Cross-over trial of treatment for bradycardia attributed to gastroesophageal reflux in preterm infants

Abstract

Objective: To determine whether anti-reflux medications reduce bradycardia episodes attributed to clinically suspected gastroesophageal reflux (GER).

Study design: We conducted a masked trial comparing metoclopramide, 0.2 mg/kg/dose q 6 hours, and ranitidine, 2 mg/kg/dose q 8 hours, with saline placebo. Each infant served as his own control. Preterm infants having >3 bradycardia episodes per 2 days were eligible if the clinician intended to begin anti-reflux medications for bradycardia attributed to GER.

Results: The mean (SD) birth weight was 1238 (394) g and gestational age was 29 (3) weeks. Eighteen infants were enrolled at 35 (22) days of age. There were 4.6 (3.1) and 3.6 (2.7) bradycardia episodes per day in the drug and placebo periods, respectively. The mean difference (drug minus placebo) was 0.94 (95% CI, 0.04 to 1.95) (P = .04 by t test). There was a decrease in bradycardia episodes over time (P < .001 by nonparametric repeated-measures analysis of variance).

Conclusions: Anti-reflux medications did not reduce, and may have increased, bradycardia episodes in preterm infants with GER. Because there was an improvement of bradycardia episodes over time, unrelated to treatment, unmasked therapeutic trials of medications are likely to lead to misleading conclusions.

Conflict of interest statement

The authors declare no potential conflicts of interest, real or perceived.

Figures

Figure 1

Patient accrual.

Figure 2

Bradycardia episodes per day for all study participants by treatment period.

Figure 3

Bradycardia episodes per day for all study participants by time period.

Figure 4

Bradycardia episodes per day during the 3 time periods for each participant in whom there were fewer bradycardic episodes during the drug periods. The most striking pattern is the decrease in bradycardic episodes over time.