Transcript Emergency Management of Acute Decompensated Heart Failure

Emergency Management of
Acute Decompensated Heart
Failure
Hani Ramadan
PharmD Candidate
4/19/2007
Beaumont Hospital Royal Oak, MI
CC: Weakness and Shortness of Breath.
4/06/07 (ER)
HPI:
BH is a 95 year-old female with a known history of
CHF, HTN, anxiety. Patient presents with altered
mentation along with swelling in the legs and arms.
PMH:
HTN, CVA, chronic atrial fibrillation, anxiety.
Allergies: PCN (rash)
SH: Lives at home, has a 24 hour caregiver.
Medications at Home: Atenolol 25 mg qd, pantoprazole 40mg qd,
ASA 81 mg qd, lorazepam 1 mg qhs, clopidogrel 75 mg qd,
acetaminophen 500 mg qid prn, ciprofloxacin 500mg bid.
Physical assessment: 3+ edema from waist down.
VS: H=4’11” W=50.0kg T= 36oC, P= 96, RR=18,BP=114/86
HEENT: conjunctivae and lids have no pallor and no
jaundice. Pupils equal, round and reactive to light and
accomodation. Ears, nose and throat normal.
Lungs: bilateral basilar crackles.
CV: heart rhythm irregular.
Abd: soft. no n/v/d, no hepatosplenomegaly.
Neuro: lethargic. GCS:14.
Labs:
Na 139
WBC 10.5 Scr 1.8 BNP 1343
K 4.1
HGB 9.6 BUN 30 AG 9
Cl 108
HCT 48
Plt 296 CK 171 MB 6.4
X-Ray: small left effusion, atelectasis, no pneumothorax.
EKG: atrial fibrillation w ventricular response, with T
wave inversions.
Physician’s assessment/plan:
1. Congestive Heart Failure: Patient will receive IV
diuretics and monitor for electrolytes.
2. UTI: Continue Cipro until the completion of the course.
3. Abnormal cardiac enzymes: Represent myocardial
injury. Cardiology consulted.
4. Acute Renal insufficiency: Monitor creatinine, diuresis
and BP.
Epidemiology
~ 5 million
Dx in
US
~550 000 new
cases/yr
~ 1 million
hospitalizations/ yr
Mortality is approx. 50% at 5 years
Economic Costs approx. 29.6 billion $
(direct and indirect costs)
Heart disease and stroke statistics- 2006 Update, American Heart Association
Objectives
 Review the pathophysiology of ADHF.
 Describe the clinical presentation of ADHF.
 Apply effective therapeutic strategies using consensus
guidelines from the (HFSA) and the (ESC).
 Examine the clinical evidence of milrinone and
niseritide in the treatment of ADHF.
 Evaluate the appropriateness of treatment.
ADHF
 Rapid onset of signs and symptoms secondary to abnormal cardiac
function due to systolic, diastolic dysfunction, abnormalities in
cardiac rhythm or to pre-load and after-load mismatch.
 De novo or acute decompensation of CHF.
 ~50% of patients have a systolic blood pressure >140mmHg.
 ~46% of patients have a preserved (LVEF).
 Patients often present with multiple co-morbidities.
 Killip Classification.
 Forrester Classification.
 Clinical Severity Classification.
Pathophysiology
 LV dysfunction:
Accumulation of fluid.
Decrease in CO
Hypoperfusion.
 Reciprocal Activation of (RAAS)
Na, water retention.
AGII
ET1 + Vasopressin.
Reflex activation of SNS: Epi, NE.
Killip Classification
 Stage I: No clinical signs of decompensation.
 Stage II: Heart failure. Rales, S3, PVH.
 Stage III: Severe heart failure. Pulmonary edema with
rales throughout the lung fields.
 Stage IV: Cardiogenic Shock: Hypotension, peripheral
vasoconstriction, oliguria, cyanosis and diaphoresis.
Forrester Classification
Cardiac Index
(L/min/m2)
5
Subset I
4
18 mmHg
(Normal)
Warm and Dry
Subset II
(Congestion)
Warm and Wet
3
2.2L/min/m2
2
1
Subset III
(Hypoperfusion)
Cold and Dry
10
Subset IV
(Congestion and
hypoperfusion)
Cold and Wet
20
Pulmonary Capillary Wedge Pressure (mmHg)
30
Nohria A et al. JAMA.2002:287; 628-40
Common Precipitating Factors
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Medication non-adherence.
