Changes in Diaphragmatic Activity Due to Caffeine Citrate Administration and Discontinuation in Preterm Infants

Background: Caffeine citrate is a commonly prescribed drug in preterm neonates. The direct effect of caffeine citrate on the activation of diaphragmatic motion has not been extensively researched. Objectives: This observational study aimed to assess the changes in electrical activity of the diaphragm in response to caffeine citrate administration and discontinuation in preterm neonates. Methods: Preterm infants [< 34 weeks’ gestational age (GA)] admitted to a level-IV neonatal intensive care unit in South Korea supported by invasive or non-invasive neurally adjusted ventilatory assist with caffeine citrate administration were prospectively enrolled in this observational study. The electrical activities of the diaphragm (Edi), Edipeak and Edimin values, before and after administering the loading and initial maintenance doses of caffeine citrate, and before and up to 48 hours after discontinuation, were analyzed. Results: Thirteen infants with a GA and birthweight of 28.8 ± 2.1 weeks and 1231 ± 441 g, respectively, were included. Edipeak and Edimin tended to increase when the neural respiration rate was ≥ 30 breaths/min. Edipeak and Edimin showed a higher trend after caffeine citrate loading and maintenance dose administration, particularly in infants born at < 28 weeks of GA or with a birthweight of < 1250 g, compared with those born at ≥ 28 weeks of GA or with a birthweight ≥ 1250 g. Caffeine citrate discontinuation resulted in an increased number of episodes of apnea and desaturation. Conclusions: Changes in Edipeak and Edimin showed different trends depending on perinatal factors. On caffeine citrate cessation, monitoring changes in clinical symptoms in near-term post-menstrual age may be prudent.