Alan M Fujii

Poractant alfa and beractant treatment of very premature infants with respiratory distress syndrome

Objective:Comparison of the differences between availability of animal-derived surfactant preparations used to treat premature infants is incomplete. The objective of this study was to assess the short-term treatment efficacy of the two most commonly used surfactant preparations in the United States, beractant (100 mg kg–1 initial and subsequent doses) and poractant alfa (200 mg kg–1 initial and 100 mg kg–1 subsequent doses), in very premature, mechanically ventilated infants <30 weeks gestation with respiratory distress syndrome (RDS).Study Design:Inborn infants at two institutions, open label, 1:1, randomized controlled trial. Level of respiratory support for first 72 h of life. Morbidities of prematurity observed during the neonatal intensive care unit hospitalization.Result:We studied 52 infants 24 0/7 to 29 6/7 weeks gestation; 25 received poractant alfa (27.1±1.6 weeks, birth weight of 930±231 g) and 27 received beractant (26.7±1.7 weeks, P=0.343 and birth weight 900±271 g, P=0.668). Respiratory support for the first 72 h of life was lower in the poractant alfa than beractant group for mean airway pressure (MAP, P=0.003) and respiratory index (MAP × FiO2, P=0.032). Infants in the poractant alfa group had a greater number of infants extubated at 48 (13/25 vs 6/27, P=0.027) and 72 h (15/25 vs 8/27, P=0.029) than the beractant group. Although the study was not powered to detect morbidities of prematurity, the prevalence of PDA and air leaks was less in the infants treated with poractant alfa than in those treated with beractant. Rates of bronchopulmonary dysplasia (8/23 vs 11/22, P=0.303) or death (2/15 vs 5/27, P=0.272) were similar in the infants treated with poractant alfa and beractant, respectively.Conclusion:This study suggests significant short-term benefits to the use of the larger initial dose of poractant alfa than beractant in very premature infants with RDS. Further studies involving a larger number of preterm infants are needed to assess long-term effects.

Percutaneous Catheter Evacuation of a Pneumatocele in an Extremely Premature Infant with Respiratory Failure

Progression of pulmonary interstitial emphysema (PIE) to single or multiple pneumatoceles is uncommon, but may be seen in extremely premature infants with respiratory distress syndrome (RDS) on mechanical ventilation, after bacterial pneumonia and after suction catheter-induced airway trauma. While most premature infants with pneumatoceles are managed conservatively, mechanical decompression may be necessary.1–3 Prior descriptions of neonatal intensive-care management of pneumatoceles in premature infants are individual case reports. We report the case of a 1-month-old extremely premature infant with RDS and respiratory failure from superimposed respiratory syncytial viral pneumonitis, PIE, and an enlarging pneumatocele, which was successfully managed with a percutaneously placed pigtail catheter.

Pregnancy in a Patient With Primary Membranous Nephropathy and Circulating Anti-PLA2R Antibodies: A Case Report

There is little information about pregnancy outcomes in patients with active membranous nephropathy (MN), especially those with circulating autoantibodies to M-type phospholipase A₂receptor (PLA₂R), the major autoantigen in primary MN. We present what we believe to be the first known case of successful pregnancy in a 39-year-old woman with PLA₂R-associated MN. In the year prior to pregnancy, the patient developed anasarca, hypoalbuminemia (albumin, 1.3-2.2g/dL), and proteinuria (protein excretion, 29.2 g/d). Kidney biopsy revealed MN with staining for PLA₂R, and the patient was seropositive for anti-PLA₂R autoantibodies. She did not respond to conservative therapy and was treated with intravenous rituximab (2 doses of 1 g each). Several weeks after presentation, she was found to be 6 weeks pregnant and was closely followed up without further immunosuppressive treatment. Proteinuria remained with protein excretion in the 8- to 12-g/d range. Circulating anti-PLA₂R levels declined but were still detectable. At 38 weeks, a healthy baby girl was born, without proteinuria at birth or at her subsequent 6-month postnatal visit. At the time of delivery, the mother still had detectable circulating anti-PLA₂R of immunoglobulin G1 (IgG1), IgG3, and IgG4 subclasses, although at low titers. Only trace amounts of IgG4 anti-PLA₂R were found in cord blood. Potential reasons for the discrepancy between anti-PLA₂R levels in the maternal and fetal circulation are discussed.

