High-dose caffeine suppresses postoperative apnea in former preterm infants. Post-operative recovery after inguinal herniotomy in ex-premature infants: comparison between sevoflurane and spinal anaesthesia. Postoperative apnea in former preterm infants: prospective comparison of spinal and general anesthesia. Postoperative apnea, bradycardia, and oxygen desaturation in formerly premature infants: prospective comparison of spinal and general anesthesia. Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups. The efficacy of caffeine in the treatment of recurrent idiopathic apnea in premature infants. Does caffeine prevent hypoxaemic episodes in premature infants? A randomized controlled trial. Thoracic epidural anesthesia as an adjunct to general anesthesia for cardiac surgery: effects on ventilation-perfusion relationships. Caffeine citrate for the treatment of apnea of prematurity: a double-blind, placebo-controlled study.
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. We prospectively studied the post-operative recovery profile of 28 ex-premature infants undergoing inguinal herniotomy. All infants had a post-conceptual age of less than 46 weeks at the time of surgery and were randomized to receive either sevoflurane (group 1, 14 patients) or spinal anaesthesia (group 2, 14 patients). All patients received supplemental caudal analgesia before skin incision. Cardiorespiratory function was continuously recorded in all patients before and after surgery. A blinded observer analysed each paired recording for predefined episodes of apnoea, hypoxaemia or bradycardia and the reports were used to compare the two groups. Spinal anaesthesia was attempted unsuccessfully in four patients in group 2. Five patients in group 1 demonstrated an 'excess' number of episodes (median 4, range 3-12) of clinically silent post-operative cardiorespiratory complications. ('Excess' in our study was defined as a 3-fold or greater increase in the number of post-operative episodes of bradycardia or apnoea relative to pre-operative occurrence). Three of these patients had pre-existing abnormal respiratory function and accounted for 80% of the episodes (26/32) of post-operative bradycardia and all five episodes of post-operative apnoea identified. All episodes of bradycardia and apnoea were temporally unrelated. None of the remaining patients in group 2 demonstrated an unacceptable number of post-operative cardiorespiratory complications. Our limited study suggests that general anaesthesia with an inhalational agent such as sevoflurane may induce or unmask abnormalities of cardiopulmonary function in predisposed infants. Spinal anaesthesia may be preferable but it is potentially stressful for the infant and associated with a clinically significant failure rate. 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. Eighteen formerly premature infants scheduled for inguinal herniorrhaphy and who were less than 51 wk postconceptional age were assigned to either the general anesthesia group (GA: atropine, halothane, and nitrous oxide) or the spinal anesthesia group (SA: hyperbaric tetracaine). Twelve-hour, three-channel continuous recordings of respiratory rate (chest wall impedance), electrocardiogram (ECG), and hemoglobin O2 saturation (SpO2) were obtained preoperatively and after surgery. These were analyzed for short (11-15s) and long (> 15 s) apnea spells, periodic breathing, and episodes of hemoglobin oxygen desaturation and bradycardia. Infants in the GA group had lower postoperative minimum SpO2 (68.7% +/- 11.4%) and minimum heart rate (79 bpm +/- 19) than infants in the SA group (80.7% +/- 9.2%, and 109 bpm +/- 30, respectively; P < 0.05) and had lower postoperative minimum SpO2 and minimum heart rate than they had preoperatively (79.0% +/- 13.7%, and 93 bpm +/- 31, respectively; P < 0.05); pre- and postoperative studies in the SA group did not differ. There were no differences in the incidence of postoperative central apnea. We conclude that spinal anesthesia reduces postoperative hemoglobin oxygen desaturation and bradycardia in formerly premature infants undergoing inguinal herniorrhaphy. 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. 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. Fifty spontaneously breathing, preterm infants 48 h old, of 32 weeks' gestation or less, were assigned randomly to receive caffeine citrate (loading dose 20 mg/kg, maintenance dose 10 mg/kg per day) or a placebo (NaCl 0.9%). The study hypothesis was that caffeine reduces the proportion of infants with recurrent hypoxaemic episodes (decrease in transcutaneous PO2 of 20% within 20 s) from 50% to 25%. Transcutaneous oxygen tension (tcPO2) and heart rate were recorded continuously for 50 h and analysed by computer. The two groups were similar in gestational age, birth weight, delivery mode, sex distribution, and Apgar scores. The mean serum concentration (+/- SD) of caffeine 2 h after the second maintenance dose was 96.0 (+/- 34.5) mumol/l in the group receiving caffeine and 9.3 (+/- 12.8) mumol/l in the group receiving a placebo. The mean proportion of infants with more than six hypoxaemic episodes per 12 h in the caffeine groups was higher (57%) than in the control group (51%). The mean proportion of infants with more than six episodes of bradycardia per 12 h was not statistically different in the caffeine group (79%) from the control group (86%). Our results suggest that prophylactic caffeine has little if any effect on the risk of developing hypoxaemic episodes and bradycardia in small preterm infants and the supposed 50% reduction which was considered clinically important at the start of the trial can be rejected with confidence. To determine the effects of thoracic epidural anesthesia (TEA) on ventilation-perfusion (VA/Q) relationships, atelectasis, and oxygenation before and after coronary artery bypass graft surgery (CABG).
