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Am J Perinatol 2015; 32(09): 879-886
DOI: 10.1055/s-0034-1543981
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A Pilot Randomized Controlled Trial of Early versus Routine Caffeine in Extremely Premature Infants

Anup C. Katheria
1   Neonatal Research Institute, Sharp Mary Birch Hospital for Women and Newborns, San Diego, California
,
Jason B. Sauberan
1   Neonatal Research Institute, Sharp Mary Birch Hospital for Women and Newborns, San Diego, California
,
Devang Akotia
1   Neonatal Research Institute, Sharp Mary Birch Hospital for Women and Newborns, San Diego, California
,
Wade Rich
1   Neonatal Research Institute, Sharp Mary Birch Hospital for Women and Newborns, San Diego, California
,
Jayson Durham
1   Neonatal Research Institute, Sharp Mary Birch Hospital for Women and Newborns, San Diego, California
,
Neil N. Finer
1   Neonatal Research Institute, Sharp Mary Birch Hospital for Women and Newborns, San Diego, California
2   Department of Pediatrics, University of California, San Diego, California
› Institutsangaben
Weitere Informationen

Publikationsverlauf

27. Oktober 2014

05. Dezember 2014

Publikationsdatum:
21. Januar 2015 (online)

   Lizenzen und Reprints

Abstract

Objective This study aims to compare the effects of early and late (routine) initiation of caffeine in nonintubated preterm neonates.

Study Design A total of 21 neonates < 29 weeks gestational age were randomized to receive intravenous caffeine citrate (20 mg/kg) or placebo either before 2 hours of age (early) or at 12 hours of age (routine). This was an observational trial to determine the power needed to reduce the need for endotracheal intubation by 12 hours of age. Other outcomes included comparisons of cerebral oxygenation, systemic and pulmonary blood flow, hemodynamics, hypotension treatment, oxygen requirement, and head ultrasound findings.

Results There was no difference in the need for intubation (p = 0.08), or vasopressors (p = 0.21) by 12 hours of age. Early caffeine was associated with improved blood pressure (p = 0.03) and systemic blood flow (superior vena cava flow, p = 0.04 and right ventricular output, p = 0.03). Heart rate, left ventricular output, and stroke volume were not significantly affected. Cerebral oxygenation transiently decreased 1 hour after caffeine administration. There were no differences in other outcomes.

Conclusion This pilot study demonstrated the feasibility of conducting such a trial in extremely preterm neonates. We found that early caffeine administration was associated with improved hemodynamics. Larger studies are needed to determine whether early caffeine reduces intubation, intraventricular hemorrhage, and related long-term outcomes.

