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.

Historical perspective on surfactant therapy: Transforming hyaline membrane disease to respiratory distress syndrome.

Lung surfactant is the first drug so far designed for the special needs of the newborn. In 1929, Von Neergard described lung hysteresis and proposed the role of surface forces. In 1955-1956, Pattle and Clements found direct evidence of lung surfactant. In 1959, Avery discovered that the airway's lining material was not surface-active in hyaline membrane disease (HMD). Patrick Bouvier Kennedy's death, among half-million other HMD-victims in 1963, stimulated surfactant research. The first large surfactant treatment trial failed in 1967, but by 1973, prediction of respiratory distress syndrome using surfactant biomarkers and promising data on experimental surfactant treatment were reported. After experimental studies on surfactant treatment provided insight in lung surfactant biology and pharmacodynamics, the first trials of surfactant treatment conducted in the 1980s showed a striking amelioration of severe HMD and its related deaths. In the 1990s, the first synthetic and natural surfactants were accepted for treatment of infants. Meta-analyses and further discoveries confirmed and extended these results. Surfactant development continues as a success-story of neonatal research.

Uso convencional de surfactante en recién nacidos con enfermedad de membrana hialina / Conventional use of surfactant in newborns with hyaline membrane disease

La enfermedad de membrana hialina se debe a la deficiencia de surfactante en los pulmones de los recién nacidos especialmente los menores de 37 semanas de gestación. El manejo materno con corticoides prenatales en este grupo, disminuye la morbimortalidad asociada a esta patología neonatal. Se analiza desde el punto de la evidencia actualmente existente la administración de surfactante a estos prematuros y se revisa el tipo de surfactante a administrar, cuando es el mejor momento para administrarlo, la dosis y la forma de administrarlo.

Hyaline membrane disease is due to surfactant deficiency in the lungs of newborns, especially those younger than 37 weeks gestation. Maternal management with prenatal corticosteroids in this group reduces the morbidity and mortality associated with this neonatal pathology. The administration of surfactant to these preterm infants is analyzed from the point of the currently existing evidence and the type of surfactant to be administered is reviewed, when is the best time to administer it, the dose and the form of administration.

[Nasal CPAP versus mechanical ventilation in 28 to 32-week preterm infants with early surfactant administration]. / Presión positiva continua en la vía aérea comparada con la respiración mecánica asistida en prematuros de 28 a 32 semanas de gestación con administración precoz de surfactante pulmonar.

INTRODUCTION: Continuous positive airway pressure (CPAP) is useful in low birth weight infants with respiratory distress, but it is not known if it is a better alternative to mechanical ventilation after early pulmonary surfactant administration. OBJECTIVE: To compare the incidence of adverse events in 28 to 32-week newborns with respiratory distress managed with mechanical ventilation or CPAP after early surfactant administration. MATERIALS AND METHODS: In total, 176 newborns were treated with CPAP and 147 with mechanical ventilation, all with Apgar scores >3 at five minutes and without apnea. RESULTS: The incidence of CPAP failure was 6.5% (95% CI: 11.3-22.8%); 29 patients died: 7 with CPAP (4.0%) and 22 with mechanical ventilation (15.0%, p<0.001). The relative risk of dying with CPAP versus mechanical ventilation was 0.27 (95% CI: 0.12-0.61), but after adjusting for confounding factors, CPAP use did not imply a higher risk of dying (RR=0.60; 95% CI: 0.29-1.24). Mechanical ventilation fatality rate was 5.70 (95% CI: 3.75-8.66) deaths/1,000 days-patient, while with CPAP it was 1.37 (95% CI: 0.65-2.88, p<0.001). Chronic lung disease incidence was lower with CPAP than with mechanical ventilation (RR=0.71; 95% CI: 0.54-0.96), as were intracranial hemorrhage (RR=0.28, 95% CI: 0.09-0.84) and sepsis (RR=0.67; 95%CI: 0.52-0.86), and it was similar for air leaks (RR=2.51; 95% CI: 0.83-7.61) and necrotizing enterocolitis (RR=1.68, 95% CI: 0.59-4.81). CONCLUSION: CPAP exposure of premature infants with respiratory distress syndrome is protective against chronic lung disease, intraventricular hemorrhage and sepsis compared to mechanical ventilation. No differences were observed regarding air leak syndrome or death.

