acute decompensated heart failure - EMCREG

ACUTE DECOMPENSATED HEART FAILURE:
NOVEL APPROACHES TO CLASSIFICATION AND TREATMENT
J. Douglas Kirk MD, FACEP
Associate Professor of Emergency Medicine and Vice Chair of Clinical Operations,
Department of Emergency Medicine, University of California, Davis, Medical Center
Sacramento, California
OBJECTIVES:
1. Discuss the new and complex pathophysiology of ADHF which consists of multiple types of
heart failure patients with various forms of acute decompensation.
2. Discuss the categorization of ADHF patient types by clinical profile and hemodynamic
status and match them to specific therapies.
INTRODUCTION
As the population ages, the prevalence of
heart failure increases, as does the number
of patients requiring hospitalization for
acute decompensation.1 Between 1992 and
2001, emergency department (ED) visits
for acute decompensated heart failure
(ADHF) increased by almost 20% and
accounted for 3% (10.8 million) of the more
than 360 million ED visits made during the
decade.2 Historically, these exacerbations
were considered clinical manifestations
of the downward spiral of congestive
heart failure. These events depicted a
pathophysiologic model characterized
by systolic dysfunction and low cardiac
output which resulted in volume overload
and pulmonary congestion. The root
cause was felt to be worsening underlying
cardiac function, possibly due to dietary
indiscretion or medication noncompliance
or just progression of disease.3,4 As a result,
intravenous diuretics were used to rapidly
alleviate pulmonary congestion without
clinical trial data to support long-term
safety, efficacy, or beneficial outcome.
In much the same way, vasodilators and
inotropes eventually became elements of
usual care.
www.emcreg.org
Data from the ADHERE registry
have challenged this simple model of
ADHF and revealed a more complex
and varied pathophysiologic entityone that consists of multiple types
of heart failure patients with various
forms of acute decompensation.5 This
new pathophysiologic concept has
fostered changes in physicians’ views
of therapeutic options and targets.
Clinicians are now reconsidering how
intravenous diuretics, vasodilators, and
inotropes should be administered, which
ADHF patients should get them, and
the long-term morbidity and mortality
implications of their decisions.
Clinicians are now
reconsidering how
intravenous diuretics,
vasodilators, and
inotropes should be
administered, which
guidelines
about
the
Although
management of patients with heart failure
have been previously disseminated,
most pertain to chronic management.6
ADHF patient types have not been well
characterized or matched with specific
treatment strategies in prospective
randomized studies. Despite the recent
publication of new diagnosis and
treatment guidelines,7 there are a lack of
evidence and consensus-based treatment
ADHF patients should get
them, and the long-term
morbidity and mortality
implications of their
decisions.
33
ADVANCING THE STANDARD OF CARE:
Cardiovascular and Neurovascular Emergencies
features, a clinical profile
algorithms that address the therapeutic
needs of specific subsets of patients with
ADHF suggested by databases such as
ADHERE. It does appear however that
patient risk stratification8 and initiation
of aggressive treatment in the ED9 may
limit potentially irreversible myocardial
toxicity, especially in those with
moderate to severe ADHF. This article
will focus on therapeutic management,
with particular emphasis on identifying
ADHF patient types and matching
them to specific treatment strategies.
Management protocols and algorithms
are provided which can be implemented
in your institution.
is defined, identifying
MANAGEMENT ALGORITHMS
patients in whom
The algorithm depicted in Figure 1
provides guidance for the diagnostic
and prognostic evaluation of the
suspected ADHF patient, in addition
to recommendations for therapeutic
strategies and disposition decisions.10
Using typical historical, physical
examination, and diagnostic test
features, a clinical profile is defined,
identifying patients in whom pulmonary
congestion predominate the clinical
presentation versus those with more of
an element of hypoperfusion. Options
for initial management of imminent
respiratory failure and cardiogenic shock
are described. Patients are then further
divided based upon severity of illness
(low, moderate, or critical severity) with
recommendations for treatment and
disposition provided for each group.
Using typical historical,
physical examination,
and diagnostic test
pulmonary congestion
predominate the clinical
presentation versus
those with more of an
element of hypoperfusion.
A minority of patients (~20%) will
have mild exacerbations of ADHF (low
severity) and the mainstay of therapy
for them may be intravenous diuretics,
34
particularly if they have been noncompliant
with diet or medications. Topical or
sublingual nitrates may be warranted if
moderate hypertension (systolic blood
pressure 140-160 mmHg) is present or a
history of diastolic dysfunction exists.
