Drug Utilisation in Very Preterm Infants: Any Changes during the Past Decade?

Abstract

Background: Improved standards of perinatal care for preterm infants led to decreased hospital mortality rates during the past decade. However, studies investigating changes in drug utilisation in neonatal intensive care units (NICU) during this period are missing.

Objective: The aim of the present study therefore was to evaluate the most frequently used groups of drugs in preterm infants treated in NICUs and to analyse potential changes in drug utilisation over a period of ten years.

Methods: Drug utilisation patterns in 164 preterm infants born between 1989 and 1990 (group I; gestational age 27.2±1.2 weeks, birth weight 970±145 g) were compared to those in 113 preterm infants born between 2001 and 2004 (group II; gestational age 26.9±1.65 weeks, birth weight 930±253 g, mean and standard deviation each) with need for postnatal mechanical ventilation.

Results: Significant changes in drug utilisation patterns were observed for complete courses of antenatal corticosteroids (40 vs. 51.5%), diuretics (78 vs. 36.6%), surfactant (63.3 vs. 75%), methylxanthines (89.9 vs. 56.7%), sedatives/analgesics (82.4 vs. 91.5%) and catecholamines (38.3 vs. 52.4%) (group II vs. group I each). Postnatal corticosteroids were applied more often in group II (17.4 vs. 13.4%). However, duration of postnatal corticosteroid treatment has decreased (6d vs. 13d). The use of antibiotics remained unchanged (100 vs. 98.9%). Comparison of clinical outcome variables showed a decreased duration of mechanical ventilation and a significantly increased survival rate.

Conclusion: Drug utilisation patterns in preterms have changed considerably during the past decade. Improved standards of care and shorter duration of mechanical ventilation may be operative.

Zusammenfassung

Hintergrund: Verbesserte Standards bei der perinatalen Betreuung Frühgeborener führten zu einer höheren Überlebensrate in der letzten Dekade. Angaben zu Veränderungen im Arzneimitteleinsatz auf Neugeborenenintensivstationen innerhalb dieses Zeitraums fehlen jedoch weitgehend.

Ziel: Ziel dieser Studie war deshalb, die am häufigsten eingesetzten Arzneimittelgruppen bei intensivmedizinisch betreuten Frühgeborenen zu untersuchen und mögliche Änderungen im Arzneimitteleinsatz über einen Zeitraum von 10 Jahren zu erfassen.

Methoden: Der Arzneimitteleinsatz bei 164 beatmeten Frühgeborenen der Jahrgänge 1989 und 1990 (Gruppe I, Gestationsalter 27,2±1,2 Wochen, Geburtsgewicht 970±145 g) wurde verglichen mit dem Arzneimitteleinsatz bei 113 beatmeten Frühgeborenen der Jahrgänge 2001–2004 (Gruppe II, Gestationsalter 26,9±1,65 Wochen, Geburtsgewicht 930±253 g).

Ergebnisse: Es zeigten sich signifikante Veränderungen im Einsatz von vollständigen Zyklen antenataler Kortikosteroide (40 vs. 51,5%), Diuretika (78 vs. 36,6%), Surfactant (63,3 vs. 75%), Methylxanthinen (89,9 vs. 56,7%), Sedativa/Analgetika (82,4 vs. 91,5%) und Katecholaminen (38,3 vs. 52,4%) (jeweils Gruppe II vs. Gruppe I). Postnatale Kortikosteroide wurden in Gruppe II häufiger verabreicht (17,4 vs. 13,4%), jedoch über einen kürzeren Zeitraum (6 Tage vs. 13 Tage). Der Einsatz von Antibiotika blieb unverändert (100 vs. 98,9%). Ein Vergleich des klinischen Verlaufes zeigte einen Rückgang in der Dauer der maschinellen Beatmung sowie eine signifikant höhere Überlebensrate.

Schlussfolgerung: Der Arzneimitteleinsatz bei Frühgeborenen zeigt über einen Zeitraum von 10 Jahren deutliche Veränderungen, was unter anderem durch verbesserte Standards in der Versorgung und kürzere Beatmungszeiten bedingt sein könnte.

