Vasopressor and Inotrope Use in The Intensive Care Unit

Vasopressor and Inotrope Use in the Intensive Care Unit
Related Summaries
● Septic shock
● Hemorrhagic shock
● Cardiogenic shock
● Anaphylaxis
● Acute heart failure
● Fluid selection for IV uid resuscitation
Overview
● vasopressors and inotropes are typically used in intensive care unit to support hemodynamics of
patients with shock or nonshock conditions such as cardiac arrest, hepatorenal syndrome, or acute
kidney injury
● administration of vasopressors and inotropes (especially in shock) typically guided by following

concepts
⚬ mean arterial pressure (MAP) = cardiac output (CO) × systemic vascular resistance (SVR)
⚬ hypotension may be caused by an under lled cardiovascular system (hypovolemic), reduced
cardiac output in an adequately lled system (cardiogenic), or vasodilation
⚬ dosage of vasopressors and inotropes is typically weight dependent and should be calculated
according to dosage (mcg/kg/minute) = ([drug in mcg] / [dilutant in mL] / minutes / [patient weight
in kg]) × (infusion rate in mL/minute)
Table 1. Main Effects of Vasopressors and Inotropes
Vaso Cate Alph Alph Beta Beta Non Mai Mai

activ gory a-1 a-2 -1 -2 adre n n
e Rece Rece Rece Rece nerg E e E e
Age ptor ptor ptor ptor ic ct ct
nt Ago Ago Ago Ago E e on on
nist nist nist nist cts SVR CO
Epin Inoc ++++ +++ ++++ (+)(+) NA up up

ephr onstr (+)
ine ictor
Nore Inoc ++(+) +++ ++ (+) NA up up

pine onstr (+) or
phri ictor dow
ne n
Dop Inodi NA (+) + + Dop NA up

amin lator amin
e e
0.5-2 rece
mcg/ ptor
kg/m agon
inute ist
Dop Inodi + (+) ++ ++ Dop up up

amin lator amin
e 3- or e
10 inoc rece
mcg/ onstr ptor
kg/m ictor agon
inute ist
Dop Inoc +(+) (+) ++(+) +(+) Dop up NA

amin onstr (+) (+) amin
e> ictor e
10 rece
mcg/ ptor
kg/m agon
inute ist
Phen Vaso +++ NA NA NA NA up neut

ylep cons (+) ral
hrin tricto or
e r dow
n
Vaso Vaso NA NA NA NA Vaso up dow

pres cons pres n
sin tricto sin
(or r rece
anal ptor
og agon
terli ist
pres
sin)
Dob Inodi (+) (+) ++++ ++(+) NA up up

uta lator or
mine dow
n
Milri Inodi NA NA NA NA PDE dow up

none lator inhib n
ition
Amri Inodi NA NA NA NA PDE dow up

none lator inhib n
ition
Levo Inodi NA NA NA NA Calci dow up

sime lator um n
ndan sensi
tizati
on
Isopr Inodi NA NA ++++ ++++ NA dow up

oter lator n
enol
Abbreviations: CO, cardiac output,

NA, not applicable; PDE, phosphodiesterase; SVR,
systemic vascular resistance.
References - 1 , 2 .
● in hemorrhagic/hypovolemic shock
⚬ routine vasopressor use not recommended (CAEP Conditional recommendation)

⚬ prior to inotrope or vasopressor use, uid resuscitation should be performed to improve blood
pressure and heart rate to maintain adequate organ perfusion
– target systolic blood pressure of 80-90 mm Hg (ABC-T Grade 1C)
– use restricted volume replacement to achieve target blood pressure until bleeding or volume
loss is controlled (ABC-T Grade 1B)
– in case of life-threatening hypotension, use vasopressors (norepinephrine) in addition to uids
to sustain target arterial pressure (ABC-T Grade 1C), even when uid resuscitation is in progress
and hypovolemia has not yet been corrected
– in case of myocardial dysfunction, consider infusion of inotropic agent (dobutamine,
epinephrine) (ABC-T Grade 1C)
– inotropes may be used to support blood pressure until adequate uid resuscitation is achieved
– see also Hemorrhagic shock for additional information on uid resuscitation
⚬ in case of vasopressor therapy, consider norepinephrine as rst-line vasopressor rather than

dopamine (SSAI Weak recommendation)
● in cardiogenic shock
⚬ use norepinephrine as rst-line vasopressor for cardiogenic shock (CAEP Strong recommendation),
rather than dopamine (SSAI Weak recommendation, Low-quality evidence)
⚬ consider dobutamine if inotrope administration is deemed necessary (CAEP Strong
recommendation)
⚬ epinephrine should be restricted to patients with persistent hypotension despite adequate cardiac
lling pressures and use of other vasoactive agents, or for cardiopulmonary resuscitation (CPR)
● in distributive shock
⚬ uid resuscitation should be performed rst to improve blood pressure and heart rate to assure
adequate organ perfusion
⚬ septic shock
– uid resuscitation should ideally be achieved before use of inotropes and vasopressors
– norepinephrine recommended as rst-line vasopressor (SCCM Strong recommendation,
Moderate-quality evidence), CAEP Strong recommendation), rather than dopamine (SSAI Strong
recommendation, Moderate-quality evidence)
– epinephrine as addition to norepinephrine may be considered if additional agent needed to
raise blood pressure to target (SCCM Weak recommendation, Low-quality evidence )
– vasopressin (up to 0.03 units/minute) may be added to norepinephrine to increase mean
arterial pressure or decrease norepinephrine dose (SCCM Weak recommendation, Moderate-
quality evidence )
– dopamine only suggested as alternative to norepinephrine in highly selective patient
populations (for example, patients with low risk of tachyarrhythmia and absolute or relative
bradycardia) (SCCM Weak recommendation, Low-quality evidence )
– dobutamine infusion recommended if ongoing hypoperfusion despite adequate uid loading
and use of vasopressor (SCCM Weak recommendation, Low-quality evidence )
– if dobutamine initiated, titrate vasopressor dosing to end point perfusion and reduce or
discontinue in case of worsening hypotension or arrhythmia
⚬ anaphylaxis
– epinephrine considered rst-line treatment (AAAAI/ACAAI Strong recommendation, Grade B;

WAO Grade B-C; EAACI Grade C, Level IV)
– norepinephrine may be used if unresponsive to epinephrine
– consider glucagon in case of concomitant beta blocker use and poor response to epinephrine
(AAAAI/ACAAI Moderate recommendation, Grade B; WAO Grade B-C)
– in case of concomitant beta blocker use and epinephrine-resistant bronchospasm, consider
atropine (WAO Grade B-C)
⚬ neurogenic shock
– if hypotension persists after uid resuscitation, consider vasopressors (norepinephrine,

phenylephrine, dopamine)
● vasopressors should be chosen to minimize exacerbation of bradycardia (CSCM C, Level
III/IV, panel opinion strength 5)
● choice of vasopressor should be guided by patient characteristics and response to treatment
(CAEP Conditional recommendation)
● consider norepinephrine rather than dopamine, epinephrine, vasopressin analogues (SSAI
Weak recommendation, Low-quality evidence), or phenylephrine (SSAI Weak
recommendation, Very low-quality evidence)
– in case of hypotension in combination with bradycardia, combination of chronotropic, inotropic,
and vasoconstrictive e ects needed (dopamine, norepinephrine) (CSCM Grade NA, Level NA,
panel opinion strength 4)
– in case of hypotension mainly caused by peripheral vasodilation, consider pure vasoconstrictor
(phenylephrine) (CSCM Grade NA, Level NA, panel opinion strength 4)
⚬ adrenal insu ciency/failure
– uid resuscitation and steroid replacement therapy (hydrocortisone) should be started as soon
as possible
– vasopressors are temporizing, rst-line is typically norepinephrine with other agents considered
in case of no response (Acta Anaesthesiol Scand 2016 Nov;60(10):1347 full-text )
● in obstructive shock
⚬ consider norepinephrine rather than dopamine, epinephrine, or vasopressin analogues as rst-line

vasopressor (SSAI Weak recommendation, Low-quality evidence)
⚬ consider norepinephrine rather than phenylephrine as rst-line vasopressor (SSAI Weak
⚬ in case of obstructive shock unresponsive to indicated treatment, consider systemically active
vasopressors to preserve cerebral and cardiac perfusion (CAEP Conditional recommendation)
⚬ in case of hypertrophic obstructive cardiomyopathy or dynamic out ow obstruction, avoid
inotropic agents (CAEP Conditional recommendation) and avoid diuresis or uid depletion
⚬ in case of pulmonary embolism
– consider dobutamine and/or dopamine in patients with concomitant low cardiac index and
normal blood pressure and signs of tissue hypoperfusion
– consider restricting norepinephrine use to patients with concomitant hypotension
● in shock-related acute kidney injury
⚬ consider vasopressor use in conjunction with uids in patients with vasomotor shock with or at risk
for acute kidney injury (KDIGO Level 1, Grade C)
⚬ low-dose dopamine not recommended to prevent or treat acute kidney injury (KDIGO Level 1,
Grade A)
⚬ no evidence supporting 1 speci c vasopressor for renal protection
⚬ vasopressors titrated based on mean arterial pressure, cardiac output, urine output, or global
oxygen parameters
● in nonshock situations
⚬ postcardiopulmonary arrest
– consider vasoactive drugs
● after return of spontaneous circulation to support cardiac output, particularly heart and
brain perfusion
● if volume infusion is ine ective or pulmonary edema limits further administration of volume
(RMCCC Grade E)
– vasoactive drugs should be titrated at the bedside to secure the intended e ect while limiting
side e ects
– consider assessment of central pressures and cardiac output if vasopressors or inotropes are
required for > 2-3 hours (RMCCC Grade E)
⚬ in hepatorenal syndrome
– vasoactive drugs (vasoconstrictors) plus albumin should be considered in the treatment of type
I hepatorenal syndrome (AASLD Class IIa, Level B)
– use terlipressin plus albumin to decrease serum creatinine (EASL Level A1)
● discontinue terlipressin if serum creatinine is not reduced

● do not use terlipressin for ischemic cardiovascular disease
● repeat terlipressin treatment in case of recurrence of type 1 hepatorenal syndrome after
terlipressin discontinuation
– consider norepinephrine or midodrine plus octreotide, both with albumin as alternative to
terlipressin (EASL Level B1)
General information
● inotropes and vasopressors are typically used in intensive care unit to support hemodynamics of
patients with shock or nonshock conditions such as cardiac arrest, hepatorenal syndrome, or acute
kidney injury
● inotropes and vasopressors can have agonistic e ects on ≥ 1 receptor type which will guide choice for
hypotension treatment
● vasopressor medications may increase blood pressure via vasoconstriction and are subdivided
into 1 , 2
⚬ vasoconstrictors, which only have e ect on vascular resistance
⚬ inoconstrictors, which increase vascular resistance and simultaneously increase cardiac
contractility
● inotropic medications may increase myocardial contractility and heart rate and therefore cardiac
output and are subdivided into 1 , 2

⚬ inoconstrictors, which increase vascular resistance and cardiac contractility
⚬ inodilators, which decrease vascular resistance while increasing cardiac contractility
● administration of vasopressors and inotropes typically guided by following concepts 1 , 2
⚬ mean arterial pressure (MAP) = cardiac output (CO) × systemic vascular resistance (SVR)
⚬ hypotension may be caused by an under lled cardiovascular system (hypovolemic), reduced
cardiac output in an adequately lled system (cardiogenic), or vasodilation
⚬ dosage of vasopressors and inotropes is typically weight dependent and should be calculated
according to dosage (mcg/kg/minute) = ([drug in mcg] / [dilutant in mL] / minutes / [patient weight
in kg]) × (infusion rate in mL/minute)
● pharmacologic e ects of inotropes and vasopressors include 1 , 2
⚬ adrenergic receptor agonism
– cardiac beta-1 resulting in increased cardiac contractility

– peripheral beta-2 resulting in vasodilation
– peripheral alpha-1 and alpha-2 resulting in vasoconstriction
⚬ vasopressin receptor agonism resulting in vasoconstriction

⚬ dopaminergic receptor agonism resulting in mesenteric, renal, coronary, and intracerebral
vasodilation
⚬ phosphodiesterase 3 inhibition resulting in increased cardiac contractility and increased
vasodilation
⚬ calcium sensitization resulting in increased cardiac contractility and increased vasodilation
● correction of persistent hypotension as a result of decompensated shock may require vasopressors
and/or inotropes depending on the underlying cause 1 , 2
Table 2. Main Effects of Vasopressors and Inotropes

e Rece Rece Rece Rece nerg E ec E ec
Agen ptor ptor ptor ptor ic t on t on
t Agon Agon Agon Agon E ec SVR CO
ist ist ist ist ts
ist ist ist ist ts
Epin Inoco ++++ +++ ++++ (+)(+) NA up up

ephri nstric (+)
ne tor
Nore Inoco ++(+) +++ ++ (+) NA up up or

pine nstric (+) dow
phrin tor n
e
Dopa Inodil NA (+) + + Dopa NA up

mine ator mine
0.5-2 recep
mcg/ tor
kg/m agoni
inute st
Dopa Inodil + (+) ++ ++ Dopa up up

mine ator mine
3-10 or recep
mcg/ inoco tor
kg/m nstric agoni
inute tor st
Dopa Inoco +(+) (+) ++(+) +(+) Dopa up NA

mine nstric (+) (+) mine
> 10 tor recep
mcg/ tor
kg/m agoni
inute st
Phen Vaso +++ NA NA NA NA up neutr

yleph const (+) al or
rine rictor dow
n
ist ist ist ist ts
Vaso Vaso NA NA NA NA Vaso up dow

press const press n
in (or rictor in
anal recep
og tor
terlip agoni
ressi st
n)
Dobu Inodil (+) (+) ++++ ++(+) NA up or up

tami ator dow
ne n
Milri Inodil NA NA NA NA PDE dow up

none ator inhibi n
tion
Amri Inodil NA NA NA NA PDE dow up

none ator inhibi n
tion
Levo Inodil NA NA NA NA Calci dow up

sime ator um n
ndan sensi
tizati
on
Isopr Inodil NA NA ++++ ++++ NA dow up

otere ator n
nol
Abbreviations: CO, cardiac output, NA, not applicable; PDE, phosphodiesterase; SVR, systemic
vascular resistance.References - 1 , 2 .
Indications and Contraindications

