Treatment of myocarditis in children

Indications for hospitalization for myocarditis

The tactics of managing patients with myocarditis depend on the nature of the disease. Acute viral myocarditis often proceeds favorably and ends in recovery without any treatment. Patients with acute clinically expressed myocarditis are subject to hospitalization.

Chronic myocarditis in 30-50% of children acquires a recurrent course, leading to the progression of chronic heart failure. In this case, it is necessary to carry out a consistent multi-stage complex of treatment and rehabilitation measures first in a hospital, and then in a sanatorium or outpatient clinic. The inpatient stage of treatment of patients with chronic myocarditis lasts from 6 to 8 weeks and includes non-drug (general measures) and drug treatment, sanitation of foci of chronic infection, as well as initial physical rehabilitation.

Non-drug treatment of myocarditis in children

Non-drug treatment includes the elimination of factors that can suppress myocardial function:

• limitation of physical activity (in the acute phase, it is recommended to limit the child’s physical activity for 2-4 weeks, taking into account the severity of the disease);
• a complete, rational diet with sufficient amounts of vitamins, proteins, and limited table salt;
• The drinking regimen depends on the amount of urine excreted (200-300 ml less), on average, the amount of liquid consumed per day in children of the first years of life with acute myocarditis is from 400 to 600 ml (under the control of diuresis).

Drug treatment of myocarditis in children

The main directions of drug treatment of myocarditis are determined by the main links of the pathogenesis of myocarditis: infection-induced inflammation, inadequate immune response, death of cardiomyocytes (due to necrosis and progressive dystrophy, myocarditic cardiosclerosis), and disturbance of cardiomyocyte metabolism. It should be taken into account that in children myocarditis often occurs against the background of chronic focal infection, which becomes an unfavorable background (intoxication and sensitization of the body), contributing to the development and progression of myocarditis.

Drug treatment of myocarditis includes several directions:

• impact on inflammatory, autoimmune and allergic processes;
• reduction of the synthesis of biologically active substances;
• restoration and maintenance of hemodynamics;
• impact on myocardial metabolism;
• active treatment of infection foci.

Depending on the etiology, the treatment of myocarditis has its own characteristics.

In myocarditis caused by infectious agents, all patients require non-specific supportive and symptomatic treatment (bed rest with gradual activation, detoxification and general strengthening therapy, vitamins, antihistamines), as well as the prescription of specific drugs, if possible.

In myocarditis that occurs against the background of systemic connective tissue diseases (systemic lupus erythematosus, rheumatoid arthritis) or endocrine diseases (thyrotoxicosis, pheochromocytoma), treatment of the underlying disease is indicated first of all.

In myocarditis due to allergic reactions (most often to sulfonamides, methyldopa, antibiotics, insect bites), it is recommended to eliminate the action of the allergen and, if necessary, prescribe antihistamine drugs.

In toxic myocarditis (alcohol, cocaine, fluorouracil, cyclophosphamide, doxorubicin, streptomycin, acetylsalicylic acid), elimination of the provoking factor is indicated.

Etiotropic treatment of myocarditis in children

The severity of the inflammatory process in the myocardium is determined by the virulence of the pathogen and the adequacy of the body's immune response. The most pronounced inflammatory reaction is caused by extracellular pathogens (streptococci, staphylococci, pneumococci). Etiotropic treatment of myocarditis (usually acute) caused by extracellular bacteria is carried out quite successfully by prescribing antibiotics (cephalosporins, macrolides). The participation of intracellular pathogens (in most cases represented by an association of microorganisms) in the pathological process in myocarditis complicates the complete sanitation of the body and predetermines a different approach to etiotropic therapy. There is a need to resort to repeated courses of antibiotics that have the ability to affect the most common intracellular non-viral pathogens, for which macrolides and fluoroquinolones are used. At the same time, it is necessary to act on the viral infection, including by prescribing immunomodulatory drugs.

