1611069
Dev Pharmacol Ther 1991;17:167-171
©1991 S. Karger AG. Basel 0379-8305/91 /0174-0167$2.75/0
Drug Utilization in Very Premature Infants in Neonatal Intensive Care Units1 L. Gortner U. Bernsaub, M. Brandc. H.H. Hellweged, G. Hieronimie, G. Jorch{, H.L. Reiter^, II. Versmoldh a,
“University Children's Hospital, Ulm; '“Children’s Hospital, Augsburg; “University Children’s Hospital, Frankfurt; “'University Children’s Hospital, Hamburg; “Olgahospital, Pediatric Center, Stuttgart; 'University Children’s Hospital, Minister; ^University Children’s Hospital, Giessen; hLudwig Maximilian University, Neonatology Grosshadern, München, FRG
Key Words. Very premature infants • Drug utilization • Bovine surfactant • Respiratory distress syndrome • Antibiotics • Sedatives and analgesics Abstract. Neonatal drug utilization in very premature infants (gestational age (GA) 24-29
weeks), requiring intubation and mechanical ventilation at birth was registered as part of a multicenter controlled clinical trial of high-dose versus low-dose bovine surfactant (initial doses 100 mg/kg birth weight (b.w.) versus 50 mg/kg b.w.). Drug utilization during 4 weeks after birth was analyzed in 164 infants (mean GA 27.2 ± 1.2 (SD) weeks, b.w. 970 ± 145 g (SD)). More than half of the study infants received antibiotics (98.8%), sedatives and anal gesics (91.5%), sodium bicarbonate (78%), solutions for volume replacement (62.8%), methylxanthines (56.7%) and catecholamines (52.4%). It may be concluded that the pattern of drug usage indicates a high incidence of proven or suspected infections and circulatory and respiratory disorders reflecting the high-risk state of study infants.
Reports on drug usage during the neona tal period have been given previously includ ing all groups of infants treated in neonatal intensive care units (NICU) or nurseries [13]. However, any specific data are lacking for
1 Presented at the Second European Neonatal Workshop, Klingenthal. France, June 15. 1991.
very premature infants (gestational age (GA) 0.4) during days 1-4 after birth. The endpoint of the study was to test the hypothesis that high-dose surfactant (100 mg/kg b.w.) treatment improves oxygenation compared with low-dose (50 mg/kg b.w.) treatment 2 h after the sur factant administration. As part of the study, drug usage during the first 28 days after birth was recorded in all study infants and categorized into the following groups: Antibiotics, volume replacement solutions, catecholamines, so dium bicarbonate, pulmonary vasodilators, indomethacin, muscle relaxants, dexamethasone (for treatment of bronchopulmonary dysplasia according to Avery et al. [5]), mucolytics, methylxanthines, di uretics and sedatives/analgesics. Vitamin K was not registered, for its administration is performed rou tinely in all nurseries for prevention of neonatal hem orrhagic disease. As arterial blood gas analyses drawn from arterial lines (rinsed routinely with heparin-con taining saline) were obligate on day 1 and facultative up to day 5 after birth, heaprin administration was not registered separately. The assessment of complications in study infants included the incidence of intraventricular hemor rhage (grading according to Papile et al. [6]), patent ductus arteriosus (criteria according to Gersony et al. [7]) and bronchopulmonary dysplasia (definition: FiO? >0.3 and/or mechanical ventilation at day 28 according to Toce et al. [8]). All study infants were examined by ophthalmologists for diagnosis of reti nopathy of prematurity (grading according to the Committee for the Classification of Retinopathy of Prematurity [9]). The diagnosis of congenital pneu monia was based on microbiological criteria [10] and the diagnosis of nosocomial sepsis or pneumonia on a blood culture or a tracheal aspirate positive for bacte ria and clinical deterioration in affected infants. Sur vival was defined as discharge from the respective center to home.
