Caffeine Citrate Dosing Adjustments to Assure Stable Caffeine Concentrations in Preterm Neonates

Koch, Gilbert; Datta, Alexandre N.; Jost, Kerstin; Schulzke, Sven; Anker, John van den; Pfister, Marc

doi:10.1016/j.jpeds.2017.08.064

Cited by 37 publications

(40 citation statements)

References 28 publications

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“…In neonatology, time (i.e., postnatal age) plays an additional important role because of fast changing maturation processes in the first days of life. 19,20 Hence, the question is often extended to: What are the risk factors that a patient will be above or below a threshold within a certain time frame (e.g., 24 hours)? Such questions are typical classification tasks to predict a probability for the occurrence of a specific incident.…”

Section: Methodsmentioning

confidence: 99%

Pharmacometrics and Machine Learning Partner to Advance Clinical Data Analysis

Koch

Pfister

Daunhawer

et al. 2020

Clin Pharma and Therapeutics

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Clinical pharmacology is a multidisciplinary data sciences field that utilizes mathematical and statistical methods to generate maximal knowledge from data. Pharmacometrics (PMX) is a well‐recognized tool to characterize disease progression, pharmacokinetics, and risk factors. Because the amount of data produced keeps growing with increasing pace, the computational effort necessary for PMX models is also increasing. Additionally, computationally efficient methods, such as machine learning (ML) are becoming increasingly important in medicine. However, ML is currently not an integrated part of PMX, for various reasons. The goals of this article are to (i) provide an introduction to ML classification methods, (ii) provide examples for a ML classification analysis to identify covariates based on specific research questions, (iii) examine a clinically relevant example to investigate possible relationships of ML and PMX, and (iv) present a summary of ML and PMX tasks to develop clinical decision support tools.

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Section: Methodsmentioning

confidence: 99%

Pharmacometrics and Machine Learning Partner to Advance Clinical Data Analysis

Koch

Pfister

Daunhawer

et al. 2020

Clin Pharma and Therapeutics

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“…Individual caffeine concentration profiles over the first 5 days of life were simulated for each of the preterm neonates applying a previously published mathematical pharmacokinetic (PK) model 14 that takes birth weight (BW), GA, and PNA into account. This caffeine PK model was developed based on two clinical studies 29,30 with a total of 185 preterm neonates.…”

Section: Methodsmentioning

confidence: 99%

Caffeine preserves quiet sleep in preterm neonates

Koch

Schönfeld

Jost

et al. 2020

Pharmacology Res & Perspec

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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.

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“…Despite different studies exploring the best minimally invasive and cost-effective methods to monitor therapeutic ranges of caffeine in clinical practice, few have tried to develop a pharmacokinetic model to adjust caffeine dosage and none has investigated the relationship between caffeine biofluid levels in the first weeks of life and clinical outcomes, such as apnoea frequency [121,122]. Interestingly, in 2017 KOCH et al Further studies are needed to determine whether caffeine dosage can be optimised for the individual patient through TDM in particular situations.…”

Section: Therapeutic Drug Monitoringmentioning

confidence: 99%

“…[122] developed simulation models of caffeine concentrations, proposing the need of adjusting the maintenance doses through time in preterm neonates, with the administration of 6 mg•kg−1 •day −1 in the second week of life, 7 mg•kg −1 •day −1 in weeks 3-4 and 8 mg•kg −1 •day −1 in weeks 5-8.…”

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confidence: 99%

Caffeine in preterm infants: where are we in 2020?

et al. 2020

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The incidence of preterm birth is increasing, leading to a growing population with potential long-term pulmonary complications. Apnoea of prematurity (AOP) is one of the major challenges when treating preterm infants; it can lead to respiratory failure and the need for mechanical ventilation. Ventilating preterm infants can be associated with severe negative pulmonary and extrapulmonary outcomes, such as bronchopulmonary dysplasia (BPD), severe neurological impairment and death. Therefore, international guidelines favour non-invasive respiratory support. Strategies to improve the success rate of non-invasive ventilation in preterm infants include pharmacological treatment of AOP. Among the different pharmacological options, caffeine citrate is the current drug of choice. Caffeine is effective in reducing AOP and mechanical ventilation and enhances extubation success; it decreases the risk of BPD; and is associated with improved cognitive outcome at 2 years of age, and pulmonary function up to 11 years of age. The commonly prescribed dose (20 mg·kg−1 loading dose, 5–10 mg·kg−1 per day maintenance dose) is considered safe and effective. However, to date there is no commonly agreed standardised protocol on the optimal dosing and timing of caffeine therapy. Furthermore, despite the wide pharmacological safety profile of caffeine, the role of therapeutic drug monitoring in caffeine-treated preterm infants is still debated. This state-of-the-art review summarises the current knowledge of caffeine therapy in preterm infants and highlights some of the unresolved questions of AOP. We speculate that with increased understanding of caffeine and its metabolism, a more refined respiratory management of preterm infants is feasible, leading to an overall improvement in patient outcome.

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Caffeine Citrate Dosing Adjustments to Assure Stable Caffeine Concentrations in Preterm Neonates

Cited by 37 publications

References 28 publications

Pharmacometrics and Machine Learning Partner to Advance Clinical Data Analysis

Pharmacometrics and Machine Learning Partner to Advance Clinical Data Analysis

Caffeine preserves quiet sleep in preterm neonates

Caffeine in preterm infants: where are we in 2020?

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