Indications
● used in intensive care unit to support hemodynamics of patients with shock or nonshock conditions
such as cardiac arrest, hepatorenal syndrome, or acute kidney injury
● hemorrhagic shock
● cardiogenic shock
● distributive shock; uid resuscitation should be performed rst to improve blood pressure and heart
rate
⚬ septic shock
⚬ anaphylaxis
⚬ neurogenic shock
⚬ adrenal insu ciency/failure
● obstructive shock, such as pulmonary embolism (PE)
● nonshock situations, such as
⚬ postcardiopulmonary arrest
⚬ hepatorenal syndrome
⚬ acute kidney injury
Contraindications
● pheochromocytoma - dopamine should not be used in these patients (FDA DailyMed 2014 Apr )
● obstructive hypertrophic cardiomyopathy - dopamine, dobutamine, norepinephrine, and other IV

positive inotropic drugs are potentially harmful for treatment of acute hypotension in these patients
(Circulation 2011 Dec 13;124(24):2761 )
Hemorrhagic/Hypovolemic Shock
Recommendations from professional organizations
● Task Force for Advanced Bleeding Care in Trauma (ABC-T) 2016 guidelines on management of
bleeding and coagulopathy following major trauma
⚬ target systolic blood pressure of 80-90 mm Hg (ABC-T Grade 1C)
⚬ use restricted volume replacement to achieve target blood pressure until bleeding is controlled
(ABC-T Grade 1B)
⚬ in case of life-threatening hypotension, use vasopressors (norepinephrine, vasopressin) in addition
to uids to sustain target arterial pressure (ABC-T Grade 1C), even when uid resuscitation is in
progress and hypovolemia has not yet been corrected
⚬ in case of myocardial contractile dysfunction, consider infusion of inotropic agent (dobutamine,
epinephrine) (ABC-T Grade 1C)
⚬ Reference - Crit Care 2016 Apr 12;20:100 full-text
● Canadian Association of Emergency Physicians (CAEP) 2015 guidelines on vasopressors and inotropes
in emergency departments
⚬ routine vasopressor use not recommended (CAEP Conditional recommendation)
if vasopressor deemed necessary, consider vasopressin (CAEP Conditional recommendation)
⚬
⚬ Reference - CJEM 2015 Jan;17(1):1
● Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) 2016 clinical practice
guideline on vasopressor use in hypovolemic shock
⚬ consider norepinephrine rather than dopamine as rst-line vasopressor (SSAI Weak
recommendation, Low-quality evidence)
⚬ no recommendations on norepinephrine use vs. epinephrine, vasopressin analogues, or
phenylephrine for patients with hypovolemic shock
⚬ Reference - Acta Anaesthesiol Scand 2016 Nov;60(10):1347 full-text
● see also Hemorrhagic shock for additional information on uid resuscitation
Dosing
● no o cial guideline recommendation on dosing of vasoactive agents in hemorrhagic shock exist, but
typical dosing suggested
⚬ start norepinephrine at 0.05 mcg/kg/minute and increase in 0.05 mcg/kg/minute increments to
maximum of 0.2 mcg/kg/minute (J Trauma 2006 Jul;61(1):82 )
⚬ start dobutamine at 5 mcg/kg/minute and increase in 2.5 mcg/kg/minute increments to maximum
of 20 mcg/kg/minute (J Trauma 2006 Jul;61(1):82 )
⚬ dopamine 5-15 mcg/kg/minute IV as temporizing adjunct 2
Efficacy in hemorrhagic shock
● see Hemorrhagic shock, vasopressors section
● for patients with acute variceal hemorrhage see Acute variceal hemorrhage - treatment, vasoactive
drugs section
Cardiogenic Shock
Overview of vasoactive treatment in cardiogenic shock
● vasoactive therapy in cardiogenic shock is considered supportive while simultaneous diagnosis and
planning of de nitive solution of underlying cause take place
● inotropic agents may enhance cardiac function and vascular tone in short- to medium-term period in
patients with cardiogenic shock
● improvement in hemodynamics of inotropic support usually outweighs potential risks of increased

myocardial oxygen demand and ventricular arrhythmia when used as a bridge to de nitive treatment
● goal pulmonary capillary wedge pressure of at least 15 mm Hg with cardiac index of 0.2 L/kg/minute
● short-term inotropic support recommended to maintain systemic perfusion and to preserve end
organ performance until de nitive therapy (for example, coronary revascularization, mechanical
circulatory support, transplant) or resolution of precipitating factor occurs, including
⚬ dopamine
⚬ dobutamine
⚬ norepinephrine, which reduces arrhythmic events compared to dopamine in patients with shock
⚬ levosimendan, which may improve survival compared to enoximone in patients with refractory
cardiogenic shock
⚬ milrinone (typical dose 0.375-0.75 mcg/kg/minute) and epinephrine (starting dose 0.01-0.03
mcg/kg/minute, maximum suggested dose 0.1-0.3 mcg/kg/minute), which may be used under
speci c circumstances
● if persistent cardiogenic shock requiring continuous IV inotropic support beyond 24 hours
⚬ consider extracorporeal membrane oxygenation to provide emergency support in patients with

poor oxygenation or use as bridge to transplantation or implantation of mechanical assist device
⚬ consider left ventricular assist device for circulatory support in patients with refractory cardiogenic
shock and as bridge to recovery or bridge to decision in patients with profound hemodynamic
compromise
● if patients with cardiogenic shock after ST-elevation myocardial infarction do not quickly stabilize with
pharmacological therapy, intra-aortic balloon pump counterpulsation can be useful
● during vasoactive therapy, plan for de nitive solution, which may include
⚬ revascularization in case of myocardial infarct

⚬ valve replacement in case of acute valvular failure
⚬ cardiac transplantation in case of cardiogenic shock refractory to other therapies
● see cardiogenic shock topic for details and additional information on inotropes and vasopressors or
on surgery and procedures
⚬ use norepinephrine as rst-line vasopressor for cardiogenic shock (CAEP Strong recommendation)
⚬ use dobutamine if inotrope administration is deemed necessary (CAEP Conditional
recommendation)
● American College of Cardiology Foundation/American Heart Association (ACCF/AHA) 2013 heart failure
guideline recommendations
⚬ low-dose dopamine infusion
– may be considered in addition to loop diuretic therapy to improve diuresis and better preserve
renal function and renal blood ow (ACCF/AHA Class IIb, Level B)
– has not been shown to improve survival or outcomes and is controversial, see also Acute heart
failure
⚬ temporary IV inotropic support recommended in patients with cardiogenic shock (ACCF/AHA Class
I, Level C)
– to maintain systemic perfusion and preserve end organ performance
– until de nitive therapy (such as coronary revascularization, mechanical circulatory support, or
heart transplantation) or resolution of the acute precipitating problem
⚬ short-term, continuous IV inotropic support may be reasonable in hospitalized patients with
documented severe systolic dysfunction, low blood pressure, and signi cantly depressed cardiac
output to maintain systemic perfusion and preserve end organ performance (ACCF/AHA Class IIb,
Level B)
⚬ continuous IV inotropic support reasonable as short-term therapy while awaiting mechanical
circulatory support or cardiac transplantation in patients with stage D heart failure refractory to
guideline directed medical therapy and device therapy (ACCF/AHA Class IIa, Level B)
⚬ long-term, continuous IV inotropic support may be considered as palliative therapy for symptom
control in select patients with stage D heart failure despite optimal guideline-directed medical
therapy and device therapy who are not eligible for either mechanical circulatory support or
cardiac transplantation (ACCF/AHA Class IIb, Level B)
⚬ inotropic support potentially harmful in following cases (ACCF/AHA Class III, Level B)
– administered IV long-term (either intermittent or continuous) in absence of speci c indications

or for reasons other than palliative care
– administered IV short-term in hospitalized patients without evidence of signi cantly depressed
cardiac output (with or without congestion) and without documented severe systolic
dysfunction, hypotension, or impaired perfusion
⚬ Reference - Circulation 2013 Oct 15;128(16):e240 full-text
● European Society of Cardiology (ESC) 2016 Guidelines for the diagnosis and treatment of acute and
chronic heart failure
⚬ continuously monitor electrocardiogram while using inotropes and/or vasopressors, as they may
cause arrhythmia, myocardial ischemia, or hypotension in case of levosimendan (ESC Class I, Level
C)
⚬ consider intra-arterial blood pressure monitoring (ESC Class IIb, Level C)
⚬ inotropes
– do not use inotropes unless patient is symptomatically hypotensive or hypoperfused due to

reduced cardiac output (ESC Class III, Level A)
– consider IV infusion of inotrope (dobutamine) in case of hypotension (systolic blood pressure <
90 mm Hg) and/or hypoperfusion, or cardiogenic shock (ESC Class IIb, Level C)
– consider levosimendan IV to reverse e ect of beta blockade if thought to be contributor to
hypoperfusion (ESC Grade IIb, Level C)
⚬ vasopressors
– consider vasopressor (preferably norepinephrine) in case of cardiogenic shock despite inotrope

use to increase blood pressure and vital organ perfusion (ESC Grade IIb, Level B)
– epinephrine should be restricted to patients with persistent hypotension despite adequate
cardiac lling pressures and use of other vasoactive agents, or for resuscitation procedures
⚬ Reference - Eur J Heart Fail 2016 Aug;18(8):891
● National Institute for Health and Care Excellence (NICE) 2014 guideline on heart failure
⚬ do not routinely o er inotropes or vasopressors to people with acute heart failure

⚬ consider inotropes or vasopressors in people with acute heart failure with potentially reversible
cardiogenic shock
⚬ Reference - BMJ 2014 Oct 8;349:g5695 commentaries can be found in BMJ 2014 Nov
12;349:g6702 and BMJ 2014 Nov 12;349:g6707 , reply to commentary can be found in BMJ
2014 Nov 12;349:g6703
guideline on vasopressor use in cardiogenic shock
⚬ consider norepinephrine rather than dopamine as rst-line vasopressor (SSAI Weak
recommendation, Low-quality evidence)
⚬ no recommendations on norepinephrine use vs. epinephrine, vasopressin analogues, or
phenylephrine for patients with cardiogenic shock
Dosing in cardiogenic shock
● norepinephrine 0.1-1 mcg/kg/minute if systolic blood pressure < 70 mm Hg 2 or mean arterial
pressure < 65 mm Hg (Dtsch Arztebl Int 2012 May;109(19):343 full-text )
● dopamine
⚬ in general, 5-10 mcg/kg/minute IV for inotropic e ects and > 10 mcg/kg/minute IV for vasopressor
e ects 1 ; European Society of Cardiology considers 3-5 mcg/kg/minute to have inotropic e ects
and > 5 mcg/kg/minute to have vasopressor e ects (Eur J Heart Fail 2016 Aug;18(8):891 )
⚬ dosing
– initial dose 2-5 mcg/kg/minute in patients likely to respond to modest increments of inotropic
support
– initial dose 5 mcg/kg/minute in more seriously ill patients and increase in 5-10 mcg/kg/minute
increments
– dose may be increased up to 20-50 mcg/kg/minute; if dose > 50 mcg/kg/minute required, urine
output should be frequently checked
– Reference - FDA DailyMed 2014 Apr
⚬ 15 mcg/kg/minute recommended if systolic blood pressure 70-90 mm Hg 2
⚬ see Complications section for potential adverse e ects with dopamine, including dysrhythmia and
ischemia
● dobutamine 2-20 mcg/kg/minute if systolic blood pressure > 90 mm Hg 2
● epinephrine recommended starting dose 0.01-0.03 mcg/kg/minute (maximum suggested dose 0.1-0.3
mcg/kg/minute) (Curr Opin Cardiol 2014 May;29(3):250 )
● levosimendan loading dose 12-24 mcg/kg over 10 minutes, followed by 0.05-0.2 mcg/kg/minute in
case of cardiogenic shock refractory to catecholamine treatment (Dtsch Arztebl Int 2012
May;109(19):343 full-text )
● phosphodiesterase inhibitors; second-tier agents that are not recommended after myocardial infarct
⚬ milrinone 50 mcg/kg loading dose followed by 0.375-0.75 mcg/kg/minute (dose adjustment needed
for renal dysfunction) (Curr Opin Cardiol 2014 May;29(3):250 )
⚬ amrinone 0.75 mg/kg loading dose followed by 5-10 mcg/kg/minute 2
● for inotrope and vasopressor dosing in acute heart failure without shock, see Acute heart failure
Efficacy in cardiogenic shock and acute heart failure
● for e cacy of inotropes and vasopressors in cardiogenic shock, see Cardiogenic shock
● for e cacy of inotropes and vasopressors in acute heart failure, see Acute heart failure
Distributive Shock
Septic shock
● Surviving Sepsis Campaign (SSC) 2016 recommendations on vasoactive medications
⚬ uid resuscitation should ideally be achieved before use of inotropes and vasopressors
⚬ target mean arterial pressure of 65 mm Hg in patients with septic shock requiring vasopressors
(SCCM Strong recommendation, Moderate-quality evidence)
⚬ arterial catheter should be inserted as soon as practical if vasopressors used (SCCM Weak
Recommendation, Very low-quality Evidence)
⚬ norepinephrine recommended as rst-line vasopressor (SCCM Strong recommendation, Moderate-
quality evidence)
⚬ vasopressin (up to 0.03 units/minute) may be added to norepinephrine to
– increase mean arterial pressure (SCCM Weak recommendation, Moderate-quality evidence)