Presión positiva continua en la vía aérea comparada con la respiración mecánica asistida en prematuros de 28 a 32 semanas de gestación con administración precoz de surfactante pulmonar / Nasal CPAP versus mechanical ventilation in 28 to 32-week preterm infants with early surfactant administration

Introducción. La presión positiva continua en la vía aérea ( Continuous Positive Airway Pressure , CPAP) es útil en prematuros de 28 a 32 semanas de gestación con síndrome de dificultad respiratoria, pero no se ha precisado si es mejor que la respiración mecánica asistida después de la administración precoz de surfactante pulmonar. Objetivo. Comparar la incidencia de eventos adversos en prematuros de 28 a 32 semanas de gestación con síndrome de dificultad respiratoria atendidos con surfactante y respiración mecánica asistida o CPAP de burbuja. Materiales y métodos. Se atendieron 147 neonatos con respiración mecánica asistida y 176 con CPAP, ninguno de los cuales presentaba asfixia perinatal o apnea. Resultados. La incidencia de fracaso de la CPAP fue de 6,5 % (IC 95% 11,3-22,8 %). Fallecieron 29 pacientes, 7 de los cuales habían recibido CPAP (4,0 %) y, 22, respiración mecánica asistida (15,0 %; p<0,001). El riesgo relativo (RR) de morir de quienes recibieron CPAP, comparado con el de quienes recibieron respiración mecánica asistida, fue de 0,27 (IC 95% 0,12-0,61), pero, al ajustar por los factores de confusión, el uso de CPAP no implicó mayor riesgo de morir (RR=0,60; IC 95% 0,29-1,24). La letalidad con respiración mecánica asistida fue de 5,70 (IC 95% 3,75-8,66) muertes por 1.000 días-paciente, mientras que con CPAP fue de 1,37 (IC 95% 0,65-2,88; p<0,001). La incidencia de neumopatía crónica fue menor con CPAP (RR=0,71, IC 95% 0,54-0,96), al igual que la de hemorragia cerebral (RR=0,28; IC 95% 0,09-0,84) y la de sepsis (RR=0,67; IC 95% 0,52-0,86), pero fue similar en cuanto a escapes de aire (RR=2,51; IC 95% 0,83-7,61) y enterocolitis necrosante (RR=1,68; IC 95% 0,59-4,81). Conclusión. La incidencia de neumopatía crónica, hemorragia ventricular y sepsis es menor con el uso de CPAP.

Introduction: Continuous positive airway pressure (CPAP) is useful in low birth weight infants with respiratory distress, but it is not known if it is a better alternative to mechanical ventilation after early pulmonary surfactant administration. Objective: To compare the incidence of adverse events in 28 to 32-week newborns with respiratory distress managed with mechanical ventilation or CPAP after early surfactant administration. Materials and methods: In total, 176 newborns were treated with CPAP and 147 with mechanical ventilation, all with Apgar scores >3 at five minutes and without apnea. Results: The incidence of CPAP failure was 6.5% (95% CI: 11.3-22.8%); 29 patients died: 7 with CPAP (4.0%) and 22 with mechanical ventilation (15.0%, p<0.001). The relative risk of dying with CPAP versus mechanical ventilation was 0.27 (95% CI: 0.12-0.61), but after adjusting for confounding factors, CPAP use did not imply a higher risk of dying (RR=0.60; 95% CI: 0.29-1.24). Mechanical ventilation fatality rate was 5.70 (95% CI: 3.75-8.66) deaths/1,000 days-patient, while with CPAP it was 1.37 (95% CI: 0.65-2.88, p<0.001). Chronic lung disease incidence was lower with CPAP than with mechanical ventilation (RR=0.71; 95% CI: 0.54-0.96), as were intracranial hemorrhage (RR=0.28, 95% CI: 0.09-0.84) and sepsis (RR=0.67; 95%CI: 0.52-0.86), and it was similar for air leaks (RR=2.51; 95% CI: 0.83-7.61) and necrotizing enterocolitis (RR=1.68, 95% CI: 0.59-4.81). Conclusion: CPAP exposure of premature infants with respiratory distress syndrome is protective against chronic lung disease, intraventricular hemorrhage and sepsis compared to mechanical ventilation. No differences were observed regarding air leak syndrome or death.

