Cardiogenic Shock.pdf

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Cardiogenic Shock
Overview and Recommendations
Background
Evaluation
Management
Immediate treatment
Cardiogenic shock is characterized by persistent hypotension due to a reduced cardiac index and in the
presence of elevated pulmonary capillary wedge pressure (PCWP).
●
About 7% incidence of cardiogenic shock after acute myocardial infarction, increased incidence in patients
with STEMI risk factors. Non-STEMI patients with shock have increased mortality.
●
Acute myocardial infarction is the most common cause of cardiogenic shock, but onset may also be more
gradual due to decompensation of a chronic disorder such as ischemic or non-ischemic dilated
cardiomyopathy.
●
Complications include pulmonary edema, hepatic decompensation, and acute renal failure.
●
Prognosis improved with emergency reperfusion strategies, but remains high for cardiogenic shock due to
right coronary artery (RCA) occlusion and vessels for which flow is not restored.
●
Suspect cardiogenic shock in patients with known or suspected acute ischemia, heart failure, or chest
trauma who are hypotensive with tachycardia and that have elevated jugular venous pressure, cool
extremities and/or other signs of poor organ perfusion such as mental status changes and decreased urine
output.
●
Initial testing should include:
●
12-lead electrocardiogram with right-sided leads if right ventricular infarction is suspected
⚬
emergent transthoracic echocardiography performed at the bedside for the assessment of ventricular
function and to identify potential causes of cardiogenic shock
⚬
blood tests, including:
⚬
CBC
–
complete metabolic panel
–
cardiac troponin to evaluate acute coronary syndrome as a possible cause of cardiogenic shock
–
arterial blood gas
–
lactate
–
NT-pro BNP
–
Consider early invasive hemodynamic monitoring with pulmonary artery catheter to confirm the diagnosis
and to guide treatment.
●
Administer oxygen to patients with oxygen saturation ≤ 90% and assess the potential need for intubation
and mechanical ventilation.
●
100-200 mL fluid boluses may be required to optimize left ventricular filling pressures in patients with
developing cardiogenic shock with clinical signs suggestive of, or hemodynamic monitoring indicative of, a
pulmonary capillary wedge pressure (PCWP) < 15 mm Hg
●

Treatment for persistent cardiogenic shock
Related Topics
Avoid fluids if frank pulmonary edema is present or if PCWP is > 18 mm Hg based on invasive
hemodynamic monitoring, but consider cautious administration of small fluid boluses (100-200 mL) in
patients with pulmonary capillary wedge pressure (PCWP) < 15 mm Hg to optimize left ventricular filling
pressures.
●
Use temporary IV inotropic support to maintain systemic perfusion and to preserve end-organ
performance (Strong recommendation). Examples include:
●
norepinephrine (typical dose range is 0.01 to 0.03 mcg/kg/minute)
⚬
dopamine (typical initial dose is 2-10 mcg/kg/minute, may increase up to 20-50 mcg/kg/minute)
⚬
dobutamine (typical dose range is 2-20 mcg/kg/minute)
⚬
Consider mechanical cardiovascular support, including intra-aortic balloon pump (IABP) counterpulsation,
Impella, Tanden Heart, or ECMO, which can be useful for patients with cardiogenic shock after ST-elevation
myocardial infarction (STEMI) who do not quickly stabilize with pharmacological therapy. (Weak
recommendation). The benefit on mortality is uncertain.
●
Perform emergency revascularization with either percutaneous coronary intervention (PCI) or coronary
artery bypass graft (CABG) in patients with cardiogenic shock due to acute coronary syndromes (Strong
recommendation).
●
Perform emergent surgery as indicated in patients with papillary muscle rupture or ventricular septal
rupture after STEMI as well as for ventricular free-wall rupture following STEMI.
●
Consider extracorporeal membrane oxygenation (ECMO) to provide emergency biventricular support in
patients with poor oxygenation due to cardiac failure or use as a bridge to transplantation or implantation
of an extracorporal left ventricular or biventricular mechanical assist device (Weak recommendation).
●
Consider continuous IV inotropic support "bridge 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 (Weak recommendation).
●
Consider left ventricular assist devices (LVADs) for circulatory support (other than IABP) in patients with
refractory cardiogenic shock and as a "bridge to recovery" or "bridge to decision" in patients with profound
hemodynamic compromise (Weak recommendation).
●
Offer cardiac transplantation to selected patients with cardiogenic shock refractory to guideline-directed
medical therapy, device therapy, or surgical management (Strong recommendation).
●
Consult palliative care team in those patients with persistent multisystem organ failure and/or a lack of
social support required for a cardiac transplant or LVAD to address the goals of care.
●
Consider long-term, continuous IV inotropic support as palliative therapy 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 (Weak recommendation).
●
Acute Heart Failure
●
ST-elevation Myocardial Infarction (STEMI)
●
Revascularization for STEMI
●

General Information
Description
Types
Epidemiology
Incidence/Prevalence
Thrombolytics for ST-elevation Myocardial Infarction (STEMI)
●
Acute Coronary Syndromes
●
Mechanical Circulatory Support for Heart Failure
●
persistent hypotension (systolic blood pressure < 90 mm Hg) and reduced cardiac index (< 2.2
L/minute/m2) in presence of elevated pulmonary capillary wedge pressure (such as > 18 mm Hg) 1 , 3
●
Interagency Registry for Mechanically Assisted Support (INTERMACS) clinical profiles
●
INTERMACS Profile 1 - (critical cardiogenic shock, or "crash and burn") - characterized by life-threatening
hypotension despite rapidly escalating inotropic support with critical organ hypoperfusion (often
confirmed by worsening acidosis and elevated lactate levels)
⚬
INTERMACS Profile 2 - (progressive decline, or "sliding fast" on inotropes) - characterized by progressive
decline (for example, in nutrition, renal function, fluid retention, or other major status indicator) despite
inotropic support, or in patients with refractory volume overload with or without evidence of impaired
perfusion in whom inotropic infusions cannot be maintained due to tachyarrhythmias, clinical ischemia,
or other intolerance
⚬
INTERMACS Profile 3 - (stable but inotropic-dependent) - characterized by clinical stability on mild-
moderate doses of IV inotropes (or using temporary circulatory support device) after repeated failure to
wean without symptomatic hypotension, worsening symptoms, or progressive organ dysfunction
(usually renal)
⚬
Reference - Circulation 2013 Oct 15;128(16):e240
⚬
●
STUDY SUMMARY
3%-6.6% incidence of cardiogenic shock complicating acute coronary syndromes (mixed population of
ST-elevation myocardial infarction [STEMI] and non-ST-elevation myocardial infarction [NSTEMI])
COHORT STUDY: Eur J Heart Fail 2015 Nov;17(11):1124
COHORT STUDY: Circulation 2009 Mar 10;119(9):1211 | Full Text
COHORT STUDY: Am Heart J 2006 Dec;152(6):1035
Details
based on 3 cohort studies
⚬
28,217 patients with acute coronary syndrome between 2001 and 2014 from 5 Italian nationwide
prospective registries included
⚬
4.3% of patients developed cardiogenic shock (1.9% developed cardiogenic shock at time of
admission and 2.4% developed cardiogenic shock during hospitalization)
–
Reference - Eur J Heart Fail 2015 Nov;17(11):1124
–

Etiology and Pathogenesis
Causes
13,663 patients with acute myocardial infarction between 1975 and 2005 were included
⚬
6.6% of patients developed cardiogenic shock
–
Reference - Circulation 2009 Mar 10;119(9):1211 full-text
–
17,817,000 patients hospitalized for acute myocardial infarction between 1979 and 2003 from National
Hospital Discharge Survey were included
⚬
3% of patients developed cardiogenic shock
–
Reference - Am Heart J 2006 Dec;152(6):1035
–
●
STUDY SUMMARY
7.9% incidence of cardiogenic shock complicating STEMI and appears to be higher in women, patients ≥
75 years old, and Asian/Pacific Island patients
COHORT STUDY: J Am Heart Assoc 2014 Jan 13;3(1):e000590 | Full Text
Details
based on retrospective cohort study
⚬
1,990,486 patients ≥ 40 years old with STEMI between 2003 and 2010 were included
⚬
7.9% of patients developed cardiogenic shock
⚬
cardiogenic shock was more common in
⚬
women compared to men (8.5% vs. 7.6%, p < 0.001)
–
patients ≥ 75 years old compared to patients < 65 years old (p < 0.001)
–
Asian/Pacific Island patients compared to white patients, African American patients, and Hispanic
patients (11.4% vs. 8% vs. 6.9% vs. 8.6%, p < 0.001 pairwise comparisons not reported)
–
Reference - J Am Heart Assoc 2014 Jan 13;3(1):e000590 full-text
⚬
●
STUDY SUMMARY
incidence of cardiogenic shock in patients hospitalized with acute coronary syndrome decreased from
1997 to 2006
COHORT STUDY: Ann Intern Med 2008 Nov 4;149(9):618
Details
based on retrospective cohort study
⚬
23,696 patients with acute coronary syndrome evaluated
⚬
comparing 1997 vs. 2006
⚬
overall incidence of cardiogenic shock 12.9% vs. 5.5% (p < 0.001)
–
cardiogenic shock developing during hospitalization in 10.6% vs. 2.7% (p < 0.001)
–
in-hospital mortality 62.8% vs. 47.7% (p = 0.01)
–
increased use of percutaneous coronary intervention associated with decrease in in-hospital mortality
and decrease in-hospital development of cardiogenic shock
⚬
Reference - Ann Intern Med 2008 Nov 4;149(9):618
⚬

causes associated with acute myocardial infarction
●
myocardial infarction with significant left and/or right ventricular dysfunction most common
cause 1 , 2 , 3 , 4
⚬
acute coronary ischemia resulting in impaired cardiac contractility with or without any of the following
⚬
mitral valve papillary muscle ischemia/rupture 2 , 3 , 4
–
left ventricular free wall rupture 2 , 3 , 4
–
dynamic left ventricular outflow tract obstruction 3
–
acute arrhythmia due to acute ischemia 3
–
acute ventricular septal defect 2 , 3 , 4
–
type A dissection involving coronary arteries 3
–
causes unrelated to acute myocardial infarction 3
●
myocardial conditions
⚬
acute heart failure 1
–
myocarditis 1 , 3 , 4
–
myocardial dysfunction associated with neurogenic "stunning" (for example, Takotsubo syndrome,
subarachnoid hemorrhage) 3 , 4
–
hypertrophic cardiomyopathy with obstruction 1 , 3
–
decompensated dilated cardiomyopathy 1 , 3
–
decompensated restrictive cardiomyopathy 3
–
peripartum cardiomyopathy 1
–
cardiac contusion 1 , 3 , 4
–
septic shock with severe myocardial depression 1 , 4
–
post cardiac arrest stunning 1
–
spontaneous coronary artery dissection 1
–
myocardial dysfunction due to prolonged cardiopulmonary bypass 1 , 3 , 4
–
valvular heart disease
⚬
end-stage valvular heart disease (stenosis, regurgitation, and valvular obstruction) 1 , 3
–
prosthetic heart valve dysfunction (obstruction, leaflet failure or restriction, mechanical failure, and
valve dehiscence) 1
–
electrical abnormalities
⚬
acute arrhythmia due to chronic causes 3
–
atrial arrhythmia with rapid ventricular rate 1
–
ventricular tachycardia 1
–
bradycardia 1
–
extracardiac/obstructive conditions
⚬
cardiac tamponade 1 , 2 , 4
–
constriction 1
–

