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.

Deceiving SARS-CoV-2 molecular-tropism clues - A combinational contemporary strategy.

Several attempts to control the dreadfulness of SARS-CoV-2 are still underway. Based on the literature evidences we have speculated a prospective contemporary remedy, which was categorized into Specificity, Remedy, and a Conveyor. In which, pros and cons were discussed and inferred the possible alternatives. (a) Specificity: Implicit to express the ACE2 receptors in conveyor cells to deceive SARS-CoV-2 frompreponetargets. (b) Remedy: As depletion of pulmonary surfactants causes strong acute respiratory distress syndrome, we propose an entity of a cost-effective artificialsurfactantsystem as a remedy to pulmonary complications. (c) Conveyor: We propose red blood cells (RBCs) as a conveyor with embedded artificial surfactant and protruding ACE2 receptors for the target-specific delivery. Overall we postulate focused insights by employing a combinational contemporary strategy to steer towards a prospective direction on combating SARS-CoV-2.

Clinical, technological, and economic issues associated with developing new lung surfactant therapeutics.

Discovery of lung surfactant deficiency as a main cause of neonatal respiratory distress syndrome (NRDS) has influenced a steep increase in lung surfactant research. Although this has yielded impactful scientific discoveries, much of the basic research on lung surfactants has failed to translate into clinical practices. This is attributed to insufficient information covering the entire lung surfactant ecosystem, from the basic science to economics surrounding the development and clinical practices. In this manuscript, developments related to improving therapeutic lung surfactant as well as the degree of unmet need are analyzed from both technical and economic perspectives. Two potential opportunities are emphasized: (1) aerosolized lung surfactants to treat NRDS infants, and (2) synthetic lung surfactants for acute respiratory distress syndrome (ARDS) patients. Each has a modestly projected US market size of $120 million and $4 billion, well enough to make up for the high development costs associated with investigational drug development. Both opportunities have been pursued in the past, but to date these attempts have met with no success mainly due to technical limitations. With the recent advancements in both fields, technology improvements have created opportunities to solve both decades-old problems.

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.

Efficacy and safety of surfactant replacement therapy for preterm neonates with respiratory distress syndrome in low- and middle-income countries: a systematic review.

Surfactant replacement therapy (SRT) has been shown to reduce mortality and air leaks in preterm neonates from high-income countries (HICs). The safety and efficacy of SRT in low- and middle- income countries (LMICs) have not been systematically evaluated. The major objectives of this review were to assess the (1) efficacy and safety, and (2) feasibility and cost effectiveness of SRT in LMIC settings. We searched the following databases-MEDLINE, CENTRAL, CINAHL, EMBASE and WHOLIS using the search terms 'surfactant' OR 'pulmonary surfactant'. Both experimental and observational studies that enrolled preterm neonates with or at-risk of respiratory distress syndrome (RDS) and required surfactant (animal-derived or synthetic) were included. A total of 38 relevant studies were found; almost all were from level-3 neonatal units. Pooled analysis of two randomized controlled trials (RCTs) and 22 observational studies showed a significant reduction in mortality at the last available time point in neonates who received SRT (relative risk (RR) 0.67; 95% confidence interval (CI) 0.57 to 0.79). There was also a significant reduction in the risk of air leaks (five studies; RR 0.51; 0.29 to 0.90). One RCT and twelve observational studies reported the risk of bronchopulmonary dysplasia (BPD) with contrasting results; while the RCT and most before-after/cohort studies showed a significant reduction or no effect, the majority of the case-control studies demonstrated significantly higher odds of receiving SRT in neonates who developed BPD. Two studies-one RCT and one observational-found no difference in the proportion of neonates developing pulmonary hemorrhage, while another observational study reported a higher incidence in those receiving SRT. The failure rate of the intubate-surfactant-extubate (InSurE) technique requiring mechanical ventilation or referral varied from 34 to 45% in four case-series. No study reported on the cost effectiveness of SRT. Available evidence suggests that SRT is effective, safe and feasible in level-3 neonatal units and has the potential to reduce neonatal mortality and air leaks in low-resource settings as well. However, there is a need to generate more evidence on the cost effectiveness of SRT and its effect on BPD in LMIC settings.

Standard of care, institutional obligations, and distributive justice.