Dietary indiscretion.
Infection (pneumonia, UTI, etc.)
Renal failure.
Cardiotoxic/nephrotoxic
medication.
Uncontrolled hypertension
Cardiac Arrhythmias
Myocardial ishemia
Valvular disease
Pulmonary embolus
COPD
Anemia
Thyroid disorders
Nondihydropyridine CCB
Sodium retaining medications
Clinical Presentation
Volume Overload
Dyspnea/Fatigue
Rales/Wheezing
JVD/HJR/AJR
Pulmonary/Pitting Edema
Reduced oxygen saturation
S3 or S4
Electrolyte disturbance
Increased serum creatinine
Low Cardiac Output
Narrow Pulse Pressure
Altered Mental Status
Pre-renal azotemia
Cool extremities
Decreased urine output
Refractory to IV diuresis
Differential Diagnosis
 Pneumonia
 Reactive airway disease
 Pulmonary embolus
Diagnosis
 Diagnosis of ADHF should be primarily
based on signs and symptoms. (C)
Diagnosis
Low-Intermediate clinical suspicion of ADHF
BNP (A)
BNP > 500pg/ml
BNP 100-500pg/ml
ADHF more likely
Likely, but
consider other causes
BNP < 50-100pg/ml
ADHF less likely
Predictors of Mortality
 BUN > 43 mg/dl
 SBP < 115 mmHg
 sCr >2.75 mg/dl
}
Highest risk
of mortality
Fonarow GC et al. JAMA. 2005;293:572-80
Goals of Therapy
 Improve symptoms and signs of congestion
and/or hypoperfusion.
 Reverse hemodynamic abnormalities.
 Identify the etiology.
 Minimize side effects.
 Optimize therapy.
 Length of stay, mortality, time to hospital
readmission.*
 Educate patients on medications and self
assessment of HF.
Treatment Strategy
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Establish a Diagnosis
Oxygen and Ventilatory Assistance
Symptom Relief
Anticoagulation
Hemodynamic Support:
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Diuresis/Fluids
Vasodilators
Inotropes
Vasopressors
 Assess Patient Response
 Anti-infectives
 Glucose Control
The Principle
 Diuretics
Reduce Fluid Overload
Reduced Preload: (E-DVf), PCWP
 Inotropes
Increase Contractility
Increase CO, EF, Perfusion
 Vasodilators
Reduce Preload
Reduce Afterload
Assess Signs/Symptoms/Determine
Hemodynamic Status
EC Interventions:
Cardiac panel: (CBC w/diff & platelets, SMA-7
CK-MB, Glucose), TSH,
Pox, ECG, BNP, X-ray
Abnormal
Evaluate cardiac function by 2DE
Characterize type and severity
Is patient hypoxic?
Yes
No but difficult breathing
Oxygen C
CPAP
NIPPV
Normal
Consider
alternative diagnosis
Does Patient presents with
Distress or pain ?
yes
Morphine 3 mg IVPB IIbB
Does patient present with ischemic chest
pain resistant to opiates or tachycardia?
Metoprolol 5 mg IV* IIbC
Volume Overloaded
(A) Moderate Volume Overload
IV Diuretics
Furosmide 20-40 mg
Bumetanide 0.5-1.0 mg
Torasemide 10-20 mg
IB/B
Inadequate Response
< 250-500 ml within 2 hours
Na/fluid restriction
Add HCTZ 25-50 mg bid, or
Metolazone 2.5-10 mg qd, or
Spironolactone 25-50 mg qd
IIbC/C
Consider Dopamine <2-3 ug/kg/min IIbC
Ultrafiltration or Hemodialysis C
Consider Severe Volume Overload (B)
Or Low Cardiac Output (C)
Refractory to loop + thiazides
(B) Severe Volume Overload
SBP>90 mmHg
IV Diuretics +/- IV Vasodilators
Furosmide 40-100 mg IV then 5-40 mg/h inf.