Pathogenesis
pulmonary embolism (PE) 1
–
other
⚬
end-stage pulmonary hypertension 4
–
myxomatous degeneration of mitral valve with chordae rupture and mitral valve regurgitation 4
–
infective endocarditis 4
–
aortic dissection 4
–
trauma 4
–
hypothermic myocardial depression 1
–
toxidromes 1
–
reported causes of cardiogenic shock in SHOCK trial among 1,160 patients 3
●
74.5% had left ventricular failure
⚬
8.3% had mitral regurgitation
⚬
4.6% had ventricular septal rupture
⚬
3.4% had isolated right ventricular shock
⚬
1.7% had cardiac rupture or tamponade
⚬
8% had other causes
⚬
cardiogenic shock initiated by event severely reducing cardiac output and resulting in decreased perfusion
of coronary arteries 4
●
decreased perfusion of coronary arteries results in coronary ischemia which decreases systolic function 4
●
cardiogenic shock spiral 1
●
profound depression of myocardial contractility leads to potentially deleterious spiral of reduced cardiac
output, low blood pressure, further coronary ischemia, and additional reductions in myocardial
contractility
⚬
compensatory responses include systemic vasoconstriction from acute cardiac injury and ineffective
stroke volume
⚬
cardiogenic shock state results in acute and subacute circulatory system abnormalities
⚬
hypoperfusion in vital organs and end-organs
–
inadequate circulatory compensation, which may further contribute to shock state
–
peripheral vasoconstriction that may improve coronary and peripheral perfusion but results in
increased afterload
–
systemic inflammation triggered by acute cardiac injury may induce pathological vasodilation
–
endothelial and inducible nitric oxide (NO) synthase may result in production of high levels of NO and
peroxynitrite, which has negative inotropic effect and is cardiotoxic
–
other inflammatory mediators (interleukins and tumor necrosis factor) may contribute to systemic
vasodilation
–
changes in erythrocyte NO biology of stored blood may result in vasoconstriction, platelet
aggregation, and ineffective oxygen delivery
–
transfusion of stored blood may contribute to systemic inflammation
–

Likely risk factors
History and Physical
decreased systolic function leads to reduced cardiac output and blood pressure, which causes the following
compensatory neurohormonal responses 4
●
increased catecholamine levels, which leads to
⚬
systemic arterial and venous constriction (BMJ 2003 Jun 28;326(7404):1450 full-text )
–
increased myocardial oxygen demand and possibly direct cardiotoxic effects on myocardium
–
activation of renin-angiotensin-aldosterone system, which leads to
⚬
further peripheral vasoconstriction to maintain central blood pressure and sustain perfusion to vital
organs
–
worsening of myocardial ischemia, peripheral organ hypoperfusion, and increased risk for ventricular
arrhythmias
–
neurohormonal activation results in salt and water retention, which leads to pulmonary edema,
worsening hypoxia, and further ischemia
⚬
compensatory neurohormonal responses increase left ventricular filling pressure and volume, but high left
ventricular filling pressures may lead to pulmonary edema which can impair gas exchange
●
impaired gas exchange may cause respiratory acidosis
⚬
respiratory acidosis may result in worsening cardiac ischemia, left ventricular dysfunction, and
intravascular thromobosis
⚬
Reference - BMJ 2003 Jun 28;326(7404):1450 full-text
⚬
other factors which may contribute to clinical worsening of myocardial function include 4
●
increased interleukin-6 and tumor necrosis factor-alpha levels which have negative inotropic effect
⚬
cytokine-induced production of nitric oxide through nitric oxide synthase which may lead to
⚬
worsening hypotension
–
inappropriate vasodilation
–
lactic acidosis
–
decreased left ventricular diastolic function results in 1
●
increased left ventricular end-diastolic pressure and pulmonary edema and subsequent hypoxia
⚬
hypoxia causes cardiac ischemia and progressive cardiac dysfunction
⚬
factors associated with risk of developing cardiogenic shock due to ST-elevation myocardial infarction
(STEMI) include 3
●
older age
⚬
female sex
⚬
hypertension
⚬
anterior STEMI
⚬
diabetes mellitus type 2
⚬
multivessel coronary artery disease
⚬
previous STEMI or angina
⚬
STEMI with new left bundle branch block
⚬
prior diagnosis of heart failure
⚬

History
Clinical presentation
History of present illness (HPI)
Past medical history (PMH)
Physical
General physical
Skin
signs and symptoms may include
●
altered mental state (for example, disorientation, agitation, lethargy) 1 , 4
⚬
dyspnea 5
⚬
orthopnea 5
⚬
tachycardia 4
⚬
cool extremities 1 , 4 , 5
⚬
peripheral cyanosis 4
⚬
urine output < 30 mL/hour 1 , 5
⚬
dizziness 1
⚬
narrow pulse pressure 1
⚬
patients with cardiogenic shock commonly present following acute myocardial infarction, but may present
following other causes of cardiogenic shock 1 , 2 , 3 , 4
●
onset of cardiogenic shock variable
●
reported 11% of patients develop cardiogenic shock on admission and 89% of patients develop
cardiogenic shock within 2 weeks after acute myocardial infarction (most within 48 hours of symptom
onset) in GUSTO-1 trial (BMJ 2003 Jun 28;326(7404):1450 full-text )
⚬
may be acute onset following acute event such as myocardial infarction or more gradual onset due to
decompensation of a chronic disorder such as dilated cardiomyopathy 4
⚬
ask about history of 3
●
coronary artery disease
⚬
prior ST-elevation myocardial infarction or angina
⚬
prior diagnosis of heart failure
⚬
patients are hypotensive with systolic blood pressure < 90 mm Hg 1 , 3 , 4 , 5
●
usually tachycardic 4
●
low pulse pressure with faint pulses likely 4
●
cool 1 , 4 , 5
●
cyanotic 4
●

Neck
Cardiac
Lungs
Extremities
Neuro
Diagnosis
Making the diagnosis
suggested etiology based on neck findings
●
elevated jugular venous pressure/positive hepatojugular reflex may suggest elevated filling pressures
and/or cardiac tamponade
⚬
Kussmaul's sign may suggest right ventricular restriction or pericardial constriction
⚬
right atrial prominent Y descent may suggest restrictive cardiomyopathies
⚬
Reference - BMJ 2003 Jun 28;326(7404):1450 full-text
⚬
tachycardia 4
●
third heart sound (S3) or fourth heart sound (S4) may be present 4
●
displaced apical impulse 4
●
new systolic murmur suggests 4
●
mitral regurgitation
⚬
ventricular septal defect
⚬
rales with left ventricular failure 4 , 5
●
cold 1 , 4 , 5
●
cyanotic 4
●
possible pulsus paradoxus (present in cardiac tamponade) (BMJ 2003 Jun 28;326(7404):1450 full-text )
●
mental status may vary, including
●
agitation 4
⚬
disorientation 4
⚬
lethargy 4
⚬
obtundation 5
⚬
no consensus for diagnostic "gold standard" findings for cardiogenic shock 4
●
clinical suspicion based on the following
●
systolic blood pressure < 90 mm Hg 1 , 3 , 4
⚬
tachycardia 4
⚬
altered mental status ranging from agitation to obtundation 1 , 4
⚬

peripheral cyanosis 4
⚬
cool extremities 1 , 4 , 5
⚬
third (S3) or fourth (S4) heart sounds 4
⚬
dyspnea 5
⚬
decreased urine output 1
⚬
examples of diagnostic criteria for cardiogenic shock include the following
●
presence of all of the following 1 , 3
⚬
systolic blood pressure < 90 mm Hg ≥ 1 hour
–
cardiac index < 2.2 L/minute/m2
–
pulmonary capillary wedge pressure > 18 mm Hg
–
diagnostic criteria used in SHOCK trial included all of the following 4
⚬
systolic blood pressure < 90 mm Hg ≥ 30 minutes or need for supportive measures to maintain
systolic blood pressure ≥ 90 mm Hg
–
cool extremities or urine output < 30 mL/hour
–
heart rate ≥ 60 beats per minute
–
cardiac index ≤ 2.2 L/minute/m2
–
pulmonary capillary wedge pressure ≥ 15 mm Hg
–
diagnostic criteria used in IABP-SHOCK II trial included all of the following 1
⚬
systolic blood pressure < 90 mm Hg for ≥ 30 minutes or catecholamines to maintain systolic blood
pressure > 90 mm Hg
–
clinical pulmonary congestion
–
impaired end-organ perfusion, such as altered mental status, cold/clammy skin and extremities,
urine output < 30 mL/hour, or lactate > 2 mmol/L
–
European Society of Cardiology (ESC) diagnostic criteria include all of the following
⚬
systolic blood pressure < 90 mm Hg despite adequate filling status
–
signs of hypoperfusion, including
–
clinical signs, such as cold sweated extremities, oliguria, mental confusion, dizziness, narrow pulse
pressure
●
lab measures, such as metabolic acidosis, elevated serum lactate, elevated serum creatinine
●
Reference - Eur Heart J 2016 Jul 14;37(27):2129
–
tests that may help confirm diagnosis include
●
pulmonary artery catheter measurement of cardiac index and pulmonary capillary wedge
pressure 3 , 4 , 5
⚬
echocardiography and other tests (for example, electrocardiography, coronary angiography, and left
ventricular angiography) may confirm presence of 4
⚬
left ventricular and/or right ventricular dysfunction
–
valvular regurgitation
–
cardiac disruption
–
pericardial tamponade
–
chest x-ray showing pulmonary venous congestion or frank pulmonary edema 4
⚬

Differential diagnosis
Testing overview
Blood tests
elevated serum lactate levels to confirm visceral hypoperfusion 4
⚬
sepsis (septic shock) 3
●
hypovolemia (hypovolemic shock) 3
●
pulmonary embolism (PE)
●
tension pneumothorax
●
anaphylaxis 3
●
vasovagal reactions 3
●
electrolyte disturbances 3
●
arrhythmias 3
●
pharmacologic adverse event 3
●
immediate electrocardiogram and echocardiography recommended in all patients with suspected
cardiogenic shock (ESC Class I, Level C) (Eur Heart J 2016 Jul 14;37(27):2129 )
●
additional initial tests used to diagnose cardiogenic shock may include
●
chest x-ray to assess cardiac size and pulmonary edema
⚬
invasive hemodynamic monitoring
⚬
blood tests, including
⚬
cardiac troponin to identify myocardial infarction as possible cause of cardiogenic shock
–
arterial blood gas
–
once cardiogenic shock diagnosed, tests used to determine etiology and guide treatment may include
●
coronary angiography if ST-elevation myocardial infarction suspected but clinical doubt remains after
echocardiography and electrocardiogram testing 2
⚬
continuous electrocardiographic monitoring (ESC Class I, Level C)
⚬
continuous pulse oximetry 4
⚬
urine output monitoring with hourly measurement of urinary catheter drainage of bladder 4
⚬
blood tests
⚬
frequent measurement of electrolytes and arterial blood gases
–
serum lactate levels
–
consideration of invasive hemodynamic monitoring with
⚬
arterial line (ESC Class I, Level C)
–
pulmonary artery catheter to guide treatment
–
blood tests which may be used in patients with suspected or confirmed cardiogenic shock
●
cardiac troponin testing
⚬

Electrocardiography (ECG)
either cardiac troponin T or cardiac troponin I is preferred biomarker for evaluation of suspected
myocardial infarction
–
no standardization of assays - antibodies used in troponin assays and reference ranges vary among
manufacturers
–
for diagnosing myocardial infarction
–
initial elevation may not be detectable for up to 6 hours after myocardial infarction
●
sensitive troponin assays appear more sensitive than standard assays for early diagnosis of
myocardial infarction in emergency department, but may have more false-positives
DynaMed Level 2
●
high-sensitivity troponin T < 14 ng/L (0.014 mcg/L) (99th percentile) at 2 hours after presentation
has high (97%) negative predictive value for non-ST-elevation myocardial infarction in patients
with chest pain DynaMed Level 1
●
high-sensitivity cardiac troponin T measured twice 1 hour apart can diagnose or rule out
myocardial infarction in most patients presenting with chest pain and no ST-elevation
DynaMed Level 1
●
cardiac troponin levels after acute myocardial infarction may estimate infarct size
●
see Cardiac troponin testing for details
–
frequent measurement of arterial blood gas 1 , 3 , 4
⚬
frequent measurement of plasma electrolytes 1 , 3 , 4
⚬
full blood count 1 , 3
⚬
lactate level which may provide evidence of visceral hypoperfusion 1 , 3 , 4
⚬
natriuretic peptide levels (increased levels may suggest acute heart failure) 1
⚬
creatinine levels (elevated levels may suggest acute kidney injury) 1
⚬
liver function tests 1
⚬
●
STUDY SUMMARY
low BNP levels may rule out cardiogenic shock in patients with shock DynaMed Level 2
DIAGNOSTIC COHORT STUDY: Crit Care Med 2004 Aug;32(8):1643
Details
based on small diagnostic cohort study without validation
⚬
49 consecutive intensive care unit patients with shock had blood B-type natriuretic peptide (BNP) levels
measured at time of pulmonary artery catheter placement
⚬
BNP level < 350 picograms (pg)/mL had 95% negative predictive value for ruling out cardiogenic shock
⚬
higher BNP levels did not distinguish cardiogenic from noncardiogenic shock
⚬
Reference - Crit Care Med 2004 Aug;32(8):1643
⚬
see Natriuretic peptide and biomarkers testing for heart failure for additional information
⚬
immediate electrocardiogram recommended in all patients with suspected cardiogenic shock (ESC Class I,
Level C) (Eur Heart J 2016 Jul 14;37(27):2129 )
●
ECG with right-sided leads useful if right ventricular infarction suspected 3 , 4
●