Key words

drug utilisation - preterm infants - morbidity - surfactant - antenatal and postnatal corticosteroids

Schlüsselwörter

Arzneimitteltherapie - Frühgeborene - Morbidität - Surfactant - ante- und postnatale Kortikosteroide

Literatur

• 1 Ammari A, Suri M, Milisavljevic V, Sahni R, Bateman D, Sanocka U, Ruzal-Saphiro C, Wung JT, Polin RA. Variables associated with the failure of nasal CPAP in very low birth weight infants.  J Pediatr. 2005;  147 341-347
• 2 Aranda JV, Cohen S, Neims AH. Drug utilisation in a newborn intensive care unit.  J Pediatr. 1976;  89 315-317
• 3 Brion LP, Primhak RA, Ambrosio-Perez I. Diuretics acting on the distal tubule for preterm imfants with (or developing) chronic lung disease.  Cochrane Database Syst Rev. 2002;  1 CD001817
• 4 Chien LY, Whyte R, Aziz K, Thiessen P, Matthew D, Lee SK. Improved outcome of preterm infants when delivered in tertiary care centers.  Obstet Gynecol. 2001;  98 247-252
• 5 Doyle LW, Davis PG, Morley CJ, MacPhee A, Carlin JB. Low-dose dexamethasone facilitates extubation among chronically ventilator-dependent infants: A multicenter, international, randomized, controlled trial.  Pediatrics. 2006;  117 75-83
• 6 Du W, Warrier I, Lehr VT, Salari V, Ostrea E, Aranda JV. Changing patterns of drug utilization in a neonatal intensive care population.  Am J Perinatol. 2006;  23 279-285
• 7 Gortner L, Bernsau U, Brandt M, Hellwege HH, Hieronimi G, Jorch G, Reiter HL, Versmold H. Drug utilisation in very premature infants in neonatal intensive care units.  Dev Pharmacol Ther. 1991;  17 167-171
• 8 Gortner L. Drug utilisation in preterm and term neonates.  PharmocoEconomics. 1993;  4 437-445
• 9 Hansmann G, Humpl T, Zimmermann A, Bührer C, Wauer R, Stannigal H, Hoehn T. ILCOR . ILCOR's new resuscitation guidelines in preterm and term infants: critical discussion and suggestions for implementation.  Klin Padiatr. 2007;  219 50-57
• 10 Hintz SR, Poole WK, Wright LL, Fanaroff AA, Kendrick DE, Laptook AR, Goldberg R, Duara S, Stoll BJ, Oh W. NICHD Neonatal Research Network . Changes in mortality and morbidities among infants born at less than 25 weeks during the post-surfactant era.  Arch Dis Child Fetal Neonatal Ed. 2005;  90 128-133
• 11 Hünseler C, Roth B. Medikamentöse und nichtmedikamentöse Schmerztherapie in der Neonatologie: Zusammenstellung der aktuellen Datenlage.  Klin Padiatr. 2008; 
• 12 Italian Collaborative Group on Preterm Delivery . Early neonatal drug utilisation in preterm newborns in neonatal intensive care units.  Dev Pharmacol Ther. 1988;  11 1-7
• 13 Kao LC, Durand DJ, MacCrea RC, Birch M, Powers RJ, Nickerson BG. Randomized trial of long-term diuretic therapy for infants with oxygen-dependent bronchopulmonary dysplasia.  J Pediatr. 1994;  124 772-781
• 14 Lamer P. Current controversies surrounding the use of repeated courses of antenatal steroids.  Adv Neonatol Care. 2002;  2 290-300
• 15 Lemons JA, Bauer CR, Oh W, Korones SB, Papile LA, Stoll BJ, Verter J, Temprosa M, Wright LL, Ehrenkrank RA, Fanaroff AA, Stark A, Carlo W, Tyson JE, Donovan EF, Shankaran S, Stevenson DK. Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1995 through December 1996.  Pediatrics. 2001;  107 1
• 16 Lesko SM, Epstein MF, Mitchell AA. Recent patterns of drug use in newborn intensive care.  J Pediatr. 1990;  116 985-990
• 17 Papile L, Burstein J, Burstein R, Koffler H. Incidence and evaluation of subependymal hemorrhage: A study of infants with birth weights less then 1500 grams.  J Pediatr. 1978;  92 529-534
