Treatment of myocarditis in children

Indications for hospitalization with myocarditis

The management of patients with myocarditis depends on the nature of the course of the disease. Acute viral myocarditis often proceeds favorably and ends with recovery without any treatment. Patients with acute clinically expressed myocarditis are hospitalized.

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 conduct a consistent multi-stage complex of treatment and recovery measures first in the hospital, and then in a sanatorium or polyclinic. The stationary stage of treatment of patients with chronic myocarditis is from 6 to 8 weeks and includes non-drug (general measures) and drug treatment, sanation of foci of chronic infection, and initial physical rehabilitation.

Non-drug treatment of myocarditis in children

Non-drug treatment includes the removal of factors that can inhibit myocardial function:

• restriction of physical activity (in the acute phase it is recommended to limit the motor activity of the child within 2-4 weeks, taking into account the severity of the disease);
• a full-fledged rational diet with enough vitamins, proteins, restriction of table salt;
• drinking regime depends on the amount of urine allocated (200-300 ml less), the average amount of fluid consumed per day in children of the first years of life in acute myocarditis is from 400 to 600 ml (under the control of diuresis).

Medical treatment of myocarditis in children

The main directions of medical treatment of myocarditis are determined by the main links in the pathogenesis of myocarditis: infectious-caused inflammation, inadequate immune response, death of cardiomyocytes (due to necrosis and progressive dystrophy, myocarditis cardiosclerosis), metabolic disturbance of cardiomyocytes. It should be borne in mind that in children myocarditis often occurs against a background of chronic focal infection, which becomes an unfavorable background (intoxication and sensitization of the body), which contributes to the development and progression of myocarditis.

Medical treatment of myocarditis involves several areas:

• influence on inflammatory, autoimmune and allergic processes;
• reduction of synthesis of biologically active substances;
• restoration and maintenance of hemodynamics;
• effects on myocardial metabolism;
• active sanation of foci of infection.

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

In myocarditis caused by infectious agents, all patients need non-specific maintenance and symptomatic treatment (bed rest with gradual activation, detoxification and restorative therapy, vitamins, antihistamines), and the appointment, if possible, of specific drugs.

With myocarditis, which appeared against the background of systemic connective tissue diseases (systemic lupus erythematosus, rheumatoid arthritis) or endocrine diseases (thyrotoxicosis, pheochromocytoma), treatment of the underlying disease is primarily indicated.

In myocarditis due to allergic reactions (most often to sulfanilamides, methyldopa, antibiotics, insect bites) shows the elimination of the effect of the allergen and, if necessary, the appointment of antihistamine medicines.

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

Etiotropic treatment of myocarditis in children

The severity of the inflammatory process in the myocardium is due to the virulence of the pathogen and the adequacy of the immune response of the organism. 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 the appointment of antibiotics (cephalosporins, macrolides). The involvement of intracellular pathogens (in most cases represented by the association of microorganisms) in the pathological process in myocarditis makes it difficult to completely sanitize the organism 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, fluoroquinolones are used. Simultaneously, it is necessary to influence the viral infection, including by the appointment of immunomodulating agents.

