrhythmias — Many vasopressors and inotropes exert powerful chronotropic effects via stimulation of beta-1
adrenergic receptors. This increases the risk of sinus tachycardia (most common), atrial fibrillation (potentially
with increased atrioventricular nodal [A-V] conduction and therefore an increased ventricular response), re-
entrant atrioventricular node tachycardia, or ventricular tachyarrhythmias.

Adequate volume loading may minimize the frequency or severity of dysrhythmias. Despite this, dysrhythmias
often limit the dose and necessitate switching to another agent with less prominent beta-1 effects. The degree to
which the agent affects the frequency of dysrhythmias was illustrated by a randomized trial of 1679 patients with
shock [28]. Dysrhythmias were significantly more common among patients who received dopamine than among
those who received norepinephrine (24.1 versus 12.4 percent).

Myocardial ischemia — The chronotropic and inotropic effects of beta-adrenergic receptor stimulation can
increase myocardial oxygen consumption. While there is usually coronary vasodilation in response to
vasopressors [56], perfusion may still be inadequate to accommodate the increased myocardial oxygen demand.
Daily electrocardiograms on patients treated with vasopressors or inotropes may screen for occult ischemia, and
excessive tachycardia should be avoided because of impaired diastolic filling of the coronary arteries.
Local effects — Peripheral extravasation of vasopressors into the surrounding connective tissue can lead to
excessive local vasoconstriction with subsequent skin necrosis. To avoid this complication, vasopressors should
be administered via a central vein whenever possible. If infiltration occurs, local treatment with phentolamine (5
to 10 mg in 10 mL of normal saline) injected subcutaneously can minimize local vasoconstriction [57].

Hyperglycemia — Hyperglycemia may occur due to the inhibition of insulin secretion. The magnitude of
hyperglycemia generally is minor and is more pronounced with norepinephrine and epinephrine than dopamine
[21]. Monitoring of blood glucose while on vasopressors can prevent complications of untreated hyperglycemia.

CONTROVERSIES — Several controversies exist regarding the use of vasopressors and inotropic agents in
critically ill patients. Most stem from the relative paucity of large-scale studies comparing similar patient
populations treated with different regimens. The development of clear definitions for the systemic inflammatory
response syndrome, sepsis, and septic shock is a step forward toward comparative trials among standardized
patient populations. (See "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis,
and prognosis".)

Choice of agent in septic shock — The optimal agent in patients with septic shock is unknown and practice
varies considerably among experts. However, based upon meta-analyses of small randomized trials and
observational studies, a paradigm shift in practice has occurred such that most experts prefer to avoid dopamine
in this population and favor norepinephrine as the first-choice agent the details of which are discussed
separately. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on
'Vasopressors'.)

"Renal dose" dopamine — Dopamine selectively increases renal blood flow when administered to normal
volunteers at 1 to 3 mcg/kg per minute [58,59]. Animal studies also suggest that low-dose dopamine in the
setting of vasopressor-dependent sepsis helps preserve renal blood flow [60]. (See "Renal actions of dopamine"
and "Possible prevention and therapy of ischemic acute tubular necrosis".)

However, a beneficial effect of low or "renal dose" dopamine is less proven in human patients with sepsis or other
critical illness. Critically ill patients who do not have evidence of renal insufficiency or decreased urine output will
develop a diuresis in response to dopamine at 2 to 3 mcg/kg per minute, with variable effects on creatinine
clearance, but the benefit of this diuresis is questionable [10,23]. The intervention is not entirely benign because
hypotension and tachycardia may ensue. One small study demonstrated that the addition of low dose dopamine
to patients receiving other vasopressors increases splanchnic blood flow but does not alter other indices of
mesenteric perfusion, such as gastric intramucosal pH (pHi) [61].