Most ADHF visits are of moderate
severity (~70%) and typically require
a longer duration of therapy which
necessitates a hospital stay. More
aggressive therapy with loop diuretics
plus
intravenous
vasodilators
is
warranted, especially if significant
hypertension is present. Preliminary
data suggest these patients should be
aggressively treated with intravenous
vasodilators early in the ED course9 and
a substantial number may be appropriate
for observation unit management.11 The
ideal choice of a specific vasodilator
in these cases is contentious but both
nitroglycerin and nesiritide are effective
in symptomatic and hemodynamic
improvement, however, their safety
profiles remain controversial.12-14 Other
factors, such as the need for titration
with nitroglycerin which may require
admission to an intensive care unit, and
play a role in the choice of a specific
agent. Using the guidelines to estimate
severity from Figure 1, the majority of
patients classified as moderate risk and
those at low risk can all be managed in
an ED observation unit.
Patients who are critically ill (~10%),
with complications of respiratory failure and/or cardiogenic shock are not
surprisingly, the most difficult to manage.
They typically require advanced airway
support (endotracheal intubation or noninvasive ventilation) plus a complex
www.emcreg.org
ACUTE DECOMPENSATED HEART FAILURE:
NOVEL APPROACHES TO CLASSIFICATION AND TREATMENT
combination of pharmacological therapy (inotropes,
diuretics, vasodilators), the
choices of which depend
upon the patient’s hemodynamic status. These patients
are admitted to an intensive
care unit and frequently require pulmonary artery catheterization to guide therapy.
Figure 1. Algorithm for the early stabilization of acute decompensated heart failure
in the emergency department. ADHF, acute decompensated heart failure; BNP, Btype natriuretic peptide; BUN, blood urea nitrogen; CBC, complete blood count; Cr,
creatinine; CXR, chest radiograph; ECG, electrocardiogram; ETT, endotracheal tube;
ICU, intensive care unit; LVH, left ventricular hypertrophy; NIV, non-invasive ventilation;
O2SAT, oxygen saturation; prn, as needed; SBP, systolic blood pressure; SL, sublingual.
Adapted from Peacock WF, Allegra J, Ander D, et al. Management of acutely
decompensated heart failure in the emergency department. CHF 2003; 9(suppl 1):3-18
www.emcreg.org
Another algorithm with
more
patient
specific
treatment recommendations
for management of ADHF
in the ED was reported by
DiDomenico et al15 and is
described in Figure 2. The
timeline for key elements of
these guidelines is depicted
in Figure 3 and provides
clinicians with specific
clinical targets that should
be achieved during the ED
or observation unit stay. In
this strategy, treatment of
ADHF is generally based
on the presence or absence
of volume overload and an
assessment of the patient’s
cardiac output. On the left side
of Figure 2 [A, C, D, E, F],
treatment recommendations
are given for patients with
ADHF experiencing signs
and symptoms of volume
overload, manifested by
pulmonary congestion. One
of the limitations of this
algorithm is grouping all
patients with pulmonary
congestion
together,
regardless of the etiology.
35
ADVANCING THE STANDARD OF CARE:
Cardiovascular and Neurovascular Emergencies
Figure 2. Acute decompensated
heart failure treatment algorithm.
ADHF, acute decompensated heart
failure; AJR, abdominal jugular reflex;
BiPAP, bi-level positive airway pressure;
BNP, B-type natriuretic peptide; CI,
cardiac index; CPAP, continuous positive
airway pressure; DOE, dyspnea on
exertion; HJR, hepatojugular reflex;
JVD, jugular venous distention; PCWP,
pulmonary capillary wedge pressure;
PND, paroxysmal nocturnal dyspnea;
SBP, systolic blood pressure; SCr,
serum creatinine; SOB, shortness
of breath; SVR, systemic vascular
resistance. Adapted with permission from
DiDomenico RJ, Park HY, Southworth
MR, et al.. Guidelines for acute
decompensated heart failure treatment.
Ann Pharmacother. 2004;38:649-660.