Echocardiography
Chest x-ray
Invasive hemodynamic monitoring
continuous ECG monitoring once cardiogenic shock diagnosed
●
recommended in all patients (ESC Class I, Level C) (Eur Heart J 2016 Jul 14;37(27):2129 )
⚬
may help determine etiology and guide therapy 1 , 4
⚬
immediate echocardiography recommended in all patients with suspected cardiogenic shock (ESC Class I,
Level C) (Eur Heart J 2016 Jul 14;37(27):2129 )
●
during ST-elevation myocardial infarction, transthoracic echocardiography can assess left ventricular
function and mechanical complications such as cardiac muscle rupture, pseudoaneurysm, and
tamponade 2
●
urgent transthoracic echocardiography performed at bedside 3
●
to quantify left ventricular function
⚬
may identify mechanical and potentially operable causes of cardiogenic shock, such as
⚬
papillary muscle rupture
–
ventricular septal defect related to infarction
–
consider transesophageal echocardiography if clinically indicated due to suspicious of pulmonary
embolism or acute aortic syndrome 1 , 4
●
chest x-ray can provide information on cardiac size and pulmonary congestion 1 , 4
●
chest x-ray may help determine etiology and other pathogeneses, such as 1
●
pulmonary embolism (PE)
⚬
aortic dissection
⚬
pericardial effusion
⚬
pneumothorax
⚬
other
⚬
chest x-ray can be used to confirm position of endotracheal tube and support devices (such as temporary
pacing wires and mechanical circulatory support devices) 1
●
invasive monitoring with arterial line recommended in all patients with cardiogenic shock (ESC Class I, Level
C) (Eur Heart J 2016 Jul 14;37(27):2129 )
●
American Heart Association (AHA) suggestions for invasive hemodynamic monitoring in patients with
cardiogenic shock 1
●
use of pulmonary artery catheter suggested if diagnostic or management uncertainty or in patients with
moderate to severe cardiogenic shock who are unresponsive to initial therapy
⚬
hemodynamic monitoring should complement, but not replace, other markers of end-organ perfusion
⚬
optimal mean arterial pressure (MAP) differs from patient to patient and risk of hypoperfusion with
lower MAP target must be balanced with potentially deleterious effect of vasoactive agents on
myocardial oxygen demand, ischemia, and arrhythmia associated with higher MAP targets
⚬

when targeting MAP, assessment of adequate end-organ and tissue perfusion integration of serial
markers of systemic perfusion suggested, including (but not limited to) arterial lactate levels, mixed or
central venous oxygen saturations, urine output, creatinine levels, liver function tests, mental status,
temperature, and other noninvasive hemodynamic parameters
⚬
pulmonary artery catheter
●
consider left heart catheterization if ischemia or infarction is possible cause of shock
⚬
role of pulmonary artery catheter monitoring in cardiogenic shock 4 2
⚬
may eliminate diagnostic uncertainty
–
may distinguish between different hemodynamic profiles, including
–
left ventricular failure - findings may include
●
high pulmonary artery occlusion pressures (PAOP)
⚬
low cardiac output
⚬
high systemic vascular resistance
⚬
right ventricular failure - findings may include increase in
●
right atrial pressure
⚬
ratio of right atrial pressure/PAOP > 0.8
⚬
mitral regurgitation - large v-wave in PAOP tracing
●
ventricular septal rupture - significant step-up in oxygen saturation between right atrium and
pulmonary artery
●
may guide inotropic therapy and fluid management
–
may provide prognostic information (for example, cardiac power)
–
hemodynamic criteria for cardiogenic shock include 1 , 3
Image 1 of 3
Pulmonary artery catheter
Invasive cardiac monitoring may assist in distinguishing between different hemodynamic profiles
of cardiogenic shock such as left ventricular failure, right ventricular failure, mitral regurgitation, or
ventricular septal rupture.
BruceBlaus. Pulmonary Artery Catheter.png. 2016 Sep 21. Wiki Commons. Reproduced with permission under
Creative Commons Attribution-Share Alike 4.0 International license.
⚬
reduced cardiac index (< 2.2 L/minute/m2 )
–
increased pulmonary capillary wedge pressure (≥ 15 mm Hg and > 18 mm Hg have both been used)
–
cardiogenic shock may be classified based on hemodynamic presentation 1
●
classic cardiogenic shock (most common and may be referred to as cold and wet)
⚬
decreased cardiac index (CI)
–
increased systemic vascular resistance index (SVRI)
–
increased pulmonary capillary wedge pressure (PCWP)
–

Management
Management overview
euvolemic cardiogenic shock (diuretic responsive patients with chronic heart failure and subacute
decompensation and may be referred to as cold and dry)
⚬
decreased CI
–
increased SVRI
–
PCWP lower than patients with classic cardiogenic shock
–
vasodilatory cardiogenic shock or mixed shock (may be referred to as warm and wet)
⚬
decreased CI
–
decreased or normal SVRI
–
increased PCWP
–
Administer oxygen to patients with oxygen saturation ≤ 90% and assess the need for intubation and
mechanical ventilation.
●
short-term inotropic support recommended to maintain systemic perfusion and to preserve end organ
performance until definitive therapy (for example, coronary revascularization, mechanical circulatory
support) or resolution of precipitating factor occurs
●
dopamine (typical initial dose 2-5 mcg/kg/minute, may increase up to 20-50 mcg/kg/minute)
⚬
dobutamine (typical dose range 2-20 mcg/kg/minute)
⚬
norepinephrine reduces arrhythmic events compared to dopamine in patients with shock
DynaMed Level 3
⚬
levosimendan may improve survival compared to enoximone in patients with refractory cardiogenic
shock DynaMed Level 2
⚬
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) may be used under specific
circumstances
⚬
for patients with ST-elevation myocardial infarction (STEMI)
●
emergency revascularization with either percutaneous coronary intervention (PCI) or coronary artery
bypass graft (CABG) is recommended in suitable patients (ACCF/AHA Class I, Level B); early
revascularization may improve survival in patients with acute myocardial infarction and cardiogenic
shock DynaMed Level 2 , benefit may be limited to patients < 75 years old DynaMed Level 2
⚬
in absence of contraindications, administer fibrinolytic therapy to patients who are unsuitable
candidates for either PCI or CABG (ACCF/AHA Class I, Level B)
⚬
intra-aortic balloon pump (IABP) counterpulsation can be useful for patients with cardiogenic shock
after ST-elevation myocardial infarction (STEMI) who do not quickly stabilize with pharmacological
therapy (ACCF/AHA Class IIa, Level B) but does not reduce 30-day mortality or reinfarction rate
DynaMed Level 1
⚬
percutaneous left ventricular assist device is an alternative (ACCF/AHA Class IIb, Level C) which may not
decrease mortality in patients with cardiogenic shock DynaMed Level 2 but may be associated with
greater hemodynamic support than intra-aortic balloon pump DynaMed Level 3
⚬
consider urgent surgery for mitral regurgitation due to papillary muscle rupture following STEMI
⚬
emergent surgery indicated for ventricular septal or free-wall rupture following STEMI
⚬

Treatment setting
Fluid and electrolytes
for patients with persistent cardiogenic shock requiring continuous intravenous inotropic support beyond
24 hours
●
consider extracorporeal membrane oxygenation (ECMO) to provide emergency biventricular support in
patients with poor oxygenation due to cardiac failure or use as a bridge to transplantation or
implantation of mechanical assist device
⚬
consider left ventricular assist devices (LVADs) for circulatory support (other than IABP) in patients with
refractory cardiogenic shock and as a "bridge to recovery" or "bridge to decision" in patients with
profound hemodynamic compromise
⚬
see also Mechanical circulatory support for heart failure topic
⚬
consider cardiac transplantation in selected patients with cardiogenic shock refractory to other therapies.
See also Selection and timing of patients for cardiac transplantation topic
●
European Society of Cardiology recommends patients with cardiogenic shock should be rapidly transferred
to tertiary care center which has both of following (ESC Class I, Level C)
●
24/7 service of cardiac catheterization
⚬
dedicated intensive care unit/coronary care unit with availability of short-term mechanical circulatory
support
⚬
⚬
American Heart Association (AHA) scientific statement proposes that patients with cardiogenic shock be
transferred to tertiary care centers that have all of the following 1
●
cardiac intensive care unit or intensive care unit
⚬
24/7 service of primary percutaneous coronary intervention
⚬
onsite cardiology specialists, such as interventionalists, echocardiographers, advanced heart
failure/transplantation specialists, and elecrophysiology
⚬
onsite palliative care and neurology specialists
⚬
onsite pharmacy
⚬
100-200 mL fluid boluses may be required to optimize left ventricular filling pressures in patients with
developing cardiogenic shock with clinical signs suggestive of or hemodynamic monitoring indicative of a
pulmonary capillary wedge pressure (PCWP) < 15 mm Hg 3
●
goal PCWP approximately 15 mm Hg 3
●
do not give intravenous fluids if
●
PCWP > 18 mm Hg 3
⚬
frank pulmonary edema present 4
⚬
European Society of Cardiology recommends fluid challenge (saline or Ringer's lactate, > 200 mL over 15-30
minutes) as first-line treatment if no sign of overt fluid overload (ESC Class I, Level C) (Eur Heart J 2016 Jul
14;37(27):2129 )
●
American Heart Association (AHA) suggestions for fluids in patients with cardiogenic shock 1
●