Treatment of myocarditis depending on the pathogen

The causative agent of myocarditis	Etiotropic therapy
Influenza A and B viruses	Rimantadine orally 1.5 mg/kg/day (children 3-7 years old), 100 mg/day (children 7-10 years old). 150 mg/day (children over 10 years old), in 3 doses for 7 days. The drug is prescribed no later than 48 hours from the onset of symptoms.
Varicella zoster, herpes simplex, Epstein-Barr viruses	Acyclovir orally 15-80 mg/kg/day or intravenously 25-60 mg/kg/day in 3 doses for 7-10 days
Cytomegalovirus	Ganciclovir intravenously 5 mg/kg/day in 2 administrations for 14-21 days + human immunoglobulin anti-cytomegalovirus (cytotect) 2 ml/kg 1 time per day intravenously slowly (5-7 ml/h) every other day 3-5 infusions
Chlamydia and mycoplasma	Azithromycin orally 10 mg/kg/day in 2 doses on the first day, then 5 mg/kg/day once a day from the 2nd to the 5th day or erythromycin intravenously by drip 20-50 mg/kg/day, infusion every 6 hours
Borrelia burgdorferi (Lyme disease)	Azithromycin orally 10 mg/kg/day in 2 doses for 1 day, then 5 mg/kg once a day for 4 days or benzylpenicillin intravenously by drip 50,000-100,000 IU/kg/day in 6 doses for 2-3 weeks or ceftriaxone intravenously by drip 50-100 mg/day once a day for 2-3 weeks. Due to frequent conduction disturbances, patients require constant monitoring of ECG data. If high-degree AV blocks occur, temporary cardiac pacing may be required.
Staphylococcus aureus	Before determining the sensitivity to antibiotics, vancomycin therapy is administered: intravenously by drip 40 mg/kg/day in 2 doses for 7-10 days. Based on the results of determining the sensitivity to antibiotics, antimicrobial therapy is adjusted if necessary.
Corynebacterium diphtheriae	An emergency administration of diphtheria antitoxin is performed. The dose depends on the severity of the disease. Human immunoglobulin antidiphtheria (purified concentrated liquid equine antidiphtheria serum) intravenously by drip over 1 hour 20,000-150,000 IU once + erythromycin intravenously by drip 20-50 mg/kg/day in 2-3 administrations over 14 days. Due to the frequent development of arrhythmias and conduction disorders, patients require constant monitoring of ECG data and, if necessary, the administration of antiarrhythmic drugs. If high-degree AV blocks occur, temporary cardiac pacing may be required.
Cryptococcus neolormans	Amphotericin B IV slowly 0.1-0.3 mg/kg once a day, then gradually increase the dose to 1.0 mg/kg/day. The exact duration of treatment has not been established
Toxoplasma gondii (toxoplasmosis)	Pyrimethamine orally 2 mg/kg/day in 2 doses for 3 days, then 1 mg/kg/day in 2 doses once every 2 days for 4-6 weeks + sulfadiazine orally 120 mg/kg/day in 3 doses for 4-6 weeks + folic acid orally 5-10 mg once a day until the end of pyrimethamine therapy. Folic acid is administered to prevent suppression of hematopoiesis
Trichinella spiralis (trichinosis)	Mebendazole 200 mg/day in 3 doses for 10 days
In rheumatic myocarditis, regardless of the culture of beta-hemolytic streptococcus A	Benzylpenicillin intramuscularly 50,000-100,000 IU/kg/day 3 times a day for 10 days or amoxicillin orally 45-90 mg/kg/day 3 times a day for 10 days or benzathine benzylpenicillin intramuscularly 600,000 IU for children under 25 kg and 1,200,000 IU for children weighing more than 25 kg once

Specific treatment for myocarditis caused by Coxsackie viruses A and B, ECHO viruses, polio virus, enteroviruses, as well as mumps, measles, and rubella viruses has not been developed.

Non-specific anti-inflammatory therapy

In addition to infectious agents, inflammatory and autoimmune processes have a direct negative impact on the myocardium, which explains the need for anti-inflammatory and immunomodulatory therapy.