Results
From August 1989 through May 1990, 164 infants were enrolled. Eighty-one infants were randomly assigned to low-dose treat ment, whereas 83 infants received high-dose treatment. Major clinical characteristics in study infants are given in table 1. Thirtyfour infants were born elsewhere. Twentynine study infants were delivered vaginally, cesarean section was performed in 136 in fants. Drugs most commonly administered to mothers before birth were ß2-agonists for tocolysis (most commonly fenoterol) and ste roids for induction of fetal lung maturity (most commonly betamethasone). Table 2 shows neonatal drug utilization in study infants. The drugs most commonly used in the participating NICUs were antibi otics (penicillins, cephalosporins and amino glycosides), sedatives/analgesics (barbitu rates and benzodiazepines/morphine or de rivatives), sodium bicarbonate, solutions for volume replacement (mainly albumin or plasma solutions as colloids), methylxan-
Table 1. Clinical data and prenatal drug utiliza tion in study infants
27.2 ± 1.21 Gestational age, weeks 970± 1451 Birth weight, g Females/males 76/89 Singletons/multiple births I 19/45 Apgar 12 h before birth) Ambroxol 5 ßi-Agonists 108 19 Antihypertensive drugs
(n = 164)
(19.0%) (9.1%) (8.5%) (51.8%) (3.1 %) (65.9%) (11.6%)
Means ± SD.
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168
Neonata] Drug Utilization
169
thines (caffeine or theophylline) and cate cholamines (dopamine or dobutamine). No significant differences could be observed with respect to the pattern of drug utilization in high-dose compared to low-dose surfac tant-treated infants. The outcome and major clinical compli cations in study infants are given in table 3. Patent ductus arteriosus of hemodynamic significance was ligated surgically in 26 in fants (15.8%). Pharmacological treatment of bronchopulmonary dysplasia with dexamethasone was usually started 2-3 weeks after birth, only 1 infant received steroids at day 3. Surgical treatment of necrotizing en terocolitis was necessary in 3 infants. As to the endpoint of the study, oxygena tion was significantly improved in high-dose compared to low-dose surfactant-treated in fants (pa02/Fi02 230.2 ± 114.5 vs. 176.7 ± 116.2 mm Hg; p < 0.05 [11]).
The neonatal characteristics of our study infants are different form those for which reports on drug utilization have been pub lished in the past [1, 3] and represents a selected high-risk group due to the fact that only very premature infants with need for intubation and mechanical ventilation after birth were enrolled. Nevertheless, the fre quency of treatment with antibiotics in our study infants is consistent with the above mentioned reports [1, 3]. If the 18% inci dence of microbiologically proven congeni tal bacterial infections is considered, a high number of very premature infants is treated with antibiotics immediately after birth only for suspected infections. We observed noso comial infections in about one half of study infants, which in part may result form fre quent and long-term use (median 19 days) of
Table 2. Drug utilization in study infants during the neonatal period
Table 3. Outcome and major clinical complica tions in study infants
Antibiotics Volume replacement Pulmonary vasodilators Methylxanthines Diuretics Sedatives/analgesics Catecholamines Sodium bicarbonate Indomethacin Mucolytics Dexamethasone Muscle relaxants
98.8 62.8 3 56.7 36.6 91.5 52.4 78.0 9 20.1
13.4 31.7
19 6 ?
22
7 6
4 3 14 13 4
1-28 1-28 1-4 1-28 1-28 1-28 1-28 1-28 2-4 2-28 4-25 1-28
%
n Surviving infants Days of hospitalization Days of mechanical ventilation IVH (grades III and IV) ROP (grades III and IV) Patent ductus arteriosus Pneumothorax Bronchopulmonary dysplasia Nosocomial infections Pneumonia Sepsis Necrotizing enterocolitis
121
91 (44-238) 17(1-131) 32 14 58 29 44 30 45 6
73.8
19.5 8.5 35.4 17.7 26.8 18.3 27.4 3.6
IVH = Intraventricular hemorrhage, ROP = reti nopathy of prematurity. Values are given as frequencies or mean (range).