At present, there are no data to support the routine use of low dose dopamine to prevent or treat acute renal
failure or mesenteric ischemia. In general, the most effective means of protecting the kidneys in the setting of
septic shock appears to be the maintenance of mean arterial pressure (MAP) >60 mmHg while attempting to
avoid excessive vasoconstriction (ie, the systemic vascular resistance [SVR] should not exceed 1300 dynes x
sec/cm5) [7,12,62,63].

Optimal dosage — Although norepinephrine doses of up to 100 mcg/min in adults are typically used in refractory
shock and as salvage therapy in combination with a second vasopressor agent, there is no well-established
maximum dose. Several studies have suggested improved tissue perfusion when higher doses of norepinephrine
(up to 350 mcg/min) are used [12,63] but no survival benefit of high-dose norepinephrine has been conclusively
proven.

Supranormal cardiac index — Elevation of the cardiac index with inotropic agents to supranormal values (ie, >4.5
L/minute per m2) potentially increases oxygen delivery to peripheral tissues. In theory, increased oxygen delivery
may prevent tissue hypoxia and improve outcomes, and initial studies appeared to support this hypothesis [64-
66]. However, later larger trials showed that goal-oriented hemodynamic therapy to increase either cardiac index
to >4.5 L/min per m2 or oxygen delivery to >600 to 650 mL/min per m2 with volume expansion or dobutamine
resulted in either no improvement or worsened morbidity or mortality [13,14,67]. Therefore, the routine
administration of vasopressors or inotropes to improve cardiac output or oxygen delivery to supranormal levels is
not advocated. (See "Oxygen delivery and consumption".)

The American Thoracic Society (ATS) statement on the detection, correction, and prevention of tissue hypoxia, as
well as other ATS guidelines, can be accessed through the ATS web site at www.thoracic.org/statements.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries
and regions around the world are provided separately. (See "Society guideline links: Sepsis in children and
adults".)

SUMMARY AND RECOMMENDATIONS

● Vasopressors are a powerful class of drugs that induce vasoconstriction and elevate mean arterial pressure
(MAP). (See 'Introduction' above.)

● Alpha-1 adrenergic receptors induce vasoconstriction, while beta-1 receptors induce inotropy plus
chronotropy, and beta-2 receptors induce vasodilation. One subtype of dopamine receptor induces
norepinephrine release with subsequent vasoconstriction, although many dopamine receptors induce
vasodilation. Some agents increase the sensitivity of the myocardial contractile apparatus to calcium while
others cause direct vasoconstriction via angiotensin II receptor stimulation. (See 'Physiologic mechanisms
of vasoconstriction' above.)

● Vasopressors are indicated for a MAP <60 mmHg, or a decrease of systolic blood pressure that exceeds 30
mmHg from baseline, when either condition results in end-organ dysfunction due to hypoperfusion. (See
'Principles' above.)

● Hypovolemia should be corrected prior to the institution of vasopressor therapy for maximum efficacy.
Patients should be re-evaluated frequently once vasopressor therapy has been initiated. Common issues
that arise include tachyphylaxis, which may require dose titration, and additional hemodynamic insults,
which should be recognized and managed. (See 'Practical Issues' above.)

● Choice of an initial agent should be based upon the suspected underlying etiology of shock (eg, dobutamine
for cardiogenic shock without significant hypotension, norepinephrine for septic and cardiogenic shock with
hypotension, epinephrine for anaphylactic shock). (See 'Practical Issues' above and "Prognosis and
treatment of cardiogenic shock complicating acute myocardial infarction", section on 'Vasopressors and
inotropes'.)

● Complications of vasopressor therapy include hypoperfusion (particularly affecting the extremities,

mesentery or kidneys), dysrhythmias, myocardial ischemia, peripheral extravasation with skin necrosis, and
hyperglycemia. (See 'Complications' above.)