Figure 3. Timeline for the management
Assess response to initial therapy
Add additional therapy as needed
Initiate IV ADHF therapy
Diuretic (mild-mod volume overload)
Diuretic + IV vasodilators (mod-sev volume overload)
Inotrope (if low CO state)
Reassess response to therapy
Add additional therapy as needed
Transfer out of ED or
Observation Unit
Determine patient disposition
Admit (ICU vs. observation unit vs. floor)
or discharge home
Establish ADHF
diagnosis
Initial ED
contact
0
2
4
6
8
12
24
of acute decompensated heart failure in
the emergency department/observation
unit. ADHF, acute decompensated
heart failure; CO, cardiac output; ED,
emergency department; ICU, intensive
care unit; mod-sev, moderate to
severe. Adapted with permission from
DiDomenico RJ, Park HY, Southworth
MR, et al. Guidelines for acute
decompensated heart failure treatment.
Ann Pharmacother. 2004;38:649-660.
Time (hours) from initial ED physician evaluation
36
www.emcreg.org
ACUTE DECOMPENSATED HEART FAILURE:
NOVEL APPROACHES TO CLASSIFICATION AND TREATMENT
There is no consideration of the patient with
severe hypertension and acute pulmonary edema,
occasionally referred to as “vascular failure”3 whose
primary therapy should be control of blood pressure
with intravenous vasodilators. Nonetheless, it is quite
helpful with general management principles.
The right side of the algorithm provides treatment
recommendations for patients with signs and
symptoms consistent with low cardiac output
[B]. Inotropic support is recommended, with
specific choice of therapy based upon the degree of
hypotension and whether or not a beta-blocker is being
used [G]. Patients may require vasopressor support
if symptomatic hypotension develops. Patients with
low cardiac output who fail to respond to inotropic
therapy should be evaluated for the presence of
very low cardiac output and may require additional
aggressive management [J]. Typically, these patients
require admission to an intensive care unit and may
require the placement of a pulmonary artery catheter
to more accurately assess their hemodynamic status.
Patients with very low cardiac output who have
sufficient systolic blood pressure (>90 mmHg) may
benefit from the addition of intravenous diuretic
therapy and/or intravenous vasodilators [F].
The major emphasis of this protocol is managing
volume overload which is further divided into mild and
moderate-severe groups. Patients with mild volume
overload [C] are treated with intravenous diuretic
therapy, typically loop diuretics [D]. Dosages for
patients previously taking diuretics are guided by the
total home daily dose, given as an intravenous bolus.
Therapy for patients not taking oral diuretics at home
is based upon renal function, and clinicians should
exercise caution with diuretic therapy in patients with
renal dysfunction to avoid further injury. Success
of diuretic therapy is driven by urine output goals,
and recommendations for repeat diuretic dosing are
described in the algorithm. Again, caution should be
exercised with extremely high doses of loop diuretics,
because in addition to prerenal azotemia, electrolyte
www.emcreg.org
abnormalities (hypokalemia/hypomagnesemia) are
common and should be recognized and treated quickly.
Standing orders for management of electrolyte
disturbances can be quite helpful.
The authors recognized that patients with more severe
volume overload are likely to have an inadequate
response to intravenous diuretic therapy alone. In
these patients the initial pharmacologic regimen
should be more aggressive and include both an
intravenous diuretic and vasodilator [F]. Nitroglycerin
or nesiritide should be used to produce a more rapid
response and more effectively relieve the signs and
symptoms of congestion in these patients. Again, no
specific recommendations are provided as to which
vasodilator should be used, but the suggested starting
dose of nitroglycerin (5-10 mcg/min) noted should
be considerably higher. A corresponding physician
order set was developed which can be modified
accordingly to accommodate institutional variations
in practice. These are a vital part of any management
algorithm and are typically necessary to standardize
the treatment of ADHF patients.
ADHF Patient Types
Other methods of categorizing ADHF patient types
have recently been described by a consensus panel
of heart failure experts comprised of cardiologists,
emergency physicians, hospitalists and pharmacists.16
These classifications are based more on hemodynamic
characteristics rather than clinical symptom profile or
severity of disease. While most EDs don’t have the
luxury of obtaining hemodynamic parameters such
as pulmonary capillary wedge pressure or cardiac
output via invasive means, they do have a reliable
and easily obtainable parameter—the patient’s blood
pressure. Patients can be classified into normotensive,
hypertensive, and hypotensive ADHF. The exact
pathophysiology, clinical characteristics, and
treatment options of each of these patient types has
yet to be fully elucidated but some recommendations
based upon expert consensus can be suggested.