Treatment of myocarditis depending on the pathogen

Pathogen of myocarditis	Etiotropic therapy
Influenza A and B viruses	Rimantadine inside 1.5 mg / kg / day (children 3-7 years), 100 mg / day (children 7-10 years). 150 mg / day (children older than 10 years), in 3 doses for 7 days. The drug is prescribed no later than 48 hours after the onset of symptoms
Viruses Varicella zoster, herpes simplex, Epstein-Barr	Acyclovir inside 15-80 mg / kg / day or iv in 25-60 mg / kg / day in 3 injections for 7-10 days
Cytomegalovirus	Ganciclovir iv 5 mg / kg / day in 2 injections for 14-21 days + human immunoglobulin anticytomegalovirus (cytotect) 2 ml / kg once a day in. In slowly (5-7 ml / h) every other day 5 5 infusions
Chlamydia and mycoplasma	Azithromycin inside 10 mg / kg / day in 2 doses on the first day, then 5 mg / kg / day once a day from day 2 to day 5 or erythromycin IV drip 20-50 mg / kg / day, infusion every 6 hours
Borrelia burgdorferi (Lyme disease)	Azithromycin inside 10 mg / kg / day in 2 doses for 1 day, then 5 mg / kg once a day for 4 days or benzylpenicillin intravenously in drip 50,000-100,000 IU / kg / day in 6 doses for 2-3 weeks or ceftriaxone IV drip 50-100 mg / day once a day for 2-3 weeks. Due to frequent conduction disorders, patients need constant monitoring of ECG data. If high-degree AV blockades occur, temporary pacing may be required
Staphylococcus aureus	Prior to determining the sensitivity to antibiotics, vancomycin therapy is administered: intravenous drip 40 mg / kg / day in 2 injections for 7-10 days. Based on the results of determining the sensitivity to antibiotics, if necessary, antimicrobial therapy is adjusted
Corynebacterium diphtheriae	An emergency antidiphtheria antitoxin is administered. The dose depends on the severity of the disease. Immunoglobulin human antidiphtheria (serum antidiphtherist horse purified concentrated liquid) IV drip for 1 hour 20 000-150 000 IU once + erythromycin iv drip 20-50 mg / kg / day in 2-3 injections for 14 days. In connection with the frequent development of arrhythmias and conduction disorders, patients need constant monitoring of ECG data and, if necessary, the appointment of antiarrhythmic drugs. If high-degree AV blockades occur, temporary pacing may be required
Cryptococcus neolormans	Amphotericin B in the / in 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 is not established
Toxoplasma gondii (toxoplasmosis)	Pyrimethamine inside 2 mg / kg / day in 2 doses for 3 days, then 1 mg / kg / day in 2 doses 1 every 2 days for 4-6 weeks + sulfadiazine inside 120 mg / kg / day in 3 doses in for 4-6 weeks + folic acid inside 5-10 mg once a day until the end of therapy with pyrimethamine. Folic acid is administered to prevent the suppression of hemopoiesis
Trichinella spiralis (trichinosis)	Mebendazole 200 mg / day in 3 doses for 10 days
With rheumatic myocarditis, regardless of the seeding of beta-hemolytic streptococcus A	Benzylpenicillin in / m 50 000-100 000 IU / kg / day 3 times a day for 10 days or amoxicillin inside 45-90 mg / kg / day 3 times a day for 10 days or benzathine benzylpenicillin im / m 600 000 units children up to 25 kg and 1 200 000 units for children with a body weight of more than 25 kg once

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

Nonspecific anti-inflammatory therapy

Direct negative impact on the myocardium, in addition to infectious pathogens, have inflammatory and autoimmune processes, 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, which leads to the limitation of the formation of adenosine triphosphate (ATP), reduce the increased permeability of capillaries, and have a stabilizing effect on the membranes of lysosomes.

It should be borne in mind that with the viral etiology of myocarditis in the acute phase of the disease (the first 2-3 weeks), the purpose of NSAIDs is contraindicated, since they can enhance damage to cardiomyocytes, but in later life their use is justified.

Inside NSAIDs should be taken after meals, washed down with acid, milk:

• acetylsalicylic acid inside after eating 0.05 mg / kg / day in 4 doses for 1 month, then 0.2-0.25 mg / kg / day for 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 inside after meals or rectally 3 mg / kg / day in 3 divided doses for 2-3 months.

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

Treatment of myocarditis in children with glucocorticoids

Glucocorticoid agents are prescribed only in extremely severe myocarditis (pronounced progressive heart failure or severe rhythm abnormalities refractory to antiarrhythmic therapy) and in those cases when a pronounced autoimmune component of inflammation is proven (antibodies to the myocardium in large titres were detected).

