Medical Care: Initial management of patients with CPE should address the ABCs of resuscitation, that is, airway, breathing, and circulation. Oxygen should be administered to all patients to keep oxygen saturation >90%. The method of oxygen delivery varies from use of a face mask to bilevel noninvasive positive-pressure ventilation (NPPV) or continuous positive airway pressure (CPAP) or intubation and mechanical ventilation depending on presence of hypoxemia and acidosis and on the patient's level of consciousness. In case of persistent hypoxemia, acidosis or altered mental status, intubation and mechanical ventilation may become necessary. Any associated arrhythmia or myocardial infarction should be treated appropriately.
Medical therapy of CPE focuses on 3 main goals: (1) reduction of pulmonary venous return (preload reduction), (2) reduction of systemic vascular resistance (afterload reduction), and (3) inotropic support. Preload reduction decreases pulmonary capillary hydrostatic pressure and reduces fluid transudation into the pulmonary interstitium and alveoli. Afterload reduction increases cardiac output and improves renal perfusion, which allows for diuresis in the patient with fluid overload. Patients with severe LV dysfunction or acute valvular disorders may present with hypotension. These patients may not tolerate medications to reduce their preload and afterload. Therefore, the third goal in this subset of patients is to provide inotropic support to maintain adequate BP.
Patients who remain hypoxic despite supplemental oxygenation and patients who have severe respiratory distress require ventilatory support in addition to maximal medical therapy.
Ventilatory support
Noninvasive pressure-support ventilation
Consider noninvasive pressure-support ventilation (NPSV) early when treating patients with severe CPE.
In NPSV, the patient breathes through a face mask against a continuous flow of positive airway pressure. NPSV maintains the patency of the fluid-filled alveoli and prevents them from collapsing during exhalation. As a result, the patient saves the energy spent trying to reopen collapsed alveoli. NPSV improves pulmonary air exchange, and it increases intrathoracic pressure, reducing preload and afterload and improving cardiac output.
NPSV is associated with decreased length of stay in the ICU, decreased need for mechanical ventilation, and decreased hospital costs.
Two types of NPSV are continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP). In CPAP, a single airway pressure is maintained throughout all phases of the respiratory cycle. In BiPAP, high pressures can be applied during inspiration and low pressures, during expiration, increasing the patient's comfort.
In 1 small study, researchers compared the 2 types of NPSV and found that BiPAP was associated with more rapid improvement in vital signs but an increased rate of MIs. However, patients who received BiPAP initially had more chest pain than patients who received CPAP. A recent randomized clinical trial did not show any increased rate of MI in patients who received CPAP or BiPAP compared with those who received oxygen by means of a face mask. As of now, the data are sufficient to compare the efficacy and safety of BiPAP with CPAP. Therefore, the authors suggest that CPAP is the preferred method unless the patient has obstructive airway disease.
Mechanical ventilation
In general, use endotracheal intubation and mechanical ventilation when patients with CPE remain hypoxic despite maximal noninvasive supplemental oxygenation, when patients have evidence of impending respiratory failure (eg, lethargy, fatigue, diaphoresis, worsening anxiety), or when patients have hemodynamically compromise (eg, hypotension, severe tachycardia).
Mechanical ventilation maximizes myocardial oxygen delivery and ventilation.
Positive end-expiratory pressure is generally recommended to increase alveolar patency and to enhance oxygen delivery and carbon dioxide exchange.
Medical therapy
Preload reduction
" Nitroglycerin
o Nitroglycerin (NTG) is the most effective, predictable, and rapid-acting medication available for preload reduction.
o Several studies demonstrated greater efficacy and safety and a faster onset of action with NTG than with furosemide or morphine sulfate.
o Use of sublingual NTG is associated with preload reduction within 5 minutes and some afterload reduction.
o Topical NTG may be as effective as sublingual NTG in most patients with CPE, but it should be avoided in patients with severe LV failure because of poor skin perfusion (manifesting as skin pallor or mottling) and resultant poor absorption.
o Intravenous (IV) NTG at high dosages provides rapid and titratable preload and afterload reduction and is excellent mono therapy for patients with severe CPE.
