Pharmacoeconomic evaluation of different doses of Curosurf for treating neonatal acute respiratory distress syndrome.

Neonatal acute respiratory distress syndrome (ARDS) is a serious stage of acute lung injury (ALI) which can be treated by exogenous surfactant. The aim of this study was to explore the clinical efficacy of two different doses of Poractant alfa (Curosurf®) for treating neonatal ARDS and to perform an economic evaluation. Fifty-four patients were divided into Group A (high dose) and Group B (low dose). Pharmacoeconomic evaluation was performed on the two groups regarding the treatment expenses, and the output was the cure rate and complication rate. There were significant differences between Group A and Group B for the duration of receiving oxygen therapy in moderate cases (6.4±3.5d:8.9±2.6d) (P<0.05) and severe cases (10.0±2.6d:14.8±1.3d) (P<0.05). There were significant differences between them for the duration of undergoing mechanical ventilation in severe cases (1.7±2.3d:5.5±2.4d) (P=0.01). There was a significant difference between Group A and Group B for hospitalization expenses in severe cases (P<0.05). There were no significant differences between them in all types of cases for the cure rate (P>0.05). A high dose of Curosurf had an advantage in treating neonatal ARDS, especially in severe cases, with lower final costs and better effects.

Treatment Patterns and Clinical Outcomes in Neonates Diagnosed With Respiratory Distress Syndrome in a Low-Income Country: A Report From Bangladesh.

Respiratory distress syndrome remains a leading cause of neonatal mortality worldwide. This retrospective study describes practice patterns for respiratory distress syndrome in a resource-limited setting and seeks to identify both risk factors for mortality and beneficial treatment modalities. Health, demographic, and treatment data were collected. Potential associations were analyzed using univariable and multivariable logistic regression. Of 104 children included for analysis, 38 died. Although most children were initially treated with noninvasive respiratory support, 59 progressed to invasive ventilation. Requirement for invasive ventilation was associated with death. A clear trend toward improved survival in mechanically ventilated patients was seen with surfactant administration.

Short-term costs of preeclampsia to the United States health care system.

BACKGROUND: Preeclampsia is a leading cause of maternal morbidity and mortality and adverse neonatal outcomes. Little is known about the extent of the health and cost burden of preeclampsia in the United States. OBJECTIVE: This study sought to quantify the annual epidemiological and health care cost burden of preeclampsia to both mothers and infants in the United States in 2012. STUDY DESIGN: We used epidemiological and econometric methods to assess the annual cost of preeclampsia in the United States using a combination of population-based and administrative data sets: the National Center for Health Statistics Vital Statistics on Births, the California Perinatal Quality Care Collaborative Databases, the US Health Care Cost and Utilization Project database, and a commercial claims data set. RESULTS: Preeclampsia increased the probability of an adverse event from 4.6% to 10.1% for mothers and from 7.8% to 15.4% for infants while lowering gestational age by 1.7 weeks (P < .001). Overall, the total cost burden of preeclampsia during the first 12 months after birth was $1.03 billion for mothers and $1.15 billion for infants. The cost burden per infant is dependent on gestational age, ranging from $150,000 at 26 weeks gestational age to $1311 at 36 weeks gestational age. CONCLUSION: In 2012, the cost of preeclampsia within the first 12 months of delivery was $2.18 billion in the United States ($1.03 billion for mothers and $1.15 billion for infants), and was disproportionately borne by births of low gestational age.

Economic and health consequences of non-invasive respiratory support in newborn infants: a difference-in-difference analysis using data from the Norwegian patient registry.

