Pharmacokinetic profile of caffeine in the premature newborn infant with apnea (original) (raw)
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Caffeine Administration to Prevent Apnea in Very Premature Infants
Pediatrics & Neonatology, 2016
Background: Apnea intervals frequently occur in premature infants. Periods of apnea occur more often with decreases in gestational age. Periods of apnea can cause damage to the infant's developing brain and other organs. This study was designed to investigate the preventive effects of caffeine on apnea incidence in higher-risk neonates. Methods: In this single-center randomized control trial study, premature infants with a birth weight of 1200 g were eligible for enrollment. Twenty-six infants were randomly assigned to receive 20 mg/kg caffeine, as the loading dose, which was followed by 5 mg/kg daily as the maintenance dose until the 10 th day of life; these infants were compared with 26 infants in the control group. Primary outcomes were incidence of apnea, bradycardia, and cyanosis. Results: Fifty-two infants were enrolled (26 in the caffeine group and 26 in the control group). The preventive effect of caffeine on apnea was significant in these infants. The relative risk for incidence of apnea in preterm neonates with a birth weight of <1200 g was 0.250 (95% confidence interval, 0.097e0.647). Only four infants (15.4%) in the caffeine group developed apnea, compared with 16 (61.5%) in the control group (p Z 0.001). Conclusion: It seems that preventative effects of caffeine on apnea become apparent by using the drug in very premature infants.
Population pharmacokinetics of caffeine in premature neonates
European Journal of Clinical Pharmacology, 1997
Objective: To determine population pharmacokinetic parameters of caeine in premature neonates. Methods: This population analysis was done using 145 serum concentration measurements gathered from 75 hospitalized patients during their routine clinical care. The data were analysed by use of NONMEM (mixed eects modelling) according to a one-compartment open model with either zero or ®rst-order absorption and ®rst-order elimination. The eect of a variety of developmental, demographic and clinical factors (gender, birth weight, current weight, gestational age, postnatal age, postconceptional age and concurrent treatment with phenobarbital and parenteral nutrition) on clearance and volume of distribution was investigated. Forward selection and backward elimination regression identi®ed signi®cant covariates. Results: The ®nal pharmacostatistical model with inuential covariates were as follows: clearance (ml á h )1 ) 5.81 á current weight (kg) + 1.22 á postnatal age (weeks), multiplied by 0.757 if gestational age £ 28 weeks and 0.836 if the current primary source of patients' nutrition is parenteral nutrition, and volume of distribution (ml) 911 á current weight (kg). The interindividual variability in clearance and the residual variability, expressed as coecients of variation, were 14.87% and 18.44%, respectively. Due to the lack of information on the data set we were unable to characterize the interindividual variability for volume of distribution. Conclusion: In this study, which involved on average only two serum concentrations of caeine per patient, the use of NONMEM gave us signi®cant and consistent information about the pharmacokinetic pro®le of caffeine when compared with available bibliographic information. Additionally, parenteral nutrition and low gestational age (£ 28 weeks) may even come to be considered as risk factors, and their presence may serve as an indicator of the need for periodic monitoring of caeine concentrations in premature infants.
The efficacy of caffeine in the treatment of recurrent idiopathic apnea in premature infants
The Journal of Pediatrics, 1981
This prospective controlled study was aimed at evaluating the efficacy of caffeine in treating recurrent idiopathic apnea in the premature infant. Eighteen preterm infants (29 to 35 weeks" gestation) were studied. Recordings during the first 24 hours and on the fifth day of caffeine treatment showed a significant decrease of severe apnea (P < 0.01) and of mild apnea (P < 0.001) in the treated group (group 1) as compared with the control group (group II). No treatment of apnea other than cqff'eine was required in group L whereas six neonates in group H had such severe and frequent apneic episodes for more than 48 hours that withholding additional treatment was believed to be unethical. No undesirable side effects of caffeine treatment were observed.
BMC pharmacology & toxicology, 2016
This study sought to assess the pharmacokinetic and pharmacodynamic relationships of caffeine citrate therapy in preterm neonates who had therapeutic drug monitoring (TDM) in the post-extubation period. A retrospective observational study was conducted in preterm neonates who received caffeine citrate therapy for apnea of prematurity and had TDM done in the post-extubation period between January 2006 and October 2011. The relationships between pharmacodynamic effects (heart rate, respiratory rate, episodes of apnea, adverse events) and caffeine serum concentrations were explored. A total of 177 blood samples were obtained from 115 preterm neonates with a median (range) gestational age of 29 (24 - 33) weeks and birth weight of 1230 (607 - 2304) kg. Caffeine citrate therapy was initiated at a median (interquartile range) postnatal age of 1 (1 - 3) day and TDM was performed at a postnatal age of 15 (10 - 24) days. No direct correlations were found between respiratory rate or apneic epi...