Effect of young sibling visitation on respiratory syncytial virus activity in a NICU

Objective:To determine whether the restriction of young sibling (<13 years) visitation in the neonatal intensive care unit (NICU) during the respiratory syncytial virus (RSV) season was associated with a reduction in the rate of RSV infection among NICU patients.Study Design:A retrospective chart review of all RSV positive infants from the 2001–2010 RSV seasons. The 2001–2006 RSV seasons (group 1) contained 639 admissions and the 2007–2010 (group 2, with sibling restriction) contained 461 admissions. Groups were compared by using the Fisher’s Exact Test.Results:There was a reduction of RSV positive infants from 6.7% in Group 1 to 1.7% in Group 2 (P<0.0001). There was a reduction of symptomatic infants from the number of infants with symptomatic RSV infection from 23/639 infants with young sibling visitation to 2/461 (P<0.001).Conclusion:Exclusion of young sibling visitors <13 years of age during RSV season was associated with a significant reduction in the number of RSV positive infants in the NICU.

Diagnostic ionizing radiation exposure in premature patients

Objective:Concern regarding the magnitude and consequences of diagnostic radiation exposure in premature infants in neonatal intensive care units (NICUs) has increased as survival of premature infants has improved. Radiation exposure is not often rigorously monitored in NICU patients. The purpose of this observational study was to quantify the amount of ionizing radiation exposure in infants <33 weeks gestational age and to identify the indications for diagnostic imaging.Study Design:We conducted a retrospective review of 215 premature infants who were <33 weeks gestation and who received central venous line (CVL) placement during their NICU stay during the period from 2006 to 2011. Absorbed ionizing radiation was estimated using the method of Puch-Kapst and colleagues (2009) and compared with recommended radiation exposure limits. All infants were 29.2±2.3 weeks (mean±s.d.) and 1262±433 g birth weight.Result:Subjects received 15±15 radiographs (4.4±2.9 for CVL placement, 5.7±9.8 for gastrointestinal (GI) evaluations and 5.2±9.3 for respiratory indications). Eleven infants (5.1%) received more than the maximum recommended radiation from radiographs (>1000 μSv). Inclusion of fluoroscopic procedures increased to 26 the number of infants (12.1%) who received more than the maximum recommended 1000 μSv.Conclusion:Ionizing radiation exposure that exceeded the recommended maximum in premature infants at high risk for long-term sequelae occurred in 12.1% of infants who were <33 weeks gestation and who were cared for in our NICU over the past 5 years. CVL placement accounted for 22% of this radiation exposure. GI evaluations accounted for the greatest amount of ionizing radiation exposure. We suggest that the increased use of other imaging strategies may reduce total ionizing radiation exposure in this vulnerable population.

Is there a Difference in Surfactant Treatment of Respiratory Distress Syndrome in Premature Neonates? A Review

Exogenous surfactant treatment of premature infants with Respiratory Distress Syndrome (RDS) has been the standard of care for more than two decades. There are now many studies comparing various surfactant preparations. Data are clear that the synthetic surfactants without surfactant proteins are inferior to animal derived surfactant preparations. In the United States, commercially available surfactants are beractant, calfactant, poractant alfa, and lucinactant. Relative efficacy of the various available animal derived surfactants in the United States appear to favor poractant alfa, the surfactant preparation with the highest concentrations of phospholipids and high concentration of surfactant proteins, allowing a higher initial dose of phospholipids in preterm infants less than 32 weeks. A new synthetic surfactant with a surfactant protein analog, lucinactant, has been recently been approved for use in the United States. Synthetic surfactants hold the possibility of surfactant treatments without potential animal-born infectious agents or animal proteins that could induce an immune response in fragile premature infants with multiple medical problems. New surfactant administration strategies are described, complimenting new respiratory support strategies, designed to minimize invasive mechanical ventilation and decrease the frequency of chronic lung disease. Minimally invasive surfactant administration strategies are being developed to accommodate these new respiratory support strategies. The goal of this manuscript is to review the available surfactant preparations and their administration strategies.

Patent ductus arteriosus hemodynamics in very premature infants treated with poractant alfa or beractant for respiratory distress syndrome.