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Frequency Duration, days of admini- -----------------stration, % median range
Discussion
Gortner/Bernsau/Brand/Hellwege/Hieronimi/Jorch/Reiter/Versmold
antibiotics [12, 13], As it has been shown in the past that nosocomial infections are sub stantially operative in NICU mortality in extremely low birth weight infants [14], it is necessary to reduce the incidence of noso comial infections. It therefore seems manda tory to further work out rules for timing and treatment of very premature infants with antibiotics. Further strategies for reduction of nosocomial infections like protective iso lation, which has been proven to reduce the incidence in children cared for in pediatric intensive care units [15], should be consid ered. The usage of intravenous volume re placement, sodium bicarbonate and cate cholamines indicates a high incidence of cir culatory problems in study infants. Although there are clear-cut reference values for blood pressure in very premature infants [16, 17], from which guidelines for antihypotensive therapy may be derived, there may be some overuse especially of catecholamines. Dopa mine which was most commonly used and dobutamine have been proven to be effective in premature infants with hypotension [18], Sedatives/analgesics and muscle relaxants were frequently administered during the first week, indicating respiratory distress with the need for mechanical ventilation in study in fants. On the other hand, methylxanthines proven to be of value for weaning from me chanical ventilation and for apnea of prema turity [19, 20], have been administered to more than half of the very premature infants. Despite the fact that beneficial effects of mucolytics in premature infants have not been demonstrated yet [21], these agents were administered to about 20% of study infants. On the basis of the criteria for treat ment of bronchopulmonary dysplasia pro posed by Avery et al. [5], about one half of study infants with bronchopulmonary dys
plasia were treated with dexamethasone. Al though follow-up data in premature infants after a 6-week course of dexamethasone for bronchopulmonary dysplasia have demon strated improved neurodevelopmental out come compared with control infants [22], further endocrine and long-term follow-up studies seem to be mandatory for evaluation of safety [23], In general, drug utilization in study in fants reflects the high-risk state secondary to extreme prematurity and need for mechani cal ventilation. Care must be taken, how ever, to reconsider drugs commonly used in older infants as new insight of drugs and of physiology on very premature infants are acquired.
References 1 Aranda JV, Cohen S, Neims AH: Drug utilization in a newborn intensive care unit. J Pediatr 1976; 89:315-317. 2 Aranda JV, Türmen T, Cote-Boileau T: Drug monitoring in the perinatal patient: Uses and abuses. Ther Drug Monit 1980;2:39-49. 3 Italian Collaborative Group on Preterm Delivery: Early neontal drug utilization in preterm new borns in neonatal intensive care units. Dev Phar macol Ther 1988;11:1-7. 4 Hcinonen K, Hakulinen A, Jokela V: Time trends and determinants of mortality in a very preterm population during the 1980s. Tancet 1988;ii:204— 207. 5 Avery GB, Fletcher AB, Kaplan M, et al: Con trolled trial of dexamethasone in respirator-de pendent infants with bronchopulmonary dyspla sia. Pediatrics 1985;75:106-111. 6 Papile L, Burstein J, Burstein R, et al: Incidence and evaluation of subependymal hemorrhage: A study of infants with birth weights less than 1,500 grams. J Pediatr 1978:92:529-534. 7 Gersony WM, Peckham GJ, Ellison CR, et al: Effects of indomethacin in premature infants with Downloaded by: University of Exeter 144.173.6.94 - 5/8/2020 9:44:15 AM
170
r
Neonatal Drug Utilization
9
10
11
12
13
14
15
16
17 Tan KL: Blood pressure in very low birth weight infants in the first 70 days of life. J Pediatr 1988; 112:266-270. 18 Miall-Allen VM, Whitelaw AGL: Response to do pamine and dobutamine in the preterm infant less than 30 weeks’ gestation. Crit Care Med 1989; 17: 1166-1169. 19 Harris MC, Baumgart S, Rooklin AR; et al: Suc cessful extubation of infants with respiratory dis tress syndrome using aminophylline. J Pediatr 1983;103:303-305. 20 Viscardi RM, Faix RG, Nicks JJ, et al: Efficacy of theophylline for prevention of post-extubation re spiratory failure in very low birth weight infants. J Pediatr 1985;107:469-472. 21 Burgess WR, Chernick V: Respiratory therapy in newborn infants and children. New York, Thieme-Stratton, 1982, pp 98-100. 22 Cummings JJ, D’Eugenio DB, Gross SJ: A con trolled trial of dexamethasone in preterm infants at high risk for bronchopulmonary dysplasia. N Engl J Med 1989;320:1505-1510. 23 Ng PC, Blackburn ME, Brownlee KG, et al: Adre nal response in very low birthweight babies after dexamethasone treatment for bronchopulmonary dysplasia. Arch Dis Child 1989;64:1721-1726.
