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Does indomethacin affect the control of breathing in premature infants?
Insights
Indomethacin therapy in premature infants with patent ductus arteriosus increased breathing control but did not improve cardiovascular function or close the ductus. Prostaglandins may regulate infant respiration.
Area of Science:
- Neonatal Medicine
- Respiratory Physiology
- Pharmacology
Background:
- Premature infants often have patent ductus arteriosus (PDA).
- Indomethacin is used to treat PDA, but its effect on respiratory control is unclear.
- Advanced postnatal age infants may respond differently to indomethacin.
Purpose of the Study:
- To evaluate the effect of indomethacin on breathing control in premature infants with PDA.
- To assess cardiovascular parameters and ductus closure after indomethacin therapy.
- To explore the role of prostaglandins in respiratory regulation.
Main Methods:
- 10 premature infants (≥6 weeks postnatal age) with significant PDA received intravenous indomethacin (0.3 mg/kg every 8 hours for 3 doses).
- Breathing control was assessed by measuring tidal volume, minute ventilation, and airway pressures (P0.1, Pmax).
- Cardiovascular function, blood gases, and ductus closure were evaluated.
Main Results:
- Indomethacin significantly increased tidal volume, minute ventilation, tidal volume/inspiratory time, and airway pressures.
- Seven infants required reduced ventilatory support post-therapy.
- No significant improvement in cardiovascular dysfunction, blood gases, or ductus closure was observed despite adequate plasma indomethacin levels.
Conclusions:
- Indomethacin may stimulate respiration in premature infants with PDA.
- Endogenous prostaglandins might play a role in regulating breathing in this population.
- Indomethacin's efficacy in improving respiratory control does not guarantee PDA closure or cardiovascular improvement.
Abstract:
The effect of indomethacin on the control of breathing was simultaneously evaluated in 10 premature infants who had significant patent ductus arteriosus and received indomethacin therapy. In an attempt to maintain high plasma level in these infants of advanced postnatal age (greater than or equal to 6 weeks), indomethacin was administered intravenously at a dosage of 0.3 mg/kg, at 8-hour intervals, for a total of three doses. Following indomethacin therapy, there was a significant increase in tidal volume, minute ventilation, tidal volume/inspiratory time and in airway pressure (P0.1, Pmax) generated during airway occlusion. Seven infants required lower ventilatory rates after study. In spite of desirable plasma indomethacin level, there was no significant improvement in echo left atrium/aortic root dimension ratio, cardiovascular dysfunction score and in blood pH, PO2 and PCO2. None of the infants showed clinical evidence of ductus closure. The results of the study suggested that indomethacin may stimulate respiration and that endogenous prostaglandin may play a role in the regulation of breathing.