Download Management of Acute Heart Failure

Management of Acute Heart Failure Bruce W. Keene, DVM, DACVIM (Ca) and Clarke E. Atkins, DVM, DACVIM (Ca and IM) North Carolina State University OVERVIEW OF HEART FAILURE Heart failure (HF) describes the situation in which the heart cannot maintain cardiac output sufficient to meet the perfusion needs of the metabolizing tissues while maintaining normal venous pressures, and exercise capacity is thus limited. In heart failure, decreased cardiac output and blood pressure trigger a cascade of events designed to return those parameters toward normal. These events include the neuroendocrine system, kidney, heart muscle, and peripheral vasculature, and they activate vasoconstrictor and sodium–retaining control systems as well as tissue mediators of inflammation. Short‐term activation of these control systems helps maintain arterial blood pressure and flow in the face of reduced cardiac output, but chronic output compensation achieved through these mechanisms comes at the expense of damage to the heart. Progression of heart disease triggers increasing dependence on neurohormonal activity, subsequent cardiac remodeling, and increased heart rate to maintain output. These chronic changes also predispose to arrhythmias and sudden death. Chronic activation of these “compensatory” mechanisms is maladaptive – a concept that has become central to the management of chronic heart failure. Clinical signs of congestive heart failure (CHF) are explained by a combination of elevated venous pressures (pulmonary edema, pleural effusion, jugular venous distension, hepatomegaly, ascites), inadequate tissue perfusion (exercise intolerance, azotemia, episodic weakness or syncope), and metabolic disturbances (loss of appetite, cachexia). The hemodynamic changes caused by the combination of underlying heart malfunction (e.g. mitral valve insufficiency) and the body’s responses to that malfunction (e.g. arterial vasoconstriction, increased catecholamine secretion, activation of the renin‐angiotensin‐aldosterone system along with secretion of an alphabet soup of inflammatory and vasoactive cytokines and hormones) explain the constellation of acute clinical signs of heart failure. The acute management of symptomatic heart failure in veterinary medicine is involves the relatively systematic pharmacologic adjustment of the major determinants of heart function to achieve a new level of hemodynamic compensation in the face of the disease and the body’s response to the disease that is present. Chronic therapy of CHF is currently aimed at maintaining those hemodynamic gains while modulating and blunting the body’s neuroendocrine responses in an attempt to minimize the clinical signs of CHF, protect the heart and vascular tissues, and prolong life. Table 1 summarizes the commonly used drugs and dosages employed in the acute and chronic management of heart failure in dogs and cats. A FRAMEWORK FOR MANAGING ACUTE HEART FAILURE IN DOGS A practical therapeutic framework for managing acute heart failure in dogs might include specific diagnostic, treatment, and educational plans. Treatment plans should consider the natural history of the disease, and carefully weigh what is known regarding the potential benefits and risks of each medication, and their combination, when used in a specific clinical setting. Canine patients with symptomatic heart failure most commonly present to their veterinarian for dyspnea (shortness of breath / diffculty breathing, often associated with orthopnea or a history of not wanting to lie down) and coughing, most often in conjunction with a history of some days or weeks of exercise intolerance, lethargy, reduced appetite, and weight loss. While small dogs (less than 15 – 20kg) in heart failure almost ALL have a significant systolic heart murmur, it is certainly not true that all small dogs with a heart murmur and a cough are in heart failure. It is important to note that cough (especially cough in the face of a normal appetite, sleep patterns, and respiratory rate when not coughing) is not usually the primary complaint of dogs presenting for congestive heart failure. If the patient is not too anxious or dyspneic, confirmation of the diagnosis with thoracic radiographs is always indicated. In animals where there is a question regarding the underlying cause of cough/dyspnea, measurement of serum n‐
terminal pro brain natriuretic peptide (proBNP) concentrations can be a useful adjunct in the diagnosis of heart failure in this group (Cardiopet© proBNP concentrations less than 900pmol/ml are rarely associated with CHF; concentrations above 1800pmol/ml are often associated with CHF, and would be expected in CHF patients under these circumstances). Most dogs presenting with their first onset of heart failure secondary to longstanding mitral valve disease respond to standard therapy with:  pimobendan (0.25 – 0.3mg/kg BID to improve contractile function and reduce afterload and preload),  furosemide, 2mg/kg administered parenterally hourly until the respiratory rate and effort have decreased substantially or a dose of 6mg/kg has been reached; with or without nitroglycerine ointment or patch,  plus or minus an angiotensin converting enzyme inhibition (e.g. enalapril, 0.5mg/kg q12‐24H for additional mild preload and afterload reduction).  