– decrease norepinephrine dose (SCCM Weak recommendation, Moderate-quality evidence)
⚬ consider adding epinephrine to norepinephrine to increase mean arterial pressure to target (SCCM
Weak recommendation, Low-quality evidence)
⚬ dopamine
– only suggested as alternative to norepinephrine in highly selective patient populations (for

example, patients with low risk of tachyarrhythmia and absolute or relative bradycardia) (SCCM
Weak recommendation, Low-quality evidence)
– low-dose dopamine should NOT be used for renal protection (SCCM Strong recommendation,
High-quality evidence)
⚬ dobutamine
– consider in patients with persistent hypoperfusion despite adequate uid resuscitation and
vasopressor use (SCCM Weak recommendation, Low-quality evidence)
– if initiated, titrate dosing to end point perfusion and reduce or discontinue in case of worsening
hypotension or arrhythmia
⚬ use of sodium bicarbonate therapy to improve hemodynamics or reduce vasopressor
requirements not suggested for patients with hypoperfusion-induced lactic acidemia with pH ≥
7.15 (SCCM Weak recommendation, Moderate-quality evidence)
⚬ Reference - SSC international guideline on management of severe sepsis and septic shock
(Intensive Care Med 2017 Mar;43(3):304 ), commentary can be found in JAMA 2017 Feb
28;317(8):807
in emergency departments during septic shock
⚬ use norepinephrine as rst-line vasopressor in septic shock (CAEP Strong recommendation)
⚬ use dobutamine in case of septic shock with low cardiac output despite volume resuscitation (CAEP
Strong recommendation)
⚬ consider vasopressin in case of septic shock refractory to catecholamines (CAEP Conditional
recommendation)
● Canadian Association of Emergency Physicians 2008 Sepsis Guidelines
⚬ after adequate volume resuscitation, vasopressor medications should be used to maintain blood
pressure (MAP > 65 mm Hg) and organ perfusion (CAEP Grade B)
– vasopressor medications may be required to maintain blood pressure prior to adequate
volume resuscitation (CAEP Grade D)
– various vasopressors including norepinephrine and dopamine may be used (CAEP Grade C)
⚬ dobutamine is considered rst line in septic shock patients who require inotropic support (CAEP
Grade D)
⚬ inotropes should be used to maintain central venous oxygen saturation over 70% (CAEP Grade D)
and adequate cardiac output (CAEP Grade D) in volume-replete septic patients with adequate
blood pressure
⚬ hemodynamically unstable patients who do not respond to volume resuscitation and vasopressor
infusion may be considered for low-dose corticosteroid replacement in the emergency department
(CAEP Grade D)
⚬ doses of 200-300 mg/day of hydrocortisone may be considered in patients requiring vasopressor
support (CAEP Grade D)
⚬ Reference - CJEM 2008 Sep;10(5):443 , commentary in CJEM 2008 Sep;10(5):461-3, 464 ,
commentary in CJEM 2009 Jul;11(4):320
guideline on vasopressor use in septic shock
⚬ use norepinephrine rather than dopamine as rst-line vasopressor (SSAI Strong recommendation,
Moderate-quality evidence)
⚬ consider norepinephrine rather than epinephrine, vasopressin analogues, or phenylephrine as
rst-line vasopressor (SSAI Weak recommendation, Low-quality evidence)
Dosing
● norepinephrine
⚬ initial dose typically 0.01-0.04 mcg/kg/minute, nal dose range typically 0.04-1 mcg/kg/minute 1 , 2
⚬ should be titrated based on patient response including blood pressure and urinary output (CJEM
2015 Jan;17(1):1 )
● vasopressin
⚬ dose typically 0.01-0.04 units/minute 1
⚬ up to 0.03 units/minute can be added to norepinephrine to increase mean arterial pressure or

decrease norepinephrine dose (SCCM Weak recommendation, Moderate-quality evidence )
(Intensive Care Med 2017 Mar;43(3):304 )
● dobutamine
⚬ initial dose 2.5-5 mcg/kg/minute, nal dose typically 2.5-10 mcg/kg/minute 1 , 2
⚬ 2-28 mcg/kg/minute e ectively raises cardiac output (CJEM 2015 Jan;17(1):1 )
● dopamine
⚬ 1-25 mcg/kg/minute recommended for septic shock (CJEM 2015 Jan;17(1):1 )

⚬ typical dose range 2-20 mcg/kg/minute, with dose-dependent e ects 1 , 2
– 5-10 mcg/kg/minute inotropic

– > 10 mcg/kg/minute vasopressor
● epinephrine 0.02 mcg/kg/minute may be used as second-tier agent 2
Efficacy
● see Sepsis treatment in adults
STUDY
● SUMMARY
inotropes may not be associated with lower overall mortality compared to nonvasoactive
treatment in critically ill patients, but might decrease mortality in patients with septic shock
DynaMed Level 2
SYSTEMATIC REVIEW: Br J Anaesth 2015 Nov;115(5):656 | Full Text
Details
⚬ based on systematic review limited by clinical heterogeneity
⚬ systematic review of 177 trials comparing mortality outcomes in 28,280 critically ill patients treated
with inotropes and/or vasopressors vs. nonvasoactive agents
⚬ most common nonvasoactive treatments were placebo in 111 trials and standard treatment in 32
trials
⚬ trials were clinically heterogeneous in
– patient population (condition, age)

– clinical setting
– drug comparisons
⚬ comparing inotropes vs. nonvasoactive agents
– overall mortality 22.4% vs. 22.2% (not signi cant) in analysis of 145 trials with 22,012 patients
– 1-month mortality 7.1% vs. 10.3% (risk ratio [RR] 0.37, 95% CI 0.51-0.89) in analysis of 28 trials
with 2,077 patients
⚬ comparing inotropes vs. nonvasoactive agents in subgroup analyses
– overall mortality in sepsis 26.8% vs. 52.9% (RR 0.58, 95% CI 0.35-0.98) in analysis of 2 trials with
90 patients
– overall mortality in vasoplegia 26.8% vs. 52.9% (RR 0.58, 95% CI 0.35-0.98) in analysis of 2 trials
with 90 patients
⚬ comparing vasopressors vs. nonvasoactive agents
– overall mortality 62.5% vs. 56.5% (not signi cant) in analysis of 33 trials with 6,213 patients
– 1-month mortality 58.1% vs. 59% (not signi cant) in analysis of 8 trials with 753 patients
⚬ comparing vasopressors vs. nonvasoactive agents in subgroup analyses
– overall mortality in vasoplegia 19.5% vs. 25.3% (RR 0.74, 95% CI 0.6-0.91) in analysis of 14 trials
with 610 patients
– overall mortality in cardiac surgery 0% vs. 5.6% (RR 0.13, 95% CI 0.03-0.56) in analysis of 7 trials
with 412 patients
⚬ levosimendan associated with decreased overall mortality compared to nonvasoactive treatment
(RR 0.8, 95% CI 0.68-0.94) in analysis of 48 trials with 4,219 patients
⚬ Reference - Br J Anaesth 2015 Nov;115(5):656 full-text
STUDY
● SUMMARY
in critically ill adults ≥ 65 years old with vasodilatory hypotension in intensive care unit, IV
vasopressor therapy guided by mean arterial pressure target of 60-65 mm Hg might decrease
90-day mortality compared to clinician's discretion DynaMed Level 2
RANDOMIZED TRIAL: JAMA 2020 Feb 12 early online
Details
⚬ based on randomized trial with con dence interval that includes di erences that are not clinically
important
⚬ 2,600 critically ill adults ≥ 65 years old (mean age 75 years, 57% men) with vasodilatory hypotension
(48% had septic shock) in intensive care unit were randomized to IV vasopressor therapy guided by
mean arterial pressure target of 60-65 mm Hg (permissive hypotension) vs. therapy at clinician's
discretion
– all adults were randomized within 6 hours of vasopressor infusion and had ongoing or
completed adequate uid resuscitation and were expected to need vasopressor for ≥ 6 hours;
none had contraindication to permissive hypotension
– vasopressors included norepinephrine, metaraminol, vasopressin, epinephrine, phenylephrine,
terlipressin, and dopamine
⚬ at baseline, mean arterial pressure 69.9 mm Hg in permissive hypotension group and 71.1 mm Hg
in usual care group
⚬ 95% completed 90-day follow-up and included in analysis
⚬ comparing permissive hypotension vs. clinician's discretion
– 90-day all-cause mortality 41% vs. 43.8% (95% CI for absolute di erence -6.75% to +1.05%), not
signi cant, but CI includes both clinically important and unimportant di erences
– median total duration of vasopressors 33 hours vs. 38 hours (p < 0.05)
– median total dose of norepinephrine equivalents 17.7 mg vs. 26.4 mg (p < 0.05)
– serious adverse event in 6.2% vs. 5.8% (not signi cant)
● renal failure in 3.2% vs. 2.5%

● supraventricular cardiac arrhythmia in 0.9% vs. 1%
● ventricular cardiac arrhythmia in 0.9% vs. 0.4%
⚬ no signi cant di erences in mean duration of intensive care unit or hospital stay, health-related
quality of life, or cognitive decline
⚬ Reference - 65 trial (JAMA 2020 Feb 12 early online ), editorial can be found in JAMA 2020 Feb 12
early online
STUDY
● SUMMARY
addition of vasopressin to catecholamines may reduce risk of atrial fibrillation and death at 28
or 30 days in patients with distributive shock DynaMed Level 2
SYSTEMATIC REVIEW: JAMA 2018 May 8;319(18):1889
Details
⚬ based on systematic review with inconsistent results in high-quality trials
⚬ systematic review of 23 randomized trials comparing vasopressin plus catecholamines vs.
catecholamines alone in 3,088 adults with distributive shock
– trials included patients with septic shock (21 trials), postcardiac surgery vasoplegia (1 trial), or
both (1 trial)
– 13 trials evaluated vasopressin, 9 trials evaluated terlipressin, 1 trial evaluated selepressin, and
1 trial evaluated pituitrin (vasopressin plus oxytocin)
⚬ vasopressin plus catecholamines associated with
– decreased risk of atrial brillation in analysis of 13 trials with 1,462 patients
● risk ratio [RR] 0.77 (95% CI 0.67-0.88)

● NNT 10-28 with atrial brillation in 30% of catecholamine only group
● no signi cant di erence in 3 of 4 high-quality trials included in analysis
– reduced 28-day or 30-day mortality in analysis of 17 trials with 2,904 patients
● RR 0.89 (95% CI 0.82-0.97)

● NNT 14-82 with 41% mortality in catecholamine-only group
● no signi cant di erence in any high-quality trial included in analysis
– increased risk of digital ischemia in analysis of 9 trials with 1,963 patients
● RR 2.38 (95% CI 1.37-4.12)

● NNH 18-159 with digital ischemia in 1.7% of catecholamine-only group
⚬ no signi cant di erences in
– requirement for renal replacement therapy in analysis of 6 trials with 805 patients
– risk of myocardial injury in analysis of 11 trials with 1,957 patients
– risk of ventricular arrhythmias in analysis of 9 trials with 837 patients
– risk of stroke in analysis of 4 trials with 1,358 patients
⚬ Reference - JAMA 2018 May 8;319(18):1889
STUDY
● SUMMARY
vasopressin and vasopressin analogues might reduce need for renal replacement therapy
compared to norepinephrine in critically ill adults with septic shock DynaMed Level 2
SYSTEMATIC REVIEW: Crit Care Med 2019 Jan;47(1):e44
Details
⚬ based on systematic review with con dence interval that includes di erences that are not clinically
important
⚬ systematic review of 17 randomized trials comparing vasopressin or vasopressin analogues vs.
other vasopressors (controls) in 2,833 critically ill adults with distributive shock
⚬ 11 trials with 2,691 patients with septic shock (8 trials) or postoperative vasoplegic shock (3 trials)
had suitable data for analysis
⚬ interventions included
– vasopressin plus norepinephrine (4 trials) or catecholamine (1 trial), and vasopressin alone (3

