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Am Fam Physician. 2007;76(1):130

Background: Syncope affects up to 15 percent of children before the end of adolescence, with vasovagal syncope being most common. Although increasing fluid and salt intake or avoiding known triggers can help prevent recurrent vasovagal syncope, pharmacotherapy remains the most common treatment option. Beta blockers may help some patients, although they are often discontinued because of adverse effects. Midodrine (Proamatine) is a selective peripheral alpha-adrenergic agonist that can effectively treat vasovagal syncope in adults. Qingyou and colleagues examined midodrine's effects in children with vasovagal syncope.

The Study: The unblinded, randomized trial included children who had been hospitalized for recurrent syncope and who had a positive tilt-table test. Patients with non-vasovagal causes of syncope were excluded. The control group was instructed on nonpharmacologic treatment measures (e.g., increasing water and salt intake, avoiding blood-pooling activities such as leg-crossing). The treatment group was given the same instructions plus 1.25 mg of midodrine twice a day. Both groups had repeat tilt-table testing after one week. Children in the treatment group who had a positive repeat tilt-table test received an increased dosage of midodrine (2.5 mg twice a day) and were retested one week later. All patients were followed for at least six months to evaluate patients' clinical status and to assess for potential adverse effects of midodrine, such as elevated blood pressure or heart rate.

Results: The study included 26 children six to 16 years of age. The mean number of syncopal episodes was 3.5 per year with a range of three to 40 episodes. Three participants in the control group and one in the treatment group were excluded because of failure to have a repeat tilt-table test.

At one week, repeat positive tilt-table tests were observed in eight out of 10 (80 percent) participants in the control group and in nine out of 12 (75 percent) participants in the treatment group. The latter nine patients received 2.5 mg of midodrine twice a day and were retested one week later; at that time, six out of the nine had a negative tilt-table test. The overall improvement rate was 75 percent (nine out of 12) in the treatment group and 20 percent (two out of 10) in the control group, which was statistically significant. After six months, the treatment group showed no significant changes in mean heart rate or blood pressure, and no episodes of supine hypertension occurred. The only adverse event reported was mild gastrointestinal discomfort in one patient.

Conclusion: The authors conclude that midodrine is a well tolerated and effective treatment for vasovagal syncope in children.

editor's note: Qingyou and colleagues conducted the first study of midodrine use in children with vasovagal syncope. It is an attractive treatment option for this population because, as an alpha-adrenergic agonist, it increases venous return and blood pressure by constricting the peripheral vasculature while avoiding the cardiac inotropic and arrhythmic effects that can occur with beta-adrenergic agents. Midodrine also does not cross the blood-brain barrier and, therefore, will not affect the central nervous system. Of course, its use does have some caveats. Ischemic or myopathic hearts are more sensitive to alpha-adrenergic stimulation, and the agent should be used cautiously in patients with these conditions. Midodrine also should not be used for at least three to four hours before lying down because of its potential to cause supine hypertension.1

This study was not placebo-controlled or blinded, and larger controlled studies should be performed. Recent studies have not shown that traditional medications (e.g., metoprolol [Lopressor], propranolol [Inderal]) improve vasovagal syncope symptoms compared with placebo.2,3 Until further research is complete, midodrine could be a useful and effective treatment for vasovagal syncope in children.—k.t.m.

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