Pulmonary edema resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2], Farnaz Khalighinejad, MD [3]

Overview

Pulmonary edema is fluid accumulation in the lungs. This fluid accumulation leads to impaired gas exchange and hypoxia. The history of a patient with pulmonary edema varies according to the underlying cause. The most common symptom of pulmonary edema is shortness of breath (dyspnea). Depending on the cause, it may occur acutely or have a gradual onset. When pulmonary edema is due to an acute myocardial infarction chest pain is common symptom. Patients with pulmonary edema usually appear agitated. Physical examination of patients with pulmonary edema is usually remarkable for dyspnea, tachypnea. The presence of abnormal cardiac examination on physical examination is diagnostic of cardiogenic pulmonary edema. Patients with noncardiogenic pulmonary edema may have warm extremities, whereas patients with cardiogenic pulmonary edema may have cool extremities. Pulmonary artery catheterization is the gold standard test for the diagnosis of pulmonary edema. Elevated pulmonary-artery pressure indicates cardiogenic pulmonary edema or pulmonary edema due to volume overload. The main goal of a treatment are alleviate symptoms and improving hemodynamics. The initial management of patients is following the ABCs of resuscitation, that is, airway, breathing, and circulation. Medical treatment of cardiogenic pulmonary edema focuses on preload reduction, afterload reduction and inotropic support.

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

• Acute decompensated heart failure
• Acute respiratory distress syndrome
• High altitude pulmonary edema
• Pulmonary embolism

Common Causes

• Congestive heart failure
• Coronary Heart Disease
• Aortic Regurgitation
• Aortic Stenosis
• Mitral Regurgitation
• Mitral Stenosis
• Myocarditis
• Pericardial Disease
• Infection
• Sepsis

Classification

Pulmonary edema may be classified according to etiology into 2 groups:

Cardiogenic pulmonary edema, which can be secondary to:

• Left ventricular failure
• Dysrhythmia
• Left ventricular hypertrophy cardiomyopathy
• Volume overload
• Myocardial Infarction
• Left ventricular outflow obstruction

Non-cardiogenic pulmonary edema which can be secondary to:

• Acute respiratory distress syndrome (ARDS)
• High altitude pulmonary edema
• Neurogenic pulmonary edema
• Reperfusion pulmonary edema
• Re-expansion pulmonary edema
• Others(opioid overdose, salicylate toxicity, viral infections)

FIRE: Focused Initial Rapid Evaluation

A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients of pulmonary edema in need of immediate intervention.

Boxes in red signify that an urgent management is needed.

Abbreviations: BU: Blood urea nitrogen; COPD: Chronic obstructive pulmonary disease; D5W: 5% dextrose solution in water ; HF: Heart failure; IV: Intravenous; MAP: Mean arterial pressure; Na: Sodium; NSAID: Non steroidal anti-inflammatory drug; SBP: Systolic blood pressure; S3: Third heart sound;

Identify cardinal findings that increase the pretest probability of pulmonary edema ❑ Anxiety, restlessness ❑ Dyspnea ❑ Cool extremities/Warm extremities ❑ Cough, particularly coughing up blood or bloody froth ❑ Excessive sweating or diaphoresis ❑ Grunting or gurgling sounds with breathing ❑ Pale or blue skin ❑ Blue or cyanotic lips ❑ Orthopnea ❑ Wheezing ❑ Peripheral edema ❑ Decreased urine output ❑ Pulmonary crepitations/rales/crackles ❑ Third heart sound (S3) ❑ Past medical history of heart failure ❑ History of opioid and aspirin overdose ❑ History of rapidly ascend to altitudes above 12,000 to 13,000 feet ❑ History of recent pulmonary embolism ❑ History of infections ❑ History of head injury, intracranial surgery, grand mal seizures, subarachnoid or intracerebral hemorrhage, and electroconvulsive therapy ❑ History of paroxysmal nocturnal dyspnea

Does the patient have any of the following findings that require hospitalization and urgent management? ❑ Hypotension (SBP < 90 mmHg or drop in MAP >30 mmHg) and/or cardiogenic shock ❑ Altered mental status ❑ Cold and clammy extremities ❑ Urine output <0.5mL/kg/hr ❑ Dyspnea at rest manifested by tachypnea or oxygen saturation <90% ❑ Atrial fibrillation with a rapid ventricular response resulting in hypotension ❑ Acute coronary syndrome