trials)
– terlipressin or vasopressin plus norepinephrine (2 trials) and terlipressin plus alpha-adrenergic
drug (1 trial)
⚬ controls included norepinephrine (10 trials) and catecholamine (1 trial)
⚬ comparing vasopressin or analogues to norepinephrine in patients with septic shock (including
VASST and VANISH trials)
– vasopressin or analogues associated with nonsigni cant decrease in need for renal replacement
therapy (odds ratio [OR] 0.75, 95% CI 0.54-1.04) in analysis of 4 trials with 1,263 adults, but CI
includes both clinically important and unimportant di erences
– no signi cant di erence in acute kidney injury (OR 0.84, 95% CI 0.67-1.05) in analysis of 7 trials
with 1,366 adults, but CI cannot exclude di erences that may be clinically important
⚬ comparing vasopressin to norepinephrine or catecholamines in patients with vasoplegic shock
– vasopressin associated with reduced need for renal replacement therapy in analysis of 2 trials
with 382 adults
● OR 0.23 (95% CI 0.09-0.61)
● NNT 9-22 with need for renal replacement therapy in 13% of control group
– no signi cant di erence in acute kidney injury in analysis of 3 trials with 474 adults, results
limited by signi cant heterogeneity
⚬ Reference - Crit Care Med 2019 Jan;47(1):e44
STUDY
● SUMMARY
early vasopressin may not reduce kidney failure compared to norepinephrine in patients with
septic shock DynaMed Level 2
RANDOMIZED TRIAL: JAMA 2016 Aug 2;316(5):509
Details
⚬ based on randomized trial with wide con dence intervals
⚬ 421 patients (median age 66 years) with septic shock in 18 intensive care units in United Kingdom
between 2013 and 2015 randomized to 1 of 4 treatments
– vasopressin titrated up to 0.06 units/minute plus hydrocortisone
– vasopressin plus placebo
– norepinephrine titrated up to 12 mcg/minute plus hydrocortisone
– norepinephrine plus placebo
⚬ dosing of hydrocortisone 50 mg IV 4 times daily for 5 days, twice daily for 3 days, and once daily for
3 days
⚬ 409 patients included in analysis
⚬ 26.1% did not have study drug 2 (hydrocortisone or placebo)
⚬ comparing vasopressin vs. norepinephrine
– 28-day survival without kidney failure 57% vs. 59.2% (absolute di erence -2.3%, 95% CI -13% to
8.5%)
– median number of kidney failure-free days in nonsurviving patients 9 days vs. 13 days (absolute
di erence -4 days, 95% CI -11 days to 5 days)
– renal replacement therapy required by 25.4% vs. 35.3% (absolute di erence -9.9%, 95% CI
-19.6% to -0.6%)
– 28-day mortality 30.9% vs. 27.5% (not signi cant)
– serious adverse events in 10.7% vs. 8.3% (not signi cant)
⚬ Reference - VANISH trial (JAMA 2016 Aug 2;316(5):509 )
STUDY
● SUMMARY
vasopressin might reduce mortality compared to norepinephrine in patients with less severe
septic shock DynaMed Level 2
RANDOMIZED TRIAL: N Engl J Med 2008 Feb 28;358(9):877
Details
⚬ based on subgroup analysis of randomized trial with borderline statistical signi cance
⚬ 802 patients ≥ 16 years old with septic shock taking norepinephrine ≥ 5 mcg/minute were
randomized to low-dose vasopressin (0.01-0.03 units/minute) vs. norepinephrine (5-15
mcg/minute) infusions
– all patients had open-label vasopressors
– all vasopressor infusions titrated and tapered according to protocols to maintain target blood
pressure
⚬ 778 (97%) patients analyzed
⚬ no statistically signi cant di erences comparing vasopressin vs. norepinephrine in overall analysis
– 28-day all-cause mortality 35.4% vs. 39.3%

– 90-day all-cause mortality 43.9% vs. 49.6%
– days free of any organ dysfunction 0 vs. 0
– median length of stay in intensive care unit 15 days vs. 16 days
– serious adverse events in 10.3% vs. 10.5%
● cardiac arrest in 0.8% vs. 2.1% (p = 0.14)

● digital ischemia in 2% vs. 0.5% (p = 0.11)
⚬ heart rate signi cantly lower with vasopressin compared to norepinephrine during rst 4 days of
treatment (p < 0.001), but not signi cantly di erent throughout trial
⚬ comparing vasopressin vs. norepinephrine in prospectively de ned subgroup of patients with less
severe septic shock (infusion of norepinephrine 5-14 mcg/minute at baseline)
– 28-day mortality 26.5% vs. 35.7% (p = 0.05, NNT 11, 95% CI 6 to in nity)
– 90-day mortality 35.8% vs. 46.1% (p = 0.04, NNT 10, 95% CI 5-250)
⚬ no signi cant di erences in 28-day or 90-day mortality in patients with more severe septic shock
⚬ Reference - VASST trial (N Engl J Med 2008 Feb 28;358(9):877 ), editorial can be found in N Engl J
Med 2008 Feb 28;358(9):954 , commentary can be found in N Engl J Med 2008 Jun
19;358(25):2736 , ACP J Club 2008 Sep 16;149(3):14
⚬ vasopressin may reduce progression to renal failure in patients with septic shock at risk of
kidney injury
DynaMed Level 2
– based on post hoc analysis of VASST trial with borderline statistical signi cance
– kidney injury present in 464 (59.6%) patients at baseline
– p ≤ 0.01 considered statistically signi cant due to multiple simultaneous comparisons
– comparing vasopressin vs. norepinephrine
● progression to renal failure or loss in 20.8% vs. 39.6% (p = 0.03)

● use of renal replacement therapy in 17% vs. 37.7% (p = 0.02)
– Reference - Intensive Care Med 2010 Jan;36(1):83
STUDY
● SUMMARY
dopamine associated with increased mortality compared to norepinephrine as initial vasopressor
in patients with septic shock DynaMed Level 2
COHORT STUDY: Crit Care Med 2015 Oct;43(10):2141 | Full Text
Details
⚬ based on retrospective cohort
⚬ 61,122 patients (mean age 68 years) with septic shock were treated with dopamine vs.
norepinephrine as initial vasopressor during rst 2 days of hospitalization
⚬ 22.4% received dopamine, 77.6% received norepinephrine
⚬ in propensity score-matching analysis of 38,788 patients, dopamine had higher mortality compared
to norepinephrine (25% vs. 23.7%, odds ratio 1.08, 95% CI 1.02-1.14)
⚬ Reference - Crit Care Med 2015 Oct;43(10):2141 full-text
STUDY
● SUMMARY
addition of levosimendan to standard care does not appear to reduce acute organ dysfunction
and may increase rate of tachyarrhythmias and need for continued mechanical ventilation in
patients with septic shock DynaMed Level 2
RANDOMIZED TRIAL: N Engl J Med 2016 Oct 27;375(17):1638 | Full Text
Details
⚬ based on randomized trial with di erential discontinuation rate
⚬ 516 patients (aged 58-77 years) with septic shock randomized to levosimendan 0.05-0.2
mcg/kg/minute vs. placebo for 24 hours in addition to standard care
– levosimendan initiated at 0.1 mcg/kg/minute and uptitrated to 0.2 mcg/kg/minute after 2-4
hours in absence of rate-limiting side e ects
– levosimendan could be reduced to 0.05 mcg/kg/minute or discontinued to avoid hypotension or
severe tachycardia
⚬ treatment discontinued before 24 hours due to hemodynamic instability in 13.5% of levosimendan
group vs. 7.7% of placebo group (p value not reported)
⚬ primary outcome was sequential organ failure assessment (SOFA) up to day 28 (higher score
indicating more severe dysfunction, maximum score 20)
⚬ comparing levosimendan vs. placebo at 28 days
– mortality 34.5% vs. 30.9% (not signi cant)

– mean SOFA score 6.68 vs. 6.06 (not signi cant)
– tachyarrhythmia in 3.1% vs. 0.4% (p = 0.04, NNH 37)
⚬ among 417 patients (81%) requiring mechanical ventilation at baseline, levosimendan associated
with reduced likelihood of weaning from mechanical ventilation (hazard ratio 0.77, 95% CI 0.6-0.97,
p = 0.03)
⚬ Reference - LeoPARDS trial N Engl J Med 2016 Oct 27;375(17):1638 full-text
Anaphylactic shock
in emergency departments during anaphylactic shock
⚬ use epinephrine infusion in case of anaphylactic shock unresponsive to epinephrine intramuscular
or IV bolus (CAEP Strong recommendation)
● Clinical Practice Parameters 2014 for treatment of anaphylaxis by the American Academy of Allergy,
Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology
(ACAAI)
⚬ anaphylaxis
– inject epinephrine intramuscularly in the anterolateral thigh as initial treatment for acute
anaphylaxis immediately after the diagnosis of anaphylaxis is made (AAAAI/ACAAI Strong
recommendation, Grade B)
⚬ anaphylactic shock
– if the patient is not responding to epinephrine injections, administer
● epinephrine IV in a monitored setting (AAAAI/ACAAI Moderate recommendation, Grade C)

● epinephrine through intraosseous access (AAAAI/ACAAI Moderate recommendation, Grade
D)
⚬ refractory shock
– in case of unresponsiveness to epinephrine and uid resuscitation, especially with concomitant

beta blocker use, consider glucagon (AAAAI/ACAAI Moderate recommendation, Grade B)
– in case of bronchospasm, consider inhalation of beta agonist (AAAAI/ACAAI Moderate
recommendation, Grade B)
⚬ Reference - Ann Allergy Asthma Immunol 2014 Dec;113(6):599
● World Allergy Organization 2011 guidelines for management of anaphylaxis and anaphylactic shock
⚬ anaphylaxis (WAO Grade B-C)
– inject epinephrine 0.01 mg/kg of a 1 mg/mL solution intramuscularly in mid-anterolateral aspect

of the thigh
● maximum dose 0.5 mg for adults or 0.3 mg for children
● record time of dose and repeat in 5-15 minutes if needed
– establish IV access and give 1-2 L saline solution rapidly

– monitor blood pressure, heartrate and function, respiratory status, and oxygenation at least at
frequent intervals and continuously if possible
– drug absorption from subcutaneous injection may be inadequate
⚬ anaphylactic shock (WAO Grade B-C)
– administer epinephrine by slow IV titrated according to cardiac monitoring

– in case of cardiac arrest, administer epinephrine as IV bolus
⚬ refractory shock (WAO Grade B-C)
– administer epinephrine IV
– consider vasopressor (dopamine, dobutamine, norepinephrine, or vasopressin) either alone or
in addition to epinephrine
– titrate dose according to clinical response
– in case of concomitant beta blocker use and poor response to epinephrine, consider glucagon
– in case of concomitant beta blocker use and epinephrine-resistant bronchospasm, consider
atropine
⚬ Reference - World Allergy Organ J 2011 Feb;4(2):13 full-text , Curr Opin Allergy Clin Immunol
2012 Aug;12(4):389
● European Academy of Allergy and Clinical Immunology (EAACI) 2014 food allergy and anaphylaxis
guidelines
⚬ epinephrine is potentially life-saving and must immediately be administered as rst-line treatment
(EAACI Grade C, Level IV)
⚬ consider prophylactic administration of epinephrine in case of likely development of anaphylaxis
(EAACI Grade D, Level V)
⚬ inject epinephrine intramuscularly in mid-anterolateral aspect of the thigh (EAACI Grade B, Level I)
⚬ repeat doses of epinephrine should be ≥ 5 minutes apart (EAACI Grade D, Level V)
⚬ in case of inadequate response to 2 or more doses of intramuscular epinephrine, consider
epinephrine IV by experienced intensive care, emergency department, and critical care physicians
with appropriate cardiac monitoring (EAACI Grade D, Level IV)
Dosing
● for evidence on di erent epinephrine administration routes, see Anaphylaxis

● dosing from World Allergy Organization
⚬ inject epinephrine 0.01 mg/kg of 1 mg/mL solution intramuscularly in mid-anterolateral aspect of

the thigh (WAO Grade B-C)
– maximum dose 0.5 mg for adults or 0.3 mg for children
– record time of dose and repeat in 5-15 minutes if needed
⚬ if unresponsive to epinephrine intramuscularly
– administer epinephrine 1 mcg/mL IV at rate of 1 mcg/minute, uptitrated to maximum 10

mcg/minute
– in children, start epinephrine IV at 0.1 mcg/kg/minute
⚬ if unresponsive to epinephrine IV, impending cardiovascular collapse, or unavailability of

epinephrine IV
– administer epinephrine 50 mcg IV bolus of 100 mcg/mL solution
⚬ when concomitant beta blockers complicate vasopressor treatment, consider glucagon
– 1-5 mg (in children 20-30 mcg/kg up to 1 mg) IV over 5 minutes, then infusion 5-15 mcg/minute
titrated to clinical response
– protect airway due to risk for vomiting and aspiration in drowsy or obtunded patients
⚬ Reference - World Allergy Organ J 2011 Feb;4(2):13 full-text
● in case of persistent hypotension due to unresponsiveness to epinephrine and volume expansion or

cardiac arrest, consider vasopressors
⚬ dopamine 2-20 mcg/kg/minute titrated to maintain systolic blood pressure
– for adults - 400 mg in 500 mL of 5% dextrose

– for children - 6 times body weight (in kg) equals number of mg diluted to total 100 mL saline,
then 1 mL/hour delivers 1 mcg/kg/minute
– dose > 10 mcg/kg/minute usually needed to maintain systolic blood pressure
⚬ norepinephrine may also be used

⚬ Reference - J Allergy Clin Immunol 2010 Sep;126(3):477
● in case of persistent hypotension due to unresponsiveness to epinephrine, consider norepinephrine
0.1-1 mcg/kg/minute (0.5-30 mcg/minute) 2
Efficacy
STUDY
● SUMMARY
no randomized or quasi-randomized trials identified evaluating epinephrine in patients with
anaphylaxis
COCHRANE REVIEW: Cochrane Database Syst Rev 2008 Oct 8;(4):CD006312
Details
⚬ based on Cochrane review
⚬ systematic review of randomized or quasi-randomized trials evaluating epinephrine with no
intervention, placebo, or other adrenergic agonists in patients with anaphylaxis
⚬ Reference - Cochrane Database Syst Rev 2008 Oct 8;(4):CD006312 updated in 2010
Neurogenic shock
in emergency departments during neurogenic shock
⚬ choice of vasopressor (dopamine, phenylephrine) should be guided by patient characteristics and
response to treatment (CAEP Conditional recommendation)
● Congress of Neurological Surgeons (CNS) 2013 guidelines on management of cervical spinal cord
injuries recommendations for patients with hypotension
⚬ correct hypotension (mean systolic blood pressure < 90 mm Hg) as soon as possible (CNS Level III)
⚬ maintain mean arterial blood pressure between 85 and 90 mm Hg for rst 7 days after acute spinal
cord injury (CNS Level III)
⚬ no speci c recommendations regarding vasopressor or inotrope use in case of neurogenic shock
⚬ Reference - Neurosurgery 2013 Mar;72 Suppl 2:93 , commentary can be found in Neurosurgery
2013 Aug;73(2):E384 , Neurosurgery 2013 Aug;73(2):E383
● Consortium for Spinal Cord Medicine (CSCM) 2008 clinical practice guidelines for early acute
management in adults with spinal cord injuries recommendations for patients with hypotension
and/or neurogenic shock
⚬ prevent and treat hypotension (CSCM Grade B, Level II/IV, panel opinion strength 4)
– uid resuscitation rst priority