Medications
Inotropes and vasopressors
General information and recommendations
fluid boluses for initial vasoactive management based on hemodynamic presentation or etiology may be
considered in
⚬
euvolemic cardiogenic shock (left ventricular end-diastolic pressure may be low and patients may
tolerate small fluid bolus)
–
right ventricular infarction
–
dynamic left ventricular outflow tract (LVOT) obstruction
–
pericardial tamponade
–
inotropic agents may enhance cardiac function and vascular tone in short- to medium-term period in
patients with cardiogenic shock 3
●
improvement in hemodynamics of inotropic support usually outweighs potential risks of increased
myocardial oxygen demand and ventricular arrhythmia when used as a bridge to definitive treatment 3
●
goal pulmonary capillary wedge pressure of at least 15 mm Hg with cardiac index of 0.2 L/kg/minute 3
●
American College of Cardiology Foundation/American Heart Association (ACCF/AHA) heart failure guideline
recommendations
●
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 definitive 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 significantly 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)
⚬
Reference - Circulation 2013 Oct 15;128(16):e240
⚬
European Society of Cardiology heart failure guideline recommendations
●
IV inotropic agents (dobutamine) may be considered to increase cardiac output (ESC Class IIb, Level C)
⚬
vasopressors (norepinephrine preferable over dopamine) may be considered if there is need to
maintain systolic blood pressure in presence of persistent hypoperfusion (ESC Class IIb, Level B)
⚬
⚬
American Heart Association (AHA) suggestions for inotropes and vasopressors in patients with cardiogenic
shock 1
●

optimal first-line vasoactive medication unknown, but norepinephrine associated with fewer
arrhythmias and may be first choice in many patients
⚬
initial vasoactive management consideration based on hemodynamic presentation or etiology
⚬
based on hemodynamic presentation
–
for classic cardiogenic shock (decreased cardiac index [CI], increased systemic vascular resistance
index [SVRI], and increased pulmonary capillary wedge pressure [PCWP])
●
consider hemodynamic stabilization with norepinephrine (preferred if increased heart rate or
arrhythmias) or dopamine (preferred if decreased heart rate but associated with risk of
arrhythmias)
⚬
consider addition of inotropic agent when stabilized and after revascularization in patients with
⚬
for euvolemic cardiogenic shock (decreased CI, increased SVRI, and PCWP lower than patients with
classic cardiogenic shock)
●
arrhythmias)
⚬
⚬
for vasodilatory cardiogenic shock or mixed shock (decreased CI, decreased or normal SVRI, and
increased PCWP), consider norepinephrine and hemodynamic-guided therapy
●
based on etiology or clinical presentation
–
for patients with right ventricular (RV) infarction
●
hemodynamic goals include maintaining preload, lowering RV afterload, treating absolute or
relative bradycardias, and maintaining atrioventricular synchrony
⚬
dopamine preferred if decreased heart rate but associated with risk of arrhythmia
⚬
vasopressin may raise SVR and have neutral effect on pulmonary vascular resistance (PVR)
⚬
consider adding or transitioning to inotrope after initial hemodynamic stabilization and
revascularization
⚬
consider inhaled pulmonary vasodilator
⚬
for patients with normal blood pressure, initial inotropic therapy may be appropriate due to
relatively high SVRI
●
for patients with aortic stenosis
●
consider phenylephrine or vasopressin
⚬
consider dobutamine titrated (guided by echocardiography or pulmonary artery catheter) if
reduced left ventricular ejection fraction (LVEF)
⚬
inotropic therapy may not improve hemodynamics if LVEF preserved
⚬
for patients with aortic regurgitation
●
consider dopamine or temporary pacing
⚬
maintaining elevated heart rate may shorten diastolic filling time and reduce left ventricular
end-diastolic pressure
⚬
for patients with mitral stenosis
●
⚬
consider esmolol or amiodarone
⚬

avoidance of chronotropic agents, slowing heart rate, and maintaining atrioventricular
synchrony may improve preload
⚬
for patients with mitral regurgitation
●
consider norepinephrine or dopamine
⚬
consider addition of inotropic agent after hemodynamic stabilization with vasopressor
⚬
for patients with postinfarction ventral septal defect
●
arrhythmias)
⚬
⚬
for patients with dynamic left ventricular outflow tract (LVOT) obstruction
●
⚬
consider avoidance of inotropic agents and vasodilating agents
⚬
consider esmolol or amiodarone
⚬
for patients with bradycardia, consider chronotropic agents or temporary pacing (chronotropic
agents may include atropine, isoproterenol, dopamine, dobutamine, or epinephrine)
●
for patients with pericardial tamponade, consider norepinephrine
●
Table 1. Main Vasoactive Agents Used in Cardiogenic Shock
Vas
oact
ive
Age
nt
Dosi
ng
Cate
gory
Alph
a-1
Rec
epto
r
Ago
nist
Alph
a-2
Rec
epto
r
Ago
nist
Beta
-1
Rec
epto
r
Ago
nist
Beta
-2
Rec
epto
r
Ago
nist
Non
adre
nerg
ic
Effe
cts
Mai
n
Effe
ct
on
SVR
Mai
n
Effe
ct
on
CO
Nor
epin
ephr
ine
Inoc
onst
ricto
r
++(+)
(+)
+++ ++ (+) NA Up Up
or
dow
n
St
ar
ti
n
g
d
os
e
0.
0
1-
⚬

Vas
oact
ive
Age
nt
Dosi
ng
Cate
gory
Alph
a-1
Rec
epto
r
Ago
nist
Alph
a-2
Rec
epto
r
Ago
nist
Beta
-1
Rec
epto
r
Ago
nist
Beta
-2
Rec
epto
r
Ago
nist
Non
adre
nerg
ic
Effe
cts
Mai
n
Effe
ct
on
SVR
Mai
n
Effe
ct
on
CO
0.
0
3
m
cg
/k
g/
m
in
ut
e
(
m
ax
i
m
u
m
d
os
e
0.
1
m
cg
/k
g/
m
in
ut
e)

Vas
oact
ive
Age
nt
Dosi
ng
Cate
gory
Alph
a-1
Rec
epto
r
Ago
nist
Alph
a-2
Rec
epto
r
Ago
nist
Beta
-1
Rec
epto
r
Ago
nist
Beta
-2
Rec
epto
r
Ago
nist
Non
adre
nerg
ic
Effe
cts
Mai
n
Effe
ct
on
SVR
Mai
n
Effe
ct
on
CO
Dop
ami
ne
0.5-2
mcg
/kg/
min
ute
Inodi
lator
NA (+) + + Dop
amin
e
rece
ptor
agon
ist
NA Up
Dop
ami
ne
3-10
mcg
/kg/
min
ute
Inodi
lator
or
inoc
onst
ricto
r
+ (+) ++ ++ Dop
amin
e
rece
ptor
agon
ist
Up Up
Dop
ami
ne >
10
mcg
/kg/
min
ute
Inoc
onst
ricto
r
+(+)
(+)
(+) ++(+)
(+)
+(+) Dop
amin
e
rece
ptor
agon
ist
Up NA
St
ar
ti
n
g
d
os
e
⚬
2
-
5
m
c
g
/
k
g
/
m
i
n
u
t
e
i
n
p
a
t
i
e
–

Vas
oact
ive
Age
nt
Dosi
ng
Cate
gory
Alph
a-1
Rec
epto
r
Ago
nist
Alph
a-2
Rec
epto
r
Ago
nist
Beta
-1
Rec
epto
r
Ago
nist
Beta
-2
Rec
epto
r
Ago
nist
Non
adre
nerg
ic
Effe
cts
Mai
n
Effe
ct
on
SVR
Mai
n
Effe
ct
on
CO
n
t
s
l
i
k
e
l
y
t
o
r
e
s
p
o
n
d
t
o
m
o
d
e
s
t
i
n
c
r
e
m

Vas
oact
ive
Age
nt
Dosi
ng
Cate
gory
Alph
a-1
Rec
epto
r
Ago
nist
Alph
a-2
Rec
epto
r
Ago
nist
Beta
-1
Rec
epto
r
Ago
nist
Beta
-2
Rec
epto
r
Ago
nist
Non
adre
nerg
ic
Effe
cts
Mai
n
Effe
ct
on
SVR
Mai
n
Effe
ct
on
CO
e
n
t
s
5
m
c
g
/
k
g
/
m
i
n
u
t
e
i
n
m
o
r
e
s
e
r
i
o
u
s
l
–

Vas
oact
ive
Age
nt
Dosi
ng
Cate
gory
Alph
a-1
Rec
epto
r
Ago
nist
Alph
a-2
Rec
epto
r
Ago
nist
Beta
-1
Rec
epto
r
Ago
nist
Beta
-2
Rec
epto
r
Ago
nist
Non
adre
nerg
ic
Effe
cts
Mai
n
Effe
ct
on
SVR
Mai
n
Effe
ct
on
CO
y
i
l
l
p
a
t
i
e
n
t
s
(
i
n
c
r
e
a
s
e
i
n
5
-
1
0
m
c
g
/
k

Vas
oact
ive
Age
nt
Dosi
ng
Cate
gory
Alph
a-1
Rec
epto
r
Ago
nist
Alph
a-2
Rec
epto
r
Ago
nist
Beta
-1
Rec
epto
r
Ago
nist
Beta
-2
Rec
epto
r
Ago
nist
Non
adre
nerg
ic
Effe
cts
Mai
n
Effe
ct
on
SVR
Mai
n
Effe
ct
on
CO
g
/
m
i
n
u
t
e
i
n
c
r
e
m
e
n
t
s
)
D
os
e
m
ay
b
e
in
cr
ea
se
d
u
⚬

Vas
oact
ive
Age
nt
Dosi
ng
Cate
gory
Alph
a-1
Rec
epto
r
Ago
nist
Alph
a-2
Rec
epto
r
Ago
nist
Beta
-1
Rec
epto
r
Ago
nist
Beta
-2
Rec
epto
r
Ago
nist
Non
adre
nerg
ic
Effe
cts
Mai
n
Effe
ct
on
SVR
Mai
n
Effe
ct
on
CO
p
to
2
0-
5
0
m
cg
/k
g/
m
in
ut
e;
if
>
5
0
m
cg
/k
g/
m
in
ut
e
re
q
ui
re
d,
ur

Vas
oact
ive
Age
nt
Dosi
ng
Cate
gory
Alph
a-1
Rec
epto
r
Ago
nist
Alph
a-2
Rec
epto
r
Ago
nist
Beta
-1
Rec
epto
r
Ago
nist
Beta
-2
Rec
epto
r
Ago
nist
Non
adre
nerg
ic
Effe
cts
Mai
n
Effe
ct
on
SVR
Mai
n
Effe
ct
on
CO
in
e
o
ut
p
ut
sh
o
ul
d
b
e
fr
e
q
u
e
nt
ly
ch
ec
ke
d

Vas
oact
ive
Age
nt
Dosi
ng
Cate
gory
Alph
a-1
Rec
epto
r
Ago
nist
Alph
a-2
Rec
epto
r
Ago
nist
Beta
-1
Rec
epto
r
Ago
nist
Beta
-2
Rec
epto
r
Ago
nist
Non
adre
nerg
ic
Effe
cts
Mai
n
Effe
ct
on
SVR
Mai
n
Effe
ct
on
CO
Epin
ephr
ine
Start
ing
dose
0.01-
0.03
mcg/
kg/m
inut
e
(max
imu
m
sugg
este
d
dose
0.1-
0.3
mcg/
kg/m
inut
e)
Inoc
onst
ricto
r
++++ +++ ++++ (+)(+)
(+)
NA Up Up

Vas
oact
ive
Age
nt
Dosi
ng
Cate
gory
Alph
a-1
Rec
epto
r
Ago
nist
Alph
a-2
Rec
epto
r
Ago
nist
Beta
-1
Rec
epto
r
Ago
nist
Beta
-2
Rec
epto
r
Ago
nist
Non
adre
nerg
ic
Effe
cts
Mai
n
Effe
ct
on
SVR
Mai
n
Effe
ct
on
CO
Dob
uta
min
e
Usua
lly 2-
15
mcg/
kg/m
inut
e,
but
up
to 40
mcg/
kg/m
inut
e
may
be
requ
ired
Inodi
lator
(+) (+) ++++ ++(+) NA Up
or
dow
n
Up

Vas
oact
ive
Age
nt
Dosi
ng
Cate
gory
Alph
a-1
Rec
epto
r
Ago
nist
Alph
a-2
Rec
epto
r
Ago
nist
Beta
-1
Rec
epto
r
Ago
nist
Beta
-2
Rec
epto
r
Ago
nist
Non
adre
nerg
ic
Effe
cts
Mai
n
Effe
ct
on
SVR
Mai
n
Effe
ct
on
CO
Milri
non
e
0.37
5-
0.75
mcg/
kg/m
inut
e
(dos
e
adju
stme
nt
need
ed
for
rena
l
dysf
uncti
on)
Inodi
lator
NA NA NA NA PDE
inhib
ition
Dow
n
Up
Levo
sime
nda
n
0.05-
0.2
mcg/
kg/m
inut
e
Inodi
lator
NA NA NA NA Calci
um
sens
itizat
ion
Dow
n
Up

Vas
oact
ive
Age
nt
Dosi
ng
Cate
gory
Alph
a-1
Rec
epto
r
Ago
nist
Alph
a-2
Rec
epto
r
Ago
nist
Beta
-1
Rec
epto
r
Ago
nist
Beta
-2
Rec
epto
r
Ago
nist
Non
adre
nerg
ic
Effe
cts
Mai
n
Effe
ct
on
SVR
Mai
n
Effe
ct
on
CO
Phe
nyle
phri
ne
40-
60
mcg/
min
ute
Vaso
cons
trict
or
+++
(+)
NA NA NA NA Up Neut
ral
or
dow
n
Vaso
pres
sin
(or
anal
og
terli
pres
sin)
0.01-
0.04
units
/min
ute
Vaso
cons
trict
or
NA NA NA NA Vaso
pres
sin
rece
ptor
agon
ist
Up Dow
n