Yes

No

Admit to to a level of care that allows for constant ECG monitoring given the risk of arrhythmia and order a stat chest X-ray

Proceed to complete diagnostic approach

Initial stabilization: ❑ Assess the airway ❑ Position the patient upright at an angle of 45 degrees, with legs dangling off the bedside (decrease preload) ❑ Monitor heart rate and blood pressure continuously ❑ Monitor oxygen saturation continuously ❑ If hypoxemia is present (Sa02 < 90% or Pa02 <60 mmHg), administer oxygen with/without noninvasive ventilation ❑ Morphine to decrease symptoms and Afterload (avoid IV morphine, may increase mortality / duration of intubation, generally not advisable, may relieve refractory symptoms) ❑ Secure intravenous access with 18 gauge cannula ❑ Monitor fluid intake and urine output carefully (guide the adjustment of the diuretics dose) Assess congestion and perfusion: Congestion at rest (dry vs. wet) "Wet" suggested by orthopnea, ↑JVP, rales, S3, pedal edema Low perfusion at rest (warm vs. cold) "Cold" suggested by narrow pulse pressure, cool extremities, hypotension The patient is: ❑ Warm and dry, OR ❑ Warm and wet, OR ❑ Cold and dry, OR ❑ Cold and wet Identify precipitating factor and treat accordingly: Click on the precipitating factor for more details on the management ❑ Myocardial infarction ❑ Myocarditis ❑ Renal failure ❑ Hypertensive crisis ❑ Non adherence to medications ❑ Worsening Aortic stenosis ❑ Drugs (NSAIDS, thiazides, calcium channel blocker, beta blockers) ❑ Toxins (alcohol, anthracyclines) ❑ Atrial fibrillation Rate control of atrial fibrillation is the mainstay of arrhythmia therapy. Avoid the use of drugs with negative inotropic effects such as beta blockers and non-dihydropyridine calcium channel blockers e.g., verapamil in the treatment of acute decompensated systolic heart failure Consider cardioversion if the patient is in cardiogenic shock or if new onset atrial fibrillation is the clear precipitant of the hemodynamic decompensation ❑ COPD ❑ Pulmonary embolism ❑ Anemia ❑ Thyroid abnormalities ❑ Systemic infection ❑ Opioid and aspirin overdose ❑ Recent pulmonary embolism ❑ Recent ascend from high altitude ❑ Head injury, intracranial surgery, grand mal seizures, subarachnoid or intracerebral hemorrhage, and electroconvulsive therapy Treat congestion and optimize volume status: Diuretics ❑ Administer IV loop diuretics as intermittent boluses or continuous infusion (I-B) ❑ If patient is already on loop diuretics: IV dose ≥ home PO dose (I-B); rule of thumb: IV dose = 2.5x equivalent oral daily dose ❑ If patient is not already on loop diuretics, administer IV starting dose: Furosemide 20 to 40 mg, OR Torsemide 5 to 10 mg, OR Bumetanide 0.5 to 1 mg ❑ Adjust dose according to volume status (I-B) ❑ Perform serial assessment of fluid intake and output, vital signs, daily body weight (measured every day, with the same scale, at the same time, after first void) and symptoms ❑ Order daily electrolytes, BUN, creatinine (I-C) ❑ Low sodium diet (<2 g daily) ❑ In case of persistent symptoms: ❑ Increase dose of IV loop diuretics (I-B)- double dose at 2 hour interval up to maximal daily dose Furosemide maximal dose: 40 to 80 mg Torsemide maximal dose: 20 to 40 mg Bumetanide maximal dose: 1 to 2 mg OR ❑ Add a second diuretics, such as thiazide (I-B) ❑ Consider low dose dopamine infusion for improved diuresis and renal blood flow (IIb-B) ❑ Consider renal replacement therapy/ultrafiltration in obvious volume overload (IIb-B) refractory to higher dose/combination of IV diuretics Venodilators ❑ Consider IV nitroglycerin, nitroprusside, or nesiritide as add-on to diuretics to relieve dyspnes (IIb-A) Do not administer vesodilators among patients with hypotension. Treat low perfusion: ❑ Inotropes (click here for details) If the total body and intravascular volumes are overloaded and the patient is normotensive, then diuresis alone should be undertaken. If the patient is volume overloaded but hypotensive, then inotropes must be administered in addition to diuretics. Invasive hemodynamic monitoring: ❑ Consider pulmonary artery catheterization in case of failure to respond to medical therapy, respiratory distress, shock, uncertainty regarding volume status, or increase in creatinine; assess the following parameters: ❑ PCWP ❑ Cardiac output ❑ Systemic vascular resistance Pulmonary embolism: ❑ Anticoagulation in the absence of contraindications (I-B) Aspirin toxicity: ❑ Sodium bicarbonate is the treatment for aspirin toxicity, usually common in elderly Opioid overdose treatment ❑ Naloxone is used to reverse for opioid overdose Infections treatment ❑ Start antibiotics depending upon the type of infections Chronic medical therapy: ❑ Chronic ACE inhibitor: Hold if patient is hemodynamically unstable ❑ Chronic beta blocker: ❑ Hold if patient is hemodynamically unstable and/or in need or inotropes ❑ Decrease dose by ≥ half if patient is in moderate heart failure ❑ DO NOT INITIATE ACE INHIBITORS during an acute decompensation ❑ DO NOT INITIATE BETA BLOCKER during an acute decompensation; initiate beat blockers at a low dose in stable patients following optimization of volume status and D/C IV diuretics and inotropes (I-B) Monitor laboratory tests: ❑CBC with differentials ❑ESR ❑Lactate ❑Urine toxins ❑Albumin ❑ BUN ❑ Creatinine ❑ Sodium (to detect hyponatremia which carries a poor prognosis), chloride, bicarbonate (to detect contraction alkalosis), serum potassium (to detect hypokalemia as a result of diuresis and which can precipitate arrhythmias), and magnesium Management of hyponatremia: ❑ Water restriction ❑ <2 L/day if the Na is < 130 meq/L ❑ < 1 L/day or more if the Na is < 125 meq/L Keep in mind that juices are essentially free water with sugar. In the hyponatremia patient, drips should not be in D5W. ❑ Optimization of chronic home medications ❑ Persistent hyponatremia and risk of cognitive impairment: vasopressin antagonist for short term (hypervolemic)