– vasopressors may be used to further treat hypotension
⚬ rule out causes of hypotension other than neurogenic shock (CSCM Grade C, Level III/IV, panel
opinion strength 5)
⚬ recognize and treat neurogenic shock (CSCM Grade C, Level III/IV, panel opinion strength 5)
– rst ensure restoration of intravascular volume

– if hypotension persists, consider vasopressors (dopamine, norepinephrine, phenylephrine)
⚬ monitor and treat bradycardia (CSCM Grade C, Level III/IV, panel opinion strength 5)
– vasopressors may be required

– vasopressors should be chosen to minimize exacerbation of bradycardia
– ideal agent should have both alpha- and beta-adrenergic activity (dopamine, norepinephrine,
epinephrine)
⚬ maintain mean arterial pressure with balance of uids and inotropes (CSCM Grade NA, Level NA,
panel opinion strength 4)
– optimal target mean arterial pressure for maintenance of spinal cord perfusion unknown
– choice of vasoactive agent depends on level of spinal cord injury and patient hemodynamics
– in case of hypotension in combination with bradycardia, combination of chronotropic, inotropic,
and vasoconstrictive e ects needed (dopamine, norepinephrine)
– in case of hypotension mainly caused by peripheral vasodilation (for example, in low thoracic
lesions), consider pure vasoconstrictor (phenylephrine)
⚬ in case of intubation of tetraplegic patient, anticipate bradycardia and hypotension which often
requires vasopressor support (CSCM Grade C, Level III, panel opinion strength 5)
⚬ Reference - J Spinal Cord Med 2008;31(4):403 full-text , commentary in J Spinal Cord Med
2008;31(4):360 full-text
guideline on vasopressor use in shock types other than septic or cardiogenic shock
vasopressor (SSAI Weak recommendation, Low quality evidence)
Dosing in neurogenic shock
● no o cial recommendations for vasopressor dosing in neurogenic shock exist, but commonly used
doses include
⚬ dopamine
– 5-15 mcg/kg/minute IV 2
● 5-10 mcg/kg/minute IV for inotropic e ect with mild vasodilation

● > 10 mcg/kg/minute IV for inotropic e ect with peripheral vasoconstriction
⚬ phenylephrine 10-20 mcg/kg/minute 2
⚬ norepinephrine 0.1-1 mcg/kg/minute 2
⚬ other vasoactive agents in neurogenic shock
– epinephrine 1-10 mcg/kg/minute

– dobutamine 5-15 mcg/kg/minute
– vasopressin 0.01-0.04 units/minute
– milrinone 0.3-1.5 mcg/kg/minute
– Reference - Spinal Cord 2010 May;48(5):356 , commentary in Spinal Cord 2010 May;48(5):362
Efficacy in neurogenic shock
STUDY
● SUMMARY
vasopressors may be required more frequently in complete spinal cord injuries compared to
incomplete injuries and in cervical cord injuries compared to thoracolumbar injuries in patients
with acute spinal cord injuries DynaMed Level 2
SYSTEMATIC REVIEW: Spinal Cord 2010 May;48(5):356
Details
⚬ based on systematic review with trial-speci c quality measures not reported
⚬ systematic review of 7 case series with 423 patients treated with vasopressors for acute spinal cord
injuries
⚬ vasopressors used were dobutamine, dopamine, norepinephrine, epinephrine, phenylephrine,
ephedrine, isoproterenol, and terbutaline
⚬ vasopressor support more frequently required in
– complete spinal cord injury compared to incomplete injuries (p < 0.01) in analysis of 4 studies
with 264 patients
– cervical cord injuries compared to thoracolumbar injuries (p < 0.001) in analysis of 4 studies with
268 patients
⚬ no signi cant di erence in neurologic improvement between vasopressor support initiation at < 85
mm Hg vs. < 90 mm Hg mean arterial pressure
⚬ no analysis possible on optimal vasopressor agent due to clinical heterogeneity of studies
⚬ Reference - Spinal Cord 2010 May;48(5):356
STUDY
● SUMMARY
dopamine and phenylephrine may not result in neurological improvement and associated with
increased complication rates in patients with spinal cord injury DynaMed Level 2
COHORT STUDY: J Neurotrauma 2014 Feb 1;31(3):284
Details
⚬ based on retrospective cohort study
⚬ 131 patients with spinal cord injury who received vasopressors to maintain blood pressure were
evaluated for complications
⚬ vasopressors used were dopamine (60%), phenylephrine (34%), and dopamine plus phenylephrine
(4%) norepinephrine (5%), epinephrine (1.5%), and vasopressin (0.5%)
⚬ neither dopamine nor phenylephrine associated with signi cant neurological improvement
⚬ 74% of patients receiving vasopressors had complication, including
– tachycardia in 41.2%
– bradycardia in 24.4%
– atrial brillation in 12.2%
– ventricular tachycardia in 10.7%
⚬ vasopressors associated with increased complication rates in logistic regression
– dopamine (odds ratio [OR] 8.97, 95% CI 2.72-29.56)

– phenylephrine (OR 5.92, 95% CI 1.74-20.13)
⚬ Reference - J Neurotrauma 2014 Feb 1;31(3):284
STUDY
● SUMMARY
combination of fluid resuscitation plus vasopressors to target mean arterial blood pressure > 85
mm Hg reported to improve neurological status in patients with acute spinal cord injury, but
not in patients with neurogenic shock DynaMed Level 3
COHORT STUDY: J Neurosurg 1997 Aug;87(2):239
Details
⚬ based on cohort study without direct statistical comparison between groups
⚬ 64 patients with acute spinal cord injury (35 cervical, 29 thoracic) were treated with IV uids, colloid,
and vasopressors to maintain mean arterial pressure (MAP) > 85 mm Hg and followed for mean 17
months
– 48% received dopamine 2.5-5 mcg/kg/minute IV if MAP < 85 mm Hg persisted after volume
resuscitation, followed by norepinephrine 0.01-0.2 mcg/kg/minute if needed
– all patients treated with methylprednisolone
⚬ 92% had neurological improvement from baseline after 12 months follow-up

⚬ no patients with neurogenic shock at baseline had neurological improvement
⚬ no instances of hypertensive hemorrhage, stroke, myocardial infarction, or death reported
⚬ Reference - J Neurosurg 1997 Aug;87(2):239
STUDY
● SUMMARY
enteral pseudoephedrine reported to facilitate discontinuation of vasopressors in patients with
neurogenic shock due to acute spinal cord injury DynaMed Level 3
CASE SERIES: Pharmacotherapy 2014 Jan;34(1):89 | Full Text

Details
⚬ based on case series
⚬ 38 patients (mean age 39 years, 76% men) with acute spinal cord injuries had pseudoephedrine for
> 1 day in case of ≥ 1 of following
– bradycardia (heart rate < 50 beats/minute) and/or hypotension (systolic arterial pressure ≤ 90
mm Hg)
– IV vasopressor support and/or atropine
⚬ maximum daily pseudoephedrine dose 60-720 mg orally

⚬ vasopressors used for support were dopamine (in 71%), norepinephrine (in 34%), epinephrine (in
13%), and phenylephrine (in 11%)
⚬ success de ned as discontinuation of vasopressors or improvement in number of bradycardia
episodes after initiating pseudoephedrine
⚬ mean pseudoephedrine therapy duration 32 days
⚬ pseudoephedrine was successful in 82%, failed in 5%, and inconclusive in 13%
⚬ Reference - Pharmacotherapy 2014 Jan;34(1):89 full-text
Adrenal insufficiency/failure
in emergency departments in patients with adrenal insu ciency or failure
⚬ uid resuscitation and steroid replacement therapy (hydrocortisone) should be started as soon as
possible
⚬ choice of vasopressor in patients unresponsive to steroid replacement is unclear and should be
guided by patient response to treatment (CAEP Conditional recommendation)
Obstructive Shock
Causes/Types of obstructive shock
● recommendations for vasopressors and inotropes in patients with obstructive shock may refer to
various underlying causes, including
⚬ pulmonary embolism
⚬ obstructive hypertrophic cardiomyopathy
⚬ use systemically active vasopressors to preserve cerebral and cardiac perfusion in case of
obstructive shock unresponsive to indicated treatment (CAEP Conditional recommendation)
⚬ in case of obstructive hypertrophic cardiomyopathy or dynamic out ow obstruction (CAEP
Conditional recommendation)
– avoid inotropic agents
– consider judicious use of vasoconstrictors in case of imminent decompensation and/or
mortality
⚬
CLINICIANS' PRACTICE POINT
Assure adequate volume resuscitation to avoid left ventricular under lling.
● European Respiratory Society (ESC) 2014 Guidelines on the diagnosis and management of acute
pulmonary embolism
⚬ no o cial recommendations on vasopressor or inotrope use, but following suggestions made
– consider dobutamine and/dopamine in case of pulmonary embolism in combination with low
cardiac index and normal blood pressure
– consider restricting norepinephrine use to patients with hypotension
– epinephrine may be bene cial in patients with pulmonary embolism and shock as it combines
bene cial properties of norepinephrine and dobutamine
⚬ Reference - Eur Heart J 2014 Nov 14;35(43):3033-69, 3069a full-text , correction in Eur Heart J
2015 Oct 14;36(39):2666 full-text , correction in Eur Heart J 2015 Oct 14;36(39):2642 full-text
, commentary in Rev Esp Cardiol (Engl Ed) 2015 Jan;68(1):10 PDF
guideline on vasopressor use in shock types other than septic or cardiogenic shock
vasopressor (SSAI Weak recommendation, Low-quality evidence)
Dosing in obstructive shock
● for acute massive pulmonary embolism leading to hypotension secondary to right ventricle failure 2
⚬ rst-tier agents
– dobutamine 5 mcg/kg/minute
– norepinephrine 0.1-1 mcg/kg/minute
⚬ second-tier agents - phenylephrine 10-20 mcg/kg/minute
● no recommended dosing strategies speci c for other causes of obstructive shock
Efficacy
● pulmonary embolism
⚬ no outcome data available to support particular agent over other agents for hypotension resulting
from right ventricle failure secondary to acute pulmonary embolism 2

⚬ ideal agent should have positive inotropic e ects and increase mean arterial pressure through
systemic vasoconstriction without signi cantly increasing pulmonary vascular resistance 2

⚬ milrinone may be used as inotrope that may decrease pulmonary vascular resistance
⚬ levosimendan 0.2 mcg/kg/minute in combination with vasodilators reported to result in successful
treatment of 49-year-old man with decompensated right heart failure secondary to pulmonary
embolism in case report (Anaesth Intensive Care 2013 Jul;41(4):554 )
⚬ levosimendan 0.2 mcg/kg/minute in addition to uid resuscitation and norepinephrine reported to
result in successful treatment of 72-year-old man with submassive pulmonary embolism can be
found in Anaesth Intensive Care 2007 Oct;35(5):771
Shock-related Acute Kidney Injury
● Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline on acute kidney injury
⚬ vasopressor use in conjunction with uids recommended in patients with vasomotor shock with or
at risk for acute kidney injury (KDIGO Level 1, Grade C)
⚬ low-dose dopamine not recommended to prevent or treat acute kidney injury (KDIGO Level 1,
Grade A)
⚬ after optimization of intravascular volume, no evidence supporting 1 speci c vasopressor for renal
protection
⚬ vasopressors titrated based on mean arterial pressure, cardiac output, or global oxygen
parameters
⚬ Reference - Nephron Clin Pract 2012;120(4):c179 full-text , Curr Opin Crit Care 2013
Dec;19(6):544
Efficacy
● see Management, Complications, and Prevention of Acute Kidney Injury (AKI), section on low-dose
(renal dose) dopamine e cacy
STUDY
● SUMMARY
vasopressin may reduce progression to renal failure in patients with septic shock and kidney
injury DynaMed Level 2
RANDOMIZED TRIAL: Intensive Care Med 2010 Jan;36(1):83
Details
⚬ based on post hoc analysis of VASST trial with borderline statistical signi cance
⚬ in VASST trial
– 802 patients ≥ 16 years old with septic shock taking norepinephrine ≥ 5 mcg/minute were
randomized to low-dose vasopressin (0.01-0.03 units/minute) vs. norepinephrine (5-15
mcg/minute) infusions
– all patients had open-label vasopressors
– all vasopressor infusions titrated and tapered according to protocols to maintain target blood
pressure
⚬ kidney injury present in 464 (59.6%) patients at baseline
⚬ p ≤ 0.01 considered statistically signi cant due to multiple simultaneous comparisons
⚬ comparing vasopressin vs. norepinephrine
– progression to renal failure or loss in 20.8% vs. 39.6% (p = 0.03)