Eficacia de tres tipos de surfactante exógeno en prematuros con enfermedad de membrana hialina / Effectiveness of three types of exogenous surfactant in preterm infants with hyaline membrane disease

Introducción: La enfermedad de membrana hialina es causa importante de mortalidad neonatal. El objetivo de esta investigación fue evaluar la eficacia de tres tipos de surfactante exógeno en prematuros. Pacientes y Método: Estudio de cohorte retrospectiva, en 93 neonatos prematuros, > 24 semanas y > 500 g de peso al nacer, 31 para cada surfactante. La exposición fue la administración de 1ª dosis bovactant (Alveofact®) 50 mg/kg, beractant (Survanta®) 100 mg/kg inicial, y poractant alfa (Curosurf®) 200 mg/kg. Las variables en estudio incluyeron tiempo de ventilación mecánica, tiempo de oxigenoterapia, estancia hospitalaria, necesidad de segunda dosis de surfactante, eventos adversos por la administración del surfactante y complicaciones por prematuridad. Además, se evaluó mortalidad, displasia broncopulmonar (DBP) y mortalidad o DBP. Análisis estadístico mediante Stata® 11.0, empleando X² o Prueba Exacta de Fisher para variables cualitativas y Pruebas ANOVA o Kruskal-Wallis para cuantitativas y riesgo relativo para las asociaciones, todas con su intervalo de confianza de 95%. Resultados: No hubo diferencias para sexo, peso y edad gestacional al nacer entre los 3 grupos. No se hallaron diferencias estadísticamente significativas para tiempo de ventilación mecánica, tiempo de oxigenoterapia, administración de una segunda dosis de surfactante, estancia hospitalaria y complicaciones entre los 3 grupos. Los eventos adversos por administración de surfactante se presentaron para beractant y poractant alfa. Ocurrieron 30 (32,3 por ciento) muertes, 8 (25,8 por ciento) para bovactant, 10 (32,3 por ciento) beractant y 12 (38,7 por ciento) poractant alfa (p > 0,05). La mortalidad y/o DBP ocurrió en 10 (32,2 por ciento) neonatos con bovactant, 10 (32,2 por ciento) con beractant y 14 (45,2 por ciento) con poractant alfa (p > 0,05). Conclusiones: Los resultados primarios y secundarios entre los tres surfactantes evaluados fueron muy similares...

Introduction: Hyaline membrane disease is an important cause of neonatal mortality. The objective of this research is to evaluate the efficacy of three different exogenous surfactants in premature infants. Patients and Method: A retrospective cohort analysis in 93 preterm infants > 24 weeks and birth weight > 500 g was performed, 31 infants for each surfactant. Exposure consisted of the 1st dose of bovactant (Alveofact®) 50 mg/kg, beractant (Survanta®) 100 mg/kg initially, and poractant alfa (Curosurf®) 200 mg/kg. The variables included duration of mechanical ventilation, duration of oxygen therapy, hospital stay, need for second dose of surfactant, adverse events surfactant administration and prematurity complications. Mortality and bronchopulmonary dysplasia (BPD) were evaluated. Statistical analysis was performed using Stata® 11.0, X² or Fisher exact test for qualitative variables and ALNOVA or Kruskal-Wallis tests for quantitative and association relative risk, all with 95 percent confidence level. Results: There were no gender, weight and gestational age differences at birth among the three groups. No statistically significant differences were found regarding duration of mechanical ventilation, duration of oxygen therapy, administration of a second dose of surfactant, hospital stay and complications among the three groups. Adverse events related to surfactant administration occurred for beractant and poractant alpha. There were 30 (32.3 percent) deaths, 8 (25.8 percent) associated to bovactant, 10 (32.3%) to beractant and 12 (38.7 percent) to poractant alpha (p > 0.05). Mortality and/or BDP occurred in 10 (32.2 percent) infants who received bovactant, 10 (32.2 percent) beractant and 14 (45.2 percent) with poractant alpha (p > 0.05). Conclusions: The primary and secondary outcomes among the three surfactants tested were similar, taking into account the limitations of the work.

