Incidence of respiratory viral infection in infants with respiratory symptoms evaluated for late-onset sepsis.

OBJECTIVE: To determine the frequency, etiology and impact of respiratory viral infection (RVI) on infants evaluated for late-onset sepsis (LOS), defined as sepsis occurring >72 h of life, in the neonatal intensive care unit. STUDY DESIGN: Prospective observational study conducted from 6 March 2014 to 3 May 2016 on infants evaluated for LOS. PCR viral panel performed on nasopharyngeal specimens among infants with clinical suspicion for RVI. Sequence analysis was performed to determine viral subtypes. Fisher's exact or χ2 tests were done to determine the impact of RVI. RESULTS: During the 26-month study, there were 357 blood cultures obtained for LOS evaluations, 29 (8%) had a respiratory virus detected. Only 88 (25%) of infants evaluated for LOS also had clinical suspicion for a respiratory viral infection. RSV (14 of 29; 48%) was the predominant virus detected. Almost all infants (13 of 14; 93%) with RSV required increased respiratory support. Antimicrobial therapy was withheld or discontinued on most infants with a virus detected (18 of 29; 62%) and in the majority where there was no confirmed bacterial co-infection (18 of 20; 90%). CONCLUSION: The incidence of RVI in infants being evaluated for LOS is about 8%. RVI should be considered in LOS evaluation to prevent unnecessary antibiotic therapy.

Prevention of postnatal growth restriction by the implementation of an evidence-based premature infant feeding bundle.

OBJECTIVE: To develop an evidence-based feeding bundle to safely decrease the rate of PNGR in VLBW infants. STUDY DESIGN: The bundle was developed and implemented in January 2010, followed by 3 years of monitoring bundle compliance and infant outcomes (days to first feed (FD), days to reach full feeds (FF), and birth-discharge growth trajectories (delta z-score)). RESULTS: Data were collected on 482 infants (119 pre-bundle). PNGR decreased from 35% to 19% (P<0.01) and weight delta z-score improved from -0.82 to -0.45 (P<0.001). Percentage of infants with head circumference (HC) below 10th percentile at discharge decreased from 21% to 9% (P<0.01) and HC delta z-score improved from -0.65 to -0.17 (P<0.001). FD and FF also decreased significantly. Rates of necrotizing enterocolitis, peak alkaline phosphatase and peak direct bilirubin levels all trended downward. CONCLUSIONS: An evidence-based, standardized feeding bundle was safe and effective in reducing the rate of PNGR and in improving head growth in VLBW infants.

A meta-analysis comparing outcomes of microsurgery and gamma knife radiosurgery.

OBJECTIVES/HYPOTHESIS: Surgery has been the most common treatment for acoustic neuromas, but gamma knife radiosurgery has emerged as a safe and efficacious alternative to microsurgery. This meta-analysis compares the outcomes of the two modalities. STUDY DESIGN: A retrospective MEDLINE search was used to find all surgical and gamma knife studies published from 1990 to 1998 and strict inclusion criteria were applied. RESULTS: For tumors less than 4 cm in diameter, there is no difference in hearing preservation (P = .82) or facial nerve outcome (P = .2). Surgery on all sized tumors has a significantly lower complication rate than radiosurgery performed on tumors smaller than 4 cm (P = 3.2 x 10(-14)). Surgery also has a lower major morbidity rate than gamma knife radiosurgery (P = 2.4 x 10(-14)). Tumor control was defined as no tumor recurrence or no tumor regrowth. Surgery has superior tumor control when tumors are totally resected (P = 9.02 x 10(-11)). Assuming that all partially resected tumors will recur, surgery still retains a significant advantage over radiosurgery for tumor control (P = .028). CONCLUSION: Data from these studies date back to the late 1960s and do not completely reflect outcomes using current imaging and procedures. A major difficulty encountered in this study is inconsistent data reporting. Future surgical and radiation reports should use standardized outcomes scales to allow valid statistical comparisons. In addition, long-term results from gamma knife radiosurgery using lower dosimetry have not been reported. Surgery should remain the therapy of choice for acoustic neuromas until tumor control rates can be established.