Keywords

caffeine - hemodynamics - intubation - vasopressors
 

  • References

  • 1 Committee on Fetus and Newborn; American Academy of Pediatrics. Respiratory support in preterm infants at birth. Pediatrics 2014; 133 (1) 171-174
    CrossrefPubMedGoogle Scholar
  • 2 Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin JB ; COIN Trial Investigators. Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med 2008; 358 (7) 700-708
    CrossrefPubMedGoogle Scholar
  • 3 Finer NN, Carlo WA, Walsh MC , et al; SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med 2010; 362 (21) 1970-1979
    CrossrefPubMedGoogle Scholar
  • 4 Schmidt B, Roberts RS, Davis P , et al; Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnea of prematurity. N Engl J Med 2006; 354 (20) 2112-2121
    CrossrefPubMedGoogle Scholar
  • 5 Dobson NR, Patel RM, Smith PB , et al. Trends in caffeine use and association between clinical outcomes and timing of therapy in very low birth weight infants. J Pediatr 2014; 164 (5) 992-998.e3
    CrossrefPubMedGoogle Scholar
  • 6 Tracy MB, Klimek J, Hinder M, Ponnampalam G, Tracy SK. Does caffeine impair cerebral oxygenation and blood flow velocity in preterm infants?. Acta Paediatr 2010; 99 (9) 1319-1323
    CrossrefPubMedGoogle Scholar
  • 7 Soloveychik V, Bin-Nun A, Ionchev A, Sriram S, Meadow W. Acute hemodynamic effects of caffeine administration in premature infants. J Perinatol 2009; 29 (3) 205-208
    CrossrefPubMedGoogle Scholar
  • 8 Walther FJ, Erickson R, Sims ME. Cardiovascular effects of caffeine therapy in preterm infants. Am J Dis Child 1990; 144 (10) 1164-1166
    PubMedGoogle Scholar
  • 9 Kribs A, Vierzig A, Hünseler C , et al. Early surfactant in spontaneously breathing with nCPAP in ELBW infants—a single centre four year experience. Acta Paediatr 2008; 97 (3) 293-298
    CrossrefPubMedGoogle Scholar
  • 10 Aguar M, Cernada M, Brugada M, Gimeno A, Gutierrez A, Vento M. Minimally invasive surfactant therapy with a gastric tube is as effective as the intubation, surfactant, and extubation technique in preterm babies. Acta Paediatr 2014; 103 (6) e229-e233
    CrossrefPubMedGoogle Scholar
  • 11 Katheria A, Leone T. Altered transitional circulation in infants of diabetic mothers with strict antenatal obstetric management: a functional echocardiography study. J Perinatol 2012; 32 (7) 508-513
    CrossrefPubMedGoogle Scholar
  • 12 Kluckow M, Evans N. Low superior vena cava flow and intraventricular haemorrhage in preterm infants. Arch Dis Child Fetal Neonatal Ed 2000; 82 (3) F188-F194
    CrossrefPubMedGoogle Scholar
  • 13 Harris PA, Taylor R, Thielke R , et al. Research electronic data capture (REDCap) - A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42 (2) 377-381
    CrossrefPubMedGoogle Scholar
  • 14 Henderson-Smart DJ, Davis PG. Prophylactic methylxanthines for endotracheal extubation in preterm infants. Cochrane Database Syst Rev 2010; (12) CD000139
    PubMedGoogle Scholar
  • 15 Steer P, Flenady V, Shearman A , et al; Caffeine Collaborative Study Group Steering Group. High dose caffeine citrate for extubation of preterm infants: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2004; 89 (6) F499-F503
    CrossrefPubMedGoogle Scholar
  • 16 Erenberg A, Leff RD, Haack DG, Mosdell KW, Hicks GM, Wynne BA. Caffeine citrate for the treatment of apnea of prematurity: a double-blind, placebo-controlled study. Pharmacotherapy 2000; 20 (6) 644-652
    CrossrefPubMedGoogle Scholar
  • 17 Evans N, Kluckow M. Early determinants of right and left ventricular output in ventilated preterm infants. Arch Dis Child Fetal Neonatal Ed 1996; 74 (2) F88-F94
    CrossrefPubMedGoogle Scholar
  • 18 Song R, Rich W, Kim JH, Finer NN, Katheria AC. The use of electrical cardiometry for continuous cardiac output monitoring in preterm neonates: a validation study. Am J Perinatol 2014; 31 (12) 1105-1110
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 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) 784-787
    CrossrefPubMedGoogle Scholar
  • 20 Smits P, Lenders JW, Thien T. Caffeine and theophylline attenuate adenosine-induced vasodilation in humans. Clin Pharmacol Ther 1990; 48 (4) 410-418
    CrossrefPubMedGoogle Scholar
  • 21 Lemmers PM, Toet MC, van Bel F. Impact of patent ductus arteriosus and subsequent therapy with indomethacin on cerebral oxygenation in preterm infants. Pediatrics 2008; 121 (1) 142-147
    CrossrefPubMedGoogle Scholar
  • 22 Schmidt B, Asztalos EV, Roberts RS, Robertson CM, Sauve RS, Whitfield MF ; Trial of Indomethacin Prophylaxis in Preterms (TIPP) Investigators. Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms. JAMA 2003; 289 (9) 1124-1129
    CrossrefPubMedGoogle Scholar
  • 23 Gupta D, Gupte A, Chouthai ND. Effect of early caffeine on the neurodevelopmental outcome of very low birth weight newborns: A cohort study. EPAS 2014; 1555: 792
    PubMedGoogle Scholar
  • 24 Patel RM, Leong T, Carlton DP, Vyas-Read S. Early caffeine therapy and clinical outcomes in extremely preterm infants. J Perinatol 2013; 33 (2) 134-140
    CrossrefPubMedGoogle Scholar
  • 25 Lodha A, Seshia M, McMillan DD , et al; for the Canadian Neonatal Network. Association of early caffeine administration and neonatal outcomes in very preterm neonates. JAMA Pediatr 2014; (e-pub ahead of print). doi: 10.1001/jamapediatrics.2014.2223
    PubMedGoogle Scholar
  • 26 Weichelt U, Cay R, Schmitz T , et al. Prevention of hyperoxia-mediated pulmonary inflammation in neonatal rats by caffeine. Eur Respir J 2013; 41 (4) 966-973
    CrossrefPubMedGoogle Scholar
  • 27 Köroğlu OA, MacFarlane PM, Balan KV , et al. Anti-inflammatory effect of caffeine is associated with improved lung function after lipopolysaccharide-induced amnionitis. Neonatology 2014; 106 (3) 235-240
    CrossrefPubMedGoogle Scholar