Complete Diagnostic Approach

A complete diagnostic approach should be carried out after a focused initial rapid evaluation is conducted and following initiation of any urgent intervention.

Abbreviations: ANA: Antinuclear antibody; ARDS: Acute respiratory distress syndrome; BNP: B-type natriuretic peptide; BUN: Blood urea nitrogen; CAD: Coronary artery disease; CBC: Complete blood count; CCB: Calcium channel blocker; CHF: Congestive heart failure; CT: Computed tomography; CXR: Chest X-ray; DM: Diabetes mellitus; ECG: Electrocardiogram; JVP: Jugular venous pressure; HF: Heart failure; HTN: Hypertension; LVEF: Left ventricular ejection fraction; LVH: Left ventricular hypertrophy; MI: Myocardial infarction; MRI: Magnetic resonance imaging; NT-pro BNP: N-terminal pro-brain natriuretic peptide; OCPs: Oral contraceptive pills; PAWP: Pulmonary artery wedge pressure; SBP: Systolic blood pressure; S1: First heart sound; S3: Third heart sound; TSH: Thyroid stimulating hormone

Characterize the symptoms: Symptoms of Cardiogenic pulmonary edema ❑ Anxiety, restlessness ❑ Dyspnea ❑ At rest ❑ Exertional ❑ Paroxysmal nocturnal dyspnea ❑ Orthopnea ❑ Cough ❑ Excessive sweating or diaphoresis ❑ Grunting or gurgling sounds with breathing ❑ Pale or blue skin ❑ Blue or cyanotic lips Symptoms of Noncardiogenic pulmonary edema ❑ Symptoms of noncardiogenic pulmonary edema are similar to cardiogenic pulmonary edema, the only difference is the acute onset of symptoms after inciting event Symptoms suggestive of precipitating events ❑ Chest pain (suggestive of myocardial ischemia) ❑ Palpitations (suggestive of arrhythmias) ❑ Fever (suggestive of infection) ❑ Seizures (suggestive of CNS insult) Nonspecific symptoms ❑ Nausea ❑ Weight gain Obtain a detailed history: ❑ Past medical history ❑ Atrial fibrillation ❑ Cardiomyopathy ❑ Diabetes mellitus ❑ Hypertension ❑ Myocarditis ❑ Previous myocardial infarction ❑ Prior heart failure ❑ COPD ❑ Valvular heart disease ❑ Central nervous system injury ❑ Medication history ❑ Noncompliance with previously prescribed medications for heart failure ❑ Intake of the following drugs: ❑ Anticoagulants ❑ Aspirin ❑ Narcotics ❑ Heroin ❑ NSAID ❑ Morphine ❑ Methadone ❑ Dextropropoxyphene ❑ Family history ❑ History of dilated cardiomyopathy ❑ Radiation to the chest ❑ Surgical history ❑Recent surgery ❑Valve replacement surgeries ❑Recent history ❑ Opioid and aspirin overdose ❑ High altitudeascend ❑ Pulmonary embolism ❑ Head injury ❑ Seizures ❑ Electroconvulsive therapy

Examine the patient: General appearance: ❑ Ill-looking ❑ In respiratory distress ❑ Inability to speak in full sentences Vitals: ❑ Temperature ❑ Fever (suggestive of underlying infection) ❑ Pulse ❑ Tachycardia ❑ Narrow pulse pressure (<25% of SBP) ❑ Blood pressure ❑ Hypotension (suggestive of circulatory collapse) ❑ Hypertension ❑ Respiration ❑ Tachypnea (most common symptom) ❑ Pulse oximetry (maintain oxygen sat ≥ 94% unless COPD) Weight: ❑ Measure weight daily at the same time after the first void ❑ Subtract 'dry weight' from current weight to estimate extent of volume overload and edema Skin ❑ Cool and clammy (suggestive of hypoperfusion) ❑ Cyanosis (suggestive of severe hypoxemia) ❑ Anasarca ❑ Jaundice (suggestive of liver dysfunction secondary to right-sided fluid overload) Neck examination: ❑ Jugular vein distention (suggestive of right-sided fluid overload) ❑ Positive hepatojugular reflux (suggestive of right-sided fluid overload) Respiratory examination ❑ Tachypnea ❑ Wheeze ❑ Dullness at lung bases (suggestive of pleural effusion, may be present in chronic HF secondary to lymphatic compensation) ❑ Crackles/crepitations/rales (suggestive of pleural effusion) ❑ Cheyne-stokes respiration Cardiovascular examination ❑ Displaced apex beat (suggestive of enlarged left ventricle) ❑ Parasternal heave (suggestive of elevated right ventricular pressure) ❑ S3 (typical) or S4 or both ❑ Soft S1 ❑ Pulsus alternans ❑ S4 (suggestive of diastolic dysfunction) ❑ New or changed murmur (suggestive of an underlying valvular heart diseases) ❑ Mitral regurgitation - Holosystolic murmur ❑ Aortic regurgitation - Decrescendo diastolic murmur ❑ Aortic stenosis - Crescendo-decrescendo systolic ejection murmur with ejection click Abdominal examination The following findings suggest volume overload and / or poor forward cardiac output: ❑ Hepatojugular reflux ❑ Hepatomegaly ❑ Ascites Extremity examination ❑ Pedal edema Neurological examination ❑ Altered mental status ❑ Syncope (suggestive of aortic stenosis or pulmonary embolism) Determine status of congestion and perfusion based on physical exam: Congestion at rest (dry vs. wet) "Wet" suggested by orthopnea, ↑JVP, positive hepatojugular reflux, abnormal valsalva response, rales, dullness upon percussion in bases, S3, peripheral edema, hepatomegaly, ascites, jaundice Low perfusion at rest (warm vs. cold) "Cold" suggested by narrow pulse pressure, cool extremities, hypotension, soft S1, pulsus alternans, decreased urinary output The patient is: ❑ Warm and dry, OR ❑ Warm and wet, OR ❑ Cold and dry, OR ❑ Cold and wet