– use of renal replacement therapy in 17% vs. 37.7% (p = 0.02)
⚬ Reference - VASST trial (Intensive Care Med 2010 Jan;36(1):83 )
Nonshock Situations
Post cardiopulmonary arrest
● see Cardiac arrest in adults for inotrope and vasopressor use in patients during cardiac arrest
● American Heart Association 2015 Guidelines Update for management of patients after cardiac arrest
⚬ consider avoiding and immediately correcting hypotension (systolic blood pressure < 90 mm Hg,
mean arterial pressure < 65 mm Hg) during postresuscitation care (AHA Class IIb, Level C-LD)
⚬ vasoactive drugs may be administered after return of spontaneous circulation to support cardiac
output, particularly heart and brain perfusion
⚬ Reference - Circulation 2015 Nov 3;132(18 Suppl 2):S465 full-text
● Rocky Mountain Critical Care Conference (RMCCC) 2003 recommendations on management following
resuscitation from cardiac arrest
⚬ maintain normotension (mean arterial pressure 80-100 mm Hg, or normal for the patient) after
cardiac arrest for the rst 24 hours (RMCCC Grade D)
⚬ hypotension should be managed with vasopressors and inotropes if volume infusion is ine ective
or pulmonary edema limits further administration of volume (RMCCC Grade E)
⚬ consider obtaining cardiac index over 2.5 L/minute/m2 before using large doses of adrenergic
drugs (RMCCC Grade E)
⚬ if vasopressors or inotropes are required for > 2-3 hours, consider assessment of central pressures
and cardiac output (RMCCC Grade E)
⚬ Reference - Can J Anaesth 2005 Mar;52(3):309 , commentary in Can J Anaesth 2005 Oct;52(8):892
Efficacy
STUDY
● SUMMARY
high vasopressor load in first 6 hours after cardiac arrest does not appear associated with effect
on 1-year neurological outcome in patients with out-of-hospital cardiac arrest
DynaMed Level 2
COHORT STUDY: Resuscitation 2016 Aug;105:116
Details
⚬ based on prospective cohort
⚬ 412 patients with out-of-hospital cardiac arrest were evaluated for neurological outcomes after 1-
year follow-up
– 53% received vasopressors in rst 6 hours in intensive care unit (ICU)
– neurological outcome de ned as poor with Cerebral Performance Category (CPC) score 3-5 or
good with CPC score 1-2
⚬ comparing patients with good vs. poor outcome in rst 6 hours after cardiac arrest
– total vasopressor dose 0.01 mg vs. 0.02 mg (p = 0.07)

– time at mean arterial pressure < 70 mm Hg 17 minutes vs. 31 minutes (p = 0.03)
⚬ in regression analysis, factors not associated with poor outcome
– high vasopressor load

– mean arterial pressure
– time spent at mean arterial pressure < 70 mm Hg
⚬ in regression analysis, lowest measured mean arterial pressure associated with poor outcome
(odds ratio 1.02, 95% CI 1-1.04, p = 0.03)
⚬ Reference - Resuscitation 2016 Aug;105:116
Hepatorenal syndrome
Recommendations and dosing from professional organizations for hepatorenal syndrome
● American Association for the Study of Liver Diseases (AASLD) 2009 guidelines on management of
adult patients with ascites due to cirrhosis - hepatorenal syndrome
⚬ albumin infusion plus administration of vasoactive drugs (vasoconstrictors) such as octreotide and
midodrine should be considered in the treatment of type I hepatorenal syndrome (AASLD Class IIa,
Level B)
⚬ in case of admission to intensive care unit, albumin infusion plus administration of norepinephrine
should be considered in the treatment of type I hepatorenal syndrome (AASLD Class IIa, Level A)
⚬ Reference - Hepatology 2009 Jun;49(6):2087 , commentary can be found in Hepatology 2009
Oct;50(4):1320 , commentary can be found in Hepatology 2009 Oct;50(4):1320
● European Association for the Study of the Liver (EASL) 2010 guideline recommendations for
vasopressor use in hepatorenal syndrome
⚬ for type 1 hepatorenal syndrome (HRS)
– use terlipressin 0.5-1 mg IV bolus every 4-6 hours in combination with albumin to decrease
serum creatinine to < 133 mcmol/L (complete response) (EASL Level A1)
● if serum creatinine remains at ≥ 75% of original level after 3 days, increase terlipressin dose
stepwise to 2 mg every 4 hours
● if serum creatinine does not reduce or remains ≥ 133 mcmol/L discontinue terlipressin
treatment within 14 days
– special considerations for terlipressin treatment (EASL Level A1)
● in case of ischemic cardiovascular disease, do not use terlipressin

● during terlipressin treatment, carefully monitor patient for cardiac arrhythmia, splanchnic or
digital ischemia, and uid overload, and modify or discontinue treatment accordingly
● in case of recurrence of type 1 HRS after terlipressin discontinuation, repeat treatment
– consider alternative therapies to terlipressin such as norepinephrine or midodrine plus

octreotide, both with albumin (EASL Level B1)
⚬ for type 2 HRS, terlipressin e ective in 60%-70% (EASL Level B1)
⚬ Reference - J Hepatol 2010 Sep;53(3):397 , commentary can be found in J Hepatol 2011
Oct;55(4):743 full-text
Evidence for vasoconstrictors plus albumin
● see Hepatorenal syndrome, vasoconstrictors plus albumin section
Takotsubo syndrome
● Task Force on Takotsubo syndrome of the Heart Failure Association of the European Society of
Cardiology Position Statements in 2016
⚬ Takotsubo syndrome is considered a stress response and usually involves sudden sympathetic
activation resulting in surge of catecholamines
– left or right ventricular function may be a ected
– key feature is recovery of normal cardiac function, although acute heart failure, left ventricular
out ow obstruction, arrhythmias, or cardiogenic shock may occur
⚬ in milder cases with left ventricular ejection fraction of > 35%, vasoactive drugs should be avoided
in patients with normal cardiac output
⚬ in patients with more severe cases
– use of inotropes (dobutamine, norepinephrine, epinephrine, dopamine, milrinone,

isoproterenol) should be regarded as contraindicated in Takotsubo syndrome
– cessation of drugs with sympathomimetic properties (catecholamines, beta-2 agonists) is
advised
– consider beta blocker or selective alpha-1 agonist (phenylephrine) in patients with
hemodynamically signi cant left ventricle out ow tract obstruction (> 40 mm Hg in combination
with systolic blood pressure < 110 mm Hg)
– low-dose levosimendan may be considered in patients with cardiogenic shock and is preferable
to other inotropes
⚬ Reference - Eur J Heart Fail 2016 Jan;18(1):8
● see Takotsubo syndrome for additional information
Complications and Adverse Effects of Vasopressor and Inotrope Use
General effects of vasopressors and inotropes
● Canadian Association of Emergency Physicians (CAEP) 2015 guidelines on vasopressor and inotrope
use in emergency departments' graded statements on side e ects
⚬ dopamine
– increases risk of tachyarrhythmia compared to norepinephrine (CAEP Grade A)

– increases mortality in septic shock compared to norepinephrine (CAEP Grade A)
⚬ epinephrine
– increases metabolic abnormalities compared to norepinephrine (CAEP Grade A)

– increases metabolic abnormalities in cardiogenic shock without acute cardiac ischemia
compared to norepinephrine-dobutamine (CAEP Grade B)
⚬ vasopressin may be associated with cellular ischemia and skin necrosis, especially when combined
with sustained infusion of norepinephrine (CAEP Grade C)
● typical adverse e ects reported with use of vasopressors and inotropes include
⚬ dysrhythmias
– due to beta-receptor e ects (tachyarrhythmia) or re ex bradycardia

– increased risk mainly associated with
● dopamine
● norepinephrine
● epinephrine
● isoproterenol
● dobutamine
● milrinone
● phenylephrine
⚬ myocardial ischemia
– due to increased myocardial oxygen consumption, especially with inotropes
– increased risk mainly associated with
● dopamine
● norepinephrine
● epinephrine
● isoproterenol
● dobutamine
⚬ hypoperfusion
– due to excessive and/or prolonged vasoconstriction

– increased risk mainly associated with vasopressin and epinephrine
⚬ hypotension
– mainly associated with inodilators with relatively strong vasodilatory activity

– increased risk mainly associated with milrinone, levosimendan, and high-dose dobutamine
⚬ Reference - Emerg Med Clin North Am 2014 Nov;32(4):823
Dysrhythmias
STUDY
● SUMMARY
dopamine may increase arrhythmias compared to norepinephrine in patients with hypotensive
shock DynaMed Level 2
COCHRANE REVIEW: Cochrane Database Syst Rev 2016 Feb 15;(2):CD003709
Details
⚬ based on Cochrane review of trials with methodologic limitations
⚬ systematic review of 28 randomized trials evaluating vasopressor regimens in 3,497 patients with
hypotensive shock
⚬ 18 trials enrolled patients with septic shock, 3 trials enrolled patients with perioperative shock, and
2 trials enrolled pediatric patients
⚬ all trials comparing norepinephrine vs. dopamine, epinephrine, phenylephrine or terlipressin had
unclear or no allocation concealment, early termination, di erential loss to follow-up, or small
sample sizes
⚬ dopamine increased arrhythmias compared to norepinephrine (risk ratio 2.34, 95% CI 1.46-3.78) in
analysis of 2 trials with 1,931 patients
⚬ Reference - Cochrane Database Syst Rev 2016 Feb 15;(2):CD003709
STUDY
● SUMMARY
vasopressors may not provide neurologic improvement and associated with high complication
rate in patients with spinal cord injury DynaMed Level 2
COHORT STUDY: J Neurotrauma 2014 Feb 1;31(3):284
Details
⚬ based on retrospective cohort study
⚬ 131 patients with spinal cord injury who received vasopressors to maintain blood pressure were
evaluated for complications
⚬ most frequently used vasopressors were dopamine (60%), phenylephrine (34%), and dopamine
plus phenylephrine (4%)
⚬ no signi cant neurological improvement with dopamine or phenylephrine
⚬ complications in 74% overall and associated with
– dopamine use (odds ratio [OR] 8.97, 95% CI 2.72-29.56)

– phenylephrine use (OR 5.92, 95% CI 1.74-20.13)
– age ≥ 60 years
– complete spinal cord injury
⚬ comparing dopamine vs. phenylephrine
– adverse events in 69.2% vs. 46.5% (p = 0.0012)

– tachycardia in 35.5% vs. 15.8% (p = 0.0012)
– bradycardia in 10.3% vs. 20.8% (p = 0.036)
– atrial brillation in 14% vs. 0% (p = 0.0015)
– acidosis in 0% vs. 4% (p = 0.038)
⚬ Reference - J Neurotrauma 2014 Feb 1;31(3):284
Metabolic effects
STUDY
● SUMMARY
epinephrine associated with similar mortality, but increased rate of adverse metabolic effects
compared to norepinephrine in patients with severe sepsis DynaMed Level 2
RANDOMIZED TRIAL: Intensive Care Med 2008 Dec;34(12):2226
Details
⚬ based on randomized trial with di erential loss to follow-up
⚬ 280 critically ill patients randomized to norepinephrine vs. epinephrine and followed for 90 days
⚬ 158 patients (56.4%) had severe sepsis
⚬ 2.8% of patients in norepinephrine group and 12.9% of patients in epinephrine group (p = 0.002)
withdrawn by clinicians due to development of signi cant but transient metabolic e ects
⚬ no signi cant di erences in 28-day mortality
⚬ Reference - Intensive Care Med 2008 Dec;34(12):2226 , commentary can be found in Intensive
Care Med 2009 Jul;35(7):1310
Hypoperfusion
STUDY
● SUMMARY
epinephrine may impair splanchnic circulation compared to dopamine and norepinephrine in
patients with severe septic shock DynaMed Level 3
RANDOMIZED TRIAL: Crit Care Med 2003 Jun;31(6):1659
Details
⚬ based on small randomized trial without clinical outcomes
⚬ 20 patients with septic shock treated with dopamine had dopamine progressively withdrawn and
were then randomized to replacement with norepinephrine and epinephrine (order of 2 agents
randomly assigned)
– 10 patients had severe shock, with dopamine alone unable to maintain mean arterial pressure >
65 mm Hg
– 10 patients had moderate shock, with dopamine alone able to maintain target mean arterial
pressure
⚬ in patients with moderate shock
– dopamine and norepinephrine associated with lower cardiac index compared to epinephrine (p
< 0.01 for each)
– no signi cant di erence between 3 agents in splanchnic blood ow
⚬ comparing epinephrine vs. norepinephrine in patients with severe shock
– cardiac index 4.6 L/minute/m2 vs. 3.4 L/minute/m2 (p < 0.01)

– splanchnic blood ow 860 L/minute/m2 vs. 977 L/minute/m2 (p < 0.05)
⚬ Reference - Crit Care Med 2003 Jun;31(6):1659 , editorial can be found in Crit Care Med 2003
Jun;31(6):1866
Hypotension
● use of inodilators (dobutamine, levosimendan, milrinone, low-dose dopamine) carries risk of
hypotension from excessive vasodilation 1
Other complications
● pressure ulcers
STUDY
⚬ SUMMARY
vasopressin reported to be associated with pressure ulcers in adult patients in intensive care
units
COHORT STUDY: Am J Crit Care 2015 Nov;24(6):501 | Full Text
Details
– based on retrospective cohort study
– 306 adults (mean age 71 years) on medical-surgical and cardiothoracic intensive care units who
received vasopressors were evaluated for pressure ulcers
● patients in intensive care unit for > 24 hours
● patients most commonly had cardiogenic shock (26%), septic shock (22%), and hypovolemic
shock (8%)
– vasoactive agents used were norepinephrine (84%), epinephrine (20%), vasopressin (18%),
dopamine (18%), and phenylephrine (7%)
– factors associated with pressure ulcer development in logistic regression
● vasopressin use (p = 0.004)