Unexpected extra-renal effects of loop diuretics in the preterm neonate.

UNLABELLED: The loop diuretics furosemide and bumetanide are commonly used in neonatal intensive care units (NICUs). Furosemide, because of its actions on the ubiquitous Na(+) -K(+) -2Cl(-) isoform cotransporter and its promotion of prostanoid production and release, also has non-diuretic effects on vascular smooth muscle, airways, the ductus arteriosus and theoretically the gastrointestinal tract. Loop diuretics also affect the central nervous system through modulation of the GABA-A chloride channel. CONCLUSION: The loop diuretics have a variety of biological effects that are potentially harmful as well as beneficial. Care should be taken with the use of these agents because the range of their effects may be broader than the single action sought by the prescribing physician.

Estrategia de intervención para disminuir la mortalidad por Síndrome de Dificultad Respiratoria del recién nacido en Maternidad Provincial, de Matanzas / Interventional strategy to diminish mortality by Respiratory Distress Syndrome of the newborn at the Provincial Maternity Hospital, of Matanzas

En la presente investigación se expone una estrategia de intervención dirigida a disminuir la mortalidad por Síndrome de Dificultad Respiratoria del Recién Nacido, en el Hospital Provincial Ginecobstétrico Docente Julio Alfonso Medina, de Matanzas. Sobre la base de la propia experiencia de los autores y mediante la aplicación de métodos científicos, basados en la literatura internacional actual, se presenta el resultado de un minucioso estudio de 48 recién nacidos que padecieron la enfermedad y que fueron tratados en la Unidad de Cuidados Intensivos Neonatales de esa institución hospitalaria durante los años 2006 y 2007. Las acciones estratégicas que se dan a conocer como resultado de la investigación, unido a las recomendaciones ofrecidas por los autores, constituyen una herramienta imprescindible para emprender un mejor manejo con los pacientes que padecen la enfermedad. Apoyados en el uso de una secuencia correcta del CPAP y del surfactante porcino cubano denominado SURFACEN, se dan a conocer nuevos enfoques en el tratamiento del Síndrome de Dificultad Respiratoria del Recién Nacido. Se propone el nuevo término de Enfermedad Pulmonar por Inmadurez Congénita (EPIC), para designar esta patología en lugar del término anatomopatológico de membrana hialina...

In the current investigation we expose the interventional strategy to diminish mortality by Respiratory Difficulty Syndrome of the Newborn, in the Provincial Gynecoobstetric Teaching Hospital Julio Alfonso Medina, of Matanzas. On the basis of the authors' proper experience and applying scientific methods, taking into account the current international literature, we present the results of a detailed study of 48 newborns who suffered the disease and were treated in the Neonatal Intensive Care Unit of this institution during 2006 and 2007. The strategic actions resulting from our investigation, together with the recommendations offered by the authors are indispensable for a better management of the patients suffering the disease. We offer new approaches in the treatment of the Respiratory Distress Syndrome of the Newborn on the basis of the usage of a correct sequence of the Continuous Positive Airway Pressure and the porcine Cuban surfactant called SURFACEN. We propose the new term Pulmonary Disease by Congenital Immaturity, to denominate this pathology in the place of the anatomopathologic term of hyaline membrane...

The effects of surfactant and antenatal corticosteroid treatment on the pulmonary pathology of preterm infants with respiratory distress syndrome.