Early dexamethasone-attempting to prevent chronic lung disease.

BACKGROUND: We previously demonstrated improved survival and early outcomes in a pilot trial of 2 doses of intravenous dexamethasone for infants with surfactant-treated respiratory distress syndrome. (1) A multicenter, randomized, double-blind trial was undertaken to confirm these results. METHODS: Infants <30 weeks' gestation were eligible if they had respiratory distress syndrome, required mechanical ventilation at 12 to 18 hours of age, and had received at least 1 dose of exogenous surfactant. Infants were excluded if sepsis or pneumonia was suspected or if congenital heart disease or chromosomal abnormalities were present. A total of 384 infants were enrolled-189 randomized to dexamethasone (.5mg/kg birth weight at 12-18 hours of age and a second dose 12 hours later) and 195 to an equal volume of saline placebo. RESULTS: No differences were found in the dexamethasone versus placebo groups, respectively, regarding the primary outcomes of survival (79% vs 83%), survival without oxygen at 36 weeks' corrected gestational age (CGA; both 59%), and survival without oxygen at 36 weeks' CGA and without late glucocorticoid therapy (46% vs 44%). No significant differences between the groups in estimates from Kaplan-Meier survival analyses were found for median days on oxygen (50 vs 56 days), ventilation (20 vs 27 days), days to regain birth weight (15.5 vs 14 days), or length of stay (LOS; 88 vs 89 days). Infants given early dexamethasone were less likely to receive later glucocorticoid therapy for bronchopulmonary dysplasia during their hospitalization (27% vs 35%). No clinically significant side effects were noted in the dexamethasone group, although there were transient elevations in blood glucose and blood pressure followed by a return to baseline by study day 10. Among infants who died (40 vs 33), there were no differences in the median days on oxygen, ventilation, nor LOS. However, in survivors (149 vs 162), the following were observed: median days on oxygen 37 versus 45 days, ventilation 14 versus 19 days, and LOS 79 versus 81 days, for the dexamethasone versus placebo groups, respectively. CONCLUSIONS: This dose of early intravenous dexamethasone did not reduce the requirement for oxygen at 36 weeks' CGA and survival was not improved. However, early dexamethasone reduced the use of later prolonged dexamethasone therapy, and among survivors, reduced the median days on oxygen and ventilation. We conclude that this course of early dexamethasone probably represents a near minimum dose for instituting a prophylactic regimen against bronchopulmonary dysplasia.

Reevaluating practice changes: return to standard precautions after an outbreak of multidrug-resistant Klebsiella oxytoca.

Change in medical practice is usually made to solve immediate problems. The continued use of these changes should then be reevaluated. Following an outbreak of K. oxytoca in our Neonatal Intensive Care Unit (NICU), glove use for all patient contact was mandated. We evaluated the need for continued glove use after resolution of the outbreak. No change in colonization patterns was seen after returning to standard precautions, and, as a secondary benefit, financial savings resulting from decreased glove use was realized. Following implementation of any practice change, routine reevaluation will help to determine when that change is no longer needed or beneficial.

Outcome measures after standardized pain management strategies in postoperative patients in the neonatal intensive care unit.

Written guidelines based on current research on infant pain assessment and management were developed by an interdisciplinary team in a neonatal intensive care unit of a regional medical center. Charts for infants who had undergone abdominal surgery were reviewed to compare patient outcomes before and after use of this pain management protocol. With the standardization of pain management strategies, the following improvements were noted: decreased length of time to extubation, decreased length of stay, better fluid management, and reduced side effects of narcotics. Additional benefits included improved pain management documentation, decreased cost, and decreased nursing time.

Comparison of two strategies for surfactant prophylaxis in very premature infants: a multicenter randomized trial.