● hours of mean arterial pressure < 60 mm Hg while receiving vasopressors (p = 0.01)
● mechanical ventilation > 72 hours (p < 0.001)
● admission to intensive care unit for cardiac condition (p = 0.03)
– Reference - Am J Crit Care 2015 Nov;24(6):501 full-text , commentary in Am J Crit Care 2015
Nov;24(6):512 full-text
Monitoring
● continuously monitor electrocardiogram while using inotropes and/or vasopressors, as they may
cause arrhythmia, myocardial ischemia, or hypotension in case of levosimendan (ESC Class I, Level C)
● consider intra-arterial blood pressure monitoring (ESC Class IIb, Level C)
Guidelines and Resources
Guidelines
International guidelines
● Congress of Neurological Surgeons (CNS) 2013 guidelines on
⚬ acute cardiopulmonary management of cervical spinal cord injuries can be found in Neurosurgery
2013 Mar;72 Suppl 2:84
⚬ pharmacological therapy for acute spinal cord injury can be found in Neurosurgery 2013 Mar;72
Suppl 2:93 , commentary in Neurosurgery 2013 Aug;73(2):E384 , commentary in Neurosurgery
2013 Aug;73(2):E383
● World Allergy Organization (WAO) guideline on assessment and management of anaphylaxis can be
found in World Allergy Organ J 2011 Feb;4(2):13 full-text , update can be found in Curr Opin
Allergy Clin Immunol 2012 Aug;12(4):389
● Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline on acute kidney injury
can be found in Nephron Clin Pract 2012;120(4):c179 full-text
● Surviving Sepsis Campaign international guideline on management of severe sepsis and septic shock
can be found in Intensive Care Med 2017 Mar;43(3):304
United States guidelines
● American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and
Immunology (AAAAI/ACAAI) practice parameter on emergency department diagnosis and treatment of
anaphylaxis can be found in Ann Allergy Asthma Immunol 2014 Dec;113(6):599
● American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guideline on

management of heart failure can be found in Circulation 2013 Oct 15;128(16):e240 full-text
● American College of Cardiology/American Heart Association (ACC/AHA) guideline on management of

ST-elevation myocardial infarction can be found in J Am Coll Cardiol 2013 Jan 29;61(4):e78 full-text
● American Heart Association (AHA)
⚬ AHA guideline on adult advanced cardiovascular life support can be found in Circulation 2015 Nov
3;132(18 Suppl 2):S444 full-text
⚬ AHA guideline update on management of patients after cardiac arrest can be found in Circulation
2015 Nov 3;132(18 Suppl 2):S465 full-text
● Consortium for Spinal Cord Medicine (CSCM) clinical practice guideline on early acute management in
adults with spinal cord injury can be found in J Spinal Cord Med 2008;31(4):403 full-text ,
commentary in J Spinal Cord Med 2008;31(4):360 full-text
● American Association for the Study of Liver Diseases (AASLD) 2009 guidelines on management of
adult patients with ascites due to cirrhosis can be found in Hepatology 2009 Jun;49(6):2087 full-text
, commentary can be found in Hepatology 2009 Oct;50(4):1320; author reply 1321 and in
Hepatology 2009 Oct;50(4):1320
United Kingdom guidelines
● National Institute for Health and Care Excellence (NICE) 2014 guideline on diagnosing and managing
acute heart failure can be found in BMJ 2014 Oct 8;349:g5695 , commentary can be found in BMJ
2014 Nov 12;349:g6702 , BMJ 2014 Nov 12;349:g6707 , or in BMJ 2014 Nov 12;349:g6703
Canadian guidelines
● Canadian Association of Emergency Physicians (CAEP) guidelines on
⚬ vasopressor and inotrope use in Canadian emergency departments can be found in CJEM 2015
Jan;17(1):1
⚬ optimal management of severe sepsis in Canadian emergency departments can be found in CJEM
2008 Sep;10(5):443 , commentary can be found in CJEM 2008 Sep;10(5):461-3, 464 , CJEM 2009
Jul;11(4):320
● Canadian Critical Care Society (CCCS) guideline on use of vasopressin and vasopressin analogues in
critically ill adults with distributive shock can be found in Can J Anaesth 2020 Mar;67(3):369
● Rocky Mountain Critical Care Conference (RMCCC) 2003 recommendations on management following
resuscitation from cardiac arrest can be found in Can J Anaesth 2005 Mar;52(3):309 , commentary
can be found in Can J Anaesth 2005 Oct;52(8):892; author reply 892
European guidelines
● European Society of Cardiology (ESC) guidelines on
⚬ diagnosis and treatment of acute and chronic heart failure can be found in Eur J Heart Fail 2016
Aug;18(8):891
⚬ diagnosis and management of acute pulmonary embolism can be found in Eur Heart J 2014 Nov
14;35(43):3033-69, 3069a full-text , commentary can be found in Rev Esp Cardiol (Engl Ed)
2015 Jan;68(1):10 , correction can be found in Eur Heart J 2015 Oct 14;36(39):2666 , correction
can be found in Eur Heart J 2015 Oct 14;36(39):2642
⚬ management of acute myocardial infarction in patients presenting with ST-segment elevation can
be found in Eur Heart J 2018 Jan 7;39(2):119 full-text
● European Academy of Allergy and Clinical Immunology (EAACI) guideline on anaphylaxis can be found
in Allergy 2014 Aug;69(8):1026 full-text
● European Association for the Study of the Liver (EASL) clinical practice guideline on the management
of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis can be found in J
Hepatol 2010 Sep;53(3):397 , commentary can be found in J Hepatol 2011 Oct;55(4):743 full-text
● Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) clinical practice guideline
on choice of rst-line vasopressor for patients with acute circulatory failure can be found in Acta
Anaesthesiol Scand 2016 Nov;60(10):1347 full-text
● Task Force for Advanced Bleeding Care in Trauma (ABC-T) guidelines on management of major
bleeding and coagulopathy following trauma: fourth edition can be found in Crit Care 2016 Apr
12;20:100 full-text
Review articles
● review of vasopressors and inotropes can be found in Emerg Med Clin North Am 2014 Nov;32(4):823
● review of inotrope and vasopressor use in critically ill patients can be found in Br J Pharmacol 2012
Apr;165(7):2015 full-text , commentary in Br J Pharmacol 2012 Apr;165(7):2009 full-text ,
commentary in Br J Pharmacol 2012 Apr;165(7):2012 full-text
● review of vasoactive agents for treatment of sepsis can be found in Ann Transl Med 2016
Sep;4(17):333 full-text
● review of pharmacologic therapies for acute cardiogenic shock can be found in Curr Opin Cardiol 2014
May;29(3):250
● review of anaphylaxis can be found in J Emerg Med 2014 Aug;47(2):182
● review of vasopressor administration in patients with acute neurologic injury can be found in
Neurocrit Care 2009;11(1):112
● review of pharmacology and e ective titration of vasoactive medications can be found in J Infus Nurs
2014 Mar-Apr;37(2):82
● reviews of inotropic therapy for acute heart failure can be found in Heart Fail Rev 2007 Jun;12(2):149
, Expert Opin Pharmacother 2006 Nov;7(16):2179
Patient Information
● information on managing the intensive care unit experience from American Thoracic Society PDF
References
General references used
1. Jentzer JC, Coons JC, Link CB, Schmidhofer M. Pharmacotherapy update on the use of vasopressors
and inotropes in the intensive care unit. J Cardiovasc Pharmacol Ther. 2015 May;20(3):249-60
2. Ellender TJ, Skinner JC. The use of vasopressors and inotropes in the emergency medical treatment of
shock. Emerg Med Clin North Am. 2008 Aug;26(3):759-86, ix
Recommendation grading systems used
● Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) grading system
⚬ strength of recommendations
– Strong ("we recommend") - virtually all informed patients would choose the recommended
strategy
– Weak ("we suggest") - fully informed patients would choose di erent management strategy, and
re ects close call between bene ts and harms, uncertainty regarding treatment e ects,
questionable cost-e ectiveness, or variability in values and preferences
⚬ quality of evidence
– High - randomized trials without factors that reduce quality of evidence, or well-done
observational studies with very large magnitude of e ect
– Moderate - downgraded randomized trials or upgraded observational studies
– Low - well-done observational studies, or randomized trials with many limitations
– Very low - case series or expert opinion
⚬ Reference - SSAI clinical practice guideline on choice of rst-line vasopressor for patients with acute
circulatory failure (Acta Anaesthesiol Scand 2016 Nov;60(10):1347 full-text )
● Congress of Neurological Surgeons (CNS) grading system for guideline recommendations
⚬ levels of evidence
– Level I - evidence obtained from at least 1 properly designed randomized controlled trial
– Level II-1 - evidence obtained from well-designed controlled trials without randomization
– Level II-2 - evidence obtained from well-designed cohort or case-control analytic studies,
preferably from > 1 center or research group
– Level II-3 - evidence obtained from comparisons between times or places with or without
intervention; dramatic results from uncontrolled experiments
– Level III - opinions of respected authorities, based on clinical experience, descriptive studies
(such as case series), or reports of expert committees
⚬ Reference - CNS 2013 guideline on pharmacological therapy for acute spinal cord injury
(Neurosurgery 2013 Mar;72 Suppl 2:93 )
● Consortium for Spinal Cord Medicine (CSCM) grading system for clinical practice guidelines
⚬ grade of recommendation
– Grade A - supported by ≥ 1 level I studies

– Grade B - supported by ≥ 1 level II studies
– Grade C - supported only by ≥ 1 level III, IV, or V studies
– Level I - based on randomized controlled trials (RCTs) of adequate size or meta-analysis of such
RCTs
– Level II - based on RCTs too small to provide level I evidence
– Level III - based on nonrandomized controlled trials or cohort studies, case series, case-control
studies, or cross-sectional studies
– Level IV - based on opinion of respected authorities or expert committees
– Level V - based on opinion of individuals who have written this guideline
⚬ panel opinion strength
– 3.67-5 - strong
– 2.33-3.66 - moderate
– 1-2.32 - weak
⚬ Reference - CSCM 2008 clinical practice guideline on early acute management in adults with spinal
cord injury (J Spinal Cord Med 2008;31(4):403 full-text )
● American Association for the Study of Liver Diseases (AASLD) grading system for recommendations
⚬ grades of recommendation
– Class I - conditions for which there is evidence and/or general agreement that a given diagnostic
evaluation, procedure, or treatment is bene cial, useful, and e ective
– Class II - conditions for which there is con icting evidence and/or a divergence of opinion about
the usefulness/e cacy of a diagnostic evaluation, procedure, or treatment
● Class IIa - weight of evidence/opinion is in favor of usefulness/e cacy
● Class IIb - usefulness/e cacy is less well-established by evidence/opinion
– Class III - conditions for which there is evidence and/or general agreement that a diagnostic
evaluation, procedure/treatment is not useful/e ective and in some cases may be harmful
– Level A - data derived from multiple randomized clinical trials or meta-analyses

– Level B - data derived from a single randomized trial, or nonrandomized studies
– Level C - only consensus opinion of experts, case studies, or standard-of-care
⚬ Reference - AASLD 2012 guideline on management of adult patients with ascites due to cirrhosis
(AASLD 2012 PDF)
● European Association for Study of the Liver (EASL) guideline grading system
⚬ grading of evidence
– Level A - high-quality evidence - further research is very unlikely to change con dence in the
estimate of e ect
– Level B - moderate-quality evidence - further research is likely to have an important impact on
con dence in the estimate of e ect and may change the estimate
– Level C - low-quality evidence - further research is very likely to have an important impact on
con dence in the estimate of e ect and is likely to change the estimate; any estimate of e ect is
uncertain
⚬ strength of recommendation
– Grade 1 - strong recommendation warranted - factors in uencing the strength of the

recommendation included the quality of evidence, presumed patient-important outcomes, and
cost
– Grade 2 - weak recommendation - variability in preferences and values, or more uncertainty:
more likely a weak recommendation is warranted
⚬ Reference - EASL 2010 clinical practice guideline on management of ascites, spontaneous bacterial
peritonitis, and hepatorenal syndrome in cirrhosis (J Hepatol 2010 Sep;53(3):397 )
● Task Force for Advanced Bleeding Care in Trauma (ABC-T) guideline grading system
⚬ Grade 1A
– strong recommendation - bene ts clearly outweigh risk and burdens, or vice versa
– high-quality evidence based on randomized controlled trials without important limitations or
overwhelming evidence from observational studies
⚬ Grade 1B
– moderate-quality evidence based on randomized controlled trials with important limitations
(inconsistent results, methodological aws, indirect or imprecise) or exceptionally strong
evidence from observational studies
⚬ Grade 1C
– low quality or very low quality evidence based on observational studies or case series
⚬ Grade 2A
– weak recommendation - bene ts closely balanced with risks and burdens OR uncertainty on the
estimates of bene ts, risks, and burdens
– high-quality evidence based on randomized controlled trials without important limitations or
overwhelming evidence from observational studies
⚬ Grade 2B
– moderate-quality evidence based on randomized controlled trials with important limitations
(inconsistent results, methodological aws, indirect or imprecise) or exceptionally strong
evidence from observational studies
⚬ Grade 2C
– low-quality or very low-quality evidence based on observational studies or case series
⚬ Reference - ABC-T European guideline on management of bleeding and coagulopathy following

major trauma (Crit Care 2013 Apr 19;17(2):R76 full-text )
● World Allergy Organization (WAO) grading system for recommendations
– Grade A - directly based on meta-analysis of randomized controlled trials or evidence from at

least one randomized controlled trial
– Grade B - directly based on at least one controlled study without randomization or one other
type of quasi-experimental study, or extrapolated from such studies
– Grade C - directly based on evidence from nonexperimental descriptive studies such as
comparative studies, or extrapolated from randomized controlled trials or quasi-experimental
studies
⚬ Reference - WAO 2011 guidelines for the assessment and management of anaphylaxis (World
Allergy Organ J 2011 Feb;4(2):13 full-text )
● European Society of Cardiology (ESC) grading system for recommendations
⚬ classes of recommendations
– Class I - evidence and/or general agreement that given treatment or procedure is bene cial,
useful, and e ective
– Class II - con icting evidence and/or divergence of opinion about usefulness/e cacy of given
treatment or procedure
● Class IIa - weight of evidence/opinion in favor of usefulness/e cacy
● Class IIb - usefulness/e cacy less well established by evidence/opinion
– Class III - evidence or general agreement that given treatment or procedure is not
useful/e ective, and in some cases may be harmful