                Prospective, controlled, unblinded, randomized trial.
                Cardiothoracic clinic at a major university referral center.
                Twenty-eight patients undergoing elective CABG.
                Perioperative and postoperative TEA was added to general anesthesia (GA) in 14 patients, and 14 patients receiving GA alone served as controls.
                VA/Q relationships were measured by the multiple inert gas elimination technique, and, 20 hours postoperatively, atelectasis was assessed by computerized tomographic scans. Arterial and mixed venous blood gases and hemodynamic variables were measured by standard techniques. TEA per se caused no change in shunt, VA/Q matching, or oxygenation. Induction of GA in the control group and induction of TEA caused similar reductions in mean arterial pressure. The TEA patients needed less morphine analgesia postoperatively and were extubated earlier. Extubation caused significant improvement in VA/Q matching. On the first postoperative day, a slight reduction in PaCO2 was seen in the TEA group, but no differences in shunt, VA/Q matching, or oxygenation compared with the GA group. Both groups showed extensive bilateral atelectasis.
                TEA can reduce respirator time and the need for morphine analgesics after CABG without negative effects on VA/Q matching, oxygenation, or atelectasis formation. To evaluate the efficacy and safety of caffeine citrate for treatment of apnea of prematurity.
                Multicenter, parallel, randomized, double-blind, placebo-controlled trial with open-label rescue.
                Nine neonatal intensive care units.
                Eighty-five infants, 28-32 weeks postconception and 24 hours or more after birth who had six or more apnea episodes within 24 hours.
                Caffeine citrate 10 mg/kg (as caffeine base) administered intravenously, followed by 2.5 mg/kg/day orally or intravenously, or placebo, for up to 10 days. Infants failing double-blind therapy could receive open-label rescue.
                Success was defined as 50% or greater reduction in apnea episodes and elimination of apnea. Caffeine citrate was significantly more effective than placebo in reducing apnea episodes by at least 50% in 6 days (p<0.05), and approached statistical significance (p<0.10) in 3 days. It was significantly better than placebo in eliminating apnea in 5 days (p<0.05), and approached significance (p<0.10) in 2 days. The number of infants with an aggregate of 7-10 days of at least a 50% reduction in apnea events or elimination of apnea was significantly higher in the caffeine citrate than in the placebo group. Adverse events did not differ significantly between groups. No correlations were found between success and mean daily plasma concentrations or baseline characteristics. Volume of distribution and clearance increased with weight, supporting weight-adjusted dosing of caffeine citrate.
                Caffeine citrate 10 mg/kg caffeine base (equivalent to 20 mg/kg caffeine citrate) intravenously followed by 2.5 mg/kg/day caffeine base (equivalent to 5 mg/kg/day caffeine citrate) either intravenously or orally for 10 days is safe and effective for treating apnea of prematurity in infants 28-32 weeks postconception.
Implications for practice. After general anaesthesia, caffeine can be used to prevent postoperative apnoea/bradycardia and episodes of oxygen desaturation in growing preterm infants if this is deemed clinically necessary. In view of the small numbers of infants studied in these trials and uncertainty concerning the clinical significance of the episodes, caution is warranted in applying these results to routine clinical practice.
Implications for research. There is a need to determine which infants might benefit most by this treatment. Studies confined to those most at risk of apnoea (prior history, younger postmenstrual age) and those that might require mechanical ventilation or chronic lung disease would be of value.