Additional supportive therapy (e.g. mild narcotic sedation / analgesia, supplemental oxygen, positional support to maintain comfort in a sternal position) should be utilized as determined by the patient’s respiratory rate and effort as the response to therapy is closely monitored. Response to therapy can be assessed in a number of more or less physiologically and hemodynamically sophisticated ways, but these must include (at a minimum) actually counting the respiratory rate accurately and often until the respiratory rate and effort have decreased substantially from presentation. We (veterinarians) are an optimistic lot by nature, and our experience is that failure to count (and decrease) the respiratory rate in the acute care setting is a common cause of treatment failure in acute heart failure. In the acute setting with previously untreated patients, it is impossible to tell on initial examination which patients will be refractory to treatment. Acutely, patients that fail to respond to standard doses of furosemide, nitroglycerine, enalapril, and pimobendan may require the use of additional intravenous inotropic support (e.g. dobutamine) or a specific intravenous arterial and venous dilator (e.g. sodium nitroprusside), additional (off label) doses of pimobendan (e.g. TID), more intensive preload reduction (e.g. constant intravenous infusion of furosemide), or an additional oral arterial dilator (e.g. amlodipine or hydralazine), and arrhythmia management if needed (e.g. digoxin with or without diltiazem for atrial fibrillation). Clinical results obtained in cases treated with these medications are best when treatment can be administered in a well‐monitored environment (e.g. continuous ECG and blood pressure monitoring under the direct supervision of an experienced veterinary criticalist or cardiologist). Treatment of refractory heart failure from any cause is a challenging and potentially frustrating endeavor for both veterinarians and clients. A thorough search for factors commonly involved in the progression of heart failure (systemic hypertension, arrhythmia, progression of underlying structural heart disease, anemia, occult or untreated infection) is indicated. A large number of drugs impact the heart and the vascular system. Some treatments for CHF elicit rapid hemodynamic effects (furosemide, dobutamine, sodium nitroprusside, pimobendan). Others treatments modulate neurohormonal or inflammatory mediators of CHF (ACE–inhibitors, spironolactone, beta–blockers, fatty acids). Still others may be used for pure symptom relief (airway medications, sedatives, oxygen). Understanding the clinical use of these drugs singly and in combination with others is critical. Always consider:  the indications & contraindications for drug use;  drug dosing and administration;  monitoring findings that would indicate drug benefit;  monitoring findings that would indicate adverse effects. Patient Follow‐Up Follow‐up is critical following life‐saving acute therapy, and effective assessment of the success and tolerability of cardiovascular drug therapy is one of the keys to successful follow‐up and consolidation of the gains made during acute therapy. Most patients in sinus rhythm at the time of routine hospital discharge following their first episode of congestive heart failure go home on a combination of pimobendan, enalapril or benazepril, furosemide, and spironolactone. Follow‐
up visits to adjust medications in patients who are eating and drinking normally at the time of discharge should usually occur within 3 – 10 days, to:  Review the medications with the owner every time they come in – this means recording the drug, current dose, compliance issues and any problems noted administering medication; consider the owner’s overall assessment of quality of life; discuss the dog’s appetite, activity, ability to sleep comfortably through the night, respiratory symptoms, exercise capacity, and urinary habits.  Identify any signs of possible drug intoxication  Evaluate the physical exam for signs of CHF: elevated JVP, hepatomegaly, ascites, thoracic auscultation, and overall body condition (cachexia)  RECORD THE BODY WEIGHT  Measure the arterial blood pressure  Test renal function and measure electrolytes if indicated  Assess the cardiac rhythm by auscultation; record an ECG if indicated by auscultation (heart rate assessment by auscultation or pulse palpation in atrial fibrillation is notoriously unreliable)  Determine if thoracic radiography is indicated; review the chest films for control of edema and effusions  Determine serum concentrations of drugs if indicated (e.g., serum digoxin, if used). DRUGS / DOSES in CANINE HEART DISEASE
USUAL DOSAGE 
PREPARATIONS
DRUG
AMLODIPINE
AMIODARONE
ATENOLOL
ATROPINE
BENAZEPRIL HCl
BUTORPHANOL
Norvasc, 2.5 mg tablet size
Cordarone injection, 50 mg/ml
Cordarone and USP scored tablets, 200
mg
Tenormin® and USP tablets, 25 and 50
mg
USP: 0.4 and 0.5 mg/ml for injection
Lotensin® tablets, 5, 10, 20, 40 mg
Torbutrol® 0.5 mg/ml for injection
Torbutrol® tablets, 1,5,10 mg
Coreg® tablets, 3.125, 6.25, 12.5 mg
CARVEDILOL
DIGOXIN
DIHYDROCODONE
DILTIAZEM
DOBUTAMINE
ENALAPRIL
EPINEPHRINE
ESMOLOL
FUROSEMIDE
HYDRALAZINE
HYDROCHLORTHI
AZIDE
LIDOCAINE
MAGNESIUM
METOPROLOL
MEXILETINE
NITROGLYCERINE
OINTMENT (2%)
PIMOBENDAN
PROCAINAMIDE
SPIRONOLACTONE
SOTALOL

Lanoxin®, Cardoxin®, USP tablets,
0.125, 0.25 mg
Elixirs of 0.05 mg/ml and 0.15 mg/ml
Lanoxin® for injection, 0.25 mg/ml
Hycodan®, 5 mg tablets
Cardizem® and USP tablets, 30, 60, 90,
120 mg
Dilacor XR® capsules 120, 180, 240 mg
Diltiazem for injection 50 mg/ml
Dobutrex® for injection, 250 mg (20 ml
vial)
Enacard®, USP tablets: 1.25, 2.5, 5, 10,
20 mg tablets
Adrenaline®,
USP 1:1000 (1 mg/ml), 1:10,000
Brevibloc®
100 mg/ml (10 ml vial)
Furosemide for injection 10 mg/ml and
50 mg/ml
Veterinary Lasix® tablets, 12.5, 50 mg
Furosemide USP tablets, 20, 40, 50, 80mg
Furosemide 1% oral syrup (10 mg/ml)
Apresoline®, USP tablets, 10, 25, 50 mg
Hydrodiuril®, USP tablets, 25, 50 mg
Xylocaine®, USP for injection, 2% (20
mg/ml) without epinephrine)
20% MgCl2 solution for injection
(contains 1.97 mEq of Mg++ per mL)
Toprol-XL® scored tablets, 25 mg
Mexitil®, USP capsules, 150, 200, 250
mg
Nitrol®, Nitro-bid®, Nitrostat®, USP 15
mg per inch
Minitran transderm patches 2.5, 5, 10, 15
mg/24 hr.