Norepinephrine
Vas
oact
ive
Age
nt
Dosi
ng
Cate
gory
Alph
a-1
Rec
epto
r
Ago
nist
Alph
a-2
Rec
epto
r
Ago
nist
Beta
-1
Rec
epto
r
Ago
nist
Beta
-2
Rec
epto
r
Ago
nist
Non
adre
nerg
ic
Effe
cts
Mai
n
Effe
ct
on
SVR
Mai
n
Effe
ct
on
CO
Abbreviations: CO, cardiac output; NA, not applicable; PDE, phosphodiesterase; SVR,
systemic vascular resistance.
*The number of + signs represent the degree of receptor stimulation, with + signs
between parentheses indicating uncertainty of stimulatory effect.
References -





































                                          J Cardiovasc Pharmacol Ther 2015 May;20(3):249 ,

                                          Emerg Med Clin North Am 2008 Aug;26(3):759 ,

                                          Curr Opin Cardiol 2014 May;29(3):250 ,  FDA DailyMed 2017 Jul
.
norepinephrine
●

Dopamine
increases systemic blood pressure, pulse pressure, stroke volume, and peripheral vascular resistance 5
⚬
commonly used as first-line agent for increasing blood pressure in patients with cardiogenic shock 5
⚬
recommended starting dose 0.01 to 0.03 mcg/kg/minute (maximum dose 0.1 mcg/kg/minute) 5
⚬
⚬
STUDY SUMMARY
norepinephrine may reduce arrhythmic events compared to dopamine in patients with shock
DynaMed Level 3
RANDOMIZED TRIAL: N Engl J Med 2010 Mar 4;362(9):779 | Full Text
Details
based on randomized trial without significant differences in clinical outcomes
–
1,679 patients ≥ 18 years old who required a vasopressor for shock treatment were randomized to
norepinephrine vs. dopamine and were followed for 12 months
–
norepinephrine dose titrated by 0.02 mcg/kg/minute to maximum 0.19 mcg/kg/minute
●
dopamine dose titrated by 2 mcg/kg/minute to maximum 20 mcg/kg/minute
●
open-label rescue therapy (epinephrine, norepinephrine, or vasopressin) allowed if blood pressure
not maintained with maximal doses of study drug
–
comparing norepinephrine vs. dopamine
–
intensive care mortality 45.9% vs. 50.2% (p = 0.07)
●
in-hospital mortality 56.6% vs. 59.4% (not significant)
●
28-day mortality 48.5% vs. 52.5% (p = 0.1)
●
6-month mortality 62.9% vs. 63.8% (not significant)
●
12-month mortality 63% vs. 65.9% (not significant)
●
arrhythmic events (atrial fibrillation, ventricular tachycardia, ventricular fibrillation) in 12.4% vs.
24.1% (p < 0.001, NNT 9)
●
atrial fibrillation in 11% vs. 20.5% (NNT 10)
⚬
ventricular tachycardia in 1% vs. 2.4%
⚬
ventricular fibrillation in 0.5% vs. 1.2%
⚬
norepinephrine associated with significant reduction in 28-day mortality in predefined subgroup
analysis of 280 patients with cardiogenic shock (hazard ratio [estimated from figure] 0.75, p = 0.03)
●
Reference - N Engl J Med 2010 Mar 4;362(9):779 full-text , editorial can be found in N Engl J Med
2010 Mar 4;362(9):841 , commentary can be found in N Engl J Med 2010 Jun 17;362(24):2328
–
see Norepinephrine for additional information
⚬
dopamine
●
at low doses (≤ 2 mcg/kg/minute), dopamine causes vasodilation by stimulating receptors in splanchnic
and renal arteries 5
⚬
at higher doses (5-15 mcg/kg/minute), dopamine causes peripheral arterial and venous constriction and
may be given to improve hemodynamics in some patients with cardiogenic shock 3 , 5
⚬
dosing
⚬

Dobutamine
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 2017 Jul
–
⚬
STUDY SUMMARY
dopamine may reduce arrhythmic events less compared to norepinephrine in patients with shock
DynaMed Level 3
RANDOMIZED TRIAL: N Engl J Med 2010 Mar 4;362(9):779 | Full Text
Details
based on randomized trial without significant differences in clinical outcomes
–
1,679 patients ≥ 18 years old who required a vasopressor for shock treatment were randomized to
dopamine vs. norepinephrine and were followed for 12 months
–
dopamine dose titrated by 2 mcg/kg/minute to maximum 20 mcg/kg/minute
●
norepinephrine dose titrated by 0.02 mcg/kg/minute to maximum 0.19 mcg/kg/minute
●
open-label rescue therapy (epinephrine, norepinephrine, or vasopressin) allowed if blood pressure
not maintained with maximal doses of study drug
–
comparing dopamine vs. norepinephrine
–
intensive care mortality 50.2% vs. 45.9% (p = 0.07)
●
in-hospital mortality 59.4% vs. 56.6% (not significant)
●
28-day mortality 52.5% vs. 48.5% (p = 0.1)
●
6-month mortality 63.8% vs. 62.9% (not significant)
●
12-month mortality 65.9% vs. 63% (not significant)
●
arrhythmic events (atrial fibrillation, ventricular tachycardia, ventricular fibrillation) in 24.1% vs.
12.4% (p < 0.001, NNT 9)
●
atrial fibrillation in 20.5% vs. 11% (NNT 10)
⚬
ventricular tachycardia in 2.4% vs. 1%
⚬
ventricular fibrillation in 1.2% vs. 0.5%
⚬
norepinephrine associated with significant reduction in 28-day mortality in predefined subgroup
analysis of 280 patients with cardiogenic shock (hazard ratio [estimated from figure] 0.75, p = 0.03)
●
Reference - N Engl J Med 2010 Mar 4;362(9):779 full-text , editorial can be found in N Engl J Med
2010 Mar 4;362(9):841 , commentary can be found in N Engl J Med 2010 Jun 17;362(24):2328
–
see Dopamine for additional information
⚬
dobutamine
●
dobutamine increases heart rate, stroke volume, and cardiac output and decreases left ventricular filling
pressures 5
⚬
usual recommended dose 2-15 mcg/kg/minute 5
⚬

Levosimendan
optimal infusion rates vary (typically 2-20 mcg/kg/minute); on rare occasions infusion rates up to 40
mcg/kg/minute may be required (FDA DailyMed 2014 Apr )
⚬
see Dobutamine for additional information
⚬
levosimendan
●
levosimendan not available in United States as of July 25, 2018; available in some countries outside of
the United States
⚬
the role of levosimendan in cardiogenic shock is unclear; levosimendan not recommended in patients
with systolic blood pressure < 90 mm Hg 5
⚬
levosimendan is a calcium-sensitizing drug that binds to cardiac troponin C in a calcium-dependent
manner
⚬
levosimendan vasodilates vascular smooth muscle by opening adenosine triphosphate-sensitive
potassium channels 5
⚬
recommended dose 0.05-0.2 mcg/kg/minute 5
⚬
⚬
STUDY SUMMARY
levosimendan may not reduce short-term or long-term mortality compared to dobutamine in
patients with acute myocardial infarction, heart failure, or cardiac surgery complicated by
cardiogenic shock or low cardiac output syndrome DynaMed Level 2
COCHRANE REVIEW: Cochrane Database Syst Rev 2020 Nov 5;11:CD009669
Details
based on Cochrane review with confidence interval that cannot exclude differences that may be
clinically important for short-term mortality and wide confidence interval for long-term mortality
–
systematic review of 19 randomized trials evaluating inotropic agents and vasodilator strategies in
2,385 adults with acute myocardial infarction, heart failure, or cardiac surgery complicated by
cardiogenic shock or low cardiac output syndrome
–
4 trials included patients with acute myocardial infarction, 7 trials included patients with acute heart
failure, and 8 trials included patients with cardiac surgery
–
6 trials compared levosimendan to dobutamine
–
comparing levosimendan to dobutamine
–
no significant differences in
●
short-term (15-31 days) all-cause mortality (risk ratio [RR] 0.6, 95% CI 0.36-1.03) in analysis of 4
trials with 1,701 patients, but confidence interval cannot exclude differences that may be
clinically important
⚬
long-term (4-12 months) all-cause mortality (RR 0.84, 95% CI 0.63-1.13) in analysis of 4 trials
with 1,591 patients, but confidence interval includes possibility of benefit or harm
⚬
levosimendan associated with
●
increased mean cardiac index (mean difference [MD] 0.45, 95% CI 0.14-0.76) in analysis of 3
trials with 224 patients
⚬
decreased pulmonary capillary wedge pressure (MD -4.14 mm Hg, 95% CI -6.23 to -2.06 mm Hg)
in analysis of 3 trials with 386 patients
⚬
3 trials compared levosimendan to placebo
–

comparing levosimendan to placebo, no significant difference in long-term all-cause mortality in
analysis of 2 trials with 55 patients
–
no significant difference in short-term mortality in single trials
–
comparing levosimendan to enoximone in 32 patients
●
comparing epinephrine to norepinephrine-dobutamine in 30 patients
●
comparing enoximone to dobutamine in 37 patients
●
Reference - Cochrane Database Syst Rev 2020 Nov 5;11:CD009669
–
⚬
STUDY SUMMARY
levosimendan associated with reduced mortality compared to standard treatment in patients with
decompensated heart failure DynaMed Level 2
SYSTEMATIC REVIEW: Crit Care Med 2012 Feb;40(2):634
Details
based on systematic review with clinical heterogeneity
–
systematic review of 45 randomized trials with 5,480 patients treated with levosimendan vs. control
–
studies were heterogeneous in
–
clinical condition (decompensated heart failure, cardiac surgery, septic shock, interventional
cardiology, and vascular surgery)
●
levosimendan dosing (between 3 and 36 mcg/kg bolus and between 0.05 and 0.6 mcg/kg/minute
infusion)
●
levosimendan administration (bolus, continuous infusion, or bolus followed by infusion)
●
control treatment (placebo, dobutamine)
●
follow-up duration (1 day to 5 years)
●
mortality comparing levosimendan vs. any control treatment in subgroup analyses
–
20% vs. 25.6% in decompensated heart failure patients (RR 0.75, 95% CI 0.63-0.91, NNT 18) in
analysis of 23 studies with 4,100 patients
●
5.8% vs. 12.9% in cardiac surgery patients (RR 0.52, 95% CI 0.35-0.76, NNT 14) in analysis of 17
studies with 1,233 patients
●
mortality comparing levosimendan vs. standard treatment or placebo
–
17.4% vs. 23.3% with any control treatment (relative risk [RR] 0.8, 95% CI 0.72-0.89, NNT 17) in
analysis of all trials
●
14.7% vs. 18.7% with placebo (RR 0.82, 95% CI 0.69-0.97, NNT 25) in analysis of 25 studies with
2,674 patients
●
15% vs. 27.7% with dobutamine (RR 0.68, 95% CI 0.52-0.88, NNT 13) in analysis of 16 studies with
2,688 patients, but results limited by significant heterogeneity
●
no significant difference in mortality between levosimendan and control in patients with septic shock
–
nonsignificant increase in hypotension in levosimendan vs. any control treatment (RR 1.389, 95% CI
0.996-1.936)
–
Reference - Crit Care Med 2012 Feb;40(2):634
–
⚬
STUDY SUMMARY
levosimendan may not reduce 30-day mortality in adults requiring perioperative hemodynamic
support after cardiac surgery DynaMed Level 2