Order tests: Routine (Class I, level of evidence C) ❑ CBC with differentials(rule out anemia and infections) ❑ ESR ❑ Lactate ❑ Urine toxicology ❑ Troponin ❑ Elevated in myocardial ischemia and acute cardiogenic pulmonary edema, particularly if creatinine clearance (CrCl) is reduced ❑ Troponin T ≥ 0.1 ng/mL (associated with poor survival) ❑ Electrolytes ❑ Sodium: hyponatermia may occur due to fluid overlaod ❑ Serum calcium ❑ Serum magnesium can be lowered by diuresis ❑ Serum bicarbonate: to monitor contraction alkalosis with diuresis ❑ BUN, creatinine: may be elevated due to poor renal perfusion ❑ Urinalysis ❑ Fasting blood sugar ❑ Fasting lipid profile ❑ Liver function tests: can be elevated secondary to peripheral hypoperfusion ❑ TSH ❑ BNP or NT-pro BNP Heart failure is unlikely if: ❑ BNP ≤ 100 pg/mL, or ❑ NT-pro BNP ≤ 300 pg/mL ❑ Chest X-ray of Cardiogenic pulmonary edema (Class I, level of evidence C) ❑ Cardiomegaly (cardiothoracic ratio >50%) ❑ Cardiogenic pulmonary edema ❑ Kerley B lines ❑ Peribronchial cuffing ❑ Cephalization ❑ Chest X-ray findings of non-cardiogenic edema ❑Patchy alveolar infiltrates ❑ Air bronchograms Chest X-ray findings in a patient with acute heart failure ❑ ECG (to help identify the cause of heart failure) ❑ Low QRS voltage (suggestive of infiltrative or dilated cardiomyoapthy) ❑ Arrhythmia (atrial fibrillation carries a poor prognosis and requires slowing of the heart rate to improve filling & cardiac output) ❑ Poor R wave progression (suggestive of a prior MI) ❑ Left ventricular hypertrophy (consistent with a history of hypertension) ❑ Left bundle branch block (LBBB) due to prior MI, may result in dysynchrony) ❑ Left atrial enlargement (due to valvular disease or hypertension) ❑ Non-specific ST segment and T wave changes may suggest ischemia ❑ 2-D echocardiography with Doppler (Class I, level of evidence C) ❑ Assess chambers size, wall thickness, wall motion, and valve function ❑ Assess ejection fraction ❑ Radionuclide ventriculography or MRI ❑ To assess LVEF and volume when echocardiography is inadequate ❑ To assess myocardial infiltrative processes or scar burden (MRI) ❑ Coronary angiography looking for CAD ❑ Comprehensive metabolic panel if no evidence of CAD on coronary angiography ❑ Consider pulmonary artery catheterization in case of failure to respond to medical therapy, respiratory distress, shock, uncertainty regarding volume status, or increase in creatinine; assess the following parameters: ❑ PCWP ❑ Cardiac output ❑ Systemic vascular resistance Order additional tests to rule out other etiologies: ❑ ANA and rheumatoid factor (for rheumatologic diseases) ❑ Diagnostic tests for hemochromatosis and pheochromocytoma ❑ Endomyocardial biopsy (when myocarditis is suspected)

Consider alternative diagnoses: Alternative diagnoses Features Acute asthma ❑ Wheeze ❑ Reversal of symptoms following administration of bronchodilators COPD ❑ Increased cough ❑ Increased dyspnea ❑ Increased sputum production ARDS ❑ Severe hypoxia ❑ Bilateral opacities on chest X-ray ❑ PCWP < 15 mmHg Pneumonia ❑ Fever, cough, sputum ❑ Consolidation on chest X-ray Pulmonary embolism ❑ Pleuritic chest pain, cough, S4 ❑ Risk factors: trauma, immobilization, smoking, OCPs ❑ Clot in pulmonary artery on CT pulmonary angiography

Assess the stage of heart failure using the ACCF/AHA staging system to guide chronic therapy

