Does Indomethacin Affect the Control of Breathing in Premature Infants?

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 (≥ 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 (P(0.1), P(max)) 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, PO(2) and PCO(2). 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.

The influence of chorioamnionitis on respiratory drive and spontaneous breathing of premature infants at birth: a narrative review

“…Indomethacin, a non-steroidal antiinflammatory drug, inhibits PGE 2 synthase, resulting in an increase of the depth and rate of foetal breathing movements [48]. In addition, there is an increase of depth of breathing at birth (increase in tidal volumes), which is possibly due to increased peak phrenic nerve activity [48][49][50]. However, indomethacin also inhibits surfactant production and increases the need for surfactant and additional ventilatory support in neonates [48,[50][51][52][53].…”

“…In addition, there is an increase of depth of breathing at birth (increase in tidal volumes), which is possibly due to increased peak phrenic nerve activity [48][49][50]. However, indomethacin also inhibits surfactant production and increases the need for surfactant and additional ventilatory support in neonates [48,[50][51][52][53]. Thus, a safer alternative to indomethacin is warranted.…”

Mechanistic actions of oxygen and methylxanthines on respiratory neural control and for the treatment of neonatal apnea

“…Indomethacin infusion has been shown to increase fetal breathing movements (Kitterman et al 1979), an effect which continues beyond infancy. One small study in premature infants receiving indomethacin for PDA closure demonstrated increased tidal volume and minute ventilation after the therapy (Yeh and Wilks 1989). In adults, indomethacin alters responsiveness to carbon dioxide via reduction in cerebral blood flow, leading to increased hypercapnic ventilatory response due to increased hydrogen ion detectable by central chemoreceptors (Xie et al 2006).…”