37
ADVANCING THE STANDARD OF CARE:
Cardiovascular and Neurovascular Emergencies
Normotensive ADHF
While most EDs don’t
have the luxury of
obtaining hemodynamic
parameters such as
pulmonary capillary
wedge pressure or
cardiac output via
invasive means,
These patients are common and may
represent nearly half of the ADHF
population.5 Systolic blood pressure is
in the range of 90-140 mmHg. Clinical
characteristics include dyspnea and
peripheral edema, which are the usual
complaints and are often gradual in onset
(days/weeks). Rales and pulmonary
edema on chest radiograph may or may
not be present.3,5,7 Treatment of this group
is depicted in Figure 4 and is initiated
with an intravenous loop diuretic. The
patient’s renal function and response to
diuretics should be measured and the
blood pressure reassessed. If the patient’s
BUN is less than 43 mg/dL, creatinine
is less than 2.75 mg/dL, blood pressure
is normal, and urine output is adequate
(>1 liter in 4 hours), the patient is at
low risk for mortality.8 These patients
may be admitted to an observation unit
or in-hospital floor and re-assessed for
symptomatic improvement. However,
if the patient is resistant to diuretic
therapy and/or has poor renal function,
the addition of a vasodilator such as
nitroglycerin, nesiritide, or nitroprusside
is warranted. Vasodilators reduce
systemic vascular resistance and increase
cardiac output, which help
reduce
preload, afterload, and pulmonary
congestion.7 Because some vasodilators
require careful titration, admission to the
ICU may be appropriate, particularly in
patients with renal insufficiency or those
with inadequate urine output.7 If at any
point the patient becomes hypotensive,
the vasodilator should be discontinued.
Evidence of hypoperfusion may warrant
initiation of an intravenous inotrope.
they do have a reliable
and easily obtainable
parameter – the
patient’s blood
pressure. Patients
can be classified
into normotensive,
hypertensive, and
hypotensive ADHF.
Figure 4. Emergency Department Management Pathway for Normotensive Acute
Decompensated Heart Failure. *Nitroglycerin (NTG)/Nitroprusside (NTP) use may
require ICU admission regardless of medical status. ADHF, acute decompensated
heart failure; APE, acute pulmonary edema; ED, emergency department; ICU, intensive
care unit; IV, intravenous; NES, nesiritide; SBP, systolic blood pressure. Adapted with
permission from Kirk JD, Costanza MR. Managing Patients with Acute Decompensated
Heart Failure. Clinical Courier December 2006; 23(56).
38
www.emcreg.org
ACUTE DECOMPENSATED HEART FAILURE:
NOVEL APPROACHES TO CLASSIFICATION AND TREATMENT
Hypertensive ADHF
Occasionally referred to as vascular failure,
hypertensive ADHF may be the most common type
of ADHF patient. Data from the ADHERE registry
demonstrate that 50% of patients had a systolic BP
greater than 140 mmHg on presentation.5 Patients
with this type of ADHF are more often women, older,
and more likely to have diastolic dysfunction with
relatively preserved left ventricular function.3,7 Severe
dyspnea is the predominant complaint although signs
of end-organ hypoperfusion (altered mental status)
may be present. Acute “flash” pulmonary edema is the
hallmark of this syndrome and is usually evident on
examination (rales) and chest radiography (pulmonary
edema). Symptom onset is generally abrupt versus
the gradual onset seen in patients with normotensive
ADHF.3,5 However, response to therapy is typically
3
just as rapid, in patients who are aggressively treated.
Accordingly, the clinical target is blood pressure
control with early, aggressive vasodilation, more so
than diuresis. This is particularly true when pulmonary
congestion is related to fluid maldistribution, rather
than an increase in total fluid volume.3,7
Treatment ensues with the immediate use of a topical
or sublingual vasodilator, which is easily and rapidly
administered, followed by an intravenous diuretic
(Figure 5). This typically produces dramatic
improvement within minutes.17 An intravenous
vasodilator (nitroglycerin, nesiritide, or nitroprusside)
should then be added, and renal function, blood
pressure, and the response to therapy should be
assessed. If the patient fails to respond accordingly
or has other evidence of high risk (elevated BUN or
Figure 5. Emergency Department Management Pathway for Hypertensive Acute Decompensated Heart Failure.
*Based on clinical experience, if patients have marked improvement, an IV vasodilator may not be needed.
†Nitroglycerin (NTG)/Nitroprusside (NTP) use may require ICU admission regardless of medical status.
