Caffeine Citrate Use and Electronic Activity of the Diaphragm (EDI) Changes

Study Overview
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Brief Summary
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Caffeine citrate, the first-line agent for apnea of prematurity, enhances diaphragmatic activity. EDI values of neurally adjusted ventilatory assist (NAVA) modes can be used to quantify the diaphragmatic activity triggered by electrical impulse from the respiratory center. This study aims to evaluate the EDI changes following caffeine citrate administration and cessation in preterm infants, and whether such changes are affected by different doses used variably in clinical settings.

Detailed Description
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Caffeine citrate has been used as the first-line agent for apnea of prematurity. It works via mechanisms including stimulation of the respiratory center in medulla, increasing sensitivity to carbon dioxide retention, and increment in diaphragmatic activity. The effect of caffeine citrate has been evaluated largely based on parameters concerning clinical symptoms (e.g., decrease in the number of apnea, extubation success, decreased incidence of bronchopulmonary dysplasia) but not quantified parameters of actual diaphragmatic activity. Also, while usual doses of caffeine administration is described in the literature, consensus on the effect of caffeine citrate depending on different dosages has not been established. The current study aims to evaluate effect of caffeine citrate by quantifying the electrical impulses of diaphragmatic activity using EDI values captured from neurally adjusted ventilatory assist (NAVA) mode. Out of preterm infants necessitating invasive or non-invasive ventilators, those who are supported by invasive or non-invasive NAVA would be recruited. EDI changes would be monitored for the following timepoints: at the administration of caffeine citrate loading dose, 1st maintenance dose after loading, and at cessation of caffeine citrate.

Official Title
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Changes in Diaphragmatic Activity Before and After Caffeine Citrate Administration and Discontinuation

Conditions
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Preterm, Apnea of Prematurity, Caffeine

Intervention / Treatment
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* Drug: caffeine citrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm infants born at less than 34 weeks' gestation who are supported by invasive or non-invasive NAVA Exclusion Criteria: major congenital anomaly, chromosomal or genetic abnormality
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Low-dose group<br>Infants receiving low dose caffeine citrate (up to 10mg/kg/day) | Drug: caffeine citrate<br>* caffeine citrate administration, dosage decided by the the physician on duty, within the range of routine management (5mg/kg/day   20mg/kg/day)<br>* Other names: Neocaf solution [20mg] (Pharmbio Korea Inc.);|
| High dose group<br>Infants receiving high dose caffeine citrate (exceeding 10mg/kg/day) | Drug: caffeine citrate<br>* caffeine citrate administration, dosage decided by the the physician on duty, within the range of routine management (5mg/kg/day   20mg/kg/day)<br>* Other names: Neocaf solution [20mg] (Pharmbio Korea Inc.);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EDI change after caffeine citrate loading dose | changes in EDI min and EDI peak values (μV) after the loading dose administration | 20 minutes before   20 minutes after loading dose of caffeine citrate | 
| EDI change after caffeine citrate maintenance dose | changes in EDI min and EDI peak values (μV) after the 1st maintenance dose | 20 minutes before   20 minutes after 1st maintenance dose of caffeine citrate | 
| EDI change after caffeine citrate cessation | changes in EDI min and EDI peak values (μV) after caffeine discontinuation | 20 minutes before   48 hours after caffeine citrate discontinuation (discontinuation time point definition: 48 96 hours after the last dose of caffeine citrate administration) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| short-term effect of caffeine citrate administration | number of apnea and/or bradycardia | 24 hours before   24 hours after caffeine citrate administration |