Traditional NSAIDs are widely used in the complex treatment of myocarditis. NSAIDs have an active anti-inflammatory effect, reduce oxidative phosphorylation, leading to a limitation of adenosine triphosphate (ATP) formation, reduce increased capillary permeability, and have a stabilizing effect on lysosome membranes.

It should be taken into account that in case of viral etiology of myocarditis in the acute phase of the disease (first 2-3 weeks), the administration of NSAIDs is contraindicated, since they can increase damage to cardiomyocytes, but in a later period their use is justified.

NSAIDs should be taken internally after meals, washed down with jelly or milk:

• acetylsalicylic acid orally after meals 0.05 mg/kg/day in 4 doses for 1 month, then 0.2-0.25 mg/kg/day in 4 doses for 1.5-2 months, or
• diclofenac orally after meals or rectally 3 mg/kg/day in 3 doses for 2-3 months, or
• indomethacin orally after meals or rectally 3 mg/kg/day in 3 doses for 2-3 months.

Acetylsalicylic acid is the drug of choice for the treatment of rheumatic fever and Kawasaki disease. For Kawasaki disease, acetylsalicylic acid is prescribed orally at 30-40 mg/kg/day in 4 doses for 14 days, then at 3-5 mg/kg/day in 4 doses for 1.5-2 months.

Treatment of myocarditis in children with glucocorticoids

Glucocorticoids are prescribed only in extremely severe cases of myocarditis (severe progressive heart failure or severe rhythm disturbances refractory to antiarrhythmic therapy) and in cases where a pronounced autoimmune component of inflammation has been proven (antibodies to the myocardium have been detected in high titers).

Justified prescription of glucocorticosteroids helps to quickly stop inflammatory and autoimmune reactions. Prednisolone should be prescribed in a short course. Positive clinical effects after prednisolone prescription are noted quite quickly (edema, dyspnea decrease, ejection fraction increases). Considering that chronic intracellular pathogens persist in the body during prolonged and chronic myocarditis, a course of antiviral therapy should be conducted before prescribing glucocorticosteroids.

• Prednisolone orally 1 mg/kg per day in 3 doses for 1 month, followed by a gradual reduction by 1.25 mg every 3 days for 1.0-1.5 months.

If the effect is insufficient, the maintenance dose of prednisolone (0.5 mg/kg/day) continues to be taken as indicated for several months (6 months or more).

For acute rheumatic myocarditis, the following prescriptions are recommended:

• prednisolone orally 0.7-1.0 mg/kg per day in 3 doses, taking into account the physiological biorhythm of the adrenal cortex for 2-3 weeks, then
• diclofenac 2-3 mg/kg in 3 doses for 1-1.5 months.

Drugs that affect the autoimmune process

As immunomodulating drugs with antiviral action, it is advisable to use exogenous interferons, endogenous interferon inducers and antiviral immunoglobulins in the acute period of the disease. At present, these are the only effective drugs in case of viral myocardial damage. Their use is also advisable in case of relapses of chronic myocarditis.

• Human immunoglobulin normal |IgG + IgA + IgM] intravenously 2 g/kg once a day, 3-5 days.
• Interferon alpha-2 (suppositories) 150 thousand IU (for children under 7 years); 500 thousand IU (for children over 7 years) 2 times a day for 14 days, 2 courses with an interval of 5 days.

During the period of convalescence and remission, the child is shown a course of preventive vaccine therapy with drugs that restore the phagocytosis system, activating the functional activity of neutrophilic granulocytes and monocyte-macrophages. In our practice, we use the low-molecular therapeutic vaccine of ribosomal origin ribomunil.

Ribomunil (regardless of age) is prescribed orally in the morning on an empty stomach, 3 tablets with a single dose, 1 tablet with a triple dose or one sachet (after dilution in a glass of water) 4 days a week for 3 weeks in the 1st month of treatment, then the first 4 days of each month for the next 5 months. For young children, it is recommended to prescribe the drug in granulated form.