Milrinone
RANDOMIZED TRIAL: N Engl J Med 2017 May 25;376(21):2021
Details
based on randomized trial with early termination
–
506 adults (mean age 66 years, 64% male) with perioperative cardiovascular dysfunction requiring
hemodynamic support after cardiac surgery were randomized to levosimendan 0.05 mcg/kg/minute
vs. placebo continuous infusion for up to 48 hours
–
perioperative cardiovascular dysfunction defined as ≥ 1 of
–
preoperative support with intra-aortic balloon pump
●
preoperative left ventricular ejection fraction < 25%
●
need for support with intra-aortic balloon pump or high-dose inotropic support to wean from
cardiopulmonary bypass or within first 24 hours post surgery
●
levosimendan dose could be increased (maximum 0.2 mcg/kg/minute) or decreased (minimum 0.025
mcg/kg/minute) at physician's discretion
–
trial was terminated early for futility at suggestion of data safety and monitoring board (at 50% of
planned enrollment) without predefined stopping rule
–
mean duration of levosimendan infusion was 33 hours and mean dose was 0.066 mcg/kg/minute
–
comparing levosimendan infusion vs. placebo
–
30-day mortality 12.9% vs. 12.8% (not significant)
●
renal replacement therapy in 9.7% vs. 12.8% (not significant)
●
median duration of mechanical ventilation 19 hours vs. 21 hours (not significant)
●
median length of intensive care unit (ICU) stay 72 hours vs. 84 hours (p = 0.08)
●
infusion interruption due to adverse events in 3.8% vs. 1.6% (not significant)
●
no significant differences in acute kidney injury (according to RIFLE criteria), myocardial infarction,
neurological damage, hypotension during infusion, cardiac arrhythmias during infusion, or serious
adverse events
–
Reference - CHEETAH trial (N Engl J Med 2017 May 25;376(21):2021 )
–
IV levosimendan used in 2 patients with recurrent ventricular tachycardia/ventricular fibrillation
complicated by cardiogenic shock in case report (Ann Intern Med 2009 May 19;150(10):738 )
⚬
milrinone
●
increases heart rate, stroke volume, and cardiac output in patients with heart failure 5
⚬
milrinone recommended only for refractory cardiogenic shock due to safety concerns (such as new
atrial fibrillation/flutter and increased hypotension reported in patients with acute exacerbation of
chronic heart failure in OPTIME-HF trial; see milrinone section of acute heart failure for details of
OPTIME-HF trial) 5
⚬
recommended dose 0.375-0.75 mcg/kg/minute (dose adjustment needed for renal dysfunction) 5
⚬
evidence for milrinone in case reports
⚬
milrinone reported to successfully treat takotsubo syndrome complicated by cardiogenic shock in 64-
year-old man in case report (Heart Lung 2014 Jul-Aug;43(4):331 full-text )
–
milrinone reported to successfully treat refractory cardiogenic shock due to massive pulmonary
aspiration of gastric contents during induction of general anesthesia in 53-year-old man (Korean J
–

Epinephrine
Anesthesiol 2014 Jun;66(6):476 full-text )
see Milrinone for additional information
⚬
⚬
STUDY SUMMARY
milrinone may not improve composite outcome of in-hospital all-cause death, cardiovascular
adverse events, and renal replacement therapy compared to dobutamine in adults with cardiogenic
shock admitted to cardiac ICU DynaMed Level 2
RANDOMIZED TRIAL: N Engl J Med 2021 Aug 5;385(6):516
Details
based on randomized trial with wide confidence interval
–
192 adults (mean age 70 years, 63% men) with cardiogenic shock (defined as Society for
Cardiovascular Angiography and Interventions [SCAI] cardiogenic shock class B-E) admitted to cardiac
ICU were randomized to milrinone vs. dobutamine
–
milrinone dose based on physician assessment and ranged from 0.125 mcg/kg/minute IV to > 0.5
mcg/kg/minute IV
●
dobutamine dose based on physician assessment and ranged from 2.5 mcg/kg/minute IV to > 10
mcg/kg/minute IV
●
comorbidities included previous myocardial infarction, percutaneous coronary intervention,
coronary-artery bypass grafting, stroke or transient ischemic attack, atrial fibrillation, chronic kidney
or liver disease, and chronic obstructive pulmonary disease
–
80% of patients had SCAI cardiogenic shock class C (hypoperfusion requiring intervention)
–
primary outcome was composite of in-hospital all-cause death, resuscitated cardiac arrest, cardiac
transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic
attack or stroke, and initiation of renal replacement therapy
–
100% included in analysis
–
comparing milrinone vs. dobutamine
–
primary outcome in 49% vs. 54% (relative risk 0.9, 95% CI 0.69-1.19), not significant, but CI includes
possibility of benefit or harm
●
in-hospital all-cause death 37% vs. 43% (relative risk 0.85, 95% CI 0.6-1.21)
⚬
resuscitated cardiac arrest in 7% vs. 9% (hazard ratio [HR] 0.78, 95% CI 0.29-2.07)
⚬
cardiac transplant or mechanical circulatory support in 12% vs. 15% (HR 0.78, 95% CI 0.36-1.71)
⚬
transient ischemic attack or stroke in 1% vs. 2% (HR 0.5, 95% CI 0.05-5.5)
⚬
initiation of renal replacement therapy in 22% vs. 17% (HR 1.39, 95% CI 0.73-2.67)
⚬
median duration of cardiac ICU stay 4.5 days vs. 5.5 days (no p value reported)
●
arrhythmia requiring intervention in 50% vs. 46% (not significant)
●
ventricular arrhythmia in 15% vs. 18% (not significant)
●
Reference - DOREMI trial (N Engl J Med 2021 Aug 5;385(6):516 )
–
epinephrine
●
increases systemic blood pressure, stroke volume, and cardiac output, and decreases systemic vascular
resistance 5
⚬

increases myocardial oxygen consumption and is rarely used for acute decompensated heart failure 5
⚬
may be used
⚬
to increase heart rate, contractility, and blood pressure in extremely critical situation (usually near
cardiac arrest) 4
–
after cardiac surgery to overcome myocardial stunning and raise systemic blood pressure 5
–
recommended starting dose 0.01-0.03 mcg/kg/minute (maximum suggested dose 0.1-0.3
mcg/kg/minute) 5
⚬
⚬
STUDY SUMMARY
epinephrine associated with increased mortality compared to other vasopressors in adults with
cardiogenic shock DynaMed Level 2
COHORT STUDY: Crit Care 2016 Jul 4;20(1):208 | Full Text
Details
based on prospective cohort study
–
219 adults (mean age 67 years, 72% men) with cardiogenic shock treated with vasopressors and/or
inotropes were evaluated for 90-day mortality
–
vasopressors and inotropes used in 94% of patients
●
most common vasopressors were norepinephrine (in 75%), dopamine (in 26%), and
epinephrine (in 21%)
⚬
most common inotropes were dobutamine (in 49%) and levosimendan (in 24%)
⚬
10% received only inotropes, 29% received only vasopressors, and 55% received both
●
39% of patients receiving epinephrine resuscitated from cardiac arrest prior to study inclusion
●
propensity scores calculated using multiple patient and procedural factors
–
overall 90-day mortality was 41%
–
in propensity-score-adjusted analysis, compared to other vasopressors, epinephrine associated with
–
increased 90-day mortality (hazard ratio 1.9, 95% CI 1.1-3.3)
●
worse renal biomarker levels
●
similar results in subgroup analysis of 3 matched cohorts
–
no significant association of other vasopressors, inotropes, or combinations of vasopressors and
inotropes with increased mortality
–
Reference - Crit Care 2016 Jul 4;20(1):208 full-text , commentary with response in Crit Care 2016
Sep 28;20(1):292 , commentary with response in Crit Care 2016 Sep 20;20:289 , commentary with
response in Crit Care 2016 Sep 27;20(1):302 , commentary in Crit Care 2016 Sep 26;20(1):293
–
⚬
STUDY SUMMARY
epinephrine may increase rate of refractory shock DynaMed Level 2 without improving cardiac index
DynaMed Level 3 compared to norepinephrine in adults with cardiogenic shock after myocardial
infarction and successful revascularization with percutaneous coronary intervention
RANDOMIZED TRIAL: J Am Coll Cardiol 2018 Jul 10;72(2):173
Details

Oxygen
based on small randomized trial with early termination and post hoc analysis of refractory shock
–
57 adults (median 67 years) with cardiogenic shock after myocardial infarction and successful
revascularization using percutaneous coronary intervention (PCI) were randomized to epinephrine
0.02 mcg/kg/minute IV vs. norepinephrine 0.02 mcg/kg/minute IV and followed for 28 days
–
after inclusion in trial, blinded syringe was added to open-label vasopressor agent and as soon as
mean arterial pressure (MAP) increased, open-label vasopressor agent was decreased and then
discontinued
●
if MAP decreased to < 65-70 mm Hg during first 24 hours, study drug was reintroduced
●
thereafter, open-label vasopressor agent was used if deemed necessary
●
at baseline, all patients had
–
systolic arterial pressure < 90 mm Hg or MAP < 65 mm Hg without vasopressor agent
●
cardiac index < 2.2 L/minute/m2 without vasopressor or inotrope therapy
●
pulmonary arterial occlusion pressure > 15 mm Hg or echocardiographic ejection fraction < 40%
without inotrope support
●
≥ 1 evidence of tissue hypoperfusion
●
inserted pulmonary artery catheter
●
before inclusion
–
vasopressor treatment was norepinephrine in 75% and epinephrine in 23% of all patients
●
resuscitation after cardiac arrest in 41% of epinephrine group vs. 60% in norepinephrine group
(not significant)
●
trial was stopped early without predefined stopping rule due to higher rate of refractory shock with
epinephrine
–
refractory shock defined post hoc as cardiogenic shock assessed by echocardiography, elevated
lactate, acute decreased organ function despite vasopressor therapy or intra-aortic balloon support,
and sustained hypotension (systolic arterial pressure < 90 mm Hg or MAP < 65 mm Hg) despite
adequate intravascular volume
–
primary outcome was change in cardiac index
–
100% included in analyses
–
comparing epinephrine vs. norepinephrine
–
refractory shock in 37% vs. 7% (p = 0.008, NNH 3)
●
death or extracorporeal life support ≤ 28 days in 52% vs. 30% (p = 0.096)
●
60-day mortality 52% vs. 37% (not significant)
●
arrhythmia in 41% vs. 33% (not significant)
●
no significant difference in change in cardiac index or mean arterial pressure
–
epinephrine associated with higher arterial lactate levels over first 24 hours compared to
norepinephrine (p < 0.0001)
–
Reference - J Am Coll Cardiol 2018 Jul 10;72(2):173
–
no additional trials comparing epinephrine to norepinephrine in adults with cardiogenic shock found
in Cochrane review (Cochrane Database Syst Rev 2020 Nov 5;11:CD009669 )
–
maintain adequate oxygenation and airway protection (mechanical ventilation may be required) 4
●
for patients with ST-elevation myocardial infarction 2
●

Other medications
oxygen therapy appropriate for patients with clinically significant hypoxemia (oxygen saturation < 90%)
⚬
typically started at 2-4 L/minute via nasal cannula, but may be increased or changed to face mask as
needed
⚬
use with caution in patients with chronic obstructive pulmonary disease (COPD) and carbon dioxide
retention
⚬
American Heart Association suggestions for nonvasoactive medications in patients with cardiogenic
shock 1
●
for patients with ST-elevation myocardial infarction (STEMI)-associated cardiogenic shock
⚬
AHA supports American College of Cardiology Foundation/ American Heart Association Task Force on
Practice Guidelines recommendations for
–
avoidance of beta blockers suggested in patients with signs of heart failure or low output states
●
avoidance of renin-angiotensin-aldosterone system (RAAS) antagonists in patients with
hypotension
●
initiation of beta blockers may be reasonable in euvolemic patients off inotropes and vasopressors
for ≥ 24 hours
–
RAAS inhibition therapy can be considered if off vasopressors for ≥ 24 hours if renal function
returned to baseline and risk of RAAS-associated hyperkalemia and hypotension considered low
–
RAAS inhibition therapy may be started in conjunction with inodilator in patients with pulmonary
edema
–
statin reasonable in patients with myocardial infarction (MI)-associated cardiogenic shock
⚬
nitric oxide synthesis inhibitors do not appear clinically useful
●
tilarginine acetate is a nitric oxide synthase inhibitor
⚬
⚬
STUDY SUMMARY
tilarginine acetate does not appear to reduce mortality or improve resolution of shock
DynaMed Level 2
RANDOMIZED TRIAL: JAMA 2007 Apr 18;297(15):1657
Details
based on randomized trial with allocation concealment inadequately described
–
398 patients with myocardial infarction and refractory cardiogenic shock despite establishment of
open artery were randomized to IV tilarginine (1 mg/kg bolus then 1 mg/kg/hour for 5 hours) vs.
placebo
–
trial terminated early based on futility analysis
–
no significant differences comparing tilarginine vs. placebo
–
mortality at 30 days 46% vs. 42%
●
resolution of shock in 66% vs. 61%
●
heart failure in 48% vs. 51%
●
Reference - TRIUMPH trial (JAMA 2007 Apr 18;297(15):1657 ), editorial can be found in JAMA 2007
Apr 18;297(15):1711 , commentary can be found in JAMA 2007 Sep 5;298(9):971
–