o IV NTG can be started with 10-20 mcg/min and then rapidly uptitrated to >100 mcg/min.
o The other alternative is NTG given as 3-mg IV boluses every 5 minutes.
o The antianginal dose of NTG of 0.4 mg every 5 minutes has the bioequivalence of an NTG IV infusion of <80 mcg/min. Therefore, the dosage of NTG for patients with CPE is higher than the standard antianginal dosage.
o Physicians should be comfortable with the high dosage for CPE, especially in most patients with CPE, who present with a hyperadrenergic state and moderately elevated BP, considering short half-life of nitrates. However, nitrates should not be used in hypotensive patients, and they should be used with extreme caution in patients with aortic stenosis and pulmonary hypertension.
" Loop diuretics
o Loop diuretics have been considered the cornerstone of CPE treatment for many years. Furosemide is used most commonly.
o Loop diuretics are presumed to decrease preload through 2 mechanisms: diuresis and direct vasoactivity (venodilation).
o In most patients, diuresis does not occur for at least 20-90 minutes; therefore, the effect is delayed. Loop diuretics affect the ascending loop of Henle; therefore, the diminished renal perfusion in CPE may delay the onset of effects of loop diuretics.
o Many patients with CPE do not have fluid overload. Continued use of diuretics in these patients after their acute symptoms resolved may be associated with adverse outcomes, including electrolyte derangements and hypotension.
o The presumption that these medications have a direct vasoactive (venodilating) effect has been questioned. Some studies demonstrated initial adverse hemodynamic consequences (eg, elevations of PCWP, LV filling pressure, heart rate, and systemic vascular resistance) after the administration of IV furosemide.
o Premedication with drugs that decrease preload (eg, NTG) and afterload (eg, angiotensin-converting enzyme [ACE] inhibitors) before the administration of loop diuretics can prevent potential adverse hemodynamic changes.
" Morphine sulfate
o Use of morphine sulfate in CPE for preload reduction has been commonplace for many years.
o Good evidence supporting a beneficial hemodynamic effect is lacking.
o Data suggest that morphine sulfate may contribute to a decrease in cardiac output and that it may be associated with an increased need for ICU admission and endotracheal intubation.
o Adverse effects (eg, nausea and vomiting, local or systemic allergic reactions, respiratory depression) may outweigh any potential benefit, especially given the availability of medications that are more effective than morphine in reducing preload (eg, NTG).
o Any beneficial hemodynamic effect is probably due to anxiolysis, with a resulting decrease in catecholamine production and decrease in systemic vascular resistance. An alternative can be low-dose benzodiazepines (eg, lorazepam 0.5 mg IV) in patients who are extremely anxious. This alternative reduces the risk of respiratory depression in patients whose condition responded to initial therapy.
" Nesiritide
o Nesiritide is recombinant human BNP, which decreases PCWP, pulmonary artery pressure, right atrial pressure, and systemic vascular resistance while increasing the cardiac index and stroke volume index.
o Therapy with nesiritide has decreased plasma renin, aldosterone, norepinephrine, and endothelin-1 levels and reduced ventricular ectopy and ventricular tachycardia.
o Heart-rate variability also improves with nesiritide.
o Most of the beneficial effects of nesiritide was shown in the landmark Vasodilation in the Management of Acute Congestive Heart Failure (VMAC) study. Investigators compared IV nesiritide with IV NTG. IV nesiritide was associated with some hypotension but was otherwise well tolerated. The VMAC study also showed a trend for increased mortality with IV nesiritide group compared with IV NTG, though the difference was not statically significant (90-day mortality, 19% for nesiritide vs 13% for NTG; P = 0.8). The most important limitation of this study was the use of suboptimal dosages of IV NTG (mean 30-40 mcg/min) because the dosage was based on physician's decision and not on a protocol.
o A later meta-analysis of 3 randomized trials of 485 patients receiving nesiritide and 377 patients not receiving nesiritide showed a 7.2% 30-day mortality with nesiritide versus 4% without nesiritide.
o Another analysis included 5 randomized trials showed that patients who received nesiritide were more likely than others to have significant renal failure.
o Finally, length of hospitalization, rate of readmission because of heart failure, and cost-effectiveness of nesiritide compared with NTG therapy is not clear.
o The lack of a large randomized trial to compare nesiritide with optimal NTG therapy prevents definite conclusions about application and safety of nesiritide therapy. However, when NTG is contraindicated (eg, in a patient who has taken sildenafil), nesiritide can be an alternative in the treatment of CPE.
