الفهرس 
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Abstract
Caffeine is one of the widely used medications in the neonatal care units. Caffeine therapy for treatment of apnea of prematurity (AOP) is well established over the past few years and in spite of its widespread use in preterm infants; there has been little information about the optimal loading and maintenance efficient dose in those infants.
AOP is a developmental disorder that occurs as a result of immature respiratory control mechanisms and it may be associated with intermittent hypoxemia, hence may be related to greater incidence of deleterious neurodevelopmental outcomes and retinopathy of prematurity (ROP). AOP is a common complication of preterm birth, which affects more than 80 % of neonates with a birth weight less than 1,000 g. Methylxanthines, including caffeine and theophylline, are a mainstay in the treatment and prevention of AOP.
Methylxanthines have been used as the backbone of pharmacologic treatments of respiratory disorders in preterm and are widely used to facilitate successful extubation from mechanical ventilation. The efficiency of caffeine, as a preferred methylxanthine, to stimulate respiration has been well proven as it has a significant favorable impact on neonatal morbidity as bronchopulmonary dysplasia (BPD) and patent ductus arteriosus (PDA) ligation. Also, the results of previous studies revealed that caffeine enhances respiratory muscle strength and lung function followed by easier weaning of mechanical ventilation in premature infants. Besides, a rapid and sustained increase in diaphragmatic activity and tidal volume was reported in preterm infants followed by caffeine administration.
The aim of this study was to determine if the use of caffeine in doses higher than the currently standard dose can decrease the frequency of apnea in preterm infants without causing significant side effects.
The study was a randomized, observational clinical trial that was conducted at the Neonatal Intensive Care Unit (NICU), Ain Shams University hospitals over a period of 1 year from October 2018 to October 2019. The study was done on a total of 80 preterm infants with gestational age between 28 and 34 weeks. The infants were divided randomly into 2 equal groups each contain 40 infants. Infants in group (A) received low-dose regimen caffeine citrate loading dose of 20 mg/kg/day (equivalent to 10 mg/kg/day of caffeine base) and maintenance dose of 10 mg/kg/day (equivalent to 5 mg/kg/day of caffeine base). While infants in group (B) received high-dose regimen caffeine citrate loading dose of 40 mg/kg/day (equivalent to 20 mg /kg/day of caffeine base) and maintenance dose of 20 mg/kg/day (equivalent to 10 mg /kg/day of caffeine base).all patients were subjected to Physical examination, vital data monitoring, and anthropometric measures were all followed up during the period of intervention. Gestational age was calculated using Ballard score, antenatal US results and maternal history of last menstruation.
Success of treatment is considered when there is no apnea during the first week of treatment, and failure is considered if apnea still present within the first week of treatment.
The study showed that 27% of cases treated with low dose caffeine had apnea versus 10% among cases treated with high dose caffeine with a statistically significant difference between them meaning that there is statistically significant higher success rate among cases treated with high dose caffeine than low dose caffeine.
The study shows that there is no statistically significant difference between low dose group and high dose group regarding their sociodemographic characters, mode of delivery, maternal history of DM, SPET, PROM (p>0.05).
Regarding anthropometric measures, there is no statistically significant difference between low and high dose groups regarding their weight and OFC. While length was significantly higher among low dose group (P value is 0.04).
Also, the study illustrated that feeding intolerance have statistically significant difference between studied groups, 40% of high dose group versus 15% among low dose group (p value=0.01)
Regarding seizures frequency, our study showed that Seizures incidence has no statistically significant difference between studied groups.
Regarding Echo and cranial US findings, the study shows no statistically significant difference between studied groups.
The study also showed statistically significant increase in mean heart rate among high dose group than low dose group during the intervention.
It also showed non-statistically significant difference between studied groups regarding their mean SPO2 at all readings.
Regarding urine output, our study shows non-statistically significant difference between studied groups regarding their mean urinary output at all readings except at day 1.
Regarding blood glucose changes, our study shows that the high dose group had significantly higher RBG starting at day 5 of therapy.
Regarding blood pressure changes, our study show that both systolic and diastolic blood pressure changes are non statistically significant difference between studied groups.