Surgery and procedures
Timing of revascularization
●
STUDY SUMMARY
addition of glycoprotein IIb/IIIa inhibitor therapy to standard care may reduce mortality without
increasing risk of bleeding in patients with cardiogenic shock after acute myocardial infarction
DynaMed Level 2
SYSTEMATIC REVIEW: J Intensive Care 2020 Nov 11;8(1):85
Details
based on systematic review of mostly observational studies limited by heterogeneity
⚬
systematic review of 1 randomized trial and 6 observational studies comparing addition of glycoprotein
IIb/IIIa inhibitor therapy to standard care vs. standard care alone in 1,216 patients with cardiogenic
shock complicating acute myocardial infarction
⚬
glycoprotein IIb/IIIa inhibitors included abciximab and eptifibatide
–
follow-up ranged from 30 days to 2.5 years
–
glycoprotein IIb/IIIa inhibitor therapy associated with
⚬
reduced 30-day mortality (odds ratio [OR] 0.55, 95% CI 0.35-0.85) in analysis of 6 studies with 1,037
patients, results limited by significant heterogeneity
–
reduced 1-year mortality (OR 0.51, 95% CI 0.32-0.82) in analysis of 3 studies with 850 patients, results
limited by significant heterogeneity
–
increased successful revascularization (OR 2.05, 95% CI 1.37-3.05) in analysis of 5 studies with 960
patients
–
no significant difference in major bleeding in analysis of 4 studies with 828 patients
⚬
Reference - J Intensive Care 2020 Nov 11;8(1):85
⚬
emergency revascularization with either percutaneous coronary intervention (PCI) or coronary artery
bypass graft (CABG) is recommended in suitable patients with cardiogenic shock due to pump failure after
ST-elevation myocardial infarction (STEMI) irrespective of time from myocardial infarction onset (ACCF/AHA
Class I, Level B) 2
●
immediate coronary angiography is recommended (≤ 2 hours after hospital admission) with intent to
perform coronary revascularization in patients with cardiogenic shock complicating acute coronary
syndrome (ESC Class I, Level C) (Eur Heart J 2016 Jul 14;37(27):2129 )
●
AHA supports guidelines recommending early invasive strategy with appropriate revascularization for all
suitable patients with suspected ACS-associated cardiogenic shock, including patients with uncertain
neurological status or patients who have received prior fibrinolytic therapy, regardless of time delay from
myocardial infarction onset 1
●
●
STUDY SUMMARY
early revascularization may improve survival in patients with acute myocardial infarction and
cardiogenic shock, benefit may be limited to patients < 75 years old DynaMed Level 2
RANDOMIZED TRIAL: N Engl J Med 1999 Aug 26;341(9):625 | Full Text

Details
based on randomized trial with baseline differences
⚬
302 patients with acute myocardial infarction and shock due predominantly to left ventricular
dysfunction randomized to early revascularization vs. initial medical stabilization with delayed
revascularization after 54 hours if indicated
⚬
early revascularization consisted of angioplasty or bypass surgery within 6 hours, and intra-aortic
balloon counterpulsation recommended
–
initial medical stabilization included intensive medical therapy, intra-aortic balloon counterpulsation,
and thrombolytic therapy recommended
–
previous bypass surgery in 2% with early intervention vs. 10% with initial medical stabilization (p = 0.003)
⚬
comparing early revascularization vs. initial medical stabilization
⚬
overall 30-day mortality 46.7% vs. 56% (not significant)
–
overall 6-month mortality 50.3% vs. 63.1% (p = 0.027, NNT 8)
–
in patients < 75 years old
–
30-day mortality 41.4% vs. 56.8% (p = 0.02, NNT 7)
●
6-month mortality 44.9% vs. 65% (p = 0.002, NNT 5)
●
in patients > 75 years old
–
30-day mortality 75% vs. 53.1% (not significant)
●
6-month mortality 79.2% vs. 56.3% (p = 0.09)
●
Reference - SHOCK trial (N Engl J Med 1999 Aug 26;341(9):625 full-text ), editorial can be found in N
Engl J Med 1999 Aug 26;341(9):687 , commentary can be found in N Engl J Med 1999 Dec
30;341(27):2095
⚬
consistent survival benefit at 1 year
⚬
based on follow-up of SHOCK trial
–
1-year survival 46.7% with early revascularization vs. 33.6% with initial medical stabilization (p < 0.03,
NNT 8)
–
benefit only found for subgroup < 75 years old
–
Reference - JAMA 2001 Jan 10;285(2):190
–
consistent survival benefit at 3 and 6 years
⚬
based on follow-up of SHOCK trial
–
similar survival benefit after 1 year and 3 years
–
comparing early revascularization vs. initial medical stabilization at 6 years
–
overall survival 32.8% vs. 19.6% (hazard ratio 0.74, 95% CI 0.57-0.97)
●
survival among 143 hospital survivors 62.4% vs. 44.4% (p = 0.029, NNT 6)
●
Reference - SHOCK trial (JAMA 2006 Jun 7;295(21):2511 full-text ), commentary can be found in
ACP J Club 2006 Nov-Dec;145(3):59
–
●
STUDY SUMMARY
early angiography (and revascularization when appropriate) after thrombolytic therapy associated with
reduced mortality in patients with acute myocardial infarction and cardiogenic shock DynaMed Level 2
RANDOMIZED TRIAL: Circulation 1997 Jul 1;96(1):122 | Full Text
Details

Primary percutaneous coronary intervention (PCI) for cardiogenic shock
based on cohort analysis of data from randomized trial study
⚬
2,200 patients from GUSTO 1 trial with acute myocardial infarction complicated by cardiogenic shock
were analyzed
⚬
406 patients had early aggressive management with angiography within 24 hours, of whom 63% had
subsequent revascularization with coronary artery bypass graft (CABG) or percutaneous transluminal
coronary angioplasty (PTCA) if indicated
⚬
angiography group had younger age, less prior infarction, and shorter time to thrombolytic therapy
compared to control group
⚬
comparing angiography/revascularization vs. medical management
⚬
30-day mortality 38% vs. 62% (p < 0.001)
–
1-year mortality 44% vs. 66% (p = 0.001)
–
no significant difference in mortality rates comparing CABG vs. PTCA
⚬
Reference - (Circulation 1997 Jul 1;96(1):122 full-text )
⚬
●
STUDY SUMMARY
use of percutaneous coronary intervention and coronary artery bypass graft surgery associated with
improved survival in patients with ST-elevation myocardial infarction and cardiogenic shock
DynaMed Level 2
COHORT STUDY: JAMA 2005 Jul 27;294(4):448
Details
⚬
25,311 patients with ST-elevation myocardial infarction and cardiogenic shock from 1995 to 2004 at 775
United States hospitals evaluated
⚬
comparing year 1995 vs. 2004
⚬
rate of primary percutaneous coronary intervention (PCI) 27.4% vs. 54.4% (p < 0.001)
–
overall CABG surgery 11.5% vs. 8.8% (not significant)
–
overall in-hospital cardiogenic shock mortality 60.3% vs. 47.9% (p < 0.001)
–
decreased risk of death during hospitalization associated with use of
⚬
PCI (adjusted odds ratio [OR] 0.46, 95% CI 0.4-0.53)
–
CABG surgery (adjusted OR 0.34, 95% CI 0.25-0.47)
–
Reference - JAMA 2005 Jul 27;294(4):448
⚬
see Revascularization for STEMI, Revascularization for acute coronary syndrome, and Revascularization for
coronary artery disease (CAD) for more information
●
American Heart Association (AHA) suggestions for PCI in patients with acute coronary syndromes (ACS) and
cardiogenic shock 1
●
revascularization of both culprit lesion and hemodynamically significant nonculprit stenosis is
reasonable
⚬
preferential use of radial arterial access for angiography and PCI is supported when feasible
⚬
antiplatelet and anticoagulation therapy in patients undergoing PCI
⚬

continuation of dual antiplatelet therapy without interruption after PCI suggested in all patients with
cardiogenic shock without serious bleeding complications
–
if oral agents cannot be given or any concerns for absorption, use of IV glycoprotein IIb/IIa inhibitor
or IV P2Y12 inhibitor cangrelor can be considered
–
optimal anticoagulation unknown, but for patients requiring continued anticoagulation after PCI,
preferential use of unfractionated heparin suggested due to high prevalence of acute kidney injury
and acute liver injury in patients with cardiogenic shock
–
culprit vessel only vs. multivessel PCI
●
⚬
STUDY SUMMARY
culprit-vessel-only PCI may reduce 30-day mortality compared to multivessel PCI in patients with
multivessel disease and acute myocardial infarction complicated by cardiogenic shock
DynaMed Level 2
RANDOMIZED TRIAL: N Engl J Med 2017 Dec 21;377(25):2419 | Full Text
Details
based on randomized trial with high crossover rate
–
706 patients (median age 70 years, 76% men) with acute myocardial infarction complicated by
cardiogenic shock, multivessel coronary artery disease (≥ 2 major vessels with > 70% stenosis) with
identifiable culprit lesion were randomized to 1 of 2 PCI strategies
–
PCI of culprit vessel only with staged revascularization of nonculprit vessels
●
immediate multivessel PCI
●
cardiogenic shock defined as all of
–
systolic blood pressure < 90 mm Hg for > 30 minutes or use of catecholamines to maintain systolic
blood pressure < 90 mm Hg
●
clinical signs of pulmonary congestion
●
signs of impaired organ perfusion (≥ 1 of altered mental status, cold and clammy skin and limbs,
oliguria with urine output < 30 mL/hour, or arterial lactate > 2 mmol/L)
●
primary endpoint was composite of death or severe renal failure leading to renal-replacement
therapy ≤ 30 days after randomization
–
97% received intervention and were included in analyses
–
12.5% from culprit-vessel-only group and 9.4% from multivessel group crossed over to other
intervention
–
comparing culprit-vessel-only PCI vs. multivessel PCI at 30 days
–
death in 43.3% vs. 51.6% (p = 0.03, NNT 12)
●
renal-replacement therapy in 11.6% vs. 16.4% (p = 0.07)
●
primary endpoint in 45.9% vs. 55.4% (p = 0.01, NNT 11)
●
recurrent myocardial infarction in 1.2% vs. 0.9% (not significant)
●
rehospitalization for congestive heart failure 0.3% vs. 0.3% (not significant)
●
stroke in 3.5% vs. 2.9% (not significant)
●
bleeding (BARC type 2, 3, or 5) in 16.6% vs. 22% (p = 0.07)
●
no significant difference in time to hemodynamic stabilization, use of catecholamine therapy, ICU
stay, or use of mechanical ventilation between groups
–