L. Gortner, MD Department of Pediatrics Medical University Kahlhorststrasse 31-35 D-W-2400 Lübeck (FRG)
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8
patent ductus arteriosus: Results of a national col laborative study. J Pediatr 1983;102:895-906. Toce SS, Farrell PM, Leavitt LA, et al: Clinical and roentgenographic scoring systems for assess ing bronchopulmonary dysplasia. Am J Dis Child 1984;1 38:581-585. The Committee for the Classification of Retinop athy of Prematurity; An international classifica tion of retinopathy of prematurity. Arch Ophthal mol 1984;102:1130-1 134. Shermann MP, Goetzman BW, Ahlfors CE, et al: Tracheal aspiration and its clinical correlates in the diagnosis of congenital pneumonia. Pediatrics 1980;65:258-263. Gortner L, Bernsau U, Hellwege HH, et al: Con trolled randomized multicenter clinical trial of high-dose versus low-dose bovine surfactant in very premature infants. Pediatr Res 1991:29: 318A. Modi N, Damjanovic V, Cooke RVI: Outbreak of cephalosporin resistant Enterobacter cloacae in a neontal intensive care unit. Arch Dis Child 1987; 62:148-151. Tullus K, Burman LG: Ecological impact of ampicillin and cefuroxime in neonatal units. Lancet 19890:1405-1407. La Gamma EF, Drusin LM, Mackles AW, et al: Neonatal infections. An important determinant of late NICU mortality in infants less than 1,000 grams at birth. Am J Dis Child 1983:137:838— 841. Klein BS, Perloff WH, Maki DG: Reduction of nosocomial infection during pediatric intensive care by protective isolation. N Engl J Med 1989; 320:1714-1721. Versmold HT, Kitterman JA, Phibbs RH, et al: Aortic blood pressure during the first 12 hours of life in infants with birth weight 610 to 4,220 grams. Pediatrics 1981;67:607-613.
171
Dev Pharmacol Ther 1991;17:167-171
©1991 S. Karger AG. Basel 0379-8305/91 /0174-0167$2.75/0
Drug Utilization in Very Premature Infants in Neonatal Intensive Care Units1 L. Gortner U. Bernsaub, M. Brandc. H.H. Hellweged, G. Hieronimie, G. Jorch{, H.L. Reiter^, II. Versmoldh a,
“University Children's Hospital, Ulm; '“Children’s Hospital, Augsburg; “University Children’s Hospital, Frankfurt; “'University Children’s Hospital, Hamburg; “Olgahospital, Pediatric Center, Stuttgart; 'University Children’s Hospital, Minister; ^University Children’s Hospital, Giessen; hLudwig Maximilian University, Neonatology Grosshadern, München, FRG
Key Words. Very premature infants • Drug utilization • Bovine surfactant • Respiratory distress syndrome • Antibiotics • Sedatives and analgesics Abstract. Neonatal drug utilization in very premature infants (gestational age (GA) 24-29
weeks), requiring intubation and mechanical ventilation at birth was registered as part of a multicenter controlled clinical trial of high-dose versus low-dose bovine surfactant (initial doses 100 mg/kg birth weight (b.w.) versus 50 mg/kg b.w.). Drug utilization during 4 weeks after birth was analyzed in 164 infants (mean GA 27.2 ± 1.2 (SD) weeks, b.w. 970 ± 145 g (SD)). More than half of the study infants received antibiotics (98.8%), sedatives and anal gesics (91.5%), sodium bicarbonate (78%), solutions for volume replacement (62.8%), methylxanthines (56.7%) and catecholamines (52.4%). It may be concluded that the pattern of drug usage indicates a high incidence of proven or suspected infections and circulatory and respiratory disorders reflecting the high-risk state of study infants.