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

1. Müllner M, Urbanek B, Havel C, et al. Vasopressors for shock. Cochrane Database Syst Rev 2004;
:CD003709.
2. AHLQUIST RP. A study of the adrenotropic receptors. Am J Physiol 1948; 153:586.
 3. ALLWOOD MJ, COBBOLD AF, GINSBURG J. Peripheral vascular effects of noradrenaline,
isopropylnoradrenaline and dopamine. Br Med Bull 1963; 19:132.
4. Williamson AP, Seifen E, Lindemann JP, Kennedy RH. WB4101- and CEC-sensitive positive inotropic actions
of phenylephrine in rat cardiac muscle. Am J Physiol 1994; 266:H2462.
5. Catt KJ, Mendelsohn FA, Millan MA, Aguilera G. The role of angiotensin II receptors in vascular regulation. J
Cardiovasc Pharmacol 1984; 6 Suppl 4:S575.
6. Practice parameters for hemodynamic support of sepsis in adult patients in sepsis. Task Force of the
American College of Critical Care Medicine, Society of Critical Care Medicine. Crit Care Med 1999; 27:639.
7. Moran JL, O'Fathartaigh MS, Peisach AR, et al. Epinephrine as an inotropic agent in septic shock: a dose-
profile analysis. Crit Care Med 1993; 21:70.
8. Calvin JE, Driedger AA, Sibbald WJ. Does the pulmonary capillary wedge pressure predict left ventricular
preload in critically ill patients? Crit Care Med 1981; 9:437.
9. Packman MI, Rackow EC. Optimum left heart filling pressure during fluid resuscitation of patients with
hypovolemic and septic shock. Crit Care Med 1983; 11:165.
10. Lherm T, Troché G, Rossignol M, et al. Renal effects of low-dose dopamine in patients with sepsis syndrome
or septic shock treated with catecholamines. Intensive Care Med 1996; 22:213.
11. Unverferth DA, Blanford M, Kates RE, Leier CV. Tolerance to dobutamine after a 72 hour continuous
infusion. Am J Med 1980; 69:262.
12. Martin C, Papazian L, Perrin G, et al. Norepinephrine or dopamine for the treatment of hyperdynamic septic
shock? Chest 1993; 103:1826.
13. Gattinoni L, Brazzi L, Pelosi P, et al. A trial of goal-oriented hemodynamic therapy in critically ill patients.
SvO2 Collaborative Group. N Engl J Med 1995; 333:1025.
14. Hayes MA, Timmins AC, Yau EH, et al. Elevation of systemic oxygen delivery in the treatment of critically ill
patients. N Engl J Med 1994; 330:1717.
15. Dörffler-Melly J, de Jonge E, Pont AC, et al. Bioavailability of subcutaneous low-molecular-weight heparin to
patients on vasopressors. Lancet 2002; 359:849.
16. Gregory JS, Bonfiglio MF, Dasta JF, et al. Experience with phenylephrine as a component of the
pharmacologic support of septic shock. Crit Care Med 1991; 19:1395.
17. Yamazaki T, Shimada Y, Taenaka N, et al. Circulatory responses to afterloading with phenylephrine in
hyperdynamic sepsis. Crit Care Med 1982; 10:432.
18. De Backer D, Creteur J, Silva E, Vincent JL. Effects of dopamine, norepinephrine, and epinephrine on the
splanchnic circulation in septic shock: which is best? Crit Care Med 2003; 31:1659.
19. MacGregor DA, Smith TE, Prielipp RC, et al. Pharmacokinetics of dopamine in healthy male subjects.
Anesthesiology 2000; 92:338.
20. Goldberg LI. Dopamine--clinical uses of an endogenous catecholamine. N Engl J Med 1974; 291:707.
21. HORWITZ D, FOX SM 3D, GOLDBERG LI. Effects of Dopamine in man. Circ Res 1962; 10:237.
22. Dasta JF, Kirby MG. Pharmacology and therapeutic use of low-dose dopamine. Pharmacotherapy 1986;
6:304.
23. Duke GJ, Briedis JH, Weaver RA. Renal support in critically ill patients: low-dose dopamine or low-dose