INTRODUCTION: Previous trials of surfactant therapy in premature infants have demonstrated a survival advantage associated with prophylactic therapy as an immediate bolus, compared with the rescue treatment of established respiratory distress syndrome. The optimal strategy for prophylactic therapy, however, remains controversial. When administered as an endotracheal bolus immediately after delivery, surfactant mixes with the absorbing fetal lung fluid and may reach the alveoli before the onset of lung injury. This approach, however, causes a brief delay in the initiation of standard neonatal resuscitation, including positive pressure ventilation, and is associated with a risk for surfactant delivery into the right main stem bronchus or esophagus. As an alternative approach, surfactant prophylaxis may be administered in small aliquots soon after resuscitation and confirmation of endotracheal tube position. Although this strategy has substantial logistical advantages in clinical practice, its efficacy has not been established. OBJECTIVE: The purpose of this study was to determine whether the established benefits of the immediate bolus strategy for surfactant prophylaxis could still be achieved using a postventilatory aliquot strategy after initial standard resuscitation and stabilization. DESIGN: Multicenter randomized clinical trial with patients randomized before delivery to immediate bolus or postventilatory aliquot therapy. PARTICIPANTS: Inborn premature infants delivered to mothers at an estimated gestational age of 24[0/7] to 28[6/7] weeks. INTERVENTIONS: Those infants who were randomized to the immediate bolus strategy were intubated as rapidly as possible after birth, and a 3-mL intratracheal bolus of calf lung surfactant extract (Infasurf) was administered before the initiation of positive pressure ventilation. Those infants who were randomized to the postventilatory aliquot strategy received standard resuscitation measures with intubation by 5 minutes of age, if not required earlier. At 10 minutes after birth, 3 mL of surfactant was administered in 4 divided aliquots of 0.75 mL each. Patients in both groups were eligible to receive up to three additional doses of surfactant as rescue therapy in the neonatal intensive care unit, if needed. OUTCOME MEASURES: The primary outcome variable was survival to discharge to home. Secondary variables included neonatal complications and requirement for oxygen therapy at 36 weeks' postmenstrual age. RESULTS: Among three centers, 651 infants were enrolled and randomized before delivery. Survival to discharge to home was similar for the two strategies for surfactant therapy as prophylaxis: 76% for the immediate bolus group and 80% for the postventilatory aliquot group. In a secondary analysis, the rate of supplemental oxygen administration at 36 weeks' postmenstrual age was 18% for the immediate bolus group and 13% for the postventilatory aliquot group. CONCLUSIONS: Survival to discharge to home was similar with immediate bolus and postventilatory aliquot strategies for surfactant prophylaxis. Because of its logistical advantages in the delivery room and its beneficial effects on prolonged oxygen requirements, we recommend the postventilatory aliquot strategy for surfactant prophylaxis of premature infants delivered before 29 weeks' gestation.

Effect of standardized approach to the care of the extremely low birthweight infant.

An extremely low birthweight (ELBW) protocol was developed at this regional neonatal intensive care unit. The focus was the standardization of care related to the implementation/maintenance of a humidified environment and attention to prevention of skin excoriation in the extremely low birthweight infant (< 1000 g). Steps toward successful implementation of the standardized approach required an interdisciplinary commitment, literature review of current practice methodologies, a definition of nursing and medical approach to these infants in the first days of life, and an evaluation of the practice change focusing on patient outcomes. A comparative review was completed that evaluated the change in patient outcomes of the extremely low birthweight infants relative to fluid and electrolyte status in the first five days of life after implementation of the protocol as compared to prior to implementation of the protocol.

A multicenter randomized, masked comparison trial of natural versus synthetic surfactant for the treatment of respiratory distress syndrome.