Reports on drug usage during the neona tal period have been given previously includ ing all groups of infants treated in neonatal intensive care units (NICU) or nurseries [13]. However, any specific data are lacking for
1 Presented at the Second European Neonatal Workshop, Klingenthal. France, June 15. 1991.
very premature infants (gestational age (GA) 0.4) during days 1-4 after birth. The endpoint of the study was to test the hypothesis that high-dose surfactant (100 mg/kg b.w.) treatment improves oxygenation compared with low-dose (50 mg/kg b.w.) treatment 2 h after the sur factant administration. As part of the study, drug usage during the first 28 days after birth was recorded in all study infants and categorized into the following groups: Antibiotics, volume replacement solutions, catecholamines, so dium bicarbonate, pulmonary vasodilators, indomethacin, muscle relaxants, dexamethasone (for treatment of bronchopulmonary dysplasia according to Avery et al. [5]), mucolytics, methylxanthines, di uretics and sedatives/analgesics. Vitamin K was not registered, for its administration is performed rou tinely in all nurseries for prevention of neonatal hem orrhagic disease. As arterial blood gas analyses drawn from arterial lines (rinsed routinely with heparin-con taining saline) were obligate on day 1 and facultative up to day 5 after birth, heaprin administration was not registered separately. The assessment of complications in study infants included the incidence of intraventricular hemor rhage (grading according to Papile et al. [6]), patent ductus arteriosus (criteria according to Gersony et al. [7]) and bronchopulmonary dysplasia (definition: FiO? >0.3 and/or mechanical ventilation at day 28 according to Toce et al. [8]). All study infants were examined by ophthalmologists for diagnosis of reti nopathy of prematurity (grading according to the Committee for the Classification of Retinopathy of Prematurity [9]). The diagnosis of congenital pneu monia was based on microbiological criteria [10] and the diagnosis of nosocomial sepsis or pneumonia on a blood culture or a tracheal aspirate positive for bacte ria and clinical deterioration in affected infants. Sur vival was defined as discharge from the respective center to home.
Results
From August 1989 through May 1990, 164 infants were enrolled. Eighty-one infants were randomly assigned to low-dose treat ment, whereas 83 infants received high-dose treatment. Major clinical characteristics in study infants are given in table 1. Thirtyfour infants were born elsewhere. Twentynine study infants were delivered vaginally, cesarean section was performed in 136 in fants. Drugs most commonly administered to mothers before birth were ß2-agonists for tocolysis (most commonly fenoterol) and ste roids for induction of fetal lung maturity (most commonly betamethasone). Table 2 shows neonatal drug utilization in study infants. The drugs most commonly used in the participating NICUs were antibi otics (penicillins, cephalosporins and amino glycosides), sedatives/analgesics (barbitu rates and benzodiazepines/morphine or de rivatives), sodium bicarbonate, solutions for volume replacement (mainly albumin or plasma solutions as colloids), methylxan-
Table 1. Clinical data and prenatal drug utiliza tion in study infants
27.2 ± 1.21 Gestational age, weeks 970± 1451 Birth weight, g Females/males 76/89 Singletons/multiple births I 19/45 Apgar 12 h before birth) Ambroxol 5 ßi-Agonists 108 19 Antihypertensive drugs
(n = 164)
(19.0%) (9.1%) (8.5%) (51.8%) (3.1 %) (65.9%) (11.6%)
Means ± SD.
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168
Neonata] Drug Utilization
169
thines (caffeine or theophylline) and cate cholamines (dopamine or dobutamine). No significant differences could be observed with respect to the pattern of drug utilization in high-dose compared to low-dose surfac tant-treated infants. The outcome and major clinical compli cations in study infants are given in table 3. Patent ductus arteriosus of hemodynamic significance was ligated surgically in 26 in fants (15.8%). Pharmacological treatment of bronchopulmonary dysplasia with dexamethasone was usually started 2-3 weeks after birth, only 1 infant received steroids at day 3. Surgical treatment of necrotizing en terocolitis was necessary in 3 infants. As to the endpoint of the study, oxygena tion was significantly improved in high-dose compared to low-dose surfactant-treated in fants (pa02/Fi02 230.2 ± 114.5 vs. 176.7 ± 116.2 mm Hg; p < 0.05 [11]).
