Pediatric Viral Myocarditis Medication
- Author: Edwin Rodriguez-Cruz, MD; Chief Editor: Howard S Weber, MD, FSCAI more...
If congestive heart failure is present in a patient with viral myocarditis, digitalis may be useful in maintaining adequate function. Diuretics can be given concomitantly to remove excess extracellular fluid and to decrease preload. Caution should be exercised, because removal of fluid may cause low cardiac output and shock (see the Cardiac Output calculator). A higher venous-filling pressure may be necessary to maintain an adequate cardiac output. Intracardiac pressure monitoring can facilitate maintenance of adequate filling pressures.
Inotropic agents are used when cardiac output cannot be maintained by less invasive measures. Dopamine, dobutamine, inamrinone (formerly amrinone), and milrinone are the most commonly used vasopressors.
Afterload reduction is most important in treating acute myocarditis and is used when hypotension is not present. This decreases the workload for the compromised myocardium and can allow patients to recover from the acute phase of illness. Agents that reduce afterload improve cardiac output by decreasing systemic arterial resistance. Intravenous medications such as nitroprusside, inamrinone, and milrinone can be replaced with oral angiotensin-converting enzyme (ACE) inhibitors when the patient stabilizes.
The use of immunosuppressive agents for the treatment of viral myocarditis is still controversial. Some animal studies revealed an exacerbation of viral cytotoxicity when subjects were treated with immunosuppressive agents. Small series in humans have shown that the condition of patients improves when the patients are treated with these agents.
In a randomized study of 111 patients, the Multicenter Myocarditis Treatment Trial found that left ventricular function and survival did not significantly differ between patients given any of the following 3 treatment modalities :
Conventional therapy without immunosuppression
Intravenous gamma globulin may be important in the treatment of acute myocarditis.[18, 19] It has been associated with improved left ventricular function and improved survival.
New therapeutic agents are being studied as candidates for the treatment of myocarditis. These include agents that inhibit the virus entrance to the cells; antiviral agents that inhibit translation, transcription, or both; and interferon, among others. However, these strategies are still in early stages, and although they have shown promising results, some time may go by before they are widely accepted.
Pleconaril, an investigational agent that inhibits viral attachment to host cell receptors, has broad antienteroviral activity and, in clinical trials, has demonstrated benefit in children with enteroviral meningitis. This medicine is being tested in children with myocarditis. Pleconaril is currently an investigational drug from Schering-Plough Corporation.
These agents may improve left ventricular function by increasing myocardial contraction through inhibition of the sodium/potassium adenosine triphosphatase (ATPase) pump. This leads to sodium accumulation within the myocyte, which stimulates the sodium-calcium exchange. The increased intracellular calcium increases the force of contraction.
Digoxin is a cardiac glycoside with direct inotropic effects in addition to indirect effects on the cardiovascular system. It acts directly on cardiac muscle, increasing myocardial systolic contractions. Digoxin's indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.
Hypoperfusion of the kidneys causes retention of sodium and water, which produces peripheral and pulmonary edema. Diuretics decrease the intravascular volume overload.
This loop diuretic is the diuretic of choice in pediatric patients. It increases excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule.
This is a thiazide diuretic. If given with furosemide, it may decrease hypercalciuria. Chlorothiazide inhibits sodium reabsorption at the distal tubule in the kidney.
Spironolactone is a potassium-sparing diuretic. It acts on the distal convoluted tubule of the kidney as an aldosterone antagonist.
Angiotensin-converting enzyme (ACE) inhibitors
Cardiac output and systemic resistance determine blood pressure. When systemic resistance is decreased with afterload reduction, myocardial shortening and stroke volume improve. Therefore, cardiac output can be maintained at a lower heart rate with lower myocardial oxygen demand. ACE inhibitors decrease the production of angiotensin II, a potent vasoconstrictor. High levels of angiotensin II have also been associated with cellular damage in patients with myocarditis.
Captopril reduces afterload and myocyte necrosis. It is beneficial in all stages of chronic heart failure. The drug's pharmacologic effects result in a decrease in systemic vascular resistance, reducing blood pressure, preload, and afterload. Dyspnea and exercise tolerance are improved.
A competitive ACE inhibitor, enalapril reduces angiotensin II levels, decreasing aldosterone secretion. The drug lowers systemic arterial blood pressure, reducing injury caused by elevated blood pressure. It may slow the progression of renal failure by lowering intraglomerular pressure or other intrarenal mechanisms. Enalapril may be used every day or twice per day, which may improve compliance in comparison with a 3-time-per-day medication, such as captopril.
Adrenergic agonist agents (inotropic agents)
Dopamine is a precursor to epinephrine; thus, it augments the endogenous release of catecholamines. It also stimulates specific dopamine receptors. Dobutamine does not promote the release of endogenous epinephrine; it predominantly augments myocardial contractility via beta1 stimulation.
At lower doses, this drug stimulates beta1-adrenergic and dopaminergic receptors (renal vasodilation, positive inotropism); at higher doses, it stimulates alpha-adrenergic receptors (renal vasoconstriction).
Dobutamine stimulates beta1-adrenergic receptors. It has less alpha1 stimulation than dopamine; therefore, it produces less of an increase in systemic vascular resistance.
Cyclic adenosine monophosphate (c-AMP) phosphodiesterase inhibitors
Inotropic effects occur through the inhibition of cyclic adenosine monophosphate (c-AMP) phosphodiesterase, which increases the cellular levels of c-AMP. The sodium-potassium pump is not affected, as with digitalis. Vasodilatory activity is related to the direct relaxation effect on vascular smooth muscle.
Inamrinone produces vasodilation and increases the inotropic state. This agent is more likely to cause tachycardia than dobutamine is, and it may exacerbate myocardial ischemia.
Milrinone is a bipyridine with positive inotropic and vasodilator effects and little chronotropic activity. Milrinone is different in mode of action from digitalis glycosides and catecholamines.
Immunoglobulin is a purified preparation of gamma globulin. It is derived from large pools of human plasma and consists of 4 subclasses of antibodies, approximating the distribution of human serum.
Use of these agents in myocarditis is not widely accepted. Clinical studies have shown that intravenous immunoglobulin (IVIG) may improve left ventricular function and survival in children.
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