BACKGROUND: Newborn infants with respiratory failure are often treated with intubation and mechanical ventilation for prolonged periods of time. Our objective was to evaluate whether increasing use of non-invasive respiratory support in newborn infants can improve patient health and reduce costs. METHODS: We utilized a natural experiment that took place in October 2008 when a large neonatal intensive care unit in Norway moved into a new hospital building with new medical equipment. A change in respiratory support towards increasing use of nasal biphasic positive airway pressure (n-BiPAP) instead of invasive mechanical ventilation treatment followed the acquisition of the new equipment. We used a difference-in-difference method and data from the Norwegian National Patient Registry to assess morbidity, mortality, number of hospital days and hospital costs in our unit following this change. We stratified the results according to gestational age groups. RESULTS: We found a reduction in morbidity including bronchopulmonary dysplasia, retinopathy of prematurity and intraventricular hemorrhage. No change in mortality was found. We found a reduction in number of hospital days and hospital costs for preterm infants with gestational age <28 weeks and for term infants with diagnoses affecting respiration. CONCLUSIONS: We conclude that increasing use of n-BiPAP may improve health and reduce costs. However, more research is needed to establish best practice. Comparing hospitals where treatment practices change to hospitals where the same change does not occur may be a useful way to evaluate the efficacy of such a change, especially when hospitals can be studied over time.

Direct medical costs of neonatal respiratory distress syndrome in two specialized public hospitals in Mexico.

OBJECTIVE: To estimate direct medical costs (DMC) associated with treatment of Respiratory Distress Syndrome (RDS) in newborns (NB) in two specialized public hospitals in Mexico. MATERIALS AND METHODS: The perspective used was health care payer. We estimated DMC associated with RDS management. The pattern of resource use was established by reviewing clinical records. Microcosting and bootstrap techniques were used to obtain the DMC. Estimated costs were reported in 2011 US dollars. RESULTS: Average DMC per RDS event was 14 226 USD. The most significant items that account for this cost were hospitalization (38%), laboratory and diagnostic exams (18%), incubator time (10%), surfactant therapy (7%), and mechanical ventilation (7%). CONCLUSION: Average DMC in NB with RDS fluctuated in relation to gestational age weight at birth and clinical complications presented by patients during their hospitalization.

Curosurf surfactant application on preterm babies with respiratory complications-health-economic benefits.

Background: The implementation of surfactant for respiratory syndrome approbates the therapy as a revolutionary method in intensive neonatal therapy and respiratory resuscitation. It is important to investigate the costs of this treatment. Objective: The aim of the study is to analyze the data by the application of the surfactant Curosurf to preterm babies with respiratory complications and describe the treatment costs, healthcare resource utilization and evaluate economic benefits of surfactant use in the treatment of neonates with respiratory distress syndrome (RDS) and hyaline-membrane disease (HDM). Methods: A retrospective survey was performed covering 167 babies based on respiratory complications due to preterm birth and the necessity to apply a surfactant therapy. A documentary method was implemented and for each patient, an individual research protocol was filled out - a questionnaire created specifically for the purposes of the study. Results and discussion: An analysis of the data from the application of CUROSURF was made and the obtained therapeutic results were compared to expenditures for the therapy, short-term therapeutic effect, benefits and consequences of the therapy of preterm newborns with respiratory complications. The application of CUROSURF to babies with RDS resulted in the realization of net savings due to the elimination of the necessity of conducting several diagnostic and therapeutic procedures as well as their duration reduction of hospital stay, thus defining its health-economic benefits. Conclusions: The models of evaluation of cost effectiveness reveal that the medicinal product is expensive but effective from the aspect of short-term therapeutic results.

Economics and ethics of paediatric respiratory extra corporeal life support.