The problem of standard of care in clinical research concerns the level of treatment that investigators must provide to subjects in clinical trials. Commentators often formulate answers to this problem by appealing to two distinct types of obligations: professional obligations and natural duties. In this article, I investigate whether investigators also possess institutional obligations that are directly relevant to the problem of standard of care, that is, those obligations a person has because she occupies a particular institutional role. I examine two types of institutional contexts: (1) public research agencies - agencies or departments of states that fund or conduct clinical research in the public interest; and (2) private-for-profit corporations. I argue that investigators who are employed or have their research sponsored by the former have a distinctive institutional obligation to conduct their research in a way that is consistent with the state's duty of distributive justice to provide its citizens with access to basic health care, and its duty to aid citizens of lower income countries. By contrast, I argue that investigators who are employed or have their research sponsored by private-for-profit corporations do not possess this obligation nor any other institutional obligation that is directly relevant to the ethics of RCTs. My account of the institutional obligations of investigators aims to contribute to the development of a reasonable, distributive justice-based account of standard of care.

Economic evaluation of the use of exogenous pulmonary surfactants in preterm newborns in a Mexican population.

OBJECTIVE: To estimate the cost-effectiveness ratio of surfactant rescue treatment of premature infants with respiratory distress syndrome (RDS) who are covered by the Medical Insurance for a New Generation. MATERIALS AND METHODS: A cost-effectiveness evaluation was conducted from the third-payer perspective. Comparisons were made between the use of bovine surfactant (BS) therapy and without BS therapy. A decision tree model with a lifetime horizon was used where the measurements of effectiveness were life years gained (LYG) and quality-adjusted life years (QALYs). A 5% discount rate was considered for costs and health outcomes. All costs are expressed in Mexican pesos 2009. RESULTS: Incremental cost-effectiveness ratios (ICER) were MXN$136,670 per LYG and MXN$125,250 per QALY. CONCLUSION: Surfactant therapy was confirmed as a cost-effective strategy in accordance with World Health Organization criteria of three per capita gross domestic product (GDP) per QALY in premature infants with RDS in Mexico.

Economic evaluation of the use of exogenous pulmonary surfactants in preterm newborns in a Mexican population / Evaluación económica de la utilización de surfactantes pulmonares exógenos en recién nacidos pretérmino en población mexicana

OBJECTIVE: To estimate the cost-effectiveness ratio of surfactant rescue treatment of premature infants with respiratory distress syndrome (RDS) who are covered by the Medical Insurance for a New Generation. MATERIALS AND METHODS: A cost-effectiveness evaluation was conducted from the third-payer perspective. Comparisons were made between the use of bovine surfactant (BS) therapy and without BS therapy. A decision tree model with a lifetime horizon was used where the measurements of effectiveness were life years gained (LYG) and quality-adjusted life years (QALYs). A 5% discount rate was considered for costs and health outcomes. All costs are expressed in Mexican pesos 2009. RESULTS: Incremental cost-effectiveness ratios (ICER) were MXN$136670 per LYG and MXN$125250 per QALY. CONCLUSION: Surfactant therapy was confirmed as a cost-effective strategy in accordance with World Health Organization criteria of three per capita gross domestic product (GDP) per QALY in premature infants with RDS in Mexico.

OBJETIVO: Estimar la razón de costo efectividad incremental del tratamiento de surfactante de rescate en pacientes pretérmino con Síndrome de Dificultad Respiratoria (SDR) cubiertos por el Seguro Médico para una Nueva Generación. MATERIAL Y MÉTODOS: Evaluación de costo-efectividad desde la perspectiva del tercer pagador. Los comparadores fueron la terapia de surfactante bovino y la alternativa de no emplear ésta. Se utilizó un árbol de decisión que consideró la esperanza de vida como horizonte temporal y las medidas de efectividad fueron los años de vida ganados (AVG) y los años de vida ajustados por calidad de vida ( AVAC).Resultados en pesos mexicanos del 2009. RESULTADOS: Las RCEI por AVG y AVAC fueron de MXN$136670 y MXN$125250. CONCLUSIÓN: La razón de costo por AVG y AVAC para la terapia de surfactantes en pacientes prematuros con SDR en México fue menor a tres veces el PIB per cápita, por lo que es una estrategia costo-efectiva según los criterios de la OMS.

Development of low cost pulmonary surfactants composed of a mixture of lipids or lipids-peptides using higher aliphatic alcohol or soy lecithin.