dobutamine? Crit Care Med 1994; 22:1919.
24. Löllgen H, Drexler H. Use of inotropes in the critical care setting. Crit Care Med 1990; 18:S56.
25. Steel, A, Bihari, D . Choice of catecholamine: does it matter? Curr Opin Crit Care 2000; 6:347.
26. Hannemann L, Reinhart K, Grenzer O, et al. Comparison of dopamine to dobutamine and norepinephrine for
oxygen delivery and uptake in septic shock. Crit Care Med 1995; 23:1962.
27. Al-Hesayen A, Azevedo ER, Newton GE, Parker JD. The effects of dobutamine on cardiac sympathetic
activity in patients with congestive heart failure. J Am Coll Cardiol 2002; 39:1269.
28. De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of
shock. N Engl J Med 2010; 362:779.
29. Mutlu GM, Factor P. Role of vasopressin in the management of septic shock. Intensive Care Med 2004;
30:1276.
30. Sharshar T, Blanchard A, Paillard M, et al. Circulating vasopressin levels in septic shock. Crit Care Med
2003; 31:1752.
31. Tsuneyoshi I, Yamada H, Kakihana Y, et al. Hemodynamic and metabolic effects of low-dose vasopressin
infusions in vasodilatory septic shock. Crit Care Med 2001; 29:487.
32. Dünser MW, Mayr AJ, Ulmer H, et al. Arginine vasopressin in advanced vasodilatory shock: a prospective,
randomized, controlled study. Circulation 2003; 107:2313.
33. Kill C, Wranze E, Wulf H. Successful treatment of severe anaphylactic shock with vasopressin. Two case
reports. Int Arch Allergy Immunol 2004; 134:260.
34. Schummer C, Wirsing M, Schummer W. The pivotal role of vasopressin in refractory anaphylactic shock.
Anesth Analg 2008; 107:620.
35. Albanèse J, Leone M, Delmas A, Martin C. Terlipressin or norepinephrine in hyperdynamic septic shock: a
prospective, randomized study. Crit Care Med 2005; 33:1897.
36. Kam PC, Williams S, Yoong FF. Vasopressin and terlipressin: pharmacology and its clinical relevance.
Anaesthesia 2004; 59:993.
37. O'Brien A, Clapp L, Singer M. Terlipressin for norepinephrine-resistant septic shock. Lancet 2002; 359:1209.
38. Leone M, Albanèse J, Delmas A, et al. Terlipressin in catecholamine-resistant septic shock patients. Shock
2004; 22:314.
39. Rodríguez-Núñez A, Fernández-Sanmartín M, Martinón-Torres F, et al. Terlipressin for catecholamine-
resistant septic shock in children. Intensive Care Med 2004; 30:477.
40. Morelli A, Rocco M, Conti G, et al. Effects of terlipressin on systemic and regional haemodynamics in
catecholamine-treated hyperkinetic septic shock. Intensive Care Med 2004; 30:597.
41. Polito A, Parisini E, Ricci Z, et al. Vasopressin for treatment of vasodilatory shock: an ESICM systematic
review and meta-analysis. Intensive Care Med 2012; 38:9.
42. Gordon AC, Mason AJ, Thirunavukkarasu N, et al. Effect of Early Vasopressin vs Norepinephrine on Kidney
Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial. JAMA 2016; 316:509.
43. Torgersen C, Dünser MW, Wenzel V, et al. Comparing two different arginine vasopressin doses in advanced
vasodilatory shock: a randomized, controlled, open-label trial. Intensive Care Med 2010; 36:57.
44. Malay MB, Ashton JL, Dahl K, et al. Heterogeneity of the vasoconstrictor effect of vasopressin in septic
shock. Crit Care Med 2004; 32:1327.
45. Kahn JM, Kress JP, Hall JB. Skin necrosis after extravasation of low-dose vasopressin administered for
septic shock. Crit Care Med 2002; 30:1899.
