Multicenter study of surfactant (beractant) use in the treatment of term infants with severe respiratory failure. Survanta in Term Infants Study Group.

OBJECTIVE: The purpose of this study was to determine whether surfactant (beractant) administration to term newborns in respiratory failure and at risk for requiring extracorporeal membrane oxygenation (ECMO) treatment would significantly reduce the incidence of severe complications through 28 days of age and the need for ECMO. STUDY DESIGN: A multicenter (n = 44), randomized, double-blind, placebo-controlled trial was conducted. Infants weighing 2000 gm or more with gestational ages of 36 weeks or greater were stratified by diagnosis (meconium aspiration syndrome, sepsis, or idiopathic persistent pulmonary hypertension of the newborn) and oxygenation index (15 to 22, 23 to 30, 31 to 39) and then randomly assigned to receive four doses of beractant, 100 mg/kg (n = 167), or air placebo (n = 161) before ECMO treatment and four additional doses during ECMO, if ECMO was required. The incidence of untoward effects (including hemorrhagic, neurologic, pulmonary, renal, cardiovascular, infectious, metabolic, and technical complications) occurring before and after randomization and through 28 days of age or discharge were recorded. RESULTS: The two treatment groups were comparable in baseline parameters, including birth weight, sex, gestational age, oxygenation index, and primary diagnosis. There was no difference in the incidence of severe complications. The need for ECMO therapy was significantly less in the surfactant group than in the placebo group (p = 0.038); this effect was greatest within the lowest oxygenation index stratum (15 to 22; p = 0.013). CONCLUSIONS: Use of surfactant, particularly in the early phase of respiratory failure, significantly decreases the need for ECMO in the treatment of term newborns with respiratory failure, without increasing the risk of complications.

Bovine surfactant therapy for patients with acute respiratory distress syndrome.

Lung surfactant is deficient in patients with acute respiratory distress syndrome (ARDS). We performed a randomized, prospective, controlled, open-label clinical study of administration of a bovine surfactant to patients with ARDS to obtain preliminary information about its safety and efficacy. Patients received either surfactant by endotracheal instillation in addition to standard therapy or standard therapy only. Three different groups of patients receiving surfactant were studied: patients receiving up to eight doses of 50 mg phospholipids/kg, those receiving up to eight doses of 100 mg phospholipids/kg, and those receiving up to four doses of 100 mg phospholipids/kg. Outcome measures included ventilatory support parameters, arterial blood gases, organ system failures, bronchoalveolar lavage (BAL) analyses, immunologic analyses, survival, and adverse events during the 28-d study period. Fifty-nine study patients were evaluable; 43 in the surfactant group and 16 in the control group. The FI(O2) at 120 h after treatment began was significantly decreased only for patients who received up to four doses of 100 mg phospholipids/kg surfactant as compared with control patients (p = 0.011). Mortality in the same group of patients was 18.8%, as compared with 43.8% in the control group (p = 0.075). The surfactant instillation was generally well tolerated, and no safety concerns were identified. This pilot study presents preliminary evidence that surfactant might have therapeutic benefit for patients with ARDS, and provides rationale for further clinical study of this agent.

User adoption issues in renal telemedicine.

We carried out a longitudinal survey to evaluate the users' attitudes to the introduction of telemedicine into the dialysis units of a renal ward in South Australia. The first questionnaire was distributed to all members of staff involved with the introduction of the system. There were 44 responses (80%). Staff were fairly positive about the telemedicine system, and felt that it was easy to use and reliable. They also clearly felt that the confidentiality and privacy offered by the system in an open ward were unsatisfactory. A second questionnaire was distributed to all staff about six months later and there were 40 responses (66%). Of these, 22 could be matched with the responses from the first survey (a response rate of 50% from the first sample). There were no significant differences in the staff members' feelings between the two surveys, except in two cases: there were significant changes in staff opinion about the degree of confidentiality (P < 0.05) and privacy (P < 0.01) offered by the system, with attitudes becoming more positive in each case. The results indicate the need for dialogue with users, in order to address their concerns regarding the system and practical difficulties. This study highlights the importance of planning, effort, cooperation and an appropriate culture within a renal unit in order for telemedicine to be accepted.

Complete regression of human neuroblastoma xenografts in athymic mice after local Newcastle disease virus therapy.

