Oral administration of a high loading dose of caffeine results in marked reduction of cerebral and intestinal BFV, without changing LVO, blood pressure, and heart rate.

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Background: A single high loading dose of 25 mg/kg caffeine has been shown to be effective for the prevention of apnoea, but may result in considerable reductions in blood flow velocity (BFV) in cerebral and intestinal arteries. Objective: To assess the effects of two loading doses of 12.5 mg/kg caffeine given four hours apart on BFV in cerebral and intestinal arteries, left ventricular output (LVO), and plasma caffeine concentrations in preterm infants. Design: Sixteen preterm neonates of ,34 weeks gestation were investigated one hour after the first oral dose and one, two, and 20 hours after the second dose by Doppler sonography. Results: The mean (SD) plasma caffeine concentrations were 31 (7) and 29 (7) mg/l at two and 20 hours respectively after the second dose. One hour after the first dose, none of the circulatory variables had changed significantly. One hour after the second caffeine dose, mean BFV in the internal carotid artery and anterior cerebral artery showed significant reductions of 17% and 19% (p = 0.01 and p = 0.003 respectively). BFV in the coeliac artery and superior mesenteric artery, LVO, PCO 2 , and respiratory rate had not changed significantly. Total vascular resistance, calculated as the ratio of mean blood pressure to LVO, had increased significantly one and two hours after the second dose (p = 0.049 and p = 0.023 respectively). Conclusion: A divided high loading dose of 25 mg/kg caffeine given four hours apart had decreased BFV in cerebral arteries after the second dose, whereas BFV in intestinal arteries and LVO were not affected.

High-dose indomethacin after intermediate-dose therapy resulted in an overall closure rate of 98.5% (127 of 129). Although single indomethacin doses of up to 1 mg/kg were given, high-dose indomethacin was safe.