The aim of this study was to investigate the effects of antenatal steroid treatment and/or postnatal surfactant replacement therapy on the incidence and extent of selected histopathological findings. Seventy complete autopsies were reviewed, and only lung tissues were examined and graded. Infants were divided into treatment and control groups as follows: group 1: surfactant-treated infants (n=15); group 2: infants whose mothers were given steroid treatment (n=16); group 3: surfactant-treated infants whose mothers were given steroid treatment (n=10). The control group included 29 patients not treated with surfactant and steroid. The overall incidence and severity of hyaline membrane and pulmonary hemorrhage were similar in each treatment group when compared to the control group. However, when the treatment groups were compared with each other, the incidence of severe hyaline membrane was more common in group 1 than in group 3. A significant reduction in severe hyaline membrane was associated with combined surfactant and antenatal steroid therapy. However, the cause for the similar incidence of selected histopathological findings in the treatment groups and the control group may be linked to oxygen toxicity due to insufficient antioxidant capacity in premature infants and barotrauma from mechanical ventilation.

Comparison outcomes of surfactant therapy in respiratory distress syndrome in two periods.

BACKGROUND: Exogenous surfactant replacement therapy has been a part of the routine care of preterm neonates with respiratory distress syndrome (RDS) since 1990s. In Thailand, the utilization of surfactant replacement therapy had been limited due to the high cost until the National Health Insurance Policy began in 2003 which covered the cost of surfactant. Nowadays surfactant replacement therapy is more frequently used at Queen Sirikit National Institute of Child Health, so the authors were interested in evaluating its use in RDS. OBJECTIVES: To compare the outcome and complications of surfactant replacement therapy in newborns who were diagnosed with moderate to severe RDS during two times period. STUDY DESIGN: Retrospective study. MATERIAL AND METHOD: The data of infants who were diagnosed as moderate to severe RDS and treated with surfactant at Queen Sirikit National Institute of Child Health between January 1st, 2003 and December 31th, 2005 were reviewed. The outcome of this study (Group II) was compared to the previous study conducted in 1999-2002 (Group I). The complications, mortality rate, association time of start surfactant and duration of ventilation were reviewed. RESULTS: The data of ninety-one moderate to severe RDS patients who received surfactant replacement therapy were reviewed. The mean birth weight and gestational age in this group were 1250 +/- 435.57 gm and 29.38 +/- 2.2 week less than in the first group 1,344 +/- 452.37gm and 29.69 +/- 2.61 week. The second group showed statistical differences in antepartum hemorrhage (4.4%) and pregnancy induced hypertension (PIH) (17.6%) while the first group had 33.3% ofantepartum hemorrhage and 3% of PIH. In neonatal conditions, there were statistical significant differences in anemia 28.6% in group II compared to 9% in group I and patent ductus arteriosus 67% in group II compared to 39.4% in group I. Surfactant was given earlier in life (4.75 +/- 2.76 hours) in the second group compared to the first group (7.21 +/- 4.92 hour) and the overall duration ofpatients on mechanical ventilation in Group II (6 days) was shorter than in Group I (16 days). This was especially more evident in patients who received surfactant within the first six hours of life. The immediate complication, pulmonary hemorrhage was found in more cases in Group I (33.3%) than in Group II (12.1%) but bronchopulmonary dysplasia (BPD) was found to be a late complication in more cases in Group II (46.1%) than in Group I (21.2%). The mean length of admission was longer in Group II (61.23 +/- 41.08 days) compared to Group I (38.5 +/- 23.48 days) and the mortality rate in Group II was 18.7% (17 cases) lower than Group I 33.3% (11 cases). CONCLUSION: Surfactant therapy in moderate to severe RDS can shorten the duration of ventilation and decrease the mortality rate, but has no effect in decreasing the incidence of chronic lung disease. Nevertheless the earlier the surfactant therapy is started, the higher the survival rate.

[Antenatal betamethasone during pregnancy with severe diabetes: is better worse than good?]. / Maturation par bêtaméthasone au cours d'une grossesse de femme présentant un diabète compliqué: le mieux est-il l'ennemi du bien?

