Comparative efficacy of theophylline and caffeine in the treatment of idiopathic apnea in premature infants. High-dose caffeine suppresses postoperative apnea in former preterm infants. The effect of caffeine compared with theophylline in the treatment of idiopathic apnea in premature infants. Theophylline versus caffeine: comparative effects in treatment of idiopathic apnea in the preterm infant. The efficacy of caffeine in the treatment of recurrent idiopathic apnea in premature infants. Caffeine or theophylline for neonatal apnoea? Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups. Bronchodilator effects of caffeine in coffee. A dose-response study of asthmatic subjects. Apnoea of immaturity. 1. A controlled trial of theophylline and face mask continuous positive airways pressure.
The purpose of our prospective randomized study was to compare the efficacy of theophylline ethylenediamine and caffeine sodium citrate in the treatment of idiopathic apnea in premature infants. Sixteen infants with three or more severe apneic attacks were studied. Twenty-four-hour cardiorespiratory recordings immediately before and after randomization and four days later showed similar significant decreases of the apnea frequency in both theophylline- (group 1, n = 8) and caffeine-treated infants (group 2, n = 8). No undesirable side effects were observed, except for tachycardia in one infant in group 1. We suggest reasons for preferring caffeine to theophylline in the control of idiopathic apnea in premature infants: caffeine is as efficient and easier to administer. Thirty-two former preterm infants (less than or equal to 44 weeks postconceptual age) undergoing inguinal hernia repair were prospectively studied. General inhalational anesthesia with neuromuscular blockade was used. No barbiturates or opioids were given. Infants were randomly divided into two groups. Group 1 received iv caffeine 10 mg/kg immediately after induction of anesthesia. Group 2 received iv saline. Respiratory pattern, heart rate, and SpO2 were monitored using an impedance pneumograph and a pulse oximeter, respectively, for at least 12 h postoperatively. Tracings were analyzed for evidence of apnea, periodic breathing, and/or bradycardia by a pulmonologist unaware of the drug given. None of the patients who received caffeine developed postoperative bradycardia, prolonged apnea, or periodic breathing, and none had postoperative SpO2 less than 90%. In the control group 13 (81%) developed prolonged apnea 4-6 h postoperatively. Fifty percent of the patients had SpO2 less than 90% at the time. This study shows that iv caffeine 10 mg/kg is effective in the control of apnea in otherwise healthy expremature infants between 37 and 44 weeks of postconceptual age. It is still recommended, however, that all infants at risk be monitored for at least 12 h for apnea and bradycardia following general anesthesia. nan nan 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 less than 0.01) and of mild apnea (P less than 0.001) in the treated group (group 1) as compared with the control group (group II). No treatment of apnea other than caffeine was required in group I, whereas six neonates in group II 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. Caffeine, in the dose usually recommended (12.5 mg/kg loading dose and 3 mg/kg daily maintenance), and a higher dose regimen (25 mg/kg loading and 6 mg/kg daily maintenance), was compared with theophylline (7.5 mg/kg loading and 3 mg/kg thrice daily maintenance). The study was a randomised controlled trial in the treatment of a group of 44 infants of less than 31 weeks' gestation (mean gestational age 28.3 weeks) who were suffering from frequent apnoeic attacks. All three regimens produced a significant reduction in apnoeic attacks within 24 hours, but only the higher dose caffeine and theophylline groups showed a significant improvement in apnoea within eight hours. The use of caffeine for the treatment of neonatal apnoea is recommended, because a once daily dose is more easily administered, and because it was found that plasma concentrations were more predictable than those of theophylline. If used in very preterm infants, however, its is suggested that a higher dose regimen than that previously recommended be used to achieve a faster response. To determine whether the benefits of caffeine vary in three subgroups of 2006 participants in the Caffeine for Apnea of Prematurity (CAP) trial.
                Post-hoc subgroup analyses were performed on the basis of: (1) indication for commencement of study drug: treat apnea, prevent apnea, or facilitate extubation; (2) positive pressure ventilation (PPV) at randomization: endotracheal tube (ETT), noninvasive ventilation, or none; and (3) timing of commencement of study drug: early or late (< or =3 versus >3 days). Outcomes assessed were those showing treatment effects in the original analyses. We investigated the consistency of caffeine effects by using regression models that incorporated treatment/subgroup factor interactions.
                There was little evidence of a differential treatment effect of caffeine in subgroups defined by the clinical indication for starting study drug. The size and direction of the caffeine effect on death or disability differed depending on PPV at randomization (P = .03). Odds ratios (95% CI) were: no support, 1.32 (0.81-2.14); noninvasive support, 0.73 (0.52-1.03); and ETT, 0.73 (0.57-0.94). Adjustment for baseline factors strengthened this effect (P = .02). Starting caffeine early resulted in larger reductions in days of respiratory support. Postmenstrual age at time of discontinuing PPV was shorter with earlier treatment (P = .01). Mean differences (95% CI) were: early, 1.35 weeks (0.90-1.81); and late 0.55 weeks (-0.11-0.99). Adjustment for baseline factors weakened this effect (P = .03).
                There is evidence of variable beneficial effects of caffeine. Infants receiving respiratory support appeared to derive more neurodevelopmental benefits from caffeine than infants not receiving support. Earlier initiation of caffeine may be associated with a greater reduction in time on ventilation.
                Copyright 2010 Mosby, Inc. All rights reserved. Although caffeine is a universal drug and has multiple pharmacologic and physiologic actions in man, there are surprisingly few objective data about its effect on pulmonary function. We conducted a short-term, double-blind, randomized crossover study in nine asthmatic adults who ingested decaffeinated coffee containing varying amounts of added caffeine (mean of 0.2,2.5,5.6, and 7.2 mg/kg of body weight) on different days. The subjects also ingested decaffeinated coffee and aminophylline (200 mg) on a separate day of study. Baseline and post-drug determinations of serum levels of caffeine and theophylline, forced expired volume and flow, specific airway conductance (Gaw/VL), vital signs, and reported symptoms were obtained. Peak increases in serum caffeine concentrations (mean, 12.4 micrograms/ml +/- 1.5 micrograms/ml) occurred 45 minutes following the highest dose of caffeine (7.2 mg/kg), whereas the peak theophylline level (mean 3.8 micrograms/ml +/- 0.4 micrograms/ml) occurred 90 minutes following oral administration of aminophylline (mean theophylline, 2.6 mg/kg). Comparable peak increases in the forced expiratory volume in one second (FEV1), the forced expiratory flow during the middle half of the forced vital capacity (FEF25-75%), and Gaw/VL occurred at 120 minutes following aminophylline and the highest dose of caffeine, indicating that caffeine is an effective bronchodilator but is only 40 percent as active as an equivalent molar dose of theophylline. Regression analysis revealed statistically significant dose-response relationships between peak increases in serum caffeine concentrations and increases in FEV1, FEF25-75%, and Gaw/VL from baseline values. These findings have diagnostic and therapeutic implications regarding the use of caffeine prior to tests of pulmonary function and as a dietary agent, alone or in combination with theophylline. A randomised controlled trial of theophylline versus face-mask continuous positive airways pressure (CPAP) treatment for recurrent apnoea of immaturity was carried out in 32 infants of 25 to 32 weeks' gestation. Continuous recording of electrocardiogram and impedence pneumogram added objective assessment to the nurses' observations for 11 courses of treatment. The CPAP group had more adverse perinatal factors but the frequency of apnoeic attacks before treatment was comparable. Infants given theophylline had a greater reduction in the incidence of prolonged apnoeic attacks, and this difference persisted after allowing for the effect of perinatal complications. Continuous recordings showed a greater reduction in episodes of bradycardia of less than or equal to 80/minute with theophylline. Five of 18 infants given theophylline needed intermittent positive pressure ventilation for apnoea compared with 12 of 14 given CPAP. The poor response in 17 of 32 infants suggests a need for a more effective method of preventing or treating apnoea in very immature babies, in whom adverse perinatal factors often coexist.
Caffeine appears to have similar short-term effects on apnea/bradycardia as does theophylline although caffeine has certain therapeutic advantages over theophylline. Theophylline is associated with higher rates of toxicity. The possibility that higher doses of caffeine might be more effective in extremely preterm infants needs further evaluation in randomized clinical trials.