The neonatal characteristics of our study infants are different form those for which reports on drug utilization have been pub lished in the past [1, 3] and represents a selected high-risk group due to the fact that only very premature infants with need for intubation and mechanical ventilation after birth were enrolled. Nevertheless, the fre quency of treatment with antibiotics in our study infants is consistent with the above mentioned reports [1, 3]. If the 18% inci dence of microbiologically proven congeni tal bacterial infections is considered, a high number of very premature infants is treated with antibiotics immediately after birth only for suspected infections. We observed noso comial infections in about one half of study infants, which in part may result form fre quent and long-term use (median 19 days) of
Table 2. Drug utilization in study infants during the neonatal period
Table 3. Outcome and major clinical complica tions in study infants
Antibiotics Volume replacement Pulmonary vasodilators Methylxanthines Diuretics Sedatives/analgesics Catecholamines Sodium bicarbonate Indomethacin Mucolytics Dexamethasone Muscle relaxants
98.8 62.8 3 56.7 36.6 91.5 52.4 78.0 9 20.1
13.4 31.7
19 6 ?
22
7 6
4 3 14 13 4
1-28 1-28 1-4 1-28 1-28 1-28 1-28 1-28 2-4 2-28 4-25 1-28
%
n Surviving infants Days of hospitalization Days of mechanical ventilation IVH (grades III and IV) ROP (grades III and IV) Patent ductus arteriosus Pneumothorax Bronchopulmonary dysplasia Nosocomial infections Pneumonia Sepsis Necrotizing enterocolitis
121
91 (44-238) 17(1-131) 32 14 58 29 44 30 45 6
73.8
19.5 8.5 35.4 17.7 26.8 18.3 27.4 3.6
IVH = Intraventricular hemorrhage, ROP = reti nopathy of prematurity. Values are given as frequencies or mean (range).
Downloaded by: University of Exeter 144.173.6.94 - 5/8/2020 9:44:15 AM
Frequency Duration, days of admini- -----------------stration, % median range
Discussion
Gortner/Bernsau/Brand/Hellwege/Hieronimi/Jorch/Reiter/Versmold
antibiotics [12, 13], As it has been shown in the past that nosocomial infections are sub stantially operative in NICU mortality in extremely low birth weight infants [14], it is necessary to reduce the incidence of noso comial infections. It therefore seems manda tory to further work out rules for timing and treatment of very premature infants with antibiotics. Further strategies for reduction of nosocomial infections like protective iso lation, which has been proven to reduce the incidence in children cared for in pediatric intensive care units [15], should be consid ered. The usage of intravenous volume re placement, sodium bicarbonate and cate cholamines indicates a high incidence of cir culatory problems in study infants. Although there are clear-cut reference values for blood pressure in very premature infants [16, 17], from which guidelines for antihypotensive therapy may be derived, there may be some overuse especially of catecholamines. Dopa mine which was most commonly used and dobutamine have been proven to be effective in premature infants with hypotension [18], Sedatives/analgesics and muscle relaxants were frequently administered during the first week, indicating respiratory distress with the need for mechanical ventilation in study in fants. On the other hand, methylxanthines proven to be of value for weaning from me chanical ventilation and for apnea of prema turity [19, 20], have been administered to more than half of the very premature infants. Despite the fact that beneficial effects of mucolytics in premature infants have not been demonstrated yet [21], these agents were administered to about 20% of study infants. On the basis of the criteria for treat ment of bronchopulmonary dysplasia pro posed by Avery et al. [5], about one half of study infants with bronchopulmonary dys
plasia were treated with dexamethasone. Al though follow-up data in premature infants after a 6-week course of dexamethasone for bronchopulmonary dysplasia have demon strated improved neurodevelopmental out come compared with control infants [22], further endocrine and long-term follow-up studies seem to be mandatory for evaluation of safety [23], In general, drug utilization in study in fants reflects the high-risk state secondary to extreme prematurity and need for mechani cal ventilation. Care must be taken, how ever, to reconsider drugs commonly used in older infants as new insight of drugs and of physiology on very premature infants are acquired.