The justified appointment of glucocorticosteroids facilitates the rapid reduction of inflammatory and autoimmune reactions. Prednisolone is advisable to appoint a short course. Positive clinical effects after prescribing prednisolone are noted quite quickly (edema, dyspnea decrease, ejection fraction increases). Given that with prolonged and chronic course of myocarditis, chronic intracellular pathogens persist in the body, antiviral therapy should be administered before glucocorticosteroids are prescribed.

• Prednisolone inside 1 mg / kg per day in 3 doses for 1 month with a subsequent gradual decrease by 1.25 mg in 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 take on the indications for several months (6 months or more).

In acute rheumatic myocarditis, the following appointments are recommended:

• prednisolone inside 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 affecting the autoimmune process

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

• Immunoglobulin of a human is normal | IgG + IgA + IgM] in / in 2 g / kg once a day, 3-5 days.
• Interferon alfa-2 (suppositories) for 150 thousand ME (children under 7 years); 500 thousand ME (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, which activate the functional activity of neutrophilic granulocytes and monocyte-macrophages. We use a low molecular weight therapeutic ribosomal ribosomal vaccine in our practice.

Ribomunyl (regardless of age) is prescribed by mouth in the morning on an empty stomach, 3 tablets with a single dose, 1 tablet with a triple dose or one packet (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. Young children are recommended to prescribe the drug in granular form

[1], [2], [3], [4], [5], [6], [7]

Treatment of myocarditis in children with cytostatics

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

Cardiotrophic and metabolic therapy

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

With a decrease in the left ventricular ejection fraction, the syndrome of "small ejection", signs of myocardial remodeling, neoton is used. After intravenous administration of neoton, manifestations of energy deficiency are cut off, since, penetrating directly into the cell, it promotes a full reduction of myofibrils.

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

With chronic myocarditis, optimization of myocardial energy supply can be achieved by reducing myocardial consumption of free fatty acids, reducing the intensity of their oxidation, stimulating the synthesis (glucose-insulin mixture), and replacing the macroergs (neoton). To do this, use direct inhibitors of p-oxidation of free fatty acids (trimetazidine), as well as inhibitors of the carnitine-palmitic complex, which provides the intake of fatty acids in the mitochondria (mellonium, levocarnitine):

• trimetazidine inside 35 mg twice a day for 1 month, or
• Levocarnitine IV drip 5-10 ml of a 10% solution once a day for 5 days or inside 50-200 mg / kg per day in 1-2 doses for 1-2 months, or
• Mledonium orally 100 mg 2 times a day 1 month.

[8], [9], [10], [11], [12], [13]

Symptomatic treatment of myocarditis

Therapy of acute heart failure

In the treatment of acute heart failure, two stages can be distinguished: acute care and maintenance therapy, while providing for both an effect on the underlying disease. And carrying out cardiac therapy.

First of all, the patient needs to be given an elevated position (which will ensure a decrease in the influx of venous blood to the heart - decrease in preload), adjust oxygen inhalation (through 30% ethyl alcohol) or with 2-3 ml of 10% polyoxymethylheptamethyltetrasiloxane (antifensilane), on the lower limbs impose venous tourniquets.

To reduce the volume of circulating fluid in / in a fast acting diuretic is administered:

• furosemide iv in 2-5 mg / kg per day in 1-2 administration before clinical improvement.

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

For the purpose of relieving secondary bronchospasm and reducing pulmonary hypertension, a 2.4% aminophylline solution is also injected in / in: 2.4% solution of 1 ml / year of life (not more than 5 ml) until clinical improvement. With the introduction of more than 5 ml of aminophylline, tachycardia and arterial hypotension may increase.

When edema of the lungs, trimereperin is of great importance, it is administered intravenously or intravenously. The drug has a sedative effect, contributes to a decrease in the sensitivity of the respiratory center to hypoxia, and also leads to a redistribution of blood due to the effect on peripheral vessels with a decrease in the venous inflow to the right heart:

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

In a critical situation, glucocorticosteroids are used, their favorable hemodynamic effect is associated with positive inotropic, vasodilating, broncho-spasmolytic, antiallergic and antishock effects:

• prednisolone IV / 3-5 mg / kg per day, it is recommended to immediately enter half the daily dose, then - according to the state.