Extra corporeal membrane oxygenation (ECMO) is a form of life support, which facilitates gas exchange outside the body via an oxygenator and a centrifugal pumping system. A paediatric cardiac ECMO programme was established in 2005 at Our Lady's Children's Hospital, Crumlin (OLCHC) and to date 75 patients have received ECMO, the majority being post operative cardiac patients. The outcome data compares favourably with international figures. ECMO has been most successful in the treatment of newborn infants with life threatening respiratory failure from conditions such as meconium aspiration, respiratory distress syndrome and respiratory infections. There is no formal paediatric respiratory ECMO programme at OLCHC, or anywhere else in Ireland. Currently, neonates requiring respiratory ECMO are transferred to centres in Sweden or the UK at an average cost of 133,000 Euros/infant, funded by the Health Service Executive E112 treatment abroad scheme. There is considerable morbidity associated with the transfer of critically ill infants, as well as significant psycho-social impact on families. OLCHC is not funded to provide respiratory ECMO, although the equipment and expertise required are similar to cardiac ECMO and are currently in place. The average cost of an ECMO run at OLCHC is 65,000 Euros. There is now a strong argument for a fully funded single national cardiac and respiratory paediatric ECMO centre, similar to that for adult patients.

Effective gas exchange in paralyzed juvenile rabbits using simple, inexpensive respiratory support devices.

We have developed two devices: a high-amplitude bubble continuous positive airway pressure (HAB-CPAP) and an inexpensive bubble intermittent mandatory ventilator (B-IMV) to test the hypotheses that simple, inexpensive devices can provide gas exchange similar to that of bubble CPAP (B-CPAP) and conventional mechanical ventilation (CMV). Twelve paralyzed juvenile rabbits were intubated, stabilized on CMV, and then switched to CPAP. On identical mean airway pressures (MAPs), animals were unable to maintain pulse oximeter oxygen saturation (SpO2) >80% on conventional B-CPAP, but all animals oxygenated well (97.3 ± 2.1%) on HAB-CPAP. In fact, arterial partial pressures of O2 (Pao2) were higher during HAB-CPAP than during CMV (p = 0.01). After repeated lung lavages, arterial partial pressures of CO2 (Paco2) were lower with B-IMV than with CMV (p < 0.0001), despite identical ventilator settings. In lavaged animals, when HAB-CPAP was compared with CMV at the same MAP and 100% O2, no differences were observed in Pao2, but Paco2 levels were higher with HAB-CPAP (70 ± 7 versus 50 ± 5 mm Hg; p < 0.05). Arterial blood pressures were not impaired by HAB-CPAP or B-IMV. The results confirm that simple inexpensive devices can provide respiratory support in the face of severe lung disease and could extend the use of respiratory support for preterm infants into severely resource-limited settings.

The effectiveness of the neonatal diagnosis-related group scheme.

The goal of this study is to investigate the effectiveness of the neonatal diagnosis-related group scheme in patients affected by respiratory distress syndrome. The variable costs of individual patients in the same group are examined. This study uses the data of infants (N = 243) hospitalized in the Neonatal Intensive Care Unit of the Gaslini Children's Hospital in Italy in 2016. The care unit's operating and management costs are employed to estimate the average cost per patient. Operating costs include those related to personnel, drugs, medical supplies, treatment tools, examinations, radiology, and laboratory services. Management costs relate to administration, maintenance, and depreciation cost of medical equipment. Cluster analysis and Tobit regression are employed, allowing for the assessment of the total cost per patient per day taking into account the main cost determinants: birth weight, gestational age, and discharge status. The findings highlight great variability in the costs for patients in the same diagnosis-related group, ranging from a minimum of €267 to a maximum of €265,669. This suggests the inefficiency of the diagnosis-related group system. Patients with very low birth weight incurred costs approximately twice the reimbursement set by the policy; a loss of €36,420 is estimated for every surviving baby with a birth weight lower than 1,170 grams. On the contrary, at term, newborns cost about €20,000 less than the diagnosis-related group reimbursement. The actual system benefits hospitals that mainly treat term infants with respiratory distress syndrome and penalizes hospitals taking care of very low birth weight patients. As a result, strategic behavior and "up-coding" might occur. We conduct a cluster analysis that suggests a birth weight adjustment to determine new fees that would be fairer than the current costs.

Antenatal corticosteroid administration in late-preterm gestations: a cost-effectiveness analysis.