Reference - CULPRIT-SHOCK trial (N Engl J Med 2017 Dec 21;377(25):2419 full-text ), editorial can
be found in N Engl J Med 2017 Dec 21;377(25):2486
–
culprit-vessel-only PCI may not reduce mortality or risk of renal replacement therapy, and
may increase risk of repeat vascularization and rehospitalization for heart failure compared to
multivessel PCI at 1 year in patients with multivessel disease and acute myocardial infarction
complicated by cardiogenic shock
DynaMed Level 2
–
based on follow-up of CULPRIT-SHOCK trial with confidence intervals that cannot exclude
differences that may be clinically important for mortality and risk of renal replacement therapy
●
97% were included in 1-year follow-up
●
comparing culprit-vessel-only PCI vs. multivessel PCI at 1 year
●
death in 50% vs. 56.9% (relative risk [RR] 0.88, 95% CI 0.76-1.01), not significant, but CI cannot
exclude differences that may be clinically important
⚬
renal-replacement therapy in 11.6% vs. 16.4% (RR 0.71, 95% CI 0.49-1.03), not significant, but
confidence interval cannot exclude differences that may be clinically important
⚬
death or renal replacement therapy in 52% vs. 59.5% (RR 0.87, 95% CI 0.76-0.99, NNT 14)
⚬
recurrent myocardial infarction in 1.7% vs. 2.1% (RR 0.85, 95% CI 0.29-2.5), not significant, but
confidence interval includes possibility of benefit or harm
⚬
repeat revascularization in 32.3% vs. 9.4% (p < 0.05, NNH 4)
⚬
rehospitalization for heart failure in 5.2% vs. 1.2% (p < 0.05, NNH 25)
⚬
stroke in 4.4% vs. 4.1% (not significant)
⚬
bleeding (BARC type 2, 3, or 5) in 18.9% vs. 23.2% (not significant)
⚬
Reference - N Engl J Med 2018 Aug 25 early online full-text
●
⚬
STUDY SUMMARY
culprit-artery-only PCI associated with reduced mortality at 30 days but not 6 months compared to
multivessel PCI in patients with multivessel coronary artery disease having primary PCI for acute
myocardial infarction complicated by cardiogenic shock DynaMed Level 2
SYSTEMATIC REVIEW: Am J Cardiol 2017 May 15;119(10):1525
Details
based on systematic review of observational studies
–
systematic review of 10 observational studies comparing multiple vessels vs. culprit-artery-only PCI
vs. multiple vessel PCI in 6,068 patients with multivessel disease having primary PCI for acute
myocardial infarction complicated by cardiogenic shock
–
multivessel coronary artery disease defined as > 1 lesion with ≥ 50% stenosis by visual
examination in vessels other than culprit artery
●
80% had culprit-artery-only primary PCI
●
multivessel revascularization associated with increased in-hospital or 30-day mortality in analysis of 7
studies with 5,656 patients
–
odds ratio 1.41 (95% CI 1.15-1.71)
●
NNH 8-34 with death in 28% of culprit-artery-only group
●

no significant difference in mortality at ≥ 6 months in analysis of 7 studies with 1,910 patients, results
limited by statistical heterogeneity
–
Reference - Am J Cardiol 2017 May 15;119(10):1525
–
⚬
STUDY SUMMARY
multivessel PCI associated with reduced all-cause-mortality at 1 year compared to infarct-related
artery-only PCI in patients with STEMI multivessel disease with cardiogenic shock DynaMed Level 2
COHORT STUDY: J Am Coll Cardiol 2018 Feb 27;71(8):844
Details
–
659 patients (mean age 67 years) who had PCI for STEMI multivessel disease with cardiogenic shock
were followed for 1 year
–
39% had multivessel PCI
●
61% had infarct-related artery-only PCI
●
comparing multivessel PCI vs. infarct-related artery-only PCI at 1 year
–
all-cause mortality 21.3% vs. 31.7% (adjusted hazard ratio [HR] 0.52, 95% CI 0.38-0.73)
●
cardiac mortality 17.4% vs. 27.5% (adjusted HR 0.53, 95% CI 0.37-0.77)
●
repeat vascularization for non-infarct-related artery in 6.7% vs. 8.2% (adjusted HR 0.33, 95% CI
0.14-0.78)
●
consistent results in propensity-score matched analysis
–
Reference - J Am Coll Cardiol 2018 Feb 27;71(8):844 , editorial can be found in J Am Coll Cardiol
2018 Feb 27;71(8):857
–
●
STUDY SUMMARY
PCI with drug-eluting stent may have lower 1-year risk of death or reinfarction than PCI with bare-
metal stent in patients with acute myocardial infarction complicated by cardiogenic shock
DynaMed Level 2
RANDOMIZED TRIAL: Heart 2017 Aug;103(15):1177
Details
based on cohort analysis of data from randomized trial
⚬
652 patients with acute myocardial infarction complicated by cardiogenic shock from IABP-SHOCK II trial
who had PCI with drug-eluting stent (DES, 42%) or bare metal stent (BMS, 58%) were assessed
⚬
primary outcome was composite death and repeat acute myocardial infarction within 1 year
⚬
stenting groups had significant baseline differences in age, sex, rates of dyslipidemia, atrial fibrillation,
and anterior acute myocardial infarction
⚬
in unadjusted analyses, DES associated with reduced risk of
⚬
primary outcome (hazard ratio [HR] 0.64, 95% CI 0.51-0.79)
–
death over 1 year (HR 0.63, 95% CI 0.51-0.8)
–
after adjustment for baseline differences, no significant difference in primary outcome comparing DES
vs. BMS (adjusted hazard ratio 0.83, 95% CI 0.64-1.06), not significant, but CI includes both clinically
important and unimportant differences
⚬
Reference - Heart 2017 Aug;103(15):1177
⚬

Mechanical circulatory support
Recommendations
see also Percutaneous coronary intervention (PCI) indications and efficacy, Antiplatelet and anticoagulant
drugs for acute coronary syndromes, Antiplatelet and anticoagulant drugs for ST-elevation myocardial
infarction (STEMI) and Antiplatelet and anticoagulant drugs for elective percutaneous coronary intervention
(PCI)
●
short-term mechanical circulatory support may be considered in refractory cardiogenic shock, depending
on age, comorbidities, and neurological function (ESC Class IIb, Level C) (Eur Heart J 2016 Jul 14;37(27):2129
)
●
consider use of nondurable mechanical circulatory support devices, including percutaneous and
extracorporeal ventricular assist devices, as a bridge to recovery or a bridge to decision in patients with left
ventricular ejection fraction < 25% and acute, profound hemodynamic compromise (ACCF/AHA Class IIa,
Level B) (Reference - Circulation 2013 Oct 15;128(16):e240 )
●
consider alternative left ventricular assist devices (LVADs) for circulatory support (other than IABP) in
patients with refractory cardiogenic shock (ACCF/AHA Class IIb, Level C) 2
●
intra-aortic balloon pump (IABP) not routinely recommended for patients with cardiogenic shock (ESC Class
III, Level B) (Eur Heart J 2016 Jul 14;37(27):2129 )
●
consider IABP counterpulsation for patients with cardiogenic shock after STEMI who do not quickly stabilize
with pharmacological therapy (ACCF/AHA Class IIa, Level B) 2
●
American Heart Association (AHA) suggestions for mechanical circulatory support in patients with
cardiogenic shock 1
●
patients with persistent cardiogenic shock with or without end-organ perfusion should be evaluated for
mechanical circulatory support candidacy
⚬
temporary mechanical circulatory support devices can be implanted in patients who are not expected to
recover as early as possible as bridge to recovery, bridge to bridge, bridge to transplantation, or bridge
to decision in appropriately selected patients with cardiogenic shock
⚬
device selection
⚬
temporary devices
–
temporary device over durable device as first-line device should be considered when immediate
stabilization needed to allow recovery of heart and other organ systems if
●
surgical risk prohibitive but may be attenuated with stabilization
⚬
support required to facilitate definitive procedure or intervention (such as revascularization or
arrhythmia ablation)
⚬
time required to allow evaluation for cardiac transplantation or durable device
⚬
IABP can be considered in patients with
●
acute mitral regurgitation or ventricular septal defect
⚬
profound cardiogenic shock when other devices not available, contraindicated, or cannot be
placed
⚬
veno-arterial extracorporeal membrane oxygenation (ECMO) may be preferred temporary
mechanical circulatory support device if poor oxygenation not expected to rapidly improve with
alternate short-term device or during cardiopulmonary resuscitation
●

Intra-aortic balloon pump
durable devices
–
can be implanted as bridge to recovery, bridge to bridge, bridge to transplantation, or destination
therapy in appropriately selected patients
●
can be considered as primary devices in patients not likely to recover without long-term
mechanical circulatory support, have capacity for meaningful recovery, and do not have
irreversible end-organ dysfunction, systemic infections, or relative contraindications to long-term
device implantation
●
see also Mechanical circulatory support for heart failure
●
intra-aortic balloon pump (IABP) counterpulsation is most widely available mechanical circulatory support
method; cardiogenic shock due to acute myocardial infarction most common indication 1 , 3
●
IABP not routinely recommended for patients with cardiogenic shock (ESC Class III, Level B) (Eur Heart J
2016 Jul 14;37(27):2129 )
●
consider IABP counterpulsation for patients with cardiogenic shock after STEMI who do not quickly stabilize
with pharmacological therapy (ACCF/AHA Class IIa, Level B) 2
●
American Heart Association (AHA) suggestions for IABP in patients with cardiogenic shock 1
●
IABP can be considered in patients with
⚬
acute mitral regurgitation or ventricular septal defect
–
profound cardiogenic shock when other devices not available, contraindicated, or cannot be placed
–
the need for IABP should be assessed on an individual basis 2
●
IABP may provide temporary circulatory support while awaiting surgical correction of mechanical
complications (for example, ventricle septal rupture or mitral regurgitation) after ST-elevation myocardial
infarction 2
●
IABP general information
Image 2 of 3
Intra-aortic balloon pump
●
IABP contraindications include
⚬
aortic insufficiency
–
aortic dissection
–
chronic end-stage heart failure without anticipated recovery
–
IABP benefits include
⚬
provides diastolic augmentation of aortic pressure and left ventricular afterload reduction
–
increases coronary perfusion (potentially helpful if increased ventricular diastolic pressure)
–
IABP limitations include
⚬
limited to short duration (days) use
–
may be insufficient if severe cardiac failure
–
Reference - Emerg Med Clin North Am 2014 Nov;32(4):851
⚬

Catheter inserted in aorta and pump inflated between heart beats to increase blood flow through
coronary arteries.
Image courtesy of Bob L. Shepherd / Science Photo Library
EVIDENCE SYNOPSIS
In patients with acute myocardial infarction complicated by cardiogenic shock, intra-aortic balloon pump
counterpulsation (IABP) may not reduce mortality and may be associated with a higher rate of stroke and
bleeding.
⚬
STUDY SUMMARY
IABP may not reduce mortality in adults with acute myocardial infarction complicated by
cardiogenic shock DynaMed Level 2
COCHRANE REVIEW: Cochrane Database Syst Rev 2015 Mar 27;(3):CD007398
Details
based on Cochrane review with wide confidence intervals
–
systematic review of 7 randomized trials (including IABP-SHOCK II trial) comparing IABP vs. standard
treatment without IABP or with other percutaneous left ventricular assist device in 790 adults with
myocardial infarction complicated by cardiogenic shock
–
results for mortality comparing IABP vs. standard treatment without IABP limited by confidence
intervals that cannot exclude clinically meaningful differences
–
most mortality outcomes were evaluated in individual patient data analyses
–
comparing IABP to standard treatment without IABP, no significant differences, but CIs include
possibility of benefit or harm
–
30-day mortality (odds ratio [OR] 0.95, 95% CI 0.69-1.29) in analysis of 3 trials with 660 adults
●
in-hospital mortality (OR 0.86, 95% CI 0.63-1.18) in analysis of 3 trials with 680 adults
●
6-month mortality (OR 0.99, 95% CI 0.72-1.34) in analysis of 3 trials with 652 adults
●
1-year mortality (OR 1.06, 95% CI 0.77-1.47) in analysis of 2 trials with 627 adults
●
limited data to compare IABP to other percutaneous left ventricular assist devices
–
Reference - Cochrane Database Syst Rev 2015 Mar 27;(3):CD007398
–
IABP may not reduce 30-day mortality or reinfarction rate in patients with acute myocardial
infarction complicated by cardiogenic shock
DynaMed Level 2
–
based on randomized trial with wide confidence intervals
●
600 patients (median age 70 years) with acute myocardial infarction complicated by cardiogenic
shock randomized to IABP vs. no IABP
●
cardiogenic shock criteria included all of the following
●

Cardiogenic Shock.pdf

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