Why do four NICUs using identical RBC transfusion guidelines have different gestational age-adjusted RBC transfusion rates?

OBJECTIVE: To compare neonatal red blood cell (RBC) transfusion rates in four large Intermountain Healthcare NICUs, all of which adhere to the same RBC transfusion guidelines. STUDY DESIGN: This retrospective analysis was part of a transfusion-management quality-improvement project. De-identified data included RBC transfusions, clinical and laboratory findings, the anemia-prevention strategies in place in each NICU, and specific costs and outcomes. RESULT: Of 2389 NICU RBC transfusions given during the 4-year period studied, 98.9 ± 2.1% (mean ± S.D.) were compliant with our transfusion guidelines, with no difference in compliance between any of the four NICUs. However, RBC transfusion rates varied widely between the four, with averages ranging from 4.6 transfusions/1000 NICU days to 21.7/1000 NICU days (P < 0.00001). Gestational age-adjusted transfusion rates were correspondingly discordant (P < 0.00001). The lower-transfusing NICUs had written anemia-preventing guidelines, such as umbilical cord milking at very low birth weight delivery, use of cord blood for admission laboratory studies, and darbepoetin dosing for selected neonates. Rates of Bell stage ⩾ 2 necrotizing enterocolitis and grade ⩾ 3 intraventricular hemorrhage were lowest in the two lower-transfusing NICUs (P < 0.0002 and P < 0.0016). Average pharmacy costs for darbepoetin were $84/dose, with an average pharmacy cost of $269 per transfusion averted. With a cost of $900/RBC transfusion, the anemia-preventing strategies resulted in an estimated cost savings to Intermountain Healthcare of about $6970 per 1000 NICU days, or about $282,300 annually. CONCLUSION: Using transfusion guidelines has been shown previously to reduce practice variability, lower transfusion rates and diminish transfusion costs. Based on our present findings, we maintain that even when transfusion guidelines are in place and adhered to rigorously, RBC transfusion rates are reduced further if anemia-preventing strategies are also in place.

Childhood outcome after early high-frequency oscillatory ventilation for neonatal respiratory distress syndrome.

OBJECTIVE: In a previous multicenter controlled clinical trial, we randomly assigned surfactant-treated premature newborns with moderate to severe respiratory distress syndrome to early treatment with high-frequency oscillatory ventilation (HFOV) or to conventional ventilation (CV). Compared with control infants who were treated with CV, neonates who were treated with HFOV using a strategy designed to recruit and maintain lung volume and minimize oxygen exposure had clinical evidence of improved pulmonary outcome and less lung injury. We report a follow-up study designed to determine whether clinical differences persisted between these study groups. METHODS: Patients were recruited from 81 survivors at 1 center (Provo, Utah) and evaluated for sociodemographic and health history, growth, mental development, motor proficiency, and pulmonary function. RESULTS: Eighty-seven percent of the cohort who originally were assigned to treatment with HFOV (n = 36) or CV (n = 33) were seen in follow-up at a mean age of 77 months (6.4 years). There were no differences in the frequency of hospitalization, pulmonary illness, asthma, or disabilities. Growth, verbal IQ, and motor development were appropriate for age and not different between groups. Patients who initially were randomized to treatment with CV showed pulmonary function evidence of decreased peak expiratory flow, increased residual lung volume, and maldistribution of ventilation. CONCLUSION: Neurodevelopmental childhood outcome after early intervention HFOV was normal and not different compared with patients who were treated with CV. Surfactant replacement combined with early HFOV using a lung recruitment strategy ameliorates the acute lung injury in respiratory distress syndrome that predisposes some preterm infants to develop chronic lung disease.

The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome.