Objective: To evaluate whether administration of antenatal late-preterm betamethasone is cost-effective in the immediate neonatal period.Study design: Cost-effectiveness analysis of late-preterm betamethasone administration with a time horizon of 7.5 days was conducted using a health-system perspective. Data for neonatal outcomes, including respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), and hypoglycemia, were from the Antenatal Betamethasone for Women at Risk for Late-Preterm Delivery trial. Cost data were derived from the Healthcare Cost and Utilization Project from the Agency for Health Care Research and Quality, and utilities of neonatal outcomes were from the literature. Outcomes were total costs in 2017 United States dollars and quality-adjusted life years (QALYs) for each individual infant as well as for a theoretical cohort of the 270 000 late-preterm infants born in 2015 in the USA.Results: For an individual patient, compared to withholding betamethasone, administering betamethasone incurred a higher total cost ($6592 versus $6265) and marginally lower QALYs (0.02002 QALYS versus 0.02006 QALYs) within the studied time horizon. For the theoretical cohort of 270 000 patients, administration of betamethasone was $88 million more expensive ($1780 million versus $1692 million) with lower QALYs (5402 QALYs versus 5416 QALYs), compared to withholding betamethasone. For administration of betamethasone to be cost-effective, the rate of hypoglycemia, RDS, or TTN among late-preterm infants receiving betamethasone would need to be less than 20.0, 4.5, and 2.4%, respectively.Conclusion: Administration of betamethasone in the late-preterm period is likely not cost-effective in the short-term.

Cost-effectiveness of Antenatal Corticosteroid Therapy vs No Therapy in Women at Risk of Late Preterm Delivery: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Administration of corticosteroids to women at high risk for delivery in the late preterm period (34-36 weeks' gestation) improves short-term neonatal outcomes. The cost implications of this intervention are not known. Objective: To compare the cost-effectiveness of treatment with antenatal corticosteroids with no treatment for women at risk for late preterm delivery. Design, Setting, and Participants: This secondary analysis of the Antenatal Late Preterm Steroids trial, a multicenter randomized clinical trial of antenatal corticosteroids vs placebo in women at risk for late preterm delivery conducted from October 30, 2010, to February 27, 2015. took a third-party payer perspective. Maternal costs were based on Medicaid rates and included those of betamethasone, as well as the outpatient visits or inpatient stay required to administer betamethasone. All direct medical costs for newborn care were included. For infants admitted to the neonatal intensive care unit, comprehensive daily costs were stratified by the acuity of respiratory illness. For infants admitted to the regular newborn nursery, nationally representative cost estimates from the literature were used. Effectiveness was measured as the proportion of infants without the primary outcome of the study: a composite of treatment in the first 72 hours of continuous positive airway pressure or high-flow nasal cannula for 2 hours or more, supplemental oxygen with a fraction of inspired oxygen of 30% or more for 4 hours or more, and extracorporeal membrane oxygenation or mechanical ventilation. This secondary analysis was initially started in June 2016 and revision of the analysis began in May 2017. Exposures: Betamethasone treatment. Main Outcomes and Measures: Incremental cost-effectiveness ratio. Results: Costs were determined for 1426 mother-infant pairs in the betamethasone group (mean [SD] maternal age, 28.6 [6.3] years; 827 [58.0%] white) and 1395 mother-infant pairs in the placebo group (mean [SD] maternal age, 27.9 [6.2] years; 794 [56.9%] white). Treatment with betamethasone was associated with a total mean (SD) woman-infant-pair cost of $4681 ($5798), which was significantly less than the mean (SD) amount of $5379 ($8422) for women and infants in the placebo group (difference, $698; 95% CI, $186-$1257; P = .02). The Antenatal Late Preterm Steroids trial determined that betamethasone use is effective: respiratory morbidity decreased by 2.9% (95% CI, -0.5% to -5.4%). Thus, the cost-effectiveness ratio was -$23 986 per case of respiratory morbidity averted. Inspection of the bootstrap replications confirmed that treatment was the dominant strategy in 5000 samples (98.8%). Sensitivity analyses showed that these results held under most assumptions. Conclusions and Relevance: The findings suggest that antenatal betamethasone treatment is associated with a statistically significant decrease in health care costs and with improved outcomes; thus, this treatment may be an economically desirable strategy.