The artificial pulmonary surfactant composition in the present study is characterized by a lipid mixture system composed of higher aliphatic alcohol, egg yolk phosphatidylcholine (egg PC), soy lecithin and higher aliphatic acid as the major components or a peptide-lipid mixture system composed of a combination of the lipid mixture system to which a peptide is added. Three peptides with amphiphilic surface-staying, membrane spanning, and both properties were designed and synthesized. The evaluation of pulmonary surfactant assay was performed by a hysteresis curve drawn upon the measurement for the surface tension-area curve with the Wilhelmy surface tensometer in vitro and the recovery of lung compliance for the pulmonary surfactant-deficient rat models in vivo. Lipid-mixture systems composed of octadecanol or soy lecithins containing no peptide were favorable hysteresis curves as compared with commercially available Surfacten, but were not prominent. The peptide-lipid mixture systems composed of a combination of the lipid mixture of alkyl alcohol or soy lecithin to which peptides designed were added were desirable hysteresis curves similar to Surfacten and amphiphilic Hel 13-5 peptide-lipids mixture systems were much more effective than the lipid mixture system. Particularly, the recovery of lung compliance treated with hydrogenated soy lecithin-fractionated soy lecithin PC70-palmitic acid-peptide Hel 13-5 (40:40:17.5:2.5, w/w) was comparable to that with Surfacten. Because the artificial pulmonary surfactant compositions of this study can be prepared at lower costs, they are useful for the treatment of respiratory distress syndrome and acute respiratory distress syndrome as well as for inflammatory pulmonary diseases, dyspnea caused by asthma, etc.

Surfactant for acute respiratory failure in children: where should it fit in our treatment algorithm?

In a recent meta-analysis, surfactant administration in paediatric acute respiratory failure was associated with improved oxygenation, reduced mortality, increased ventilator-free days and reduced duration of ventilation. Surfactant is expensive, however, and its use involves installation of large volumes into the lungs, resulting in transient hypoxia and hypotension in some patients. Many questions also remain unanswered, such the as optimum dosage and the timing of administration of surfactant. The merits of surfactant administration should therefore still be decided on an individual case-by-case basis.

Surfactant replacement therapy.

Surfactant replacement therapy (SRT) has a proven role in the treatment of neonatal respiratory distress syndrome and severe meconium aspiration syndrome in infants, and may have a role in the treatment of pediatric patients with ARDS. Although newer delivery mechanisms and strategies are being studied, the classic surfactant administration paradigm consists of endotracheal intubation, surfactant instillation into the lung, and stabilization with mechanical ventilation followed by extubation when stable on low respiratory support. Currently, this surfactant administration procedure is bundled into Current Procedural Terminology (CPT) codes used when providing intensive care. A specific CPT code for surfactant administration is scheduled to be introduced in 2007. This article reviews clinical issues in SRT and the practice management considerations necessary to provide this care.

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.

[Treatment of hyaline membrane disease in the preterm newborn with exogenous lung surfactant: a controlled study]. / Estudio controlado del tratamiento de la enfermedad de membrana hialina del recién nacido pretérmino con surfactante pulmonar exógeno (porcino vs. bovino).

BACKGROUND: Hyaline membrane disease (HMD) due to lung surfactant deficiency in the preterm newborn is an important cause of neonatal morbidity and mortality. Exogenous lung surfactant has transformed HMD therapy in developed countries, but an equivalent benefit has not been accomplished in developing countries due to a variety of factors. Porcine surfactant developed in Cuba is an inexpensive alternative to other surfactants, and its use has not been studied in our settings. METHODS: A randomized, open, prospective and controlled trial was undertaken in 44 preterm newborns with HMD diagnosis. One group received bovine surfactant (BS) (Survanta) and the other Cuban porcine surfactant (PS) (Surfacen). The following clinical response variables were evaluated: oxygenation and ventilation indexes, days with supplementary oxygen, days with mechanical ventilation, incidence of complications, time of hospitalization, and mortality. RESULTS: 23 Patients received bovine surfactant and 21 the porcine type. The two groups were clinically similar, with patterns of oxygenation and ventilation response that were the same between groups, with a tendency to higher initial oxygenation increase in the PS group. The incidence of complications was similar between groups. 10 Patients (47.6%) died in the PS group, versus 12 (52.2%) in the BS group (p > 0.05). CONCLUSIONS: Porcine surfactant had similar clinical effects than bovine surfactant in the oxygenation and ventilation variables, with no significant differences in complications ormortality. Porcine surfactant is an effective and lower cost altenative to bovine surfactant in the treatment of HMD.