– Level B - data derived from single randomized clinical trial or large nonrandomized studies
– Level C - consensus of opinion of experts and/or small studies, retrospective studies, registries
⚬ Reference - ESC guideline on diagnosis and treatment of acute and chronic heart failure (Eur Heart
J 2012 Jul;33(14):1787 full-text )
● American Academy of Allergy, Asthma, and Immunology/American College of Allergy, Asthma, and
Immunology (AAAAI/ACAAI) Joint Task Force on Practice Parameters classi cation of
recommendations and evidence
⚬ recommendation grading
– Strong - bene ts clearly outweigh harms (or vice versa); excellent (Grade A or B) supporting
evidence quality
– Moderate - bene ts outweigh harms (or vice versa); moderate (Grade B or C) supporting
evidence quality
– Weak - quality of evidence suspect (Grade D), or well-done studies (Grade A, B, or C) provide
unclear advantage to approach
– No recommendation - lack of pertinent evidence (Grade D) and unclear balance of bene ts and
harms
– Grade A - directly based on category I evidence

– Grade B - directly based on category II evidence or extrapolated from category I evidence
– Grade C - directly based on category III evidence or extrapolated from category I or II evidence
– Grade D - directly based on category IV evidence or extrapolated from I, II, or III evidence
– Grade E - based on consensus of Joint Task Force on Practice Parameters
⚬ categories of evidence
– Ia - evidence from meta-analysis of randomized trials

– Ib - evidence from ≥ 1 randomized trial
– IIa - evidence from ≥ 1 controlled study without randomization
– IIb - evidence from ≥ 1 quasi-experimental study
– III - evidence from nonexperimental descriptive studies (such as comparative studies)
– IV - evidence from expert committee reports or opinions or clinical experience of respected
authorities
⚬ Reference - AAAAI/ACAAI 2014 practice parameter on emergency department diagnosis and
treatment of anaphylaxis (Ann Allergy Asthma Immunol 2014 Dec;113(6):599 )
● European Academy of Allergy and Clinical Immunology (EAACI) classi cation of recommendations and
evidence
– Grade A - consistent level I studies

– Grade B - consistent level II or III studies, or extrapolations from level I studies
– Grade C - level IV studies or extrapolations from level II or III studies
– Grade D - level V evidence or troublingly inconsistent or inconclusive studies at any level
⚬ categories of evidence
– Level I - evidence from systematic reviews, meta-analysis, randomized trials

– Level II - evidence from 2 groups, nonrandomized studies (including cohort, case-control)
– Level III - evidence from 1 group nonrandomized (including before and after test)
– Level IV - evidence from descriptive studies (including case series)
– Level V - evidence from case reports and expert opinion
⚬ Reference - EAACI guideline on anaphylaxis (Allergy 2014 Aug;69(8):1026 full-text )
● American College of Cardiology Foundation/American Heart Association (ACCF/AHA) grading system

for recommendations
⚬ classi cations of recommendations
– Class I - procedure or treatment should be performed or administered
– Class IIa - reasonable to perform procedure or administer treatment, but additional studies with
focused objectives needed
– Class IIb - procedure or treatment may be considered; additional studies with broad objectives
needed, additional registry data would be useful
– Class III - procedure or treatment should not be performed or administered because it is not
helpful or may be harmful
● Class III ratings may be subclassi ed as Class III No Bene t or Class III Harm

– Level B - data derived from single randomized trial or nonrandomized studies
– Level C - only expert opinion, case studies, or standard of care
⚬ Reference - ACCF/AHA 2013 practice guidelines for the management of heart failure (Circulation
2013 Oct 15;128(16):e240 full-text )
● American Heart Association (AHA) grading system for recommendations
⚬ classi cations of recommendations
– Class I - procedure or treatment should be performed or administered

– Class IIa - reasonable to perform procedure or administer treatment, but additional studies with
focused objectives needed
– Class IIb - procedure or treatment may be considered; additional studies with broad objectives
needed, additional registry data would be useful
– Class III - procedure or treatment should not be performed or administered because it is not
helpful or may be harmful
● Class III ratings may be subclassi ed as Class III No Bene t or Class III Harm

– Level B - data derived from single randomized trial or nonrandomized studies
● B-R - randomized studies

● B-NR - nonrandomized studies
– Level C - only consensus opinions of experts, case studies, or standard of care
● C-LD - limited data

● C-EO - consensus of expert opinion
⚬ References - 2015 American Heart Association Guidelines Update for Cardiopulmonary

Resuscitation and Emergency Cardiovascular Care (Circulation 2015 Nov 3;132(18 Suppl 2):S315
full-text and Circulation 2015 Nov 3;132(18 Suppl 2):S368 full-text )
● Kidney Disease Improving Global Outcomes (KDIGO) recommendation grading system
– Level 1 ("we recommend") - most patients should receive recommended course of action
– Level 2 ("we suggest") - di erent choices appropriate for di erent patients, based on patient's
values and preferences
– Not Graded - topic does not allow adequate application of evidence, not meant to be
interpreted as being stronger recommendations than Level 1 or 2
– Grade A - high-quality evidence, true e ect lies close to that of estimate of e ect
– Grade B - moderate-quality evidence, true e ect likely to be close to estimate of e ect, but
there is possibility it is substantially di erent
– Grade C - low-quality evidence, true e ect may be substantially di erent from estimate of e ect
– Grade D - very low-quality evidence, estimate of e ect very uncertain and often far from truth
⚬ Reference - KDIGO summary on diagnosis, evaluation, and management of acute kidney injury (Crit
Care 2013 Feb 4;17(1):204 full-text )
● Canadian Association of Emergency Physicians (CAEP) 2015 guideline uses Grades of

Recommendation, Assessment, Development, and Evaluation (GRADE)
⚬ strength of recommendations
– Strong - certainty about balance of desirable and undesirable consequences of an intervention

– Conditional - less certainty, or balance of desirable and undesirable consequences was nely
balanced
⚬ quality of evidence determination
– Grade A - high quality evidence - randomized trial without limitation in study quality,
indirectness, important inconsistency, sparse or imprecise data, or high probability of
publication bias
– Grade B - moderate quality evidence - downgraded randomized trial or upgraded observational
study
– Grade C - low quality evidence - well done observational study with control groups
– Grade D - very low quality evidence - any other evidence (for example, case reports, case series)
⚬ Reference - CAEP guideline on vasopressor and inotrope use in Canadian emergency departments
(CJEM 2015 Feb;17 Suppl 1:1 )
● CAEP 2008 guideline uses Oxford Centre for Evidence Based Medicine (CEBM) classi cations
⚬ grades of recommendation
– Grade A - consistent level 1 studies

– Grade B - consistent level 2 or 3 studies or extrapolations from level 1 studies
– Grade C - level 4 studies or extrapolations from level 2 or 3 studies
– Grade D - level 5 evidence or troublingly inconsistent or inconclusive studies of any level
– Level 1a - systematic review with homogeneity of randomized controlled trials (RCTs)

– Level 1b - individual RCT with narrow con dence interval
– Level 1c - all or none case series
– Level 2a - systematic review with homogeneity of cohort studies
– Level 2b - individual cohort study or low-quality RCT
– Level 2c - "outcomes" research, ecological studies
– Level 3a - systematic review with homogeneity of case-control studies
– Level 3b - individual case-control study
– Level 4 - case series, poor quality cohort and case-control studies
– Level 5 - expert opinion without explicit critical appraisal, or based on physiology, bench
research or " rst principles"
⚬ Reference - CAEP 2008 guideline on optimal management of severe sepsis in Canadian emergency
departments (CJEM 2008 Sep;10(5):443 )
● Rocky Mountain Critical Care Conference (RMCCC) grading system
– Grade A - Supported by at least two level I investigations
– Grade B - Supported by one level I investigation
– Grade C - Supported by level II investigations only
– Grade D - Supported by at least one level III investigation
– Grade E - Supported by level IV or V evidence
– Level I - Large, randomized trials with clear-cut results; low risk of false-positive (alpha) error or
false-negative (beta) error
– Level II - Small, randomized trials with uncertain results; moderate-to-high risk of false positive
(alpha) and/or false-negative (beta) error
– Level III - Nonrandomized, contemporaneous controls
– Level IV - Nonrandomized, historical controls, and expert opinion
– Level V - Case series, uncontrolled studies, and expert opinion
⚬ Reference - RMCCC guideline on management following resuscitation from cardiac arrest (Can J
Anaesth 2005 Mar;52(3):309 )
● Society of Critical Care Medicine (SCCM) uses Grading of Recommendations, Assessment,

Development, and Evaluation (GRADE)
– Strong - bene ts clearly outweigh risks and burdens (or vice versa) for most, if not all, patients
– Weak - bene ts and risks closely balanced and/or uncertain
– Best practice statement - recommendation not conducive to GRADE process
– High - randomized trials without factors that reduce quality of evidence, or well-done
observational studies with very large magnitude of e ect
– Moderate - downgraded randomized trials or upgraded observational studies
– Low - well-done observational studies, or randomized trials with many limitations
– Very low - case series or expert opinion
⚬ Reference - SCCM Surviving Sepsis Campaign 2016 international guideline on management of

severe sepsis and septic shock (Intensive Care Med 2017 Mar;43(3):304 )
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Vasopressor and Inotrope Use in the Intensive Care Unit

● Acute heart failure

● Fluid selection for IV uid resuscitation

● administration of vasopressors and inotropes (especially in shock) typically guided by following

Table 1. Main Effects of Vasopressors and Inotropes

Vaso Cate Alph Alph Beta Beta Non Mai Mai

Epin Inoc ++++ +++ ++++ (+)(+) NA up up

Nore Inoc ++(+) +++ ++ (+) NA up up

Dop Inodi NA (+) + + Dop NA up

Dop Inodi + (+) ++ ++ Dop up up

Dop Inoc +(+) (+) ++(+) +(+) Dop up NA

Phen Vaso +++ NA NA NA NA up neut

Vaso Vaso NA NA NA NA Vaso up dow

Dob Inodi (+) (+) ++++ ++(+) NA up up

Milri Inodi NA NA NA NA PDE dow up

Amri Inodi NA NA NA NA PDE dow up

Levo Inodi NA NA NA NA Calci dow up

Isopr Inodi NA NA ++++ ++++ NA dow up

Abbreviations: CO, cardiac output,

⚬ routine vasopressor use not recommended (CAEP Conditional recommendation)

⚬ in case of vasopressor therapy, consider norepinephrine as rst-line vasopressor rather than

– epinephrine considered rst-line treatment (AAAAI/ACAAI Strong recommendation, Grade B;

– if hypotension persists after uid resuscitation, consider vasopressors (norepinephrine,

⚬ consider norepinephrine rather than dopamine, epinephrine, or vasopressin analogues as rst-line

● in shock-related acute kidney injury

– consider vasoactive drugs

● discontinue terlipressin if serum creatinine is not reduced

output and are subdivided into 1 , 2

● administration of vasopressors and inotropes typically guided by following concepts 1 , 2

● pharmacologic e ects of inotropes and vasopressors include 1 , 2

⚬ adrenergic receptor agonism

– cardiac beta-1 resulting in increased cardiac contractility

⚬ vasopressin receptor agonism resulting in vasoconstriction

● correction of persistent hypotension as a result of decompensated shock may require vasopressors

and/or inotropes depending on the underlying cause 1 , 2

Table 2. Main Effects of Vasopressors and Inotropes

Vaso Cate Alph Alph Beta Beta Non Mai Mai

Epin Inoco ++++ +++ ++++ (+)(+) NA up up

Nore Inoco ++(+) +++ ++ (+) NA up up or

Dopa Inodil NA (+) + + Dopa NA up

Dopa Inodil + (+) ++ ++ Dopa up up

Dopa Inoco +(+) (+) ++(+) +(+) Dopa up NA

Phen Vaso +++ NA NA NA NA up neutr

Vaso Vaso NA NA NA NA Vaso up dow

Dobu Inodil (+) (+) ++++ ++(+) NA up or up

Milri Inodil NA NA NA NA PDE dow up

Amri Inodil NA NA NA NA PDE dow up

Levo Inodil NA NA NA NA Calci dow up

Isopr Inodil NA NA ++++ ++++ NA dow up

Indications and Contraindications

● obstructive shock, such as pulmonary embolism (PE)

● nonshock situations, such as

● obstructive hypertrophic cardiomyopathy - dopamine, dobutamine, norepinephrine, and other IV

Recommendations from professional organizations

● see also Hemorrhagic shock for additional information on uid resuscitation

Efficacy in hemorrhagic shock

● see Hemorrhagic shock, vasopressors section

Overview of vasoactive treatment in cardiogenic shock

● improvement in hemodynamics of inotropic support usually outweighs potential risks of increased

● if persistent cardiogenic shock requiring continuous IV inotropic support beyond 24 hours

⚬ consider extracorporeal membrane oxygenation to provide emergency support in patients with

⚬ revascularization in case of myocardial infarct

Recommendations from professional organizations