Prevention of pulmonary edema

Prevention of pulmonary edema

Non-cardiogenic pulmonary edema

Cardiogenic pulmonary edema

❑ Encourage healthy lifestyle and exercise ❑ Prevention for pulmonary edema associated with high altitude ❑ Gradual ascent ❑ Preacclimization ❑ Avoiding alcohol and drugs like ibuprofen, acetazolamide, sumatriptan, spironolactone, and steroids ❑ Adequate hydration

❑ Treat hypertension ❑ Treat dyslipidemia ❑ Control obesity ❑ Treat DM ❑ Avoid tobacco ❑ Avoid cardiotoxic agents ❑ Encourage healthy lifestyle and exercise

Consider additional measures in selected patients: ❑ Administer ACE-I if history of MI or ACS and reduced EF to prevent symptoms and reduce mortality (I-A), in all decreased EF to prevent symptoms (I-A) ❑ Administer beta-blockers if history of MI or ACS and reduced EF to reduce mortality (I-B), in all reduced EF to prevent symptoms (I-C) ❑ Administer statins if history of MI or ACS to prevent symptoms (I-A) ❑ Consider ICD placement to prevent sudden death if asymptomatic ischemic cardiomyopathy, > 40 days post-MI, LVEF ≤30%, on adequate medical therapy, and good 1 year survival

Treatment of pulmonary edema

Pulmonary edema treatment based on classification

Cardiogenic pulmonary edema

Noncardiogenic pulmonary edema

❑ First step is to stabilize the patient by following the ABCs of resuscitation, that is, airway, breathing, and circulation ❑ Any associated arrhythmia or myocardial infarction should be treated appropriately ❑Following drugs are used: ❑ ACE-I or ARB ❑Beta blockers ❑ Bisoprolol ❑ Carvedilol ❑ Sustained release metoprolol succinate PLUS ❑Loop diuretics ❑ Starting dose ❑ Furosemide 20 to 40 mg, OR ❑ Torsemide 10 to 20 mg, OR ❑ Bumetanide 0.5 to 1 mg ❑ Monitor volume status and adjust dose ❑ No response: double oral diuretics dose rather than administer BID ❑No or minimal response despite maximal diuretic dose then administer another diuretics BID or TID PLUS ❑Aldosterone antagonist ❑Vasopressin antagonists ❑ Conivaptan ❑Tolvaptan ❑ Type III phosphodiesterease inhibitors ❑Milrinone and enoximone

❑Treatment of the underlying cause is very important ❑ If the cause of pulmonary edema is overdose of opioid overdose: ❑ Naloxone is used for the reversal of symptoms ❑ Salicylate toxicity ❑ Sodium bicarbonate is used for the treatment ❑ High altitude pulmonary edema treatment: ❑ Oxygen therapy is the first line therapy ❑ Nifedipine ❑Tadalafil and Sildenafil ❑Anticoagulants are used for the treatment of pulmonary edema due to pulmonary embolism ❑Antibiotics are used to treat underlying infections

