Caffeine preserves quiet sleep in preterm neonates

Abstract

Caffeine is widely used in preterm neonates suffering from apnea of prematurity (AOP), and it has become one of the most frequently prescribed medications in neonatal intensive care units. Goal of this study is to investigate how caffeine citrate treatment affects sleep‐wake behavior in preterm neonates. The observational study consists of 64 preterm neonates during their first 5 days of life with gestational age (GA) <32 weeks or very low birthweight of < 1500 g. A total of 52 patients treated with caffeine citrate and 12 patients without caffeine citrate were included. Sleep‐wake behavior was scored in three stages: active sleep, quiet sleep, and wakefulness. Individual caffeine concentration of every neonate was simulated with a pharmacokinetic model. In neonates with GA ≥ 28 weeks, wakefulness increased and active sleep decreased with increasing caffeine concentrations, whereas quiet sleep remained unchanged. In neonates with GA < 28 weeks, no clear caffeine effects on sleep‐wake behavior could be demonstrated. Caffeine increases fraction of wakefulness, alertness, and most probably also arousability at cost of active but not quiet sleep in preterm neonates. As such, caffeine should therefore not affect time for physical and cerebral regeneration during sleep in preterm neonates.

Non‐steroidal anti‐inflammatory drugs, prostaglandins, and COVID‐19

“…Indomethacin has also been suggested to exhibit potent antiviral activity against SARS‐CoV‐2‐infected Vero E6 cells in vitro and canine CoV‐infected dogs in vivo (T. Xu, Gao, et al, 2020). A very recent study based on a multi‐stage model‐based approach showed that treatment with the sustained‐release formulation of indomethacin at the dose of 75 mg twice a day (high dose used clinically according to García Rodríguez et al, 2008) is expected to achieve a complete response in 3 days for the treatment in patients infected by SARS‐CoV‐2, suggesting that indomethacin could be considered as a promising candidate for the treatment of COVID‐19 (Gomeni, Xu, Gao, & Bressolle‐Gomeni, 2020; Koch et al, 2020). The antiviral capacity of indomethacin is conferred by activation of protein kinase R, independently of interferons and double‐stranded RNA (Amici et al, 2015) but may be via interactions with aldoketo‐reductases, aldose reductases, PPAR‐γ, and the cannabinoid CB 2 receptor (T. Xu, Gao, et al, 2020).…”

Dose‐Related Adverse Drug Events in Neonates: Recognition and Assessment

“…As another illustration, the association between caffeine exposure and sleep‐wake behavior patterns in preterm neonates has been described. The authors hereby concluded that caffeine increased the fraction of wakefulness, alertness, and arousability, at the cost of active but not quiet sleep 47 …”

“…The authors hereby concluded that caffeine increased the fraction of wakefulness, alertness, and arousability, at the cost of active but not quiet sleep. 47 …”

Leveraging Predictive Pharmacometrics-Based Algorithms to Enhance Perinatal Care—Application to Neonatal Jaundice

“…As perinatal medicine is undergoing a fundamental change transforming towards a modern data-driven patient-oriented approach new tools that will predict the dynamics of biomarkers for an individual fetus or newborn will become increasingly important in maternal, neonatal and perinatal care. We developed PMX-based algorithms to optimize and individualize dosing of therapeutics in the field of perinatal medicine ( Wilbaux et al, 2016a ; Wilbaux et al, 2016b ; Koch et al, 2017 ; Nekka et al, 2017 ; van Donge et al, 2018 ; Dallmann et al, 2019 ; van Donge et al, 2019 ; Wilbaux et al, 2019 ; van Donge et al, 2020a ; van Donge et al, 2020b ; Koch et al, 2020c ; Dao et al, 2020 ; Samiee-Zafarghandy et al, 2022 ). It is time to go beyond classical pharmacological applications and develop algorithms condensing the wealth of clinical data and physiology knowledge into predictive tools coping with the dynamics of biomarkers for an individual fetus or neonate.…”