Continuous Indomethacin Infusion May Be Less Effective than Bolus Infusions for Ductal Closure in Very Low Birth Weight Infants

ABSTRACT

The effectiveness of continuous indomethacin (INDO) infusion versus bolus infusions for closure of patent ductus arteriosus (PDA) was investigated. The study design was an open-label case series (continuous INDO) with historic controls matched for gestational age (bolus INDO). Ductal closure rates were determined in two groups: 16 preterm infants with PDA treated with continuous INDO infusion (CONTIN group) and 16 control patients, matched for gestational age, who received bolus INDO infusions (BOLUS group). The total dosage was the same for both groups. PDA closed in seven of 16 preterm infants in the CONTIN group and in 13 of 16 in the BOLUS group (p = 0.033, Fisher's exact test). In infants < 1000 g it was two of eight in the CONTIN group and 10 of 10 in the BOLUS group (p = 0.002). Continuous INDO infusion was more likely than bolus infusion to be associated with failure of ductal closure (odds ratio, 19; 95% CI, 1.5 to 247; p = 0.023). This indicates that continuous infusion of INDO may be less effective in closing PDA than bolus infusions, especially in extremely low birth weight infants.

KEYWORDS

Patent ductus arteriosus - preterm infants - indomethacin

REFERENCES

• 1 Clyman R I. Recommendations for the postnatal use of indomethacin: an analysis of four separate treatment strategies.  J Pediatr. 1996;  128 601-607
• 2 Ohlsson A, Bottu J, Govan J, Ryan M L, Fong K, Myhr T. Effect of indomethacin on cerebral blood flow velocities in very low birth weight neonates with a patent ductus arteriosus.  Dev Pharmacol Ther. 1993;  20 100-106
• 3 Pezzati M, Vangi V, Biagiotti R, Bertini G, Cianciulli D, Rubaltelli F F. Effects of indomethacin and ibuprofen on mesenteric and renal blood flow in preterm infants with patent ductus arteriosus.  J Pediatr. 1999;  135 733-738
• 4 Liem K D, Hopman JC W, Kollee LA A, Oeseburg B. Effects of repeated indomethacin administration on cerebral oxygenation and haemodynamics in preterm infants: combined near infrared spectrophotometry and Doppler ultrasound study.  Eur J Pediatr. 1994;  153 504-509
• 5 Edwards A D, Wyatt J S, Richardson C et al.. Effects of indomethacin on cerebral haemodynamics in very preterm infants.  Lancet. 1990;  335 1491-1495
• 6 Simko A, Mardoum R, Merritt T A, Bejar R. Effects of cerebral blood flow velocities of slow and rapid infusion of indomethacin.  J Perinatol. 1994;  14 29-35
• 7 Bos A F, Venema IM J, Bergervoet M, Zweens M J, Pratl B, van Eykern L A. Spontaneous motility in preterm infants treated with indomethacin.  Biol Neonate. 2000;  78 174-180
• 8 Hammerman C, Glaser J, Schimmel M S, Ferber B, Kaplan M, Eidelman A I. Continuous versus multiple rapid infusions of indomethacin: Effects on cerebral blood flow velocity.  Pediatrics. 1995;  95 244-248
• 9 Christmann V, Liem K D, Semmekrot B A, van de Bor M. Changes in cerebral, renal and mesenteric blood flow velocity during continuous and bolus infusion of indomethacin.  Acta Paediatr. 2002;  91 440-446
• 10 Richardson D K, Gray J E, McCormick M C, Workman K, Goldmann D A. Score for neonatal acute physiology: a physiologic severity index for neonatal intensive care.  Pediatrics. 1993;  91 617-623
• 11 Richardson D K, Phibbs C S, Gray J E, McCormick M C, Workman-Daniels K, Goldmann D A. Birth weight and illness severity: independent predictors of neonatal mortality.  Pediatrics. 1993;  91 969-975
• 12 Walsh M C, Kliegman R M. Necrotizing enterocolitis: treatment based on staging criteria.  Pediatr Clin North Am. 1986;  33 179-201
• 13 Lago P, Bettiol T, Salvadori S et al.. Safety and efficacy of ibuprofen versus indomethacin in preterm infants treated for patent ductus arteriosus: a randomised controlled trial.  Eur J Pediatr. 2002;  161 202-207
• 14 Van Overmeire B, Van de Broek H, Van Laer P, Weyler J, Vanhaesebrouck P. Early versus late indomethacin treatment for patent ductus arteriosus in premature infants with respiratory distress syndrome.  J Pediatr. 2001;  138 205-211
• 15 Gersony W M, Peckham G J, Ellison R C, Miettinen O S, Nadas A S. Effects of indomethacin in premature infants with patent ductus arteriosus: results of a national collaborative study.  J Pediatr. 1983;  102 895-906
• 16 Yeh T F, Luken J, Raval D, Thalji A, Carr I, Pildes R S. Indomethacin treatment in small versus large premature infants with ductus arteriosus. Comparison of plasma indomethacin concentration and clinical response.  Br Heart J. 1983;  50 27-30
• 17 Ishisaka D Y, Van Vleet J, Marquardt E. Visual compatibility of indomethacin sodium trihydrate with drugs given to neonates by continuous infusion.  Am J Hosp Pharm. 1991;  48 2442-2443
• 18 Merritt T A, Harris J P, Roghmann K et al.. Early closure of the patent ductus arteriosus in very low-birth-weight infants: a controlled trial.  J Pediatr. 1981;  99 281-286