Medications

Drug Class	Drug	Daily dose	Maximum daily dose
Loop diuretics	Furosemide (duration of action: 6 to 8 h)	PO dose for chronic heart failure: 20 to 40 mg once or twice IV dose for acute heart failure: Initial dose given slowly (1 to 2 minutes) ❑ If patient is already on loop diuretics: IV dose ≥ home PO dose (rule of thumb: IV dose = 2.5x equivalent oral daily dose) ❑ If patient is not already on loop diuretics, administer IV starting dose of 20 to 40 mg Continuous IV infusion: Initial IV bolus administered slowly over 1 to 2 minutes, then continuous IV infusion rate of 10-40 mg/h	600 mg
	Bumetanide (duration of action: 4 to 6 h)	PO dose for chronic heart failure: 0.5 to 1.0 mg once or twice	10 mg
	Torsemide (duration of action: 12 to 16 h)	PO dose for chronic heart failure: 10 to 20 mg once	200 mg
Thiazide diuretics	Chlorothiazide (duration of action: 6 to 12 h)	PO: 250 to 500 mg once or twice	1000 mg
	Hydrochlorothiazide (duration of action: 6 to 12 h)	PO: 25 mg once or twice	200 mg
	Metolazone (duration of action: 12 to 24 h)	PO: 2.5 mg once	20 mg
K+- sparing diuretic	Amiloride (duration of action: 24 h)	PO: 5 mg once	20 mg
	Spironolactone (duration of action: 1 to 3 h)	PO: 12.5 to 25.0 mg once	50 mg
	Triamterene (duration of action: 7 to 9 h)	PO: 50 to 75 mg twice	200 mg
ACE inhibitors	Enalapril	2.5 mg twice	10 to 20 mg twice
	Lisinopril	2.5 to 5 mg once	20 to 40 mg once
	Ramipril	1.25 to 2.5 mg once	10 mg once
ARBs	Candesartan	4 to 8 mg once	32 mg once
	Losartan	25 to 50 mg once	50 to 150 mg once
	Valsartan	20 to 40 mg twice	160 mg twice
Beta blockers	Bisoprolol	1.25 mg once	10 mg once
	Carvedilol	3.125 mg twice	50 mg twice
	Carvedilol CR	10 mg once	80 mg once
	Metoprolol succinate extended release	12.5 to 25.0 mg once	200 mg once
Aldosterone antagonists	Spironolactone	12.5 to 25.0 mg once	25 mg once or twice
	Eplerenone	25 mg once	50 mg once
Inotropes	Dopamine	5 to 10 mcg/kg/min, OR 10 to 15 mcg/kg/min
	Dobutamine	2.5 to 5 mcg/kg/min, OR 5 to 20 mcg/kg/min
	Milrinone	0.125 to 0.75 mcg/kg/min
Vasodilators	Nitroglycerin	5 to 10 mcg/min, increase dose by 5-10mcg/min every 3-5 mins as tolerated	Max is 400mcg/min
	Nitroprusside	5 to 10 mcg/min, increase dose by 5-10mcg/min every 5 mins as tolerated	Max is 400mcg/min
	Nesiritide	2 mcg/kg bolus; then 0.01 mcg/kg/minute continuous infusion	Max of 0.03 mcg/kg/minute
	Morphine sulfate	2.5 – 5 mg bolus	Max is 5mg
Hydralazine and isosorbide dinitrate	Fixed-dose combination	37.5 mg hydralazine/20 mg isosorbide dinitrate 3 times daily	75 mg hydralazine/40 mg isosorbide dinitrate 3 times daily
	Individual doses	Hydralazine: 25 to 50 mg 3 or 4 times daily Isosorbide dinitrate: 20 to 30 mg 3 or 4 times daily	Hydralazine: 300 mg daily in divided doses Isosorbide dinitrate: 120 mg daily in divided doses
Digoxin		Loading dose: PO- 10 to 15 mcg/kg (half the total loading dose initially, then 1/4th the loading dose every 6 to 8 hours two times), OR IV- 8 to 12 mcg/kg (half the total loading dose initially, then 1/4th the loading dose every 6 to 8 hours two times) Maintenance dose: PO- 3.4 to 5.1 mcg/kg/day once daily, OR IV- 2.4 to 3.6 mcg/kg/day once daily Drugs that increase the concentration of digoxin include amiodarone, quinidine and verapamil
Type III phosphodiesterease inhibitors (PDEIs)	Milrinone	Loading dose: IV infusion 50mcg/kg admnistered over 10 min Maintenance dose: IV infusion: 0.375 to 0.75 mcg/kg/minute Inhibit degradation of cyclic AMP
	Enoximone	IV dose ranging from two doses of 25 mg to two doses of 100 mg.
Vasopressin Antagonists	Conivaptan	For euvolemic or hypervolemic hyponatremia, following regimen is used: Loading dose: IV: 20 mg infused over 30 minutes followed by a continuous infusion of 20 mg over 24 hours (0.83 mg/hour) for 2 to 4 days	Maximum dose of 40 mg over 24 hours
	Tolvaptan
For Acute respiratory distress syndrome	Corticosteroids low-molecular-weight heparin	Moderate-dose IV methylprednisolone, to 120 mg per kg per day for up to 25 days 40 mg of enoxaparin [Lovenox] or 5,000 units of dalteparin [Fragmin] subcutaneously per day) or low-dose, unfractionated heparin(5,000 units subcutaneously twice daily)
For high-altitude pulmonary edema	Acetazolamide Dexamethasone	250 mg PO q12h 4 mg PO q6h