OBJECTIVE: To compare the efficacy and safety of two surfactant preparations in the treatment of respiratory distress syndrome (RDS). METHODS: We conducted a randomized, masked comparison trial at 21 centers. Infants with RDS who were undergoing mechanical ventilation were eligible for treatment with two doses of either a synthetic (Exosurf) or natural (Infasurf) surfactant if the ratio of arterial to alveolar partial pressure of oxygen was less than or equal to 0.22. Crossover treatment was allowed within 96 hours of age if severe respiratory failure (defined as two consecutive arterial/alveolar oxygen tension ratios < or = 0.10) persisted after two doses of the randomly assigned surfactant. Four primary outcome measures of efficacy (the incidence of pulmonary air leak (< or = 7 days); the severity of RDS; the incidence of death from RDS; and the incidence of survival without bronchopulmonary dysplasia (BPD) at 28 days after birth) were compared by means of linear regression techniques. RESULTS: The primary analysis of efficacy was performed in 1033 eligible infants and an analysis of safety outcomes in the 1126 infants who received study surfactant. Preentry demographic characteristics and respiratory status were similar for the two treatment groups, except for a small but significant difference in mean gestational age (0.5 week) that favored the infasurf treatment group. Pulmonary air leak (< or = 7 days) occurred in 21% of Exosurf- and 11% of infasurf-treated infants (adjusted relative risk, 0.53; 95% confidence interval, 0.40 to 0.71; p < or = 0.0001). During the 72 hours after the initial surfactant treatment, the average fraction of inspired oxygen (+/-SEM) was 0.47 +/- 0.01 for Exosurf- and 0.39 +/- 0.01 for infasurf-treated infants (difference, 0.08; 95% confidence interval, 0.06 to 0.10; p < 0.0001); the average mean airway pressure (+/-SEM) was 8.6 +/- 0.1 cm H2O; for Exosurf- and 7.2 +/- 0.1 cm H2O for Infasurf-treated infants (difference, 1.4 cm H2O; 95% confidence interval, 1.0 to 1.8 cm H2O; p < 0.0001). The incidences of RDS-related death, total respiratory death, death to discharge, and survival without bronchopulmonary dysplasia at 28 days after birth did not differ. The number of days of more than 30% inspired oxygen and of assisted ventilation, but not the duration of hospitalization, were significantly lower in Infasurf-treated infants. CONCLUSION: Compared with Exosurf, Infasurf provided more effective therapy for RDS as assessed by significant reductions in the severity of respiratory disease and in the incidence of air leak complications.

Relatedness of coagulase-negative staphylococci causing bacteremia in low-birthweight infants.

OBJECTIVE: To investigate coagulase-negative staphylococcus (CONS) causing bacteremia in a neonatal intensive care unit (NICU). DESIGN: A 14-month retrospective review of 47 infants in the NICU with CONS bacteremia was undertaken to determine CONS glycocalyx production, plasmid pattern, total DNA restriction fragment polymorphism, and clinical risk factors. RESULTS: The isolates included 32 Staphylococcus epidermidis, six Staphylococcus haemolyticus, four Staphylococcus warneri, four Staphylococcus saprophyticus, and one Staphylococcus hominis. Sixty-five percent of S epidermidis produced glycocalyx; other species did not. Oxacillin resistance (52%) and the antibiograms of the CONS were consistent with other units in the hospital. Five similar CONS plasmid patterns were found among 16 isolates; 31 isolates had unique patterns. Extractions of total DNA from these isolates were digested using HindIII, HaeIII, and BstEII. Those with similar restriction fragment length patterns could not linked as nosocomially transmitted among infants with bacteremia. CONCLUSION: Our observations suggest that multiple strains of CONS infect infants in the NICU who have similar risk factors. Although current infection control practices limit transmission of a pathogen, they do not prevent CONS bacteremias.

Prevention of gram-positive sepsis in neonates weighing less than 1500 grams.

A prospective, randomized study to evaluate the effectiveness of a continuous low-dose vancomycin infusion to prevent nosocomial gram-positive bacteremia was initiated within the first 2 weeks of life in neonates weighing < 1500 gm. Seventy-one infants received constant infusion of vancomycin (25 micrograms/ml) mixed with their total parenteral nutrition solution; 70 infants served as control subjects. The groups were clinically similar in birth weight, estimated gestational age, and severity of illness. Administration of vancomycin was begun at a mean age of 5.4 +/- 2.9 days. Infants had mean serum vancomycin concentrations of 2.4 micrograms/ml, and received vancomycin for a mean of 11 +/- 7 days. No vancomycin-resistant organisms were detected in surveillance cultures during the 2-year study period. Twenty-four of seventy control infants, in comparison with 1 of 71 infants receiving vancomycin, had gram-positive bacteremia (p < 0.001). The addition of a low dose of vancomycin to alimentation fluids virtually eliminated the incidence of gram-positive bacteremia in an at-risