Limitations of theophylline in the treatment of apnea of prematurity. Apnoea of immaturity. 1. A controlled trial of theophylline and face mask continuous positive airways pressure. The effect of vertical pulsating stimulation on apnea of prematurity. Sustained-release theophylline reduces dyspnea in nonreversible obstructive airway disease. The therapeutic effect of theophylline in mild obstructive sleep Apnea/Hypopnea syndrome: results of repeated measurements with portable recording devices at home. Postoperative apnea in former preterm infants: prospective comparison of spinal and general anesthesia. Aminophylline versus doxapram in idiopathic apnea of prematurity: a double-blind controlled study. Theophylline in obstructive sleep apnea. A double-blind evaluation. [Transcutaneous electric stimulation of the brain: a comparative study of the effects of its combination with peridural anesthesia using bupivacaine-fentanyl during obstetrical analgesia].
Theophylline is commonly used to treat apnea of prematurity. To determine the effectiveness of theophylline with respect to gestational and postnatal age, we conducted a controlled study in 43 premature infants with idiopathic apnea. Three of the 21 treated and eight of the 22 control infants developed respiratory failure. Eight of the 11 infants with respiratory failure had gestational ages of less than 31 weeks and had more than four apneic episodes during the first day of life. In the treated infants without respiratory failure, the number of apneic episodes by 24-hour intervals declined six days earlier than in the control infants. Apnea disappeared, however, at a similar time in both groups. Three treated infants and three control infants had apneic episodes persisting beyond the neonatal period. Patients treated with theophylline did not develop respiratory failure as often as control infants did. However, despite a reduction of apneic episodes, theophylline did not shorten the course of apnea of prematurity. 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. Placing preterm infants suffering idiopathic apnea of prematurity on the VPS had an effect on the infants' respiratory effort and achieved a reduction in the number of apneic episodes secondary to central and mixed apnea. However, VPS offered no benefits in the reduction of obstructive apnea in this study population. Because central apnea has been reported as the predominant type of apnea and VPS is a nontoxic, noninvasive, and easy-to-implement method of alleviating central and mixed apnea types, it seems prudent to give VPS which has the stimulus characteristics to preterm infants experiencing apnea of prematurity before other treatment modalities currently in use are tried. Further studies are warranted to determine if VPS is effective in a continuous long-term treatment for apnea of prematurity, for example, until the end of apnea. Although orally administered theophylline has been prescribed widely in patients with nonreversible airway obstruction, symptomatic benefit has not been established. To assess the effects of orally administered theophylline on dyspnea, we performed a randomized, double-bind, crossover, placebo-theophylline clinical trial in 12 ambulatory male patients with moderate to severe nonreversible airway obstruction. Dyspnea was rated using 2 clinical indexes based on 3 components affecting breathlessness: functional impairment, magnitude of task that evokes dyspnea, and the associated magnitude of effort. Dyspnea and physiologic parameters were measured on 4 occasions: at baseline, 4 wk after initial treatment, a second baseline after a 2-wk washout period, and 4 wk after the second medication. For the 12 patients, mean age (+/- SD) was 60 +/- 7 yr, forced expiratory volume in one second was 1.36 +/- 0.67 L (mean, 40% of predicted), and arterial oxygen tension was 71 +/- 10 mmHg. During the treatment phase, all patients had a therapeutic theophylline blood level (range, 12 to 19 micrograms/ml). Theophylline significantly decreased the components of functional impairment (p = 0.02) and magnitude of task (p = 0.02) relating to dyspnea, as well as the overall dyspnea rating (p = 0.01). There were no significant differences between placebo and theophylline therapy for spirometry, arterial blood gas tensions, and the 12-min walking distance. Thus, sustained-release theophylline significantly reduced dyspnea in these ambulatory patients with moderate to severe nonreversible airway obstruction without altering lung function, gas exchange, or exercise performance. Theophylline has been recommended in the literature as a therapeutic option in mild OSAHS. In mild obstructive sleep apnea/hypopnea syndrome (OSAHS), night-to-night variability of parameters of sleep-disordered breathing has been determined rarely, we therefore compared the results of serial measurements of sleep apnea/hypopnea parameters under the effects of placebo and theophylline. To this end, we measured the individual variability of the apnea-hypopnea index (AHI) for seven consecutive nights using a portable sleep apnea recording device, in 14 subjects (2 women, 12 men, mean age +/- [standard deviation] 50 +/- 8 years), treated with placebo or theophylline in a double blind, randomized crossover fashion, whose polysomnographically measured AHI was 13 +/- 5 /hour. Under theophylline treatment in comparison with placebo we observed a small but significant decrease in mean (of seven days) AHI at home (9.2 +/- 7.7 to 6.7 +/- 6.1 /hour), which was independent of body position. The night-to-night variability of AHI at home was high (9. 2 +/- 8.9 /hour; range: 0-31.4 /hour) and proved to be independent of body position and alcohol consumption. - In mild OSAHS, repeated measurements of sleep related breathing events should be performed. Theophylline showed a small but clinically insignificant potencial to reduce AHI. Thirty-six former preterm infants undergoing inguinal hernia repair were studied. All were less than or equal to 51 weeks postconceptual age at the time of operation. Patients were randomly assigned to receive general or spinal anesthesia. Group 1 patients received general inhalational anesthesia with neuromuscular blockade. Group 2 patients received spinal anesthesia using 1% tetracaine 0.4-0.6 mg/kg in conjunction with an equal volume of 10% dextrose and 0.02 ml epinephrine 1:1000. In the first part of the study, infants randomized to receive spinal anesthesia also received sedation with im ketamine 1-2 mg/kg prior to placement of the spinal anesthetic (group 2 A). The remainder of group 2 patients did not receive sedation (group 2 B). Respiratory pattern and heart rate were monitored using an impedance pneumograph for at least 12 h postoperatively. Tracings were analyzed for evidence of apnea, periodic breathing and/or bradycardia by a pulmonologist unaware of the anesthetic technique utilized. None of the patients who received spinal anesthesia without ketamine sedation developed postoperative bradycardia, prolonged apnea, or periodic breathing. Eight of nine infants (89%) who received spinal anesthesia and adjunct intraoperative sedation with ketamine developed prolonged apnea with bradycardia. Two of the eight infants had no prior history of apnea. Five of the 16 patients (31%) who received general anesthesia developed prolonged apnea with bradycardia. Two of these five infants had no prior history of apnea. When infants with no prior history of apnea were analyzed separately, there was no statistically significant increased incidence of apnea in children receiving general versus spinal anesthesia with or without ketamine sedation. Because of the small numbers of patients studied, and the multiple factors that may influence the incidence of postoperative apnea (e.g., prior history of neonatal apnea), standard postoperative respiratory monitoring of these high-risk infants is still recommended following all anesthetic techniques. A double-blind controlled study, in two parts, was undertaken to compare the effectiveness of aminophylline and doxapram therapy in idiopathic apnea of prematurity. In the first part of this study, eight of 15 infants responded to doxapram therapy with complete cessation of apneic spells and six of 11 infants responded similarly to administration of aminophylline. These differences were statistically insignificant. In the second part of the study, assessment was made of whether the addition of doxapram to aminophylline therapy was effective in treatment of apnea of prematurity that had been unresponsive to aminophylline alone. Of ten infants who continued to have apneic spells during treatment with aminophylline, eight responded to the addition of doxapram with complete cessation of apnea. Nine infants received placebo in addition to aminophylline, and none had a reduction in frequency of apnea. Twelve patients with documented obstructive sleep apnea were enrolled in a double-blind placebo controlled crossover trial of oral theophylline, (Uniphyllin) 800 mg, taken at night for four weeks. Overnight polysomnography, using standard techniques, was performed at the end of each treatment period. The total number of apneas (A) and hypopneas (H) decreased significantly while receiving theophylline compared to placebo, from 398 (69), mean (SEM), to 283 (72), p less than 0.01. Sleep quality was, however, significantly worse while receiving theophylline. Obstructive A and H were very much decreased with theophylline (p less than .001), and even when the data were adjusted for the more disturbed sleep with theophylline, this decrease remained significant; the obstructive A and H index fell from 49 (8.7) on placebo to 40 (9) while receiving theophylline, p = 0.02. There was no difference in the numbers of central or mixed A and H, and mean A and H duration was unchanged on the two study nights. Oxygen desaturations greater than 4 percent were less with theophylline treatment (p = 0.02), but mean overnight SaO2 was unchanged. We conclude that theophylline may be beneficial in patients with OSA, but part of the improvement is due to a deterioration in sleep quality. In order to test the effectiveness of Anesthelec (transcutaneous cranial electrical stimulation with Limoge currents) during labour and delivery, a randomized study was carried out in 120 primiparous women with extradural anaesthesia during active labor. Combination of transcutaneous cranial electrical stimulation with epidural bupivacaine administration has been showed to provide a 20% pain relief prolongation of the first bupivacaine injection. Statistical studies of drug requirement during labor, of cervical dilatation duration, of mode and duration of delivery and of analgesia quality showed no beneficial additive effect of electrical stimulation for obstetrical analgesia when extradural anaesthesia is performed.
There is insufficient evidence to recommend kinesthetic stimulation as treatment for clinically significant apnea of prematurity. Previous reviews have suggested that kinesthetic stimulation is not effective at preventing apnea of prematurity (Henderson-Smart 2005) and is not as effective as theophylline at treating clinically significant apnea of prematurity (Osborn 2005).