Prophylactic Methylxanthines for Preventing Extubation Failure in the Preterm Neonates with the Gestational Age of ≤30 Weeks: A Randomized Controlled Trial

Authors

1 Department of Pediatrics, 1st Floor, Woman and Child Block, Kasturba Medical College, Madhav Nagar, Manipal University, Manipal, Karnataka, India

2 Pediatric Critical Care, Great Ormond Street Hospital for Children, NHS Trust Foundation, Royal College of Pediatrics and Child Health, Ilford, Greater London, United Kingdom, India

3 Department of Community Medicine, Kasturba Medical College, Madhav Nagar, Manipal University, Manipal, Karnataka, India

Abstract

Background: Preterm neonates are at a high risk of respiratory depression at birth. Incidence of respiratory distress is reported in 60-80% of the neonates born with the gestational age of less than 28 weeks and 15-30% of the neonates with the gestational age of less than 32-34 weeks. The present study aimed to compare the incidence and risk of failed extubation in using caffeine and aminophylline in the preterm neonates with the gestational age of ≤30 weeks in the periextubation period.
Methods: This single-centered, parallel, open-label, randomized controlled trial was conducted in a tertiary care referral hospital in India during June 2014-2016. Neonates with the gestational age of ≤30 weeks who were intubated for a minimum of 24 hours were enrolled in the study. Neonates with major anomalies, heart disease, and sepsis were excluded from the study. After the random allocation of the infants to treatment with the standard dose of caffeine citrate and aminophylline methylxanthine, intubation continued for seven consecutive days with or without non-invasive ventilatory support. As the primary objective, the incidence and risk of failed extubation were assessed. Secondary objective of the research was to compare the relative incidence of acute adverse effects, persistent apnea, and the associated morbidities.
Results: Neonates treated by caffeine were at a higher risk of extubation failure (1.09 times) adjusted with birth weight (31.5% versus 21.4%; RR=1.09; 95% CI: 0.81-1.46; P=0.55), which was not statistically significant. In addition, risk of apnea within seven days and after seven days of methylxanthine therapy was 1.57 (95% CI: 0.95-2.61) and 1.10 (95% CI: 0.95-2.61) times higher in the neonates with caffeine treatment. Also, rate of tachycardia was high in the neonates treated by aminophylline, which was statistically significant (RR=0.27; 95% CI: 0.13-0.56; P<0.001). Duration of non-invasive ventilator support, length of admission in the neonatal intensive care unit, O2 requirement at discharge, death before hospital discharge, and the associated morbidities were similar between the groups.
Conclusion: According to the results, the incidence and risk of extubation failure were clinically high in the caffeine-treated neonates. However, aminophylline administration could continue as a prophylactic agent in developing countries under medical supervision.

Keywords

References

1. Holme N, Chetcuti P. The pathophysiology of respiratory distress syndrome in neonates. Paediatrics and child health. 2012; 22(12):507-12.
2. Miller JD, Carlo WA. Pulmonary complications of mechanical ventilation in neonates. Clin Perinatol. 2008; 35(1):273–81.
 3. Venkatesh V, Ponnusamy V, Anandaraj J, Chaudhary R, Malviya M, Clarke P, et al. Endotracheal intubation in a neonatal population remains associated with a high risk of adverse events. Eur J Pediatr. 2011; 170(2):223–7.
 4. Stefanescu BM, Murphy WP, Hansell BJ, Fuloria M, Morgan TM, Aschner JL. A randomized, controlled trial comparing two different continuous positive airway pressure systems for the successful extubation of extremely low birth weight infants. Pediatrics. 2003; 112(5):1031–8.
5. Danan C, Durrmeyer X, Brochard L, Decobert F, Benani M, Dassieu G. A randomized trial of delayed extubation for the reduction of reintubation in extremely preterm infants. Pediatr Pulmonol. 2008; 43(2):117–24.
6. Henderson-Smart DJ, Davis PG. Prophylactic methylxanthines for endotracheal extubation in preterm infants. Cochrane Database Syst Rev. 2010; (12):CD000139.
 7. Davis PG, Henderson-Smart DJ. Nasal continuous positive airways pressure immediately after extubation for preventing morbidity in preterm infants. Cochrane Database Syst Rev. 2003; (2):CD000143.
8. Sant’Anna GM, Keszler M. Weaning infants from mechanical ventilation. Clin Perinatol. 2012; 39(3):543–62.
9. Sims ME, Rangasamy R, Lee S, Chung H, Cohen J, Walther FJ. Comparative evaluation of caffeine and theophylline for weaning premature infants from the ventilator. Am J Perinatol. 1989; 6(1):72–5.
10. Armanian AM, Badiee Z, Afghari R, Salehimehr N, Hassanzade A, Sheikhzadeh S, et al. Prophylactic Aminophylline for prevention of apnea at higherrisk preterm neonates. Iran Red Crescent Med J. 2014; 16(8):e12559.
11. Harris MC, Baumgart S, Rooklin AR, Fox WW. Successful extubation of infants with respiratory distress syndrome using Aminophylline. J Pediatr. 1983; 103(2):303–5.
12. Davis PG, Schmidt B, Roberts RS, Doyle LW, Asztalos E, Haslam R, et al. Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups. J Pediatr. 2010; 156(3):382–7.
13. Steer PA, Flenady VJ, Shearman A, Lee TC, Tudehope DI, Charles BG. Periextubation caffeine in preterm neonates: a randomized dose response trial. J Paediatr Child Health. 2003; 39(7):511–5.
14. Supinski GS, Deal EC Jr, Kelsen SG. The effects of caffeine and theophylline on diaphragm contractility. Am Rev Respir Dis. 1984; 130(3):429–33.
 15. Aranda JV, Turmen T. Methylxanthines in apnea of prematurity. Clin Perinatol. 1979; 6(1):87–108.
16. Shivakumar M, Jayashree P, Najih M, Lewis LES, Bhat Y R, Kamath A, et al. Comparative efficacy and safety of caffeine and aminophylline for apnea of prematurity in preterm (≤34 weeks) neonates: a randomized controlled trial. Indian Pediatr. 2017; 54(4):279-83.
17. Steer P, Flenady V, Shearman A, Charles B, Gray PH, Henderson-Smart D, et al. High dose caffeine citrate for extubation of preterm infants: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2004; 89(6):F499-503.
 18. Lane AJ, Coombs RC, Evans DH, Levin RJ. Effect of caffeine on neonatal splanchnic blood flow. Arch Dis Child Fetal Neonatal Ed. 1999; 80(2):F128-9.
19. Hoecker C, Nelle M, Poeschl J, Beedgen B, Linderkamp O. Caffeine impairs cerebral and intestinal blood flow velocity in preterm infants. Pediatrics. 2002; 109(5):784–7.
20. Schoen K, Yu T, Stockmann C, Spigarelli MG, Sherwin CM. Use of methylxanthine therapies for the treatment and prevention of apnea of prematurity. Paediatr Drugs. 2014; 16(2):169–77. 21. Gannon BA. Theophylline or caffeine: which is best for apnea of prematurity? Neonatal Netw. 2000; 19(8):33–6.
22. Ehrenkranz RA, Walsh MC, Vohr BR, Jobe AH, Wright LL, Fanaroff AA, et al. Validation of the national institutes of health consensus definition of bronchopulmonary dysplasia. Pediatrics. 2005; 116(6):1353–60.
23. Kinsella JP, Greenough A, Abman SH. Bronchopulmonary dysplasia. Lancet. 2006; 367(9520): 1421–31.
Iranian Journal of Neonatology
Volume 8, Issue 3
September 2017
Pages 11-18

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