Bumetanide 1-4 mg
Torasemide 20-100 mg
PLUS
Nitroglycerin 5-10 ug/min inf.*
Class IIbC/C
(C) Low Cardiac Output
SBP >100 mmHg
SBP 85-100 mmHg
Vasodilator
(NTG, Nitroprusside)C
SBP < 85 mmHg
On a B-blocker chronically?
Volume repletion
Inotrope IIaC/C
Yes/No
No or D/C
And/or
Dobutamine IIaCC
Consider D/C or reducing
Dopamine
2-3 ug/kg/min inf.
dose if sign of excessive
>5ug/kg/min
-20ug/kg/min inf.
dose are suspected
Milrinone 25-75ug/kgIVPB over10-20min Hypoperfusion resolving?
Then 0.37-0.75ug/kg/min inf. IIbC/IIaC*C
yes
No
Tapper off dobutamine
by steps of 2 ug/kg/min qod
+optimize tx with hydralazine and/or ACE-I
(D)
(D) Unresolved hypoperfusion
Use of invasive
hemodynamic monitoring C
Transient use of Vasopressor therapy
Epinephrine
0.05-0.5 ug/kg/min inf. Norepinephrine 0.2-1ug/kg/min
+/- dobutamine
0.05-0.5 ug/kg/min inf.
Monitoring Parameters
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Oxygen Saturation
CBC
BP
ECG
BNP
Signs:
 Edema, Rales, Ascites, Hepatomegaly, JVD
Symptoms:
 Orthopnea, PND, Dyspnea, Fatigue, Cough
Negative/positive balance
Electrolytes
Urinalysis
BUN/Scr
ABG
(OPTIME-CHF)
Outcomes of a Prospective Trial of
Intravenous Milrinone for Exacerbations of
Chronic Heart Failure
JAMA, March 27 2002: 287(12);1541-1547
Objective: To prospectively test whether a strategy that includes short–term
use of milrinone in addition to standard therapy can improve clinical outcomes
of patients hospitalized with an exacerbation of chronic heart failure.
Study Design
 Prospective randomized double-blind placebocontrolled trial.
 ITTA.
 Similar baseline characteristics.
 Randomization to a 48 hour infusion of either
milrinone (n = 477) or placebo ( 472).
 Milrinone treatment arm: Started with an initial
infusion of 0.5ug/kg/min for 48hrs. (Rate adjusted to
0.375 ug/kg/min)
Outcome Measures
 Primary Efficacy Outcome:
 The total number of days hospitalized for cardiovascular causes or
days decreased within the 60 days after randomization.
 Secondary endpoints:
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Failed therapy because of adverse events.
Failed therapy because of worsening heart failure.
Proportion of patients achieving target doses of ACE-I therapy.
Time to achieve target ACE-I dose.
Symptom improvement in HF score.
Patient Selection
Inclusion Criteria
18 yoa
Demonstrated LVEF < 40%
Exclusion Criteria
-If physician judged that
inotropic therapy was
essential.
-Active myocardial ischemia
within past 3 months.
-Atrial fibrillation with poor
ventricular rate control.
-Sustained VT/Vf.
Results
 Treatment with milrinone did not reduce the primary
endpoint of days hospitalized for cardiovascular causes
within 60 days compared with placebo.
Results (cont’)
Placebo
(n=472)
Treatment failure cause at 48 hours:
Adverse event
Events during hospitalization:
MI
New atrial fibrillation/flutter
Ventricular tachycardia/fibrillation
Sustained hypotension
Milrinone
(n = 477)
P value
2.1%
12.6%
<0.001
0.4%
1.5%
1.5%
3.2%
1.5%
4.6%
3.4%
10.7%
<0.18
<0.04
<0.06
<0.001
Limitations
 Study did not directly address patients with
acutely decompensated chronic heart failure for
whom inotropic therapy is essential.
 Non-formal therapeutic protocol.*
 Confounding variables.
Conclusions
 Results do not support the routine use of
milrinone in patients hospitalized with an
exacerbation of chronic heart failure.
(VMAC)
Intravenous Nesiritide vs Nitroglycerin
for Treatment of Decompensated
Congestive Heart Failure
Objective: To compare the efficacy and safety of
intravenous nesiritide, intravenous nitroglycerin
and placebo.
Study Design
 Randomized double-blind, double dummy trial.