Diabetic pregnancy is a precarious situation, both for mother and fetus, because it increases the risk of prematurity and respiratory distress. We report 3 cases of severe acute complications following antenatal betamethasone treatment in mothers presenting with severe diabetes. Corticosteroids are strongly recommended to prevent prematurity complications in newborns. We highlight the high risk profile of theses pregnancies, the effect of this treatment on the mother and the child, and question the real benefit of corticotherapy for these fragile newborns. The metabolic and blood pressure balance is dangerously disturbed in such pregnancies by this treatment. This brings the question of how justified are corticosteroids in such cases?

Furosemide nephrolithiasis causing ureteral obstruction and urinoma in a preterm neonate.

Nephrolithiasis and nephrocalcinosis in low-birth-weight, preterm neonates are well-documented complications of furosemide administration. Perinephric urinomas and urinary ascites have been previously reported as complications of obstruction due to posterior urethral valves or ureteropelvic junction obstruction. We present an unusual case of furosemide-induced nephrolithiasis causing ureteral obstruction, urinoma, and acute renal failure in a preterm neonate.

Early administration of the second dose of surfactant (beractant) in the treatment of severe hyaline membrane disease.

UNLABELLED: The aim of this study was to demonstrate that administration of the second dose of beractant 2 h after the first one is more effective than 6 h after the initial dose. The inclusion criteria for the recruitment of newborn infants were: age < or = 8 h, birthweight 600-2000 g, gestational age 23-36 wk, need for mechanical ventilation with inspiratory oxygen fraction (FiO2) > or = 0.4 and mean airway pressure (MAP) > or = 7 cmH2O to obtain arterial oxygen tension (PaO2) values between 70 and 80 mmHg, and thoracic X-ray compatible with hyaline membrane disease (HMD). Newborns with major congenital malformations, hydrops fetalis or severe pulmonary hypoplasia, or being treated with high-frequency oscillatory ventilation were excluded. In total, 57 premature newborns were studied, 20 of them below 1000 g, who received 100 mg kg-1 of beractant in 2 aliquots and showed an inadequate response, i.e. after 2 h of the first dose the newborn still needed a FiO2 > or = 0.4 and a MAP > or = 7 cmH2O to achieve a PaO2 > 70 mmHg. The second dose was randomly administered 2 or 6 h from the first one. CONCLUSION: The 2 study groups were comparable except for a higher need of dopamine and seroalbumin in 2-h group. Evolution and complications were similar. Twelve hours after the first dose, the percentage improvement in the arteriolar/alveolar ratio (a/ADO2) in the 2-h group was similar to that in the 6-h group. However, in newborns below 1000 g, 12 h after the first dose the a/ADO2 percentage improvement in the 2-h group was greater than in 6-h group (median of 103.6% vs 16.3%; p = 0.035). In premature infants below 1000 g, it seems reasonable to advance the second dose of beractant if needed.

Effect of morphine on respiratory drive in trigger ventilated pre-term infants.

The response to morphine (100 microgram (microg)/kg bolus, 10 microg/kg/h infusion) of 14 babies (median birth weight/gestation 1. 37 kg/30 weeks) trigger ventilated for hyaline membrane disease was compared to a group of 26 babies (median birth weight/gestation 1.1 kg/28 weeks) also trigger ventilated for hyaline membrane disease but not treated with morphine. The effect of morphine on triggered breath rate was very variable with no significant difference between the groups seen until 12 h after starting the infusion (mean [95% CI] difference=-17 [-33, -2] breaths/min). In those babies (n=11) who had plasma morphine levels measured there was no significant reduction in triggered rate over time despite significantly increasing plasma morphine levels. Babies who produced morphine-6-glucuronide at 12 h showed a significantly greater reduction in triggered breath rate than those who did not (median change -22 breaths/min compared to -4 breaths/min).

A rat model of acute respiratory distress syndrome (ARDS) Part 2, influence of lavage volume, lavage repetition, and therapeutic treatment with rSP-C surfactant.