Afterload reduction
" ACE inhibitors
o These are generally considered the cornerstones for treating chronic CHF, and recent studies have demonstrated excellent results with ACE inhibitors for the treatment of acute decompensated CHF and CPE.
o Use of ACE inhibitors in CPE is associated with reduced admission rates to ICUs and decreased endotracheal intubation rates and length of ICU stay.
o Hemodynamic effects of ACE inhibitors include reduced afterload, improved stroke volume and cardiac output, and a slight reduction in preload. The last effects happen when renal perfusion improves after cardiac output improves and diuresis occurs.
o Enalapril 1.25 mg IV or captopril 25 mg given sublingually result in hemodynamic and subjective improvements within 10 minutes. Improvements occur much more slowly with the oral route.
" Nitroprusside
o Nitroprusside results in simultaneous preload and afterload reduction by causing direct smooth-muscle relaxation, with an increased effect on afterload.
o Afterload reduction is associated with increased cardiac output.
o The potency and rapidity of onset and offset of effect make this an ideal medication for patients who are critically ill.
o It may induce precipitous falls and labile fluctuations in BP; intra-arterial BP monitoring is often recommended.
o Nitroprusside should generally be avoided in the setting of acute MI. Its use is associated with shunting of blood away from ischemic myocardium toward healthy myocardium (ie, coronary steal syndrome), which potentiates ischemia.
o If nitroprusside is used, convert therapy to oral or alternative IV vasodilator therapy as soon as possible because prolonged use is associated with thiocyanate toxicity.
o Use in pregnancy is associated with fetal thiocyanate toxicity.
o Prolonged infusion can induce tolerance, and reflex tachycardia may occur.
" Inotropics: Inotropic support is usually used when preload- and afterload-reduction strategies are not successful or when hypotension precludes use of these strategies. Two main classes of inotropic agents are available: catecholamine agents and phosphodiesterase inhibitors (PDIs). Calcium-sensitizer agents are a new class of medications that have notably beneficial effects in acute decompensated heart failure; these drugs are under investigation.
o Dobutamine
" Dobutamine, a catecholamine agent, mainly serves as a beta1-receptor agonist, though it has some beta2-receptor and minimal alpha-receptor activity.
" IV dobutamine induces significant positive inotropic effects with mild chronotropic effects. It also induces mild peripheral vasodilation (decrease in afterload).
" The combination effect of increased inotropy with decreased afterload significantly increases cardiac output.
" Combination use with IV NTG may be ideal for patients with MI and CPE and mild hypotension to simultaneously reduce preload and increase cardiac output.
" In general, avoid dobutamine in patients with moderate or severe hypotension (eg, systolic BP <80 mm Hg) because of the peripheral vasodilation.
o Dopamine
" The vascular and myocardial receptor effects of dopamine, a catecholamine agent, are dose dependent.
" Low dosages of 0.5-5 mcg/kg/min stimulate dopaminergic receptors in the renal and splanchnic vascular beds, causing vasodilation and increasing diuresis.
" Moderate dosages of 5-10 mcg/kg/min stimulate beta-receptors in the myocardium, increasing cardiac contractility and heart rate.
" High dosages of 15-20 mcg/kg/min stimulate alpha-receptors, resulting in peripheral vasoconstriction (increased afterload), increased BP, and no further improvement in cardiac output.
" Moderate and high dosages are arrhythmogenic and increase myocardial oxygen demand (with the potential for myocardial ischemia). Therefore, use these dosages only in patients with CPE who cannot tolerate dobutamine because of severe hypotension (eg, systolic BP 60-80 mm Hg).
" Norepinephrine
o Norepinephrine, a catecholamine agent, primarily stimulates alpha-receptors, significantly increasing afterload (and the potential for myocardial ischemia) and reducing cardiac output.
o Norepinephrine is generally reserved for patients with profound hypotension (eg, systolic BP <60 mm Hg). After BP is restored, add other medications to maintain cardiac output.
" Phosphodiesterase inhibitors
o PDIs increase the level of intracellular cyclic adenosine monophosphate by preventing the breakdown of cAMP to 5'AMP and result in a positive inotropic effect on the myocardium, in peripheral vasodilation (decreased afterload) and in a reduction in pulmonary vascular resistance (decreased preload).
o Unlike the catecholamine inotropes, PDIs do not depend on adrenoreceptor activity. Therefore, patients are less likely to develop tolerance to PDIs than to other medications. Tolerance to catecholamine inotropes can rapidly develop by means of a downregulation of adrenoreceptors.
o PDIs are less likely than catecholamine inotropes to cause adverse effects that are typically associated with adrenoreceptor activity (eg, increased myocardial oxygen demand, myocardial ischemia).
o Several direct comparisons of PDIs (milrinone) to dobutamine in patients with CPE demonstrated that milrinone produced equal or greater improvements in stroke volume, cardiac output, PCWPs (preload), and systemic vascular resistance (afterload). However, milrinone was associated with the same or more tachycardia and with an increased incidence of tachyarrhythmias. Furthermore, use of milrinone, in the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF), did not reduce hospital length of stay and was associated with a significant increase in adverse events compared with placebo.
o All known IV inotropic agents are associated with an increased long-term mortality compared with placebo and therefore should be reserved for patients with heart failure and a markedly depressed cardiac index and stroke volume.
" Calcium sensitizer
o Levosimendan is a calcium sensitizer that is used in several European countries to manage moderate-to-severe heart failure. It has inotropic, metabolic, and vasodilatory effects.
o Levosimendan increases contractility by binding to troponin C. It does not increase myocardial oxygen demand, and it is not a proarrhythmogenic agent.
o Levosimendan opens potassium channels sensitive to adenosine triphosphate (ATP), causing peripheral arterial and venous dilatation. It also increases coronary flow reserve. Recent studies have shown an anti-inflammatory effect of levosimendan.
o Overall, levosimendan has been an effective and safe alternative to dobutamine. The most common adverse effects of levosimendan treatment are hypotension and headache.
Surgical Care: Kantrowitz initially described intra-aortic balloon pumping (IABP) in 1953, but IABP was first used clinically in 1969 in a patient with cardiogenic shock. Since the 1980s, IABP has been increasingly applied in various clinical situations as a life-saving intervention to achieve hemodynamic stabilization before definite therapy. The intra-aortic balloon pump decreases afterload as the pump deflates and inflates it during diastole to improve coronary blood flow.
" Procedure
o The intra-aortic balloon pump is inserted percutaneously through the femoral artery by using a modified Seldinger technique. The distal end of the pump is placed just distal to the aortic knob and the origin of left subclavian artery.
o Fluoroscopy may be used for correct positioning of the balloon, and a subsequent radiograph should be obtained to document satisfactory placement of the balloon.
o Helium, a low-density gas with minimal water solubility, is used to inflate the balloon.
" Proper timing of IABP for optimal hemodynamic support
o Proper timing of counterpulsation is necessary for maximum hemodynamic support. The timing of balloon inflation and deflation are best evaluated and adjusted at a pump ratio of 1:2.
o Inflation of the balloon should occur in early diastole, just after the aortic valve closes, and it should correspond to the dicrotic notch of the aortic pressure waveform. Balloon deflation should occur in early systole, just before the aortic valve opens.
o Proper inflation leads to an assisted peak diastolic pressure higher than the unassisted peak systolic arterial pressure. Proper deflation results in assisted aortic end-diastolic pressure of approximately 10 mm Hg lower than the unassisted end-diastolic pressure.
o Diastolic augmentation enhances perfusion of the coronary circulation and carotid arteries. The reduction in end-diastolic pressure decreases aortic impedance (afterload) and augments systole.
o IABP reduces aortic impedance and systolic pressure, leading to a 15-25% reduction in LV wall stress. This level of afterload reduction improves LV volume, LV emptying, and myocardial oxygen consumption.
o Diastolic aortic pressure augmentation improves myocardial perfusion and coronary blood flow. The effects on coronary blood flow may be variable but generally consist of a boost of 10-20% in the ischemic territories.
o IABP decreases LV filling pressures by 20-25% and improves cardiac output by 20% in patients with cardiogenic shock. Therefore, IABP substantially reduces myocardial oxygen demand, though increased oxygen supply to the myocardium may also be a beneficial effect in some clinical situations.