Clinical and Economic Analysis of Morphine Versus Fentanyl in Managing Ventilated Neonates With Respiratory Distress Syndrome in the Intensive Care Setting.

PURPOSE: Morphine and fentanyl opioids are common analgesic agents for consideration in the neonatal intensive care unit (NICU) for neonates with respiratory distress syndrome (RDS) and undergoing mechanical ventilation (MV). The aim of this study was to evaluate the clinical and economic impact of morphine versus fentanyl in neonates with RDS undergoing MV. METHODS: Retrospective cost-effectiveness analysis of critically ill neonates with RDS receiving standard doses of morphine versus fentanyl at Women's Wellness and Research Center, Qatar. Clinical data of neonates were extracted from medical records of patients from 2014 to 2016. A decision analytic model based on the hospital's perspective was constructed to follow possible consequences of the initial dosing of analgesia, before potential titration. Primary end points were successful pain relief rate based on the Premature Infant Pain Profile scale and overall direct medical cost of therapy. Study population of 126 neonates was used to achieve results with 80% power and 0.05 significance. Sensitivity analysis was conducted to enhance robustness of conclusions against input uncertainties and to increase generalizability of results. FINDINGS: Morphine achieved a success of 68% versus 43% with fentanyl (risk ratio = 1.72; 95% CI, 1.16-2.56; P = 0.0075). Morphine was associated with a minimal incremental cost-effectiveness ratio of USD 135 per additional case of successful pain relief over fentanyl. Higher morphine cost was reported in 2% of cases. Sensitivity analysis found model insensitivity to input uncertainties except NICU stay and cost of MV. IMPLICATIONS: This is the first cost-effectiveness evaluation of morphine versus fentanyl in the NICU. Morphine significantly improved the relieve of pain over fentanyl. It had 98% probability of dominance over fentanyl. Results in this study support the use of morphine over fentanyl as first-line monotherapy with MV in NICU settings.

Evaluating the efficacy of Seattle-PAP for the respiratory support of premature neonates: study protocol for a randomized controlled trial.

BACKGROUND: At birth, the majority of neonates born at <30 weeks of gestation require respiratory support to facilitate transition and ensure adequate gas exchange. Although the optimal approach to the initial respiratory management is uncertain, the American Academy of Pediatrics endorses noninvasive respiratory support with nasal continuous positive airway pressure (nCPAP) for premature neonates with respiratory insufficiency. Despite evidence for its use, nCPAP failure, requiring intubation and mechanical ventilation, is common. Recently, investigators have described a novel method to deliver bubble nCPAP, termed Seattle-PAP. While preclinical and pilot studies are encouraging regarding the potential value of Seattle-PAP, a large trial is needed to compare Seattle-PAP directly with the current standard of care for bubble nCPAP (Fisher & Paykel CPAP or FP-CPAP). METHODS/DESIGN: We designed a multicenter, non-blinded, randomized controlled trial that will enroll 230 premature infants (220/7 to 296/7 weeks of gestation). Infants will be randomized to receive Seattle-PAP or FP-CPAP. The primary outcome is respiratory failure requiring intubation and mechanical ventilation. Secondary outcomes include measures of short- and long-term respiratory morbidity and cost-effectiveness. DISCUSSION: This trial will assess whether Seattle-PAP is more efficacious and cost-effective than FP-CPAP in real-world practice among premature neonates. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03085329 . Registered on 21 March 2017.

Resource utilization patterns using non-invasive ventilation in neonates with respiratory distress syndrome.

