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Effects of prophylactic low-dose indomethacin on hemodynamics in very low birth weight infants
T D Yanowitz1, A C Yao, J C Werner
1Brown University School of Medicine, Department of Pediatrics, Women and Infants' Hospital of Rhode Island, Providence 02905-2401, USA.
Insights
Prophylactic indomethacin reduces blood flow velocity in premature infants but preserves cardiac function. This may protect against intraventricular hemorrhage by increasing cerebral vascular resistance.
Area of Science:
- Neonatal Physiology
- Pharmacology
- Pediatric Cardiology
Background:
- Indomethacin is used to prevent intraventricular hemorrhage in premature infants.
- Its effects on cerebral and mesenteric blood flow velocities and cardiac function are not well understood.
Purpose of the Study:
- To examine the hemodynamic effects of prophylactic indomethacin in very low birth weight infants.
- To test the hypothesis that it does not alter cerebral/mesenteric blood flow or cardiac function.
Main Methods:
- Studied 21 infants (24-31 weeks gestation) before and after indomethacin (0.1 mg/kg) at 6, 30, and 54 hours of life.
- Measured cerebral and mesenteric blood flow velocities and cardiac function parameters.
Main Results:
- Mean and end-diastolic velocities decreased in both cerebral and mesenteric circulations.
- Cerebral vascular resistance increased more than mesenteric vascular resistance.
- Cardiac output, stroke volume, fractional shortening, and blood pressure remained unchanged.
Conclusions:
- Prophylactic indomethacin reduces blood flow velocity without impacting cardiac function.
- It increases cerebral vascular resistance more than mesenteric vascular resistance.
- The increase in cerebral vascular resistance may offer protection against intraventricular hemorrhage.
Abstract:
Indomethacin decreases cerebral and mesenteric blood flow velocities in premature infants with symptomatic patent ductus arteriosus. Low-dose indomethacin is recommended for the prevention of intraventricular hemorrhage in very low birth weight infants. The hemodynamic effects of prophylactic indomethacin have not been previously examined. We hypothesized that prophylactic indomethacin does not change cerebral and mesenteric blood flow velocities and cardiac function in very low birth weight infants. Twenty-one infants (775 to 1245 gm, 24 to 31 weeks' gestation) were studied before and after indomethacin (0.1 mg/kg) administration at 6, 30, and 54 hours of life. Mean and end-diastolic cerebral and mesenteric blood flow velocities decreased (ANOVA, p < 0.05) after prophylactic indomethacin. The 38% increase in cerebral relative vascular resistance was significantly greater than the 18% increase in mesenteric relative vascular resistance (ANOVA, p < 0.05). In five infants who were fed 1 hour after the third indomethacin dose, the postprandial mesenteric blood flow velocity was significantly greater than the mesenteric blood flow velocity before both indomethacin and feeding (ANOVA, p < 0.05). Cardiac output, stroke volume, fractional shortening, and blood pressure did not change after prophylactic indomethacin administration. We conclude that prophylactic indomethacin (1) reduces cerebral and mesenteric blood flow velocity without affecting cardiac function, (2) increases cerebral more than mesenteric relative vascular resistance, and (3) does not prevent postprandial increases in mesenteric blood flow velocity. We speculate that the increase in cerebral relative vascular resistance is a beneficial effect that contributes to protection against intraventricular hemorrhage.