" Indications for IABP
o IABP is effective in providing temporary support to patients in cardiogenic shock and end-stage cardiomyopathy while definite therapies, such as angioplasty or cardiac bypass surgery or cardiac transplantation, are undertaken. In this case, the use of IABP is considered a bridge to a definite revascularization procedure or implementation of an LV-assist device.
o IABP is effective in stabilizing patients with unstable angina refractory to medical therapy before a definitive revascularization procedure.
o IABP may be a life-saving intervention in patients with acute mitral regurgitation secondary to papillary muscle rupture or in patients with ventricular septal defect as a complication of MI. IABP reduces afterload and thereby reduces the severity of mitral regurgitation. It enhances forward cardiac output, reduces left atrial pressure, and improves pulmonary edema. Furthermore, IABP decreases LV afterload and improves cardiac output.
o IAPB is used to stabilize patients, which allows time to plan definitive surgery in hemodynamically unstable patients.
o IABP can also provide hemodynamic support in the perioperative and postoperative period in high-risk patients, such as those with severe coronary disease, severe LV dysfunction, or recent MI.
" Contraindications
o Absolute contraindications for IABP counterpulsation are a dissecting aortic aneurysm, severe aortic regurgitation, a large arteriovenous shunt, and severe coagulopathy.
o Relative contraindications are severe peripheral vascular disease, recent thrombolytic therapy, bleeding diathesis, and descending aortic and peripheral vascular grafts.
" Complications
o IABP can cause several complications, which should be monitored while the patient is receiving IABP support. In general, the platelet counts are mildly reduced; however, the counts usually do not fall below 100 X 109/L.
o Complications also may occur during cannulation of the femoral artery. These include perforation, laceration, or dissection of the artery (1-6%). Thrombosis of the iliofemoral artery and distal emboli may also occur (1-7%), and limb ischemia is reported in up to 40% of patients. Limb ischemia is reversible by removing the intra-aortic balloon pump unless thrombosis develops; if so, embolectomy is required to save the limb.
o The other complications are localized bleeding (3-5%), infection (2-4%), thrombocytopenia (<1%), and intestinal ischemia (<1%).
Diet: Patients admitted with heart failure or pulmonary edema should be given a low-salt diet to minimize fluid retention. Closely monitor their fluid balance.
DRUG TREATMENT :
1. PRELOAD REDUCERS :
- NITROGLYCERIN
- FRUSEMIDE
2. AFTERLOAD REDUCERS :
- CAPTOPRIL
- ENALAPRIL
- NITROPRUSSIDE
3. CATECHOLAMINES :
- DOBUTAMINE
- DOPAMINE
- NOREPINEPHRINE
4. PHOSPHODIESTERASE ENZYME INHIBITORS :
- MILRINONE
PATIENT MONITORING :
. Inpatient
. Serial arterial blood gases or pulse oximetry, often in the intensive care unit with one-on-one nursing
. Strict measurement of intake and output
. Attention to optimal fluid management
. Attention to optimal ventilator settings
. Serial chest x-rays
. OUTPATIENT:
. Attention to clinical status
. Serial weights to assess fluid accumulation
PREVENTION/AVOIDANCE: Compliance with medications and diet
POSSIBLE COMPLICATIONS:
. Death
. Reversible or irreversible organ ischemia
. Pulmonary fi brosis, particularly with non-cardiogenic pulmonary edema
EXPECTED COURSE/PROGNOSIS:
. Dependent on underlying etiology
. Mortality approximately 50-60% for non-cardiogenic pulmonary edema and up to 80% for cardiogenic shock