OBJECTIVE: To compare the hospital course and clinical outcome of preterm infants with respiratory distress syndrome treated with surfactant and managed with high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CV) as their primary mode of ventilator support. DESIGN: A prospective randomized clinical trial. SETTING: Three community-based level III neonatal intensive care units. SUBJECTS: A total of 125 neonates who were 35 weeks or less estimated gestation requiring intubation and assisted ventilation for respiratory distress syndrome with arterial to alveolar oxygen ratio less than .50. INTERVENTIONS: Patients were randomized to continue CV (61 patients) or be changed to HFOV (64 patients) after exogenous surfactant administration (100 mg/kg). HFOV was used in a strategy to promote lung recruitment and maintain lung volume. Protocol respiratory care guidelines were followed; otherwise routine care was provided by each neonatal intensive care unit. MEASUREMENTS AND MAIN RESULTS: No differences were noted in demographic features between the two study groups. The study population birth weight was 1.51 +/- .47 kg (mean +/- SD), gestational age was 30.9 +/- 2.5 weeks, and study entry age was 2 to 3 hours. Patients randomized to HFOV demonstrated the following significant findings compared with CV-treated patients: vasopressor support was less intensive; surfactant redosing was not as frequent; oxygenation improved more rapidly and remained higher during the first 7 days; fewer infants required prolonged supplemental oxygen or ventilator support; treatment failure was reduced; more patients survived without chronic lung disease at 30 days; need for continuous supplemental oxygen at discharge was less; frequency of necrotizing enterocolitis illness was lower; there were fewer abnormal hearing tests; and hospital costs were decreased. No differences were seen between the two study groups in the frequency or severity of patent ductus arteriosus, air leak, retinopathy of prematurity, or intraventricular hemorrhage. Length of hospital stay and survival to discharge were similar for HFOV- and CV-treated infants. CONCLUSIONS: When used early with a lung recruitment strategy, HFOV after surfactant replacement resulted in clinical outcomes consistent with a reduction in both acute and chronic lung injury. Benefit was evident for preterm infants both less than or equal to 1 kg and more than 1 kg. In addition, early HFOV treatment may have had a more global effect on patient health throughout the hospitalization, resulting in reduced morbidity and decreased health care cost.

Nonlinear dobutamine pharmacokinetics in a pediatric population.

OBJECTIVE: To evaluate a linear kinetic model for dobutamine clearance. DESIGN: A prospective evaluation of pediatric patients receiving continuous infusions of dobutamine at varying doses. SETTING: A pediatric critical care unit. PATIENTS: Twelve patients age 2 days to 9 yrs and weighing 2.7 to 33 kg who required vasopressor therapy. Infusion rates for dobutamine ranged from 2 to 15 micrograms/kg.min. MEASUREMENTS AND MAIN RESULTS: Serum concentrations varied from 6.4 to 347 ng/mL (21 to 1151 nmol/L). Concentration was found to increase with dose. However, the relationship of clearance to steady-state concentration had a negative slope. Values for clearance varied from 32 to 625 mL/kg.min. Multiple analysis of variance on age, weight, and co-infused dopamine showed that these factors did not influence the relationship of clearance to steady-state concentration. Analysis to show an underlying model failed to differentiate Michaelis-Menten from nonlinear binding or mixed models on the basis of these data. CONCLUSIONS: Dobutamine pharmacokinetics do not appear to follow a simple linear model. Based on the current data, neither age nor the added infusion of dopamine affects the clearance of dobutamine.

Ceftizoxime disposition in neonates and infants during the first six months of life.

The single-dose pharmacokinetics of ceftizoxime sodium were studied in 52 neonates and infants between 0.1 and 189 days of age. Subjects received ceftizoxime 25 or 50 mg/kg iv over 15-30 minutes. The drug was administered q8-12h for five days to permit tolerance evaluation on repetitive dosing. No differences were observed in ceftizoxime pharmacokinetic parameter estimates relative to dose. However, marked differences were observed in ceftizoxime pharmacokinetic characteristics relative to infant age; ceftizoxime half-life and mean residence time decreased, whereas body clearance increased with infant age. Ceftizoxime volume of distribution remained relatively constant over infant age. No adverse effects associated with ceftizoxime administration were observed. These data suggest that ceftizoxime 50 mg/kg q12h be used for infants less than or equal to 2 weeks of age (less than or equal to 40 weeks postconceptional age) and that 50 mg/kg q8h be administered for older infants.

In utero ischemic injury: sonographic diagnosis and medicolegal implications.

The antenatal diagnosis of fetal neurologic injury has profound medical and legal implications. We report a case of antenatally diagnosed intracranial lesions including parenchymal hemorrhage in an otherwise physically normal infant. Computerized tomography in the newborn period demonstrated diffused ischemic damage with secondary cystic changes in addition to intracranial hemorrhage.

Successful fetal therapy for cystic adenomatoid malformation associated with second-trimester hydrops.

Fetal hydrops secondary to cystic adenomatoid malformation was detected in a second-trimester fetus. In utero thoraco-amniotic shunt placement resulted in resolution of the hydrops. At term, there was no evidence of pulmonary hypoplasia.

An improved system for reporting congenital malformations.