46. Leather HA, Segers P, Berends N, et al. Effects of vasopressin on right ventricular function in an
experimental model of acute pulmonary hypertension. Crit Care Med 2002; 30:2548.
47. Dünser MW, Mayr AJ, Tür A, et al. Ischemic skin lesions as a complication of continuous vasopressin
infusion in catecholamine-resistant vasodilatory shock: incidence and risk factors. Crit Care Med 2003;
31:1394.
48. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for
Management of Sepsis and Septic Shock: 2016. Crit Care Med 2017; 45:486.
49. Petros A, Lamb G, Leone A, et al. Effects of a nitric oxide synthase inhibitor in humans with septic shock.
Cardiovasc Res 1994; 28:34.
50. Landoni G, Lomivorotov VV, Alvaro G, et al. Levosimendan for Hemodynamic Support after Cardiac Surgery.
N Engl J Med 2017.
51. Mehta RH, Leimberger JD, van Diepen S, et al. Levosimendan in Patients with Left Ventricular Dysfunction
Undergoing Cardiac Surgery. N Engl J Med 2017.
52. Antonucci E, Gleeson PJ, Annoni F, et al. Angiotensin II in Refractory Septic Shock. Shock 2017; 47:560.
53. Chawla LS, Busse L, Brasha-Mitchell E, et al. Intravenous angiotensin II for the treatment of high-output
shock (ATHOS trial): a pilot study. Crit Care 2014; 18:534.
54. Khanna A, English SW, Wang XS, et al. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med
2017; 377:419.
55. Marik PE, Mohedin M. The contrasting effects of dopamine and norepinephrine on systemic and splanchnic
oxygen utilization in hyperdynamic sepsis. JAMA 1994; 272:1354.
56. Bohr DF. Adrenergic receptors in coronary arteries. Ann N Y Acad Sci 1967; 139:799.
57. Peters, JI, Utset, OM. Vasopressors in shock management: Choosing and using wisely. J Crit Illness 1989;
4:62.
58. Hollenberg NK, Adams DF, Mendell P, et al. Renal vascular responses to dopamine: haemodynamic and
angiographic observations in normal man. Clin Sci Mol Med 1973; 45:733.
59. D'Orio V, el Allaf D, Juchmès J, Marcelle R. The use of low doses of dopamine in intensive care medicine.
Arch Int Physiol Biochim 1984; 92:S11.
60. Schaer GL, Fink MP, Parrillo JE. Norepinephrine alone versus norepinephrine plus low-dose dopamine:
enhanced renal blood flow with combination pressor therapy. Crit Care Med 1985; 13:492.
61. Meier-Hellmann A, Bredle DL, Specht M, et al. The effects of low-dose dopamine on splanchnic blood flow
and oxygen uptake in patients with septic shock. Intensive Care Med 1997; 23:31.
62. Meadows D, Edwards JD, Wilkins RG, Nightingale P. Reversal of intractable septic shock with norepinephrine
therapy. Crit Care Med 1988; 16:663.
63. Redl-Wenzl EM, Armbruster C, Edelmann G, et al. The effects of norepinephrine on hemodynamics and renal
function in severe septic shock states. Intensive Care Med 1993; 19:151.
64. Shoemaker WC, Kram HB, Appel PL. Therapy of shock based on pathophysiology, monitoring, and outcome
prediction. Crit Care Med 1990; 18:S19.
65. Russell JA, Phang PT. The oxygen delivery/consumption controversy. Approaches to management of the
critically ill. Am J Respir Crit Care Med 1994; 149:533.
66. Tuchschmidt J, Fried J, Astiz M, Rackow E. Elevation of cardiac output and oxygen delivery improves
outcome in septic shock. Chest 1992; 102:216.
67. Alía I, Esteban A, Gordo F, et al. A randomized and controlled trial of the effect of treatment aimed at
maximizing oxygen delivery in patients with severe sepsis or septic shock. Chest 1999; 115:453.
Topic 1619 Version 27.0
GRAPHICS