OBJECTIVES: To describe the frequency of non-invasive ventilation (NIV) and endotracheal intubation use in neonates diagnosed with respiratory distress syndrome (RDS); to describe resources utilization (length of stay (LOS), charges, costs) among NIV and intubated RDS groups. STUDY DESIGN: Retrospective study from the national Kid's Inpatient Database of the Healthcare Cost and Utilization Project, for the years 1997-2012. Propensity scoring and multivariate regression analysis used to describe differences. RESULTS: A total of 595,254 out of 42,912,090 cases were identified with RDS. There was an increase in NIV use from 6% in 1997 to 17% in 2012. After matching, patients receiving NIV only were associated with shorter LOS: (95%CI) 25 (25.3,25.7) vs. 35 (34.2,34.9) days, decreased costs: ($/1k) 46.1 (45.5,46.8) vs. 65.0 (64.1,66.0), decreased charges: 130.3 (128.6,132.1) vs. 192.1 (189.5,194.6) compared to intubated neonates. CONCLUSION: There was a three-fold increase in NIV use within the 15-year study period. NIV use was associated with decreased LOS, charges and costs compared to intubated patients.

Respiratory distress in term neonates in low-resource settings.

Most neonatal deaths worldwide occur in low- and middle-income countries (LMICs). Respiratory distress is an important cause of neonatal morbidity and mortality. The epidemiology of respiratory distress among term neonates who constitute the vast majority of births is under reported. The scarcely available data from LMICs suggest an incidence of 1.2% to 7.2% among term live births and greater morbidity compared to that in high-income countries. Pneumonia and meconium aspiration syndrome are the predominant causes among outborn neonates, but next only to transient tachypnea among inborn neonates. Community management of neonatal sepsis/pneumonia using simplified antibiotic regimens when referral is not feasible, implementation of non-invasive ventilation, and innovative low-cost technologies to deliver respiratory therapy are important advances that have taken place in these settings. There is an urgent need to generate data on respiratory morbidities among term neonates so that the limited resources in these settings can be allocated judiciously.

Cost effectiveness of prevention and treatment of neonatal respiratory distress (RDS) with exogenous surfactant: what has changed in the last three decades?

In 1993, exogenous surfactant products were emerging as licensed treatments for respiratory distress syndrome (RDS), a leading cause of death in preterm newborn babies. Models of cost-effectiveness of alternative treatments showed surfactant to be an expensive but effective and also cost effective treatment. However the most efficient policy for use of surfactant depended on other parallel 'technologies' such as giving antenatal corticosteroids where preterm delivery is anticipated. Following introduction into clinical practice, questions changed from whether to use surfactant, to when, and which product to use. The early models of cost effectiveness were dependent on the neonatal technology in use, and on the costs of neonatal care and prices of surfactant at the time. Little information was available about long term outcomes. The aims of this paper are to summarise the role of surfactant in the economics of newborn care since the late 1980s; to observe the value of studies published in the early 1990s for current decisions; and to comment on recent and possible future economic studies of neonatal surfactant.

Prospective pricing system for tertiary neonatal intensive care.

This study assessed the potential impact of the federal neonatal diagnosis-related group (DRG) pricing system upon reimbursement to a state neonatal intensive care program. Data for length of intensive care unit stay, procedures, hospital charges, and audited cost reports from the state of Florida's ten regional neonatal intensive care centers were analyzed for 8,492 neonates whose charges totaled $118 million. Mean lengths of stay in these tertiary care centers were substantially longer than those reported for the federal DRGs, which were based on community hospital data. If federal DRG-based reimbursement to hospitals were implemented in Florida's perinatal intensive care program, compensation would range from 9% to 56% of actual hospital care charges. Federal DRG price rates were not predictive of hospital charges. Only 16% of the total variation in hospital charges was explained by differences among federal DRG rates (R2 = .16). Analysis of data by major determinants of resource consumption provided groups more homogeneous with respect to hospital charges and, hence, cost. Therefore, we developed a prospective pricing system that used modifications of federal newborn DRG system. These modifications resulted in a threefold increase in R2 (.52). Our proposed system permits prediction of cost and reimbursement for infants by three criteria: birth weight, need for mechanical ventilation and/or major surgery, and survival status and length of survival for those who die.