Estudio controlado del tratamiento de la enfermedad de membrana hialina del recién nacido pretérmino con surfactante pulmonar exógeno (porcino vs. bovino) / Treatment of hyaline membrane disease in the preterm newborn with exogenous lung surfanctant. A controlled study

Introducción: La enfermedad de membrana hialina (EMH) por deficiencia de surfactante pulmonar en el neonato prematuro es una causa importante de morbimortalidad. El surfactante pulmonar exógeno ha revolucionado el tratamiento de esta entidad en países desarrollados, aunque este beneficio ha sido menor en países en vías de desarrollo. El surfactante porcino de manufactura cubana es económico, y su uso comparado con otros surfactantes es desconocido. Material y métodos: Se llevó a cabo un estudio prospectivo, controlado, aleatorizado, abierto, en 44 recién nacidos prematuros con EMH. Un grupo recibió surfactante bovino (SB) (Survanta), y el otro surfactante porcino (SP) de fabricación cubana (Surfacen). Se evaluó la respuesta en variables de oxigenación y ventilación, días de oxígeno suplementario, ventilación mecánica, incidencia de complicaciones, tiempo de hospitalización y mortalidad. Resultados: 23 pacientes recibieron el surfactante bovino, y 21 el porcino. Los dos grupos fueron similares clínicamente y en sus patrones de respuesta de oxigenación y ventilación, con una tendencia a mayor incremento inicial en la oxigenación en el grupo tratado con SP. La incidencia de complicaciones fue similar en los dos grupos. Fallecieron 10 pacientes (47.6%) en el grupo SP, y 12 (52.2%) en el grupo SB (p>0.05). Conclusiones: El surfactante porcino tuvo efectos clínicos similares al bovino en las variables de oxigenación y ventilación estudiadas; no hubo diferencia significativa en complicaciones y mortalidad. El surfactante porcino es una alternativa efectiva y de menor costo que el surfactante bovino para el tratamiento de la EMH.

Background: Hyaline membrane disease (HMD) due to lung surfactant deficiency in the preterm newborn is an important cause of neonatal morbidity and mortality. Exogenous lung surfactant has transformed HMD therapy in developed countries, but an equivalent benefit has not been accomplished in developing countries due to a variety of factors. Porcine surfactant developed in Cuba is an inexpensive alternative to other surfactants, and its use has not been studied in our settings. Methods: A randomized, open, prospective and controlled trial was undertaken in 44 preterm newborns with HMD diagnosis. One group received bovine surfactant (BS) (Survanta) and the other Cuban porcine surfactant (PS) (Surfacen). The following clinical response variables were evaluated: oxygenation and ventilation indexes, days with supple mentary oxygen, days with mechanical ventilation, incidence of compli cations, time of hospitalization, and mortality. Results: 23 Patients received bovine surfactant and 21 the porcine type. The two groups were clinically similar, with patterns of oxygenation and ventilation response that were the same between groups, with a tendency to higher initial oxygenation increase in the PS group. The incidence of complications was similar between groups. Ten Patients (47.6%) died in the PS group, versus 12 (52.2%) in the BS group (p>0.05) Conclusions: Porcine surfactant had similar clinical effects than bovine surfactant in the oxygenation and ventilation variables, with no significant differences in complications or mortality. Porcine surfactant is an effective and lower cost alternative to bovine surfactant in the treatment of HMD.

Cost-effectiveness of exogenous surfactant therapy in pediatric patients with acute hypoxemic respiratory failure.

OBJECTIVE: To determine whether the use of exogenous surfactant (Infasurf) in pediatric acute hypoxemic respiratory failure is cost-effective. DESIGN: Deterministic cost-effectiveness analysis based on a Markov model. The model was calibrated using outcomes and resource utilization observed in a multiple-centered, prospective, randomized, controlled unblinded trial of Infasurf in pediatric acute hypoxemic respiratory failure. Costs were short-run direct costs estimated from the perspective of the hospital as provider. Primary outcomes were expected costs, expected survival rates, and incremental cost per life saved. SETTING: Patients in the trial were treated in one of eight pediatric intensive care units of tertiary medical centers. PATIENTS: Forty-two children with acute hypoxemic respiratory failure who were randomized to receive either standard therapy or exogenous surfactant in addition to standard therapy. MEASUREMENTS AND MAIN RESULTS: Our baseline analysis suggests that for a 10-kg child, the Infasurf strategy is both less costly (62,922 US dollars vs. 74,006 US dollars) and more effective (survival: 90.3% vs. 85.1%) and therefore dominates standard treatment. Cost savings were realized in the model because patients in the surfactant group were more likely to leave the pediatric intensive care unit sooner. The Infasurf strategy continues to dominate for children up to 60 kg. At 70 kg, the cost to save an additional life using the Infasurf strategy is 79,805 US dollars, which is still cost-effective if the provider is willing to make this tradeoff. CONCLUSIONS: For the majority of pediatric patients with acute hypoxemic respiratory failure, exogenous surfactant is cost-effective. If the use of this medication becomes standard care, a greater variety of packaging sizes could lead to decreased acquisition costs and increase the number of patients for whom this treatment is cost-effective.