Caspian journal of internal medicine, 2018
Caffeine is widely used for prevention of apnea and helps successful extubation from mechanical ventilation. It facilitates the transition from invasive to noninvasive support and reduces duration of continuous positive airway pressure (CPAP) in preterm infants. The optimum caffeine dose in preterm infants has not been well-studied in terms of benefits and risks. We compared efficacy and safety of once versus twice-daily caffeine dose in premature infants. This study was a randomized clinical trial conducted in Bu-Ali Sina Teaching Hospital, Sari. Patients with gestational age of <37 weeks were included. Both groups received 20 mg/kg loading dose of caffeine intravenously followed by maintenance dose of 5 mg/kg/day in group 1 or 2.5 mg/kg every 12 hours in group 2. Extubation failure, CPAP failure and possibly adverse reactions were evaluated. The mean of gestational age and birth weight were 32.27±3.23 (weeks) and 1824.5±702.54 (gr), respectively. The rate of extubation and CPAP...
Comparison of Caffeine Versus Aminophylline for Apnea of Prematurity
Journal of Medicine, Physiology and Biophysics, 2018
Objective: To make a comparison between the efficacy and safety of Caffeine and Aminophylline for Apnea of prematurity at standard doses. Methodology: The participants (neonates) were allocated randomly into 2 groups. Caffeine was given in loading dose of caffeine citrate (20 mg/kg) followed by 5 mg/kg/day maintenance dose every 24 hour to one group. The Aminopylline group was given (loading dose 5mg/kg and maintenance dose of 1.5 mg/kg) every 8 hour. The assesment for variations in the episodes of apnea, corresponding respiratory disorders, along with acute detrimental effects was done. The therapeutic drug levels related to the efficacy were also determined. Results: The mean apnea events/day in neonates administrated by caffeine was 0.8±0.3, 1.9±0.18, 1.4±1.8, 0.9±0.11 and 0.98±0.15 for 0, 1-3, 4-7, 8-14 and 15-21 days respectively. While, The mean apnea events/day in neonates administrated by Aminophylline was 0.6±0.4, 0.4±0.24, 0.3±1.6, 0.8±0.14 and 0.69±0.15 for 0, 1-3, 4-7,...
A Study on Outcome of Early Caffeine Administration in Very Preterm Neonates
Asian Journal of Clinical Pediatrics and Neonatology, 2019
Background: Apnea intervals frequently occur in very preterm infants. Methylxanthenes stimulate breathing efforts and hence have been used for treating apnea of prematurity. Aim: to study the outcome of early caffeine administration in very preterm neonates. Subjects and Methods: The first (1st) group babies received early caffeine within 48 hours of life before developing apnea. The second group (2nd) group babies received caffeine late after 48 hours, after onset of apneic episode. Results: There was no significant difference in the number of episodes of apnea, bradycardia and hypoxemia. Also no significant difference in the incidence of Patent ductus arteriosus (PDA), Intra ventricular hemorrhage (IVH), Necrotizing enterocolitis (NEC), Retinopathy of prematurity (ROP) or Bronchopulmonary dysplsia (BPD). Conclusion: There was no significant difference noted in the number of episodes of apnea, bradycardia and hypoxemia in the group with early caffeine administratration compared to late caffeine administration.
High versus low-dose caffeine for apnea of prematurity: a randomized controlled trial
European Journal of Pediatrics, 2015
The optimum caffeine dose in preterm infants has not been well investigated. We aimed to compare the efficacy and safety of high versus low-dose caffeine citrate on apnea of prematurity (AOP) and successful extubation of preterm infants from mechanical ventilation. We compared high-dose (loading 40 mg/kg/day and maintenance of 20 mg/kg/day) versus low-dose (loading 20 mg/kg/day and maintenance of 10 mg/kg/day) caffeine citrate in preterm infants <32 weeks gestation, presented with AOP within the first 10 days of life. A total of 120 neonates (60 in each group) were enrolled. High-dose caffeine was associated with a significant reduction in extubation failure in mechanically ventilated preterm infants (p<0.05), the frequency of apnea (p<0.001), and days of documented apnea (p<0.001). High-dose caffeine was associated with significant increase in episodes of tachycardia (p<0.05) without a significant impact on physician decision to withhold caffeine.