Vasopressors and inotropes in treatment of acute hypotensive states and shock: Adult dose and selected
characteristics

Range of
Usual maximum
US trade Role in therapy and selected
Agent Initial dose maintenance doses used
name characteristics
dose range in refractory
shock

Vasopressors (alpha-1 adrenergic)

Norepinephrine Levophed 8 to 12 2 to 4 35 to 100 Initial vasopressor of choice in septic,

(noradrenaline) mcg/minute (0.1 mcg/minute mcg/minute (0.5 cardiogenic, and hypovolemic shock.
to 0.15 (0.025 to 0.05 to 0.75 Wide range of doses utilized clinically.
mcg/kg/minute) mcg/kg/minute) mcg/kg/minute; Must be diluted; eg, a usual
A lower initial up to 3.3 concentration is 4 mg in 250 mL of
dose of 5 mcg/kg/minute D5W or NS (16 micrograms/mL).
mcg/minute may has been
be used, eg, in needed rarely)
older adults

Epinephrine Adrenalin 1 mcg/minute 1 to 10 10 to 35 Initial vasopressor of choice in

(adrenaline) (0.014 mcg/minute mcg/minute anaphylactic shock.
mcg/kg/minute) (0.014 to 0.14 (0.14 to 0.5 Typically an add-on agent to
mcg/kg/minute) mcg/kg/minute) norepinephrine in septic shock when
an additional agent is required to raise
MAP to target 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.
Must be diluted; eg, a usual
concentration is 1 mg in 250 mL D5W
(4 micrograms/mL).

Phenylephrine Neo- 100 to 180 20 to 80 80 to 360 Pure alpha-adrenergic

Synephrine, mcg/minute until mcg/minute mcg/minute (1.1 vasoconstrictor.
Vazculep stabilized (0.25 to 1.1 to 6 Initial vasopressor when
(alternatively, 0.5 mcg/kg/minute) mcg/kg/minute); tachyarrhythmias preclude use of
to 2 Doses >6 norepinephrine.
mcg/kg/minute) mcg/kg/minute Alternative vasopressor for patients
do not increase with septic shock who: (1) develop
efficacy tachyarrhythmias on norepinephrine,
according to epinephrine, or dopamine, (2) have
product persistent shock despite use of two or
information in more vasopressor/inotropic agents
the United including vasopressin (salvage
States therapy), or (3) high cardiac output
with persistent hypotension.
May decrease stroke volume and
cardiac output in patients with cardiac
dysfunction.
 May be given as bolus dose of 50
to100 micrograms to support blood
pressure during rapid sequence
intubation.
Must be diluted; eg, a usual
concentration is 10 mg in 250 mL
D5W or NS (40 micrograms/mL).

Dopamine Inotropin 2 to 5 5 to 20 20 to >50 An alternative to norepinephrine in

mcg/kg/minute mcg/kg/minute mcg/kg/minute septic shock in highly selected
patients (eg, with compromised
systolic function or absolute or
relative bradycardia and a low risk of
tachyarrhythmias).
More adverse effects (eg, tachycardia,
arrhythmias particularly at doses ≥20
mcg/kg/minute) and less effective
than norepinephrine for reversing
hypotension in septic shock.
Lower doses (eg, 1 to 3
mcg/kg/minute) should not be used
for renal protective effect and can
cause hypotension during weaning.
Must be diluted; eg, a usual
concentration is 400 mg in 250 mL
D5W (1.6 mg/mL); use of a
commercially available pre-diluted
solution is preferred.

Antidiuretic hormone

Vasopressin Pitressin, 0.03 units per 0.03 to 0.04 0.04 to 0.07 Add-on to norepinephrine to raise
(arginine- Vasostrict minute units per minute units/minute; blood pressure to target MAP or
vasopressin) (alternatively (not titrated) Doses >0.04 decrease norepinephrine requirement.
0.01 to 0.03 units/minute Not recommended as a replacement
units/minute can cause for a first-line vasopressor.
initially) cardiac Pure vasoconstrictor; may decrease
ischemia and stroke volume and cardiac output in
should be myocardial dysfunction or precipitate
reserved for ischemia in coronary artery disease.
salvage therapy Must be diluted; eg, a usual
concentration is 25 units in 250 mL
D5W or NS (0.1 units/mL).