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Treatment of myocarditis in children with cytostatics

In subacute and chronic myocarditis, glucocorticosteroids can be used in combination with immunosuppressants (cyclosporine). Convincing evidence of the effectiveness of immunosuppressive therapy has not been obtained, although according to some data, 60% of patients have shown improvement. Cyclosporine is prescribed orally 3-5 mg/kg/day in 2 doses for 3-4 weeks.

Cardiotrophic and metabolic therapy

To improve energy metabolism in the myocardium, metabolic drugs are included in the complex therapy of myocardial insufficiency.

In case of decreased left ventricular ejection fraction, "low ejection" syndrome, signs of myocardial remodeling, neoton is used. After intravenous administration of neoton, manifestations of energy deficiency are stopped, since, penetrating directly into the cell, it promotes full contraction of myofibrils.

Neoton is administered intravenously by drip, 1-2 g in 50-100 ml of 5% glucose solution 1-2 times a day, the course duration is 7-10 days.

In chronic myocarditis, optimization of myocardial energy supply can be achieved by reducing myocardial consumption of free fatty acids, decreasing the intensity of their oxidation, stimulating synthesis (glucose-insulin mixture) and replacing macroergs (neoton). For this purpose, direct inhibitors of free fatty acid β-oxidation (trimetazidine) are used, as well as inhibitors of the carnitine-palmitine complex, which ensures the supply of fatty acids to the mitochondria (meldonium, levocarnitine):

• trimetazidine orally 35 mg 2 times a day for 1 month, or
• levocarnitine intravenously by drip 5-10 ml of 10% solution once a day for 5 days or orally 50-200 mg/kg per day in 1-2 doses for 1-2 months, or
• meldonium orally 100 mg 2 times a day for 1 month.

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Symptomatic treatment of myocarditis

Treatment of acute heart failure

In the treatment of acute heart failure, two stages can be distinguished: emergency care and supportive therapy, which involves both the impact on the underlying disease and cardiac therapy.

First of all, the patient needs to be placed in an elevated position (which will reduce the flow of venous blood to the heart - reduce preload), oxygen inhalation should be established (through 30% ethyl alcohol) or with 2-3 ml of 10% polyoxymethylheptamethyltetrasiloxane (antifoamsilane), and venous tourniquets should be applied to the lower extremities.

To reduce the volume of circulating fluid, a fast-acting diuretic is administered intravenously:

• furosemide intravenously 2-5 mg/kg per day in 1-2 administrations until clinical improvement.

The first dose of furosemide is half or a third of the daily dose. Then, depending on the severity of heart failure, intramuscular or oral administration of furosemide is switched to, the dose is titrated and reduced to 0.5-1.0 mg/kg per day.

In order to relieve secondary bronchospasm and reduce pulmonary hypertension, a 2.4% aminophylline solution is also administered intravenously: 2.4% solution 1 ml/year of life (no more than 5 ml) until clinical improvement. When more than 5 ml of aminophylline is administered, tachycardia and arterial hypotension may increase.

In pulmonary edema, trimeperidine is of great importance; it is administered intravenously or intramuscularly. The drug has a sedative effect, helps reduce the sensitivity of the respiratory center to hypoxia, and also leads to redistribution of blood due to the effect on peripheral vessels with a decrease in venous inflow to the right parts of the heart:

• trimeperidine 2% solution, single dose intravenously 0.1 ml/year of life until clinical improvement in the condition.

In critical situations, glucocorticosteroids are used; their favorable hemodynamic effect is associated with positive inotropic, vasodilatory, bronchospasmolytic, antiallergic and anti-shock effects:

• prednisolone intravenously 3-5 mg/kg per day, it is recommended to immediately administer half of the daily dose, then - according to the condition.