 Patients were stratified to catheterized (n=246) and
non-catheterized (n= 243)
 Patients were then randomized to fixed dose nesiritide,
adjustable dose niseritide, nitroglycerin or placbo for
the first 3 hours.
 After 3 hours patients were in the double dummy
design of nesiritide and nitroglycerin treatment arms.
Outcome Measures
 Primary Endpoint: Change in PCWP and patient’s
self-evaluation of dyspnea from baseline at 3hours.
 Secondary Endpoints:
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Onset of effect on PCWP
Effect on PCWP 24 hrs after the start of study drug
Self-assessed dyspnea and global clinical status
Overall safety profile.
Inclusion
Inclusion Criteria
Dyspnea at rest
Cardiac etiology of dyspnea
Exclusion Criteria
SBP<90
Volume depletion
CI to IV vasodilators
Mechanical ventillation
Survival less than 35 days
Results
 Reduction in PCWP was greater in the
nesiritide group with the first measurement.
 Beyond 24hr the difference in PCWP between
nesiritide and nitroglycerin was insignificant.
 Improvement in dyspnea and global clinical
status scores in the nesiritide and nitroglycerin
were not significantly different at any time.
 HA was more common in the Nitroglycerin
group.
Limitations
 Heterogenous patient population*
 Therapeutic protocol.
 Assessment of mortality/morbidity
Conclusion
 When added to standard care in hospitalized
patients with ADHF, nesiritied improves
hemodynamic function and some selfreported symptoms more effectively than
intravenous nitroglycerin.
CC: Weakness and Shortness of Breath.
4/06/07 (ER)
HPI:
BH is a 95 year-old female with a known history of
CHF, HTN, anxiety. Patient presents with altered
mentation along with swelling in the legs and arms.
PMH:
HTN, CVA, chronic atrial fibrillation, anxiety.
Allergies: PCN (rash)
SH: Lives at home, has a 24 hour caregiver.
Medications at Home: Atenolol 25 mg qd, pantoprazole 40mg qd,
ASA 81 mg qd, lorazepam 1 mg qhs, clopidogrel 75 mg qd,
acetaminophen 500 mg qid prn, ciprofloxacin 500mg bid.
Physical assessment: 3+ edema from waist down.
VS: H=4’11” W=50.0kg T= 36oC, P= 96, RR=18,BP=114/86
HEENT: conjunctivae and lids have no pallor and no
jaundice. Pupils equal, round and reactive to light and
accomodation. Ears, nose and throat normal.
Lungs: bilateral basilar crackles.
CV: heart rhythm irregular.
Abd: soft. no n/v/d, no hepatosplenomegaly.
Neuro: lethargic. GCS:14.
Labs:
Na 139
WBC 10.5 Scr 1.8 BNP 1343
K 4.1
HGB 9.6 BUN 30 AG 9
Cl 108
HCT 48
Plt 296 CK 171 MB 6.4
X-Ray: small left effusion, atelectasis, no pneumothorax.
EKG: atrial fibrillation w ventricular response, with T
wave inversions.
Physician’s assessment/plan:
1. Congestive Heart Failure: Patient will receive IV
diuretics and monitor for electrolytes.
2. UTI: Continue Cipro until the completion of the course.
3. Abnormal cardiac enzymes: Represent myocardial
injury. Cardiology consulted.
4. Acute Renal insufficiency: Monitor creatinine, diuresis
and BP.
Summary
References
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Adams KF et al. J Card Fail. 2006; 12:10-38.
Nieminem MS et al. Eur Heart J 2005; 26:384-416.
Cherney D. et al. Management of Patients with Hypertensive Urgencies and Emergencies. JGIM
2002;17:937-944.
Krum H. et al. New and Emerging Drug Therapies for the Management of Acute Heart Failure.
Internal Medicine Journal 2003;33:515-520.
Peacock W. F. et al. Acute Emergency Department Management of Heart Failure. Heart Failure
Reviews 2003;8:335-338.
Wang T. J. et al. Plasma Natriuretic Peptide Levels and the Risk of Cardiovascular Events and Death.
NEJM 2004;350(7):655-663.