References 1 Aranda JV, Cohen S, Neims AH: Drug utilization in a newborn intensive care unit. J Pediatr 1976; 89:315-317. 2 Aranda JV, Türmen T, Cote-Boileau T: Drug monitoring in the perinatal patient: Uses and abuses. Ther Drug Monit 1980;2:39-49. 3 Italian Collaborative Group on Preterm Delivery: Early neontal drug utilization in preterm new borns in neonatal intensive care units. Dev Phar macol Ther 1988;11:1-7. 4 Hcinonen K, Hakulinen A, Jokela V: Time trends and determinants of mortality in a very preterm population during the 1980s. Tancet 1988;ii:204— 207. 5 Avery GB, Fletcher AB, Kaplan M, et al: Con trolled trial of dexamethasone in respirator-de pendent infants with bronchopulmonary dyspla sia. Pediatrics 1985;75:106-111. 6 Papile L, Burstein J, Burstein R, et al: Incidence and evaluation of subependymal hemorrhage: A study of infants with birth weights less than 1,500 grams. J Pediatr 1978:92:529-534. 7 Gersony WM, Peckham GJ, Ellison CR, et al: Effects of indomethacin in premature infants with Downloaded by: University of Exeter 144.173.6.94 - 5/8/2020 9:44:15 AM
170
r
Neonatal Drug Utilization
9
10
11
12
13
14
15
16
17 Tan KL: Blood pressure in very low birth weight infants in the first 70 days of life. J Pediatr 1988; 112:266-270. 18 Miall-Allen VM, Whitelaw AGL: Response to do pamine and dobutamine in the preterm infant less than 30 weeks’ gestation. Crit Care Med 1989; 17: 1166-1169. 19 Harris MC, Baumgart S, Rooklin AR; et al: Suc cessful extubation of infants with respiratory dis tress syndrome using aminophylline. J Pediatr 1983;103:303-305. 20 Viscardi RM, Faix RG, Nicks JJ, et al: Efficacy of theophylline for prevention of post-extubation re spiratory failure in very low birth weight infants. J Pediatr 1985;107:469-472. 21 Burgess WR, Chernick V: Respiratory therapy in newborn infants and children. New York, Thieme-Stratton, 1982, pp 98-100. 22 Cummings JJ, D’Eugenio DB, Gross SJ: A con trolled trial of dexamethasone in preterm infants at high risk for bronchopulmonary dysplasia. N Engl J Med 1989;320:1505-1510. 23 Ng PC, Blackburn ME, Brownlee KG, et al: Adre nal response in very low birthweight babies after dexamethasone treatment for bronchopulmonary dysplasia. Arch Dis Child 1989;64:1721-1726.
L. Gortner, MD Department of Pediatrics Medical University Kahlhorststrasse 31-35 D-W-2400 Lübeck (FRG)
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8
patent ductus arteriosus: Results of a national col laborative study. J Pediatr 1983;102:895-906. Toce SS, Farrell PM, Leavitt LA, et al: Clinical and roentgenographic scoring systems for assess ing bronchopulmonary dysplasia. Am J Dis Child 1984;1 38:581-585. The Committee for the Classification of Retinop athy of Prematurity; An international classifica tion of retinopathy of prematurity. Arch Ophthal mol 1984;102:1130-1 134. Shermann MP, Goetzman BW, Ahlfors CE, et al: Tracheal aspiration and its clinical correlates in the diagnosis of congenital pneumonia. Pediatrics 1980;65:258-263. Gortner L, Bernsau U, Hellwege HH, et al: Con trolled randomized multicenter clinical trial of high-dose versus low-dose bovine surfactant in very premature infants. Pediatr Res 1991:29: 318A. Modi N, Damjanovic V, Cooke RVI: Outbreak of cephalosporin resistant Enterobacter cloacae in a neontal intensive care unit. Arch Dis Child 1987; 62:148-151. Tullus K, Burman LG: Ecological impact of ampicillin and cefuroxime in neonatal units. Lancet 19890:1405-1407. La Gamma EF, Drusin LM, Mackles AW, et al: Neonatal infections. An important determinant of late NICU mortality in infants less than 1,000 grams at birth. Am J Dis Child 1983:137:838— 841. Klein BS, Perloff WH, Maki DG: Reduction of nosocomial infection during pediatric intensive care by protective isolation. N Engl J Med 1989; 320:1714-1721. Versmold HT, Kitterman JA, Phibbs RH, et al: Aortic blood pressure during the first 12 hours of life in infants with birth weight 610 to 4,220 grams. Pediatrics 1981;67:607-613.
171