In case of hypokinetic type of circulatory disorder, cardiac glycosides are used. Preference is given to fast-acting drugs - strophanthin-K and lily of the valley herb glycoside:

• lily of the valley herb glycoside 0.06% solution intravenously by slow jet stream of 0.1 ml (children 1-6 months). 0.2-0.3 ml (children 1-3 years), 0.3-0.4 ml (children 4-7 years), 0.5-0.8 ml (children over 7 years) 3-4 times a day until clinical improvement, or
• strophanthin-K 0.05% solution intravenously by slow jet stream of 0.05-0.1 ml (children 1-6 months), 0.1-0.2 ml (children 1-3 years), 0.2-0.3 ml (children 4-7 years), 0.3-0.4 ml (children over 7 years) 3-4 times a day until clinical improvement.

Sympathomimetic amines also contribute to improving myocardial contractility. These drugs can be considered the drugs of choice for short-term treatment in severe cases. Treatment with these drugs should be carried out in an intensive care unit under careful monitoring of ECG data, since they are administered by continuous intravenous infusion until the condition is stabilized:

• dobutamine IV 2-10 mcg/kg per minute, or
• dopamine intravenously 2-20 mcg/kg per minute for 4-48 hours.

For the hyperkinetic type of circulatory disorder, ganglionic blockers or neuroleptics are prescribed:

• azamethonium bromide 5% solution intravenously slowly over 6-8 minutes 0.16-0.36 ml/kg (children under 2 years), 0.12-0.16 ml/kg (children 2-4 years), 0.8-0.12 ml/kg (children 5-7 years), 0.04-0.08 ml/kg (children over 8 years) in 20 ml of 20% dextrose (glucose) solution, according to the condition, or
• Droperidol 0.25% solution 0.1 ml/kg (depending on condition).

Therapy for rhythm and conduction disorders

Treatment of tachyarrhythmias is carried out with antiarrhythmic drugs along with the means used to correct chronic heart failure. If the disorders of the systolic function of the myocardium are pronounced, then preference is given to amiodarone due to its least effect on the pumping function of the heart; sotalol can be used (provided that it is prescribed by the titration method). The use of drugs from other groups may be accompanied by a decrease in the systolic function of the myocardium.

Therapy for chronic heart failure

Medicines currently used to treat patients with chronic heart failure are divided into three main categories according to the degree of evidence: essential, additional and auxiliary agents.

• Essential drugs - drugs whose effect has been proven beyond doubt, they are recommended specifically for the treatment of chronic heart failure (level of evidence A). This group includes six classes of drugs:
  • angiotensin-converting enzyme (ACE) inhibitors are indicated for all patients with chronic heart failure, regardless of the etiology, stage of the process and type of decompensation;
  • beta-blockers - neurohormonal modulators used in addition to an ACE inhibitor;
  • aldosterone receptor antagonists used together with an ACE inhibitor and a beta-blocker in patients with severe chronic heart failure;
  • diuretics - indicated for all patients with clinical symptoms associated with excessive retention of sodium and water in the body;
  • cardiac glycosides - in small doses;
  • AN receptor antagonists can be used not only in cases of intolerance to ACE inhibitors, but also along with ACE inhibitors as a first-line agent for blocking the renin-angiotensin-aldosterone system in patients with clinically pronounced decompensation.
• Additional agents whose efficacy and safety have been demonstrated in individual large studies, but further clarification is needed (evidence level B):
  • statins recommended for use in patients with chronic heart failure associated with coronary heart disease;
  • indirect anticoagulants, indicated for use in most patients with chronic heart failure.
• Adjuvants - the effect and influence of these drugs on the prognosis of patients with chronic heart failure are unknown (not proven), which corresponds to class III recommendations, or level of evidence C:
  • antiarrhythmic drugs (except beta-blockers) for life-threatening ventricular arrhythmias;
  • acetylsalicylic acid (and other antiplatelet agents);
  • non-glycoside inotropic stimulants - in case of exacerbation of chronic heart failure, occurring with low cardiac output and persistent arterial hypotension;
  • peripheral vasodilators (nitrates), used only in case of concomitant angina; calcium channel blockers in case of persistent arterial hypertension.