Calfactant sterility in multiple doses from single-use vials.

BACKGROUND: Calfactant is an exogenous surfactant used to treat and prevent respiratory distress syndrome in the newborn infant. It is available in single-use preservative-free vials, but contains enough volume to provide multiple doses to small infants. OBJECTIVE: To measure the preservation of calfactant sterility at 12- and 24-hour intervals following initial violation of vial contents and to extrapolate cost savings associated with product conservation. METHODS: A prospective sterility study was performed using calfactant suspension obtained from vials prescribed for infants who had received their dose in the delivery room or the neonatal intensive care unit (NICU). After initial vial entry, test vials were stored in the NICU pharmacy satellite under refrigeration (temperature range 2.2-7.2 degrees C). Re-entry of test vials and sample removal was performed 12 and 24 hours after initial entry with an 18- or 20-gauge needle. All samples were removed by a neonatal respiratory therapist and placed into 3-mL latex-free, Leur-lok plastic syringes and examined by 3 culture media: MacConkey agar, blood agar, and thioglycollate broth. RESULTS: A total of 89 surfactant samples from 45 vials were cultured; 45 at a mean time of 13.36 hours (range 11-41) and 44 at a mean time of 25.8 hours (range 22-60) after initial vial entry. These samples represented the technique of multiple respiratory therapists. All samples were negative for bacterial growth at 24 and 48 hours (beta = 0.9). CONCLUSIONS: Results from this short-term sterility study represent an initial step in the evaluation of multiple doses of surfactant from a single-use vial. The data suggest that 1-2 re-entries into a vial of calfactant, within 24 hours after the initial breach, can be a safe and economical method of providing more than a single dose of surfactant to infants weighing <1 kg. We encourage each institution to reproduce these findings before applying this concept to their patients.

Surfactant replacement therapy--economic impact.

Surfactant replacement is an effective treatment for neonatal respiratory distress syndrome. (RDS). As widespread use of surfactant is becoming a reality, it is important to assess the economic implications of this new form of therapy. A comparison study was carried out at the Neonatal Intensive Care Unit (NICU) of Northwest Armed Forces Hospital, Saudi Arabia. Among 75 infants who received surfactant for RDS and similar number who were managed during time period just before the surfactant was available, but by set criteria would have made them eligible for surfactant. All other management modalities except surfactant were the same for all these babies. Based on the intensity of monitoring and nursing care required by the baby, the level of care was divided as: Level IIIA, IIIB, Level II, Level I. The cost per day per bed for each level was calculated, taking into account the use of hospital immovable equipment, personal salaries of nursing, medical, ancillary staff, overheads and maintenance, depreciation and replacement costs. Medications used, procedures done, TPN, oxygen, were all added to individual patient's total expenditure. 75 infants in the Surfactant group had 62 survivors. They spent a total of 4300 days in hospital. (av 69.35) Out of which 970 d (av 15.65 per patient) were ventilated days. There were 56 survivors in the non-surfactant group of 75. They had spent a total of 5023 days in the hospital (av 89.69/patient) out of which 1490 were ventilated days (av 26.60 d). Including the cost of surfactant (two doses), cost of hospital stay for each infant taking the average figures of stay would be SR 118, 009.75 per surfactant treated baby and SR 164, 070.70 per non-surfactant treated baby. The difference of 46,061 SR is 39.03% more in non-surfactant group. One Saudi rial = 8 Rs (approx at the time study was carried out.) Medical care cost varies from place to place. However, it is definitely cost-effective where surfactant is concerned. Quality adjusted life years (QALY) for NICU care compares favourably with cost per QALY of several forms of adult health interventions. Audit, both medical and financial, of these services, at regular intervals is essential.

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.