Surfactant replacement therapy: impact on hospital charges for premature infants with respiratory distress syndrome.

Surfactant replacement therapy for neonatal respiratory distress syndrome has the potential to reduce morbidity and mortality of very premature infants. To investigate whether surfactant replacement therapy will also reduce hospital charges for these infants, we compared the hospital charges incurred by a group of patients treated with surfactant with charges of control patients. Mortality in the surfactant-treated group (8%) was significantly decreased compared with the control patients (29%). Average daily hospital charges in the surfactant-treated patients were 25% less than for the control patients. Most of the savings in daily hospital charges were due to a 52% reduction in daily charges for laboratory, x-ray, respiratory therapy, and other ancillary services. Similarly, ancillary charges for the first full week of hospitalization were significantly reduced by $1,883 for patients who received surfactant therapy. Analysis of the charges for the entire hospitalization revealed that surfactant-treated patients had a significantly smaller proportion of their charges that resulted from ancillary services and an increased proportion due to room charges. The average total hospital charges for the two groups were similar, but the total hospital charges to produce a surviving infant were $18,500 less in the surfactant-treated group than the charges to produce a survivor from the control group. It is likely that, in addition to a reduction in neonatal mortality and morbidity from respiratory distress syndrome, surfactant replacement therapy may also significantly reduce charges for ancillary services for these patients. In this way, surfactant therapy may be cost-effective by improving survival without increasing overall hospital costs.

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.

High-versus low-threshold surfactant retreatment for neonatal respiratory distress syndrome.

UNLABELLED: Surfactant therapy has become an effective standard therapy for infants with respiratory distress syndrome (RDS). The first dose may be given either as prophylaxis immediately after delivery, or as rescue after an infant has developed RDS. Second and subsequent doses are currently recommended by the manufacturers to be administered at minimal levels of respiratory support. PURPOSE: This study compared the relative efficacy of administering second and subsequent doses of Infasurf surfactant at a low threshold (FIO(2) >30%, still requiring endotracheal intubation) versus a high threshold (FIO(2) >40%, mean airway pressure >7 cm H(2)O) of respiratory support. METHODS: A total of 2484 neonates received a first dose of surfactant; 1267 reached conventional retreatment criteria and were randomized to be retreated according to low- or high-threshold criteria. They were then retreated at a minimum of 6-hour intervals each time they reached their assigned threshold until receiving a maximum of 4 total doses. Subjects were stratified by whether they received their first dose by prophylaxis or rescue and by whether their lung disease was considered complicated (evidence of perinatal compromise or sepsis) or uncomplicated. RESULTS: Among the patients randomized, 33% of prophylaxis and 23% of rescue subjects met criteria for the complicated stratum. Although infants allocated to the high-threshold strategy were receiving slightly more oxygen at 72 hours, there was no difference in the number receiving mechanical ventilation at 72 hours or in the secondary respiratory outcomes (requirement for supplemental oxygen or mechanical ventilation at 28 days, supplemental oxygen at 36 weeks' postconceptional age, inspired oxygen concentration >60% at any time). However, there was a significantly higher mortality for infants with complicated RDS who had received retreatment according to the high-threshold strategy. CONCLUSIONS: We conclude that equal efficacy can be realized by delaying surfactant retreatment of infants with uncomplicated RDS until they have reached a higher level of respiratory support than is the current standard. We speculate that this would result in a substantial cost-saving from less utilization of drug. Conversely, we believe that infants with complicated RDS should continue to be treated by the low-threshold retreatment strategy, which is currently recommended by the manufacturers of the commercially available surfactants.