Vetmedin® 1.25, 2.5, 5 mg
Pronestyl®, USP for injection, 100
mg/ml; 500 mg/ml
Pronestyl® (-SR), Procan SR, USP
capsules & tablets, 250, 375, 500 mg
Aldactone®, USP tablets, 25 mg
Betapace®, USP scored tablets, 80, 160,
240 mg
0.05 – 0.2 mg/kg q12h-24h
Loading dose of 10 mg/kg PO once daily for two weeks; thereafter 5 to 7 mg/kg PO q24h;
DILUTE IF USED IV AND CONSULT CARDIOLOGIST
0.25 – 1.0 mg/kg PO q12h (up-titrate dosage)
0.04 mg/kg, IV, IM, SQ
0.5 mg/kg PO q12 – 24h (initial daily dose typically 0.5 mg/kg daily)
0.25 – 0.5 mg/kg, SQ, IM for sedation
0.5 mg/kg PO q 6-12h as an anti-tussive
initiate dosing in DCM at ½ to one 3.125 mg tabs q12 – 24h for 2 weeks; up-titrate the dose
every 2 – 4 weeks provided marked lethargy, progressive CHF, or relative bradycardia (HR <
100/minute during examination) do not develop.
Typical dose target is 6.25 – 12.5 mg tablet q12h.
0.005 to 0.0075 mg/kg q12h, PO; target serum conc. 0.05 – 1.5 ng/ml.
1.25 – 5.0 mg, PO q8 – 24 h for cough
0.5 to 2.0 mg/kg PO q8h (up-titrate dose)
0.1 mg/kg IV (can repeat every 2-3 minutes to 0.5 mg/kg while monitoring arterial blood
pressure).
2.5 to 20 mcg/kg/min, constant rate IV infusion.
0.25 to 0.5 mg/kg PO q12 – 24h (initial daily dose typically 0.5 mg/kg daily)
0.05 to 0.2 mg/kg, IV
500 mcg/kg (0.5mg/kg) administered over one minute,
followed by a 25 – 150 mcg/kg/min constant rate infusion.
2 – 6 mg/kg q8-12h as needed, IV, IM, SQ, PO
IV constant infusion: 1mg/kg/hour for 1 – 6 hours depending on response to therapy
following an initial 2mg/kg IV slow bolus.
0.5 – 3 mg/kg PO, q12h (up-titrate dose to ABP effect)
2-4 mg/kg q24 - 48h, PO
2 mg/kg IV, can repeat up to 8 mg/kg over a 10-minute period; 25 to 75 mcg/kg/minute
constant rate IV infusion; have IV diazepam ready to treat seizures if administering more than 6
mg/kg over a 10 minute period.
0 .75 – 1 mEq/kg/24h IV infusion
(50% of total dose can be given in 2 to 4 hours if necessary)
Start at ¼ of a 25 mg tablet once daily; up-titrate every two weeks to 12.5 mg q12h, PO (for a
20 – 30 kg dog)
5 – 8 mg/kg q8h, PO
¼ – 1 inch topically q12h; Patch: 2.5 – 10 mg (small – giant dog)
¼ inch topically q12h
0.3 – 0.6 mg/kg/day, divided; usual dose is 0.25 mg/kg q12h PO
2 mg/kg (IV) to a maximum total dose of 20 mg/kg over a 30-minute period;
25-40 mcg/kg/min IV infusion; 8 to 20 mg/kg, IM or SQ q4-6h;
10 – 20 mg/kg q8h PO (sustained release preparation)
0.5 mg/kg – 1.0 mg/kg q12-24h, PO
0.5 to 2 mg/kg q12h, PO
Check dosing information and standard textbooks for specific dosing recommendations.
Prescription of many of these drugs for dogs or cats constitutes an extra-label use; Clients should be so advised.
Recommendations are based on current (2012) standards of veterinary practice.
Many drugs must be titrated to effect, especially in dogs with heart failure. Consider drug interactions when
prescribing multiple drugs. Current information available at www.cardiologycarenetwork.org