When hypokinetic type of circulatory disorders use cardiac glycosides. Preference is given to drugs of rapid action - strophanthin-K and lily of the grass glycoside:

• lily of the valley herb glycoside 0.06% solution in / in struino slowly 0.1 ml (children 1-6 months). 0.2-0.3 ml (children 1-3 years old), 0.3-0.4 ml (children 4-7 years), 0.5-0.8 ml (children over 7 years old) 3-4 times per day before clinical improvement, or
• strabanthin-K 0.05% solution in / in slowly jetly at 0,05-0,1 ml (children 1-6 months), 0.1-0.2 ml (children 1-3 years old), 0.2- 0,3 ml (children 4-7 years), 0,3-0,4 ml (children older than 7 years) 3-4 times a day before clinical improvement.

Improvement of the contractile ability of the myocardium is also promoted by sympathomimetic amines. These drugs can be considered a means of choice for short-term treatment in severe cases. Treatment with these drugs should be carried out in an intensive care unit under close monitoring of ECG data, as they are administered by continuous intravenous infusion to stabilize the condition:

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

In the hyperkinetic type of circulatory disorders, ganglion blockers or neuroleptics are prescribed:

• azamethonium bromide 5% solution iv in slowly for 6-8 min 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 old) in 20 ml of 20% dextrose (glucose) solution, according to the state, or
• droperidol 0.25% solution 0.1 ml / kg (according to the state).

Therapy of rhythm and conduction disorders

Treatment of tachyarrhythmias is carried out with antiarrhythmic drugs along with the agents used to correct chronic heart failure. If the disturbances of the systolic function of the myocardium are expressed, then preference is given to amiodarone due to its least effect on the pumping function of the heart, it is possible to use sotalol (provided it is titrated). The use of drugs from other groups may be accompanied by a decrease in systolic function of the myocardium.

Therapy of chronic heart failure

The medicinal substances currently used for the treatment of patients with chronic heart failure are divided into three main categories according to the degree of evidence: basic, additional and auxiliary means.

• The basic means - preparations, the effect of which is proven, does not cause doubts, they are recommended precisely for the treatment of chronic heart failure (the degree of proof of A). To this group are six classes of drugs:
  • angiotensin-converting enzyme (ACE) inhibitors are shown to all patients with chronic heart failure, regardless of etiology, process stage and type of decompensation;
  • beta-blockers - neurohormonal modulators, used in addition to an ACE inhibitor;
  • antagonists of aldosterone receptors used together with ACE inhibitor and beta-adrenoblocker in patients with severe chronic heart failure;
  • diuretics - are shown to all patients with clinical symptoms associated with excess sodium and water retention in the body;
  • cardiac glycosides - in small doses;
  • receptor antagonists can be used not only in cases of intolerance to ACE inhibitors, but also along with ACE inhibitors as a first line remedy for blockade of the renin-angiotensin-aldosterone system in patients with clinically pronounced decompensation.
• Additional tools, the effectiveness and safety of which is shown in some large studies, but clarifications are required (the degree of evidence is B):
  • statins recommended for use in patients with chronic heart failure in patients with coronary heart disease;
  • indirect anticoagulants, shown for use in the majority of patients with chronic heart failure.
• Aids - the effect and effect of these drugs on the prognosis of patients with chronic heart failure are not known (not proven), which corresponds to the third class of recommendations, or the level of evidence C:
  • anti-arrhythmic drugs (except for beta-blockers) with life-threatening ventricular arrhythmias;
  • acetylsalicylic acid (and other antiplatelet agents);
  • neglikozidnye inotropic stimulants - at an exacerbation of the chronic heart failure proceeding with low cardiac output and persistent arterial hypotension;
  • peripheral vasodilators (nitrates), used only with concomitant angina: slow calcium channel blockers with persistent arterial hypertension.