UNLABELLED: The influence of lavage volume, and lavage repetition with physiological saline solution (groups 1-3: 3x4, 4x4, 5x4, groups 7-9: 3x8, 5x8, 7x8, mL per animal) was studied in a rat lung lavage model of the acute respiratory distress syndrome (ARDS). Anesthetized and tracheotomized rats (12 rats/group) were pressure-controlled ventilated with 100% oxygen at a respiratory rate of 30 breaths/min, inspiration: expiration ratio of 1:2, peak inspiratory pressure of 28 cm H2O at positive end-expiratory pressure of 8 cm H2O during the whole experimental period. To investigate the influence of therapeutic treatment, a recombinant surfactant protein C (rSP-C) containing surfactant was used. Therefore, rats which received a lavage of 4x4 mL per animal (groups 4 to 6) or 7x8 mL per animal (groups 10-12) were treated intratracheally with surfactant doses of 12.5, 25, or 100 mg phospholipids (PL) per kg body weight (bw). In all groups, partial arterial oxygen pressures (PaO2, mm Hg) and partial arterial carbon dioxide pressures (PaCO2, mm Hg) were determined 30 min before, directly after, and 5, 30, 60, 90, 120, 150, 180, and 210 min after the last lavage. Additionally, animals were euthanized 210 min after the last lavage for semiquantitative histopathological grading of coded lung slides. Grading was performed with respect to the severity of hyaline membrane formation (HM), margination and infiltration of polymorphonuclear neutrophil leukocytes (PMNL) into the lung alveoli and interstitial and intraalveolar edema (E). The intrapulmonary distribution of intratracheally applied rSP-C was estimated in selected lung slides stained with polyclonal anti-rSP-C antibody and was compared to unlavaged control rats and unlavaged rats which received 100 mg/kg bw rSP-C. The repetitive lavage depleted the lung from its natural surfactant resources leading to a pathophysiological cascade similar to that of the acute respiratory distress syndrome. PaO2 levels and HM formation showed a lavage-induced decrease. Both changes were significantly dependent on the repetition and volume of the lavage; however, the parameters PMNL and E did not show such a dependence. Treatment with rSP-C surfactant significantly improved oxygenation and reduced HM-formation in a dose-dependent manner independent from the lavage volume. All doses of rSP-C surfactant showed no clear influence on the parameters PMNL and E independently from the lavage volume. In lavaged rat lungs (ARDS-model), the exogenously applied rSP-C was distributed homogeneously along the alveolar lining. Unlavaged rats that received a similar dose of rSP-C showed a marked inhomogeneous extracellular distribution, mainly associated with larger bronchi, while the type II pneumocytes were stained positively in unlavaged control and unlavaged rSP-C treated rats. CONCLUSION: This model mimics very closely the wide spectrum of the clinical situation of human acute lung injury (ALI) because the variation of lavage volume and repetition lead to reproducible different severity grades and states of ALI. The significant reduction of pathognomic changes due to treatment with rSP-C surfactant showed that this is a useful model to estimate the influence of therapeutic concepts in ALI and ARDS.

Improved outcome of extremely premature infants in the 1990s.

OBJECTIVE: To study the impact of new treatment modalities on premature infants, we compared the effects of surfactant and antenatal steroid use on outcome in two military medical centers. STUDY DESIGN: We performed a retrospective chart review of 234 infants delivered at 22 to 26 weeks estimated gestational age (EGA) at our institutions between 1986 and 1996. The patients were divided into two groups: the presurfactant group included deliveries from 1986 to 1989; and deliveries from 1990 to 1996 were in the surfactant group. RESULTS: At 23 weeks EGA or less, there was only one survivor. At 24 weeks EGA, survival was improved in the surfactant group (46% vs. 5%; p < 0.005). Survival rates at 25 and 26 weeks EGA did not differ significantly. Combined survival at 24 to 26 weeks in the surfactant group exposed to antenatal steroids was 75% versus 44% in the presurfactant group (p = 0.02) Among survivors, the incidence of grade 3 or higher intraventricular hemorrhage was less in the surfactant group (18% vs. 42%; p = 0.038). CONCLUSIONS: Use of surfactant and antenatal steroids are associated with improved survival and decreased incidence of severe intraventricular hemorrhage among the most premature infants delivered in our institutions.