Inotrope (beta 1 adrenergic)

Dobutamine Dobutrex 0.5 to 1 2 to 20 20 to 40 Initial agent of choice in cardiogenic

mcg/kg/minute mcg/kg/minute mcg/kg/minute; shock with low cardiac output and
(alternatively, 2.5 Doses >20 maintained blood pressure.
mcg/kg/minute mcg/kg/minute Add-on to norepinephrine for cardiac
in more severe are not output augmentation in septic shock
cardiac recommended in with myocardial dysfunction (eg, in
decompensation) heart failure and elevated left ventricular filling
should be pressures and adequate MAP) or
reserved for ongoing hypoperfusion despite
salvage therapy adequate intravascular volume and
use of vasopressor agents.
Increases cardiac contractility and
rate; may cause hypotension and
tachyarrhythmias.
 Must be diluted; a usual concentration
is 250 mg in 500 mL D5W or NS (0.5
mg/mL); use of a commercially
available pre-diluted solution is
preferred.

Inotrope (nonadrenergic, PDE 3 inhibitor)

Milrinone Primacor Optional loading 0.125 to 0.75   Alternative for short-term cardiac
dose: 50 mcg/kg mcg/kg/minute output augmentation to maintain
over 10 minutes organ perfusion in cardiogenic shock
(usually not refractory to other agents.
given) 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.
Must be diluted; eg, a usual
concentration is 40 mg in 200 mL
D5W (200 micrograms/mL); use of a
commercially available pre-diluted
solution is preferred.

All doses shown are for intravenous (IV) administration in adult patients. The initial doses shown in this table may differ from those
recommended in immediate post-cardiac arrest management (ie, advanced cardiac life support). For details, refer to the UpToDate
topic review of post-cardiac arrest management in adults, section on hemodynamic considerations.
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 event of extravasation, prompt local infiltration of an antidote (eg, phentolamine) may be useful for
limiting tissue ischemia. Stop infusion and refer to extravasation management protocol.
Vasopressor infusions are high-risk medications requiring caution to prevent a medication error and patient harm. To reduce the risk
of making a medication error, we suggest that centers have available protocols that include steps on how to prepare and administer
vasopressor infusions using a limited number of standardized concentrations. Examples of concentrations and other detail are
based on recommendations used at experienced centers; protocols can vary by institution.

D5W: 5% dextrose water; MAP: mean arterial pressure; NS: 0.9% saline.

Prepared with data from:

1. Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock:
2016. Crit Care Med 2017; 45:486.
2. Hollenberg SM. Vasoactive drugs in circulatory shock. Am J Respir Crit Care Med 2011; 183:847.
3. Lexicomp Online. Copyright © 1978-2018 Lexicomp, Inc. All Rights Reserved.

Graphic 99963 Version 8.0

Vasoactive medication receptor activity and clinical effects

Receptor activity
Drug 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 ↓

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

Graphic 63100 Version 1.0

Contributor Disclosures
Scott Manaker, MD, PhD Consultant/Advisory boards: Expert witness in workers' compensation and in medical
negligence matters [General pulmonary and critical care medicine]. Equity Ownership/Stock Options (Spouse):
Johnson & Johnson; Pfizer (Numerous medications and devices). Other Financial Interest: Director of ACCP
Enterprises, a wholly owned for-profit subsidiary of ACCP [General pulmonary and critical care medicine
(Providing pulmonary and critical care medicine education to non-members of ACCP)]. Polly E Parsons,
MD Nothing to disclose Geraldine Finlay, MD Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.

Conflict of interest policy