BACKGROUND: Neuroblastoma is the most common pediatric extra-cranial solid cancer. Using conventional therapies, children older than 1 year of age with advanced neuroblastoma have a poor prognosis. The development of new approaches for treating such children with neuroblastoma continues to be one of the most important goals today in pediatric oncology. Despite numerous anecdotal reports of human tumor regression during viral infections, the use of viruses to directly lyse neuroblastoma cells has never been reported as a potential therapy. Newcastle disease virus (NDV) has been shown to replicate in and kill cultured human and rat neuroblastoma cells but not normal human fibroblasts. PURPOSE: Our purpose was to determine if this selective killing of human neuroblastoma (IMR-32) cells is maintained during the in vivo treatment of established tumors. METHODS: Two experiments were performed using NDV strain 73-T. Athymic mice with subcutaneous IMR-32 human neuroblastoma xenografts (6-12 mm) were treated intralesionally with live NDV, UV-inactivated NDV, or phosphate-buffered saline (PBS). To study virus replication in situ, mice were given intratumoral or intramuscular injections of NDV. These mice were then killed at various times, and the amount of infectious virus present in tumor or muscle was determined. RESULTS: After one injection of live NDV, 17 of 18 tumors regressed completely, whereas rapid tumor growth occurred in all 18 mice treated with PBS and in all nine mice treated with UV-inactivated NDV (P < .0001). The one tumor that showed only a partial response to a single injection regressed completely after a second NDV treatment. Six months following virus-induced regression, only one tumor had recurred. No significant acute or chronic side effects of live NDV were noted in athymic mice given doses up to 500 times that used in this study. Virus levels increased more than 80-fold between 5 and 24 hours in virus-injected tumors (P < .04), while no infectious virus was produced in NDV-injected muscle tissue. CONCLUSIONS: NDV 73-T appears to replicate selectively in human IMR-32 neuroblastoma xenografts, leading directly to a potent antitumor effect as demonstrated by long-lasting, complete tumor regression occurring after a single local injection of virus. IMPLICATION: These experiments may provide an important step in the development of new therapeutic approaches to challenging cancers such as neuroblastoma.

Treatment Investigational New Drug experience with Survanta (beractant).

From September 1989 through July 1991, before commercial availability, Survanta (beractant intratracheal suspension), a modified bovine-derived surfactant used for prevention and treatment of neonatal respiratory distress syndrome, was made available to 231 neonatal intensive care units in the United States and Canada under a Treatment Investigational New Drug protocol. Results of this open clinical experience are reported. Investigators could give one dose of Survanta soon after birth to neonates weighing 600 to 1250 g (prevention strategy). Neonates weighing 600 to 1750 g who were not treated at birth could begin Survanta therapy if respiratory distress syndrome developed within 8 hours of birth (rescue strategy). All neonates could receive up to three more doses over the first 48 hours of life at minimum intervals of 6 hours if they met retreatment criteria. Qualifications for enrollment closely matched those used in previous randomized controlled clinical trials. This report includes results from 8168 neonates who completed the study. Treatment Investigational New Drug rates for intracranial hemorrhage, patent ductus arteriosus, pulmonary hemorrhage, pulmonary air leaks, bronchopulmonary dysplasia, death or bronchopulmonary dysplasia, pulmonary interstitial emphysema, pretreatment sepsis, and posttreatment sepsis were less than for treated neonates in the controlled trials and survival was equivalent across studies. Problems with treatment administration were reported with 30.4% of doses, while adverse events were reported in 0.5% of neonates. The results of the Treatment Investigational New Drug protocol revealed no new safety concerns associated with the widespread use of Survanta and confirmed the safety profile established in earlier controlled trials.

Comparison of three dosing procedures for administration of bovine surfactant to neonates with respiratory distress syndrome.

A multicenter, randomized, double-blind, controlled trial compared three beractant (Survanta) administration procedures in the treatment of neonatal respiratory distress syndrome. Infants weighing > or = 600 gm with respiratory distress syndrome who required assisted ventilation were treated within 8 hours of birth with beractant administered intratracheally. Procedure A required administration in two fractional doses after removal of the infant from the ventilator. Procedure B required administration in two fractional doses through a neonatal suction valve and did not require removal of the infant from the ventilator, and procedure C required administration in four fractional doses during removal from the ventilator. Procedure C is the method used in all previous beractant studies. Of the 299 infants enrolled, 103 were randomly assigned to procedure A, 100 to procedure B, and 96 to procedure C. The results indicate no significant differences among the treatment groups in the clinical outcome measures of fractional inspired oxygen, mean airway pressure, and arterial-alveolar ratio of partial pressure of oxygen at 72 hours of life, or in the incidences of air leaks, pulmonary interstitial emphysema, or death through 72 hours of life. There were no significant differences in the lowest heart rates recorded during administration of doses, but there was less oxygen desaturation during administration of dose 1 with procedure B than with procedure A (p = 0.001), and more reflux of beractant after procedure B than after procedure C (p = 0.007). We conclude that the three procedures are equally effective and can be used to administer beractant safely and effectively. Procedure B has the advantage of allowing administration without interrupting mechanical ventilation.

Beneficial effects of the combined use of prenatal corticosteroids and postnatal surfactant on preterm infants.

OBJECTIVE: Our objective was to test the hypothesis that prenatal maternal corticosteroids would improve the subsequent response of infants to surfactant treatments. STUDY DESIGN: We used the data bases of two recently published large multicenter trials of multidose surfactant treatments to retrospectively evaluate the possible interactions between maternal corticosteroids and randomized surfactant treatments on short-term ventilatory effects, complications of respiratory distress syndrome and prematurity, and 28-day death rates. RESULTS: The combined use of corticosteroids and surfactant significantly decreased overall death and death caused by respiratory distress syndrome relative to either treatment alone. Ventilatory variables at 72 hours were improved in those infants receiving both treatments, and other major complications of prematurity also tended to have decreased incidences. CONCLUSION: The combined use of prenatal corticosteroids, when indicated, and postnatal surfactant improves neonatal outcome.