To improve the system of reporting congenital malformations on the birth certificates of newborns, we initiated the following procedural changes at Utah Valley Regional Medical Center in 1981: (1) transference of the responsibility of reporting congenital malformations from the mother's physician to the newborn's physician; (2) development of a congenital malformation reporting sheet included in each newborn's file; and (3) appointment of a centralized single hospital medical records person to review the files and to complete the birth certificate. For 4949 births in 1982, the results of these changes were reviewed retrospectively and compared with those of a previous study at the institution. This system markedly improved the overall completeness of reporting while it identified inaccurate reporting of some malformations, incomplete reporting of multiple malformations, and the reporting of nonmalformations as congenital malformations.

Decreased bone mineral content in small-for-gestational-age infants compared with appropriate-for-gestational-age infants: normal serum 25-hydroxyvitamin D and decreasing parathyroid hormone.

Bone mineral content was determined by photon absorptiometry, adapted for use in neonates, in 23 small-for-gestational-age (SGA) infants of 31 to 42 weeks of gestational age, for 12 weeks. At birth, term SGA infants had lower bone mineral content than term appropriate-for-gestational-age (AGA) infants; postnatal increase in bone mineral content was slow and lagged significantly behind that of term AGA infants. Preterm SGA infants had bone mineral content that was similar to that of preterm AGA infants at birth; postnatal bone mineral content was similar to that of preterm AGA infants, but was decreased compared with the expected intrauterine bone mineral content. Serum 25-hydroxyvitamin D concentrations and parathyroid hormone levels were the same for SGA and AGA infants. Serum 25-hydroxyvitamin D concentrations decreased slightly with postnatal age and remained within normal limits. Serum parathyroid hormone concentrations decreased in both SGA and AGA infants and reached undetectable levels at 10 to 12 weeks of age.

Pulmonary hemorrhage secondary to chest tube placement for pneumothorax in neonates.

We report two neonates in whom placement of a chest tube for pneumothorax was followed by hemorrhage, shock, and subsequent death. An autopsy of one of the patients led us to the conclusion that bleeding had occurred from lung perforation. The intercostal artery had been clearly severed and may have contributed to the hemorrhage. We discuss pathogenesis, diagnosis, and offer suggestions for proper placement of the tube.

Bone mineral content in term and preterm appropriate-for-gestational-age infants.

Photon absorptiometry adapted for use in small infants was utilized to measure bone mineral content in 42 term and 30 perterm appropriate-for-gestational-age infants. BMC at birth correlated significantly with gestational age and birth weight. Sequential measurements of BMC in premature infants during the first three months showed that the postnatal increase in BMC was significantly less than the BMC expected in utero. We speculate that decreased intake of calcium and phosphate effects postnatal bone mineralization in premature infants.

Gastroesophageal reflux causing respiratory distress and apnea in newborn infants.

Respiratory distress, apnea, and chronic pulmonary disease since birth were identified in 14 infants who also had symptomatic gastroesophageal reflux. Birth weights varied from 760 to 4,540 gm. All infants had radiographic changes similar to those in bronchopulmonary dysplasia. Cessation of apnea and improvement of pulmonary disease occurred only after medical (8) or surgical (6) control of gastroesophageal reflux. Simultaneous tracings of esophageal pH, heart rate, impedance pneumography, and nasal air flow in five infants demonstrated that reflux preceded apnea. Apnea could be induced by instillation of dilute acid, but not water or formula, into the esophagus. Prolonged monitoring of esophageal pH more than two hours after feeding in 14 other infants less than 6 weeks of age (birth weight 780 to 3,350 gm) without a history of recent vomiting indicated that reflux was not greater than in normal older children.

Use of pertussis vaccine in an epidemic involving hospital staff.

An epidemic of pertussis occurred among hospital staff caring for paediatric patients. Eight physicians and five nurses were affected. Pertussis developed in six newborn infants exposed to infected hospital staff in the nursery. Erythromycin prophylaxis was used to control the epidemic. Clinical pertussis developed in five adults infected with Bordetella pertussis before erythromycin was used, whereas symptoms developed in only one of the eight adults who became infected after erythromycin prophylaxis was started. Pertussis vaccine was given to adult volunteers in the hospital, and in 77% of two hundred and eighty-six vaccinees there was a fourfold rise in pertussis agglutinins. Local reactions were common, and in two vaccinees generalised rashes developed. One of these required treatment with corticosteroids. The risk of pertussis occurring in adults providing medical care for children should be recognised, and employees with symptoms should be removed from the hospital environment.