ADHF, acute decompensated heart failure; APE, acute pulmonary edema; ED, emergency department; ICU,
intensive care unit; IV, intravenous; NES, nesiritide; SBP, systolic blood pressure. Adapted with permission from Kirk
JD, Costanza MR. Managing Patients with Acute Decompensated Heart Failure. Clinical Courier December 2006;
23(56).
www.emcreg.org
39
ADVANCING THE STANDARD OF CARE:
Cardiovascular and Neurovascular Emergencies
creatinine, hypotension)8, admission to the intensive
care unit is recommended. If the patient responds
adequately to initial therapy, admission to an
observation unit or in-hospital floor is appropriate,
unless ongoing titration of the vasodilator necessitates
intensive care unit admission.
hospital mortality rate, approaching 30%.18 Admission
to the intensive care unit is warranted and many of
these patients require pulmonary artery catheterization
to guide therapy. Typical hemodynamic parameters
include elevated pulmonary capillary wedge pressure,
decreased cardiac index and left ventricular ejection
fraction, and advanced Killip class of III or IV.7
Hypotensive ADHF
Patients typically present with evidence of end-organ
hypoperfusion (altered mental status, cool extremities,
poor urine output) in addition to pulmonary
congestion.3,7 Patients with a systolic blood pressure
<90 mmHg usually have low cardiac output, but
can follow a continuum from cardiogenic shock to
reasonably well compensated heart failure.7 Although
this is the smallest subgroup of patients with ADHF,
accounting for only 3% of the ADHERE population,5
it is associated with a disproportionately high in-
This group is the most challenging to manage, given
the myriad clinical profiles, hemodynamic parameters,
and complications of therapeutic agents (hypotension,
myocardial injury, mortality risk). 12-14,19-21 Guidelines
for therapy are likewise difficult to develop given
these limitations (Figure 6). Inotropic therapy,
which has been associated with poorer outcomes,19,20
does increase cardiac output and elevate blood
pressure,4,7,22 and therefore may be appropriate in this
critically ill population. If there are ongoing signs
Figure 6. Emergency Department Management Pathway for Hypotensive Acute Decompensated Heart Failure.
*If SBP ≥90 and no improvement; ADHF, acute decompensated heart failure; ED, emergency department; IV,
intravenous; ICU, intensive care unit; NES, nesiritide; NTG, nitroglycerine; NTP, nitroprusside; SBP, systolic blood
pressure. Adapted with permission from Adams KF, Kirk JD, Costanza MR. Managing Patients with Acute
Decompensated Heart Failure. Kirk JD, Costanza MR. Managing Patients with Acute Decompensated Heart
Failure. Clinical Courier December 2006; 23(56).
40
www.emcreg.org
ACUTE DECOMPENSATED HEART FAILURE:
NOVEL APPROACHES TO CLASSIFICATION AND TREATMENT
of congestion, the addition of diuretic therapy may
also be reasonable but is frequently curtailed due to
hypotension. In some cases, vasodilator therapy may
be appropriate if blood pressure increases and there
are ongoing hemodynamic derangements such as
high systemic vascular resistance, elevated pulmonary
capillary wedge pressure, low cardiac index, or poor
urine output.7,15
6.
Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for
the evaluation and management of chronic heart failure in the
adult: executive summary. A report of the American College of
Cardiology/American Heart Association Task Force on Practice
Guidelines (Committee to revise the 1995 Guidelines for the
Evaluation and Management of Heart Failure). J Am Coll Cardiol.
2001;38:2101-2113.
7.
Nieminen MS, Bohm M, Cowie MR, et al. Executive summary
of the Guidelines on the Diagnosis and Treatment of Acute Heart
Failure: The Task Force on Acute Heart Failure of the European
Society of Cardiology. Eur Heart J. 2005;26:384-416.
8.
Fonarow GC, Adams KF Jr, Abraham WT, et al. for the
ADHERE Scientific Advisory Committee, Study Group, and
Investigators. Risk stratification for in-hospital mortality in acutely
decompensated heart failure: classification and regression tree
analysis. JAMA. 2005;293:572-580.
9.
Peacock WF, Emerman CL, Costanzo MR, et al. Early initiation
of intravenous vasoactive therapy improves heart failure outcomes:
an analysis from the ADHERE registry database. Ann Emerg Med
2003; 42(4):S26.
10.
Peacock WF, Allegra J, Ander D, et al. Management of acutely
decompensated heart failure in the emergency department. CHF.
2003; 9(suppl 1): 3-18.
11.