Objective:Respiratory distress syndrome (RDS), requiring mechanical ventilation and exogenous surfactant treatment, and patent ductus arteriosus (PDA), are common co-morbidities in very premature infants. The effects of intra-tracheal surfactant administration on the cardiovascular and pulmonary systems in very premature infants with RDS and PDAs are not well characterized. We evaluated the effects of poractant alfa and beractant, surfactants with different rapidity of onset and duration of action, in very premature infants with RDS. To assess whether there were differences in PDA hemodynamics in very premature infants with RDS treated with poractant alfa and beractant during the first week of life and to assess whether poractant alfa or beractant had a direct effect on PDAs and PDA hemodynamics following the second dose of surfactant.Study Design:We studied 50 in-born, very premature infants with RDS, 24 0 of 7 to 29 6 of 7 weeks gestation, treated with poractant alfa or beractant, in an open label, 1:1, randomized clinical trial. A subgroup of 16 patients with severe RDS, treated with a second dose of surfactant, had echocardiographical assessments before and 20 to 30 min after the second dose of surfactant.Result:There were 25 infants treated with poractant alfa (27.1±1.6 weeks, birth weight 930±231 g) and 25 treated with beractant (26.7±1.7 weeks, P=0.407 and birth weight 898±282 g, P=0.666). Clinically significant PDAs were diagnosed and treated in 8 of 25 (32%) of the poractant alfa and 19 of 25 (76%) of the beractant group (P=0.002). Indomethacin treatment was slightly earlier (3.4±2.5 days) in the poractant alfa than in the beractant group (5.1±4.9 days, P=0.038). Right ventricle pressure (RVP)/systolic arterial pressure (SAP) ratio in the first week was slightly lower in the poractant alfa (64±20%) than in the beractant (78±26%, P=0.048) group. Following a second dose of surfactant, neither poractant alfa nor beractant changed PDA flow. These hemodynamic observations were associated with less respiratory support in the poractant alfa group, allowing earlier extubation (13 of 25 at 48 h and 15 of 25 at 72 h), than in the beractant group (6 of 25 at 48 h, P=0.044, and 8 of 25 at 72 h, P=0.049).Conclusion:The more rapid improvement in pulmonary function in the poractant alfa-treated infants was associated with a lower RVP/SAP ratio and a corresponding earlier treatment with indomethacin. Neither surfactant had a significant direct effect on PDA hemodynamics. The lower frequency of clinically significant PDAs in the poractant alfa compared with the beractant group may represent an indirect effect of the differences in the pulmonary improvement induced by the two surfactants.

Superior mesenteric artery blood flow velocities following medical treatment of a patent ductus arteriosus

We examined superior mesenteric artery blood flow velocity in response to feeding in infants randomized to trophic feeds (n = 16) or nil per os (n = 18) during previous treatment for patent ductus arteriosus. Blood flow velocity increased earlier in the fed infants, but was similar in the 2 groups at 30 minutes after feeding.

Hypo-pharyngeal distension in an extremely low birth weight preterm infant

A preterm male infant was born at 25 weeks gestation weighing 780 g by emergency caesarean section to a multiparous woman presenting in active labour with breech presentation. The infant needed some initial resuscitation by bag and mask ventilation followed by commencement of nasal bubble continuous positive airway pressure (CPAP) in the delivery room. Orogastric tube was placed …

Is there really a clinical difference in surfactant preparations

Dr Lutchman poses the question, ‘Have we been down this road before?’ Is there really a clinical difference in surfactant preparations? The debate of which surfactant to use in the management of very premature infants with respiratory distress syndrome has been ongoing for two decades. In the United States, the debate began with the Food and Drug Administration’s approval of the first synthetic surfactant, Exosurf (colfosceril palmitate), closely followed by approval of the animal-derived surfactant, Survanta (beractant). The debate continued with the subsequent approval of more rapidly acting animal-derived surfactants, Infasurf (calfactant) and Curosurf (poractant), with higher concentrations of surfactant phospholipids and surfactant proteins. With preferential purchasing, clinical neonatologists showed their interest in surfactants with a faster onset of action and smaller volume of administration. Slower acting synthetic surfactant, Exosurf, is no longer marketed in the United States. Our recent studies of very premature, mechanically ventilated infants with respiratory distress syndrome continue to incrementally evaluate differences in available surfactant preparations. Although we have not shown a difference in mortality with our small sample size, it is clear that poractant alfa has a more rapid onset of action compared with beractant. Poractant alfa, with a larger initial dose (200 mg kg) compared with beractant (100 mg kg), made possible by a higher concentration of phospholipid in poractant alfa, is associated with a longer dose-related half-life, giving poractant alfa an additional longer duration of action. Smaller volumes of administration may also reduce the hypercarbia and acute increase in cerebral blood flow, in these very fragile infants. The increased clinical efficacy of multiple doses of poractant alfa (200 mg kg initial dose) was documented in a large European trial. In addition, our preliminary data suggest that improved pulmonary function in the poractant-treated very premature infants with respiratory distress syndrome may reduce the number with clinically significant patent ductus arteriosus. We agree with Dr Lutchman that the surfactant story is far from complete and that ideally a comprehensive series of definitive, randomized control trials of available surfactants, with appropriate power for subgroup analysis, be funded and conducted to assess relative efficacy of surfactant preparations and dosing on preterm infant morbidity and mortality. Unfortunately, these studies are challenging to design, expensive to conduct and the question of how to fund them persists.