• 18 Pöschl J, Kölker S, Bast T, Brüssau J, Ruef P, Linderkamp O, Bettendorf M. Gamma-hydroxybutyric acid sedation in neonates and children undergoing MR imaging.  Klin Padiatr. 2007;  219 217-219
• 19 Roberts D, Dalziel S. Antenatal corticosteroides for accelerating fetal lung maturation for women at risk of preterm birth.  Cochrane Database Syst Rev. 2006;  CD004454
• 20 Sauerwald A, Rath W. Lung maturation therapy with glucocorticoids in threatened premature labor. Considerations of risk.-benefit in evidence-based medicine.  Z Geburtshilfe Neonatol. 2000;  204 203-209
• 21 Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W. Caffeine therapy for apnea of prematurity.  N Engl J Med. 2006;  354 2112-2121
• 22 Schuchat A, Zywicki SS, Dinsmoor MJ, Mercer B, Romaguera J, O’Sullivan MJ, Patel D, Peters MT, Stoll B, Levine OS. Risk factors and opportunities for prevention of early-onset neonatal sepsis: a multicenter case-control study.  Pediatrics. 2000;  105 21-26
• 23 Schwartz RM, Luby AM, Scanlon JW, Kellog JW, Russell J. Effect of surfactant on morbidity and mortality, and resource use in newborn infants weighing 500 to 1500 g.  N Engl J Med. 1994;  330 1476-1480
• 24 Sherman MP, Goetzman BW, Ahlfors CE, Wennberg RP. Tracheal aspiration and its clinical correlates in the diagnosis of congenital pneumonia.  Pediatrics. 1980;  65 258-263
• 25 Stoelhorst GM, Rijken M, Martens SE, Brand R, den Ouden AL, Wit JM, Veen S. Leiden Follow-Up Project on Prematurity . Changes in neonatology: comparison of two cohorts of very preterm infants (gestational age <32 weeks): the project on preterm and small for gestational age infants 1983 and the Leiden follow-up project on prematurity 1996–1997.  Pediatrics. 2005;  115 396-405
• 26 Stoll BJ, Gordon T, Korones SB, Shankaran S, Tyson JE, Bauer CR, Fanaroff AA, Lemons JA, Donovan EF, Oh W, Stevenson DK, Ehrenkranz RA, Papile LA, Verter J, Wright LL. Early onset sepsis in very low birth weight neonates: A report from the National Institute of Child Health and Human Development Neonatal Research Network.  J Pediatr. 1996;  129 72-80
• 27 Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, Lemons JA, Donovan EF, Stark AR, Tyson JE, Oh W, Bauer CR, Korones SB, Shankaran S, Laptook AR, Stevenson DK, Papile LA, Poole WK. Late-onset sepsis in very low birth weight neonates: The experience of the NICHD Neonatal Research Network.  Pediatrics. 2002;  110 285-291
• 28 Thébaud B, Lacaze-Masmonteil T, Watterberg K. Postnatal glucocorticoids in very preterm infants: “The good, the bad, and the ugly”?.  Pediatrics. 2001;  107 413-441
• 29 Thome UH, Carlo WA, Pohlandt F. Ventilation strategies and outcome in randomised trials of high frequency ventilation.  Arch Dis Child Fetal Neonatal Ed. 2005;  90 466-473
• 30 Toce SS, Farrell PM, Leavitt LA, Samuels DP, Edwards DK. Clinical and roentgenographic scoring systems for assesing bronchopulmonary dysplasia.  M J Dis Child. 1984;  138 581-585
• 31 Marter LJ Van, Allred EN, Pagano M, Sanocka U, Parad R, Moore M, Susser M, Paneth N, Leviton A. Do clinical markers of barotrauma and oxygen toxicity explain interhospital variation in rates of chronic lung disease?.  Pediatrics. 2000;  105 1194-1201
• 32 Vohr BR, Wright LL, Poole K, MacDonald SA. Neurodevelopmental outcomes of extremly low birth weight infants <32 weeks’ gestation between 1993 and 1998.  Pediatrics. 2005;  116 635-643
• 33 Yeh TF, Lin YJ, Huang CC, Chen YJ, Lin CH, Lin HC, Hsieh WS, Lien YJ. Early dexamethasone therapy in preterm infants: A follow-up study.  Pediatrics. 1998;  101 E7

Correspondence