Peacock WF IV, Holland R, Gyarmathy R, et al. Observation
unit treatment of heart failure with nesiritide: results from the
PROACTION trial. J Emerg Med. 2005;29:243-252.
12.
Sackner-Bernstein JD, Kowalski M, Fox M, et al. Short-term risk
of death after treatment with nesiritide for decompensated heart
failure: a pooled analysis of randomized controlled trials. JAMA.
2005;293:1900-1905.
13.
Abraham WT. Nesiritide and mortality risk: individual and pooled
analyses of randomized controlled trials. Rev Cardiovasc Med.
2005;6:2.
14.
Abraham WT, Adams KF, Fonarow GC, et al. In-hospital mortality
in patients with acute decompensated heart failure requiring
intravenous vasoactive medications: an analysis from the ADHERE
registry. J Am Coll Cardiol. 2005; 46:57– 64.
15.
DiDomenico RJ, Park HY, Southworth MR, et al. Guidelines for
acute decompensated heart failure treatment. Ann Pharmacother.
2004;38:649-660.
16.
Kirk JD, Costanza MR. Managing Patients with Acute
Decompensated Heart Failure. Clinical Courier December 2006;
23(56).
SUMMARY
Recent data have challenged the historical model
of ADHF and revealed a more complex and varied
pathophysiologic entity-one that consists of multiple
types of heart failure patients with various forms of
acute decompensation. Clinicians and investigators
are now reconsidering their therapeutic options. Which
drugs should be administered to what type of patient,
and most importantly, what are the safety implications
are two considerations. Although there is a paucity
of evidence-based treatment strategies for patients
with ADHF, management protocols and algorithms
categorized by clinical profile and hemodynamic
status are helpful in identifying ADHF patient types
and matching them to specific therapies. Utilizing
such strategies should improve the consistency of
emergent care and hopefully patient outcome.
REFERENCES
1.
Heart disease and stroke statistics—2003 update. Dallas: American
Heart Association, 2002.
2.
Hugli O, Braun JE, Kim S, Pelletier AJ, Camargo CA Jr. United
States emergency department visits for acute decompensated heart
failure, 1992 to 2001. Am J Cardiol. 2005;96:1537-1542.
17.
Bussmann W, Schupp D. Effect of sublingual nitroglycerin in
emergency treatment of severe pulmonary edema. Am J Cardiol
1978; 41:931-936.
3.
Gheorghiade M, De Luca L, Fonarow GC, et al. Pathophysiologic
targets in the early phase of acute heart failure syndromes. Am J
Cardiol. 2005;96(suppl 6A):11G-17G.
18.
4.
Cotter G, Moshkovitz Y, Milovanov O, et al. Acute heart failure: a
novel approach to its pathogenesis and treatment. Eur J Heart Fail.
2002;4:227-234.
Harjola VP, Ylikangas S, Siirila-Waris K. Type of acute heart
failure significantly affects intensive care stay and in-hospital
mortality. Presented at: Annual Scientific Sessions of the European
Society of Cardiology; September 3-7, 2005; Stockholm, Sweden.
Abstract P4076.
19.
5.
Adams KF Jr, Fonarow GC, Emerman CL, et al. Characteristics
and outcomes of patients hospitalized for heart failure in the
United States: rationale, design, and preliminary observations from
the first 100,000 cases in the Acute Decompensated Heart Failure
National Registry (ADHERE). Am Heart J. 2005;149:209-216.
Cuffe MS, Califf RM, Adams KF Jr, et al. Short-term intravenous
milrinone for acute exacerbation of chronic heart failure: a
randomized controlled trial. JAMA. 2002;287:1541-1547.
www.emcreg.org
41
ADVANCING THE STANDARD OF CARE:
Cardiovascular and Neurovascular Emergencies
20.
O’Connor CM, Gattis WA, Uretsky BF, et al. Continuous
intravenous dobutamine is associated with an increased risk of
death in patients with advanced heart failure: insights from the
Flolan International Randomized Survival Trial (FIRST). Am Heart
J. 1999;138:78-86.
21.
Gottlieb SS, Brater DC, Thomas I, et al. BG9719 (CVT-124), an
A1 adenosine receptor antagonist, protects against the decline in
renal function observed with diuretic therapy. Circulation. 2002
Mar 19;105(11):1348-53.
22.
Felker GM, O'Connor CM. Inotropic therapy for heart failure: an
evidence-based approach. Am Heart J. 2001;142:393-401.
Copyright EMCREG-International, 2007
42
www.emcreg.org