Alan S. M. et al. Cardiac Natriuretic Peptides: A Proteomic Window to Cardiac Function and Clinical
Management. Reviews In Cardiovascular Medicine 2003;4(4):S3-S12.
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Millane T. et al. ABC of Heart Failure: Acute and Chronic Management Strategies. BMJ 2000;320:559-562.
•
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DiDomenico RJ.The Annals of Pharmacotherapy 2004 April:38;649-660
Gregg C. F. et al. The Treatment Targets in Acute Decompensated Heart Failure. Reviews In
Cardiovascular Medicine 2001;2(2):S7-S12.
Diagnosis and Treatment of Acute Heart Failure. Retrieved from www.guidelines.gov 2002.
Acute Exacerbation of CHF. Australian Heart Foundation 2006:43-49.
Rapid Optimization: Strategies for Optimal Care of Decompensated Congestive Heart-Failure Patients
in the Emergency Department. Reviews In Cardiovascular Medicine 2002;3(4):S41-S48.
Hunt S. A. et al. 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). ACC/AHA Practice Guidelines 2001:1-55.
VMAC Investigators. JAMA. 2002;287:1531-40.
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Questions?
Level of Evidence
Heart Failure Society of America:
Level A: Randomized controlled clinical trials
Level B: Cohort and case-control studies
Level C: Expert opinion
European Society of Cardiology:
Class I
Evidence and/or general agreement that a given diagnostic procedure/treatment is beneficial,
useful and effective;
Class II
Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the
treatment;
Class IIa
Weight evidence/opinion is in favour of usefulness/efficacy;
Class IIb
Usefulness/efficacy is less well established by evidence/opinion;
Class III
Evidence or general agreement that the treatment is not useful/effective and in some cases
may be harmful.
Levels of Evidence
Level of Evidence A
Data derived from multiple randomized clinical trials or meta-analysis
Level of Evidence B
studies
Data derived from a single randomized clinical trial or large non-randomized
Level of Evidence C
and registries
Consensus of opinion of the experts and/or small studies; retrospective studies
Drug
Usual
Dose
⍺
β1
β2
Vaso
dilati
on
Vasoco
nstrixn
Inotro
pic
Chronot
ropic
HR
MAP
PAP
PWP
CVP
SVR
SV
CO
Epinephrine
(Adrenaline)
0.01-0.1
µg/kg/min
0.1-0.5
µg/kg/min
(1-4
µg/min)
+
+++
++
++
-
+++
++
↑
↑
↑
↑
↑
↑/↓
↑/↓
↑
+++
++
++
-
+++
++
++
Norepinephrine
(Levophed)
0.03-1.5
µg/kg/min
(2-80
µg/min)
++++
++
-
-
++++
+*
+
O/ ↑
↑
↑
↑
↑
↑
↑/↓
↑/↓
Dopamine
(Dobutrex)
1-3
µg/kg/min
3-8
µg/kg/min
8-20
µg/kg/min
-
+
-
a
+
+
+
O/ ↑
O/ ↑
O/ ↑
O/ ↑
O/ ↑
O/ ↑
↑/↓
↑
+
++
-
a
++
++
++
+++
++
-
a
+++
++
++
Drug
Usual Dose
⍺
β1
β2
Vas
odi
lati
on
Vaso
const
rixn
Inotr
opic
Chro
notro
pic
H
R
MA
P
PAP
PW
P
CV
P
SV
R
S
V
C
O
Dobutami
ne
(Dobutrex
)
2-30
µg/kg/min
-
+++
+
+
++
-
+++
+
O/
↑
O/ ↑
O/ ↑
O/ ↓
O/
↑
O/
↓
↑
↑
Milrinone
(Primacor
)
LD 50 µg/kg
over 10 min.,
then 0.3750.75
µg/kg/min
-
-
-
++
+
-
+++
+
O/
↑
↓
↓
↓
O/
↓
↓
↑
↑
Gilman AG, Rall TW., et al. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 8th ed. 1993.
Marino P. The ICU Book. 2nd ed. 1998. Young L., Koda-Kimble M. Applied Therapeutics. 6th ed. 1995.
Kirby R., Taylor R., et. al. Handbook of Critical Care. 2nd ed. 1997.
Darovic G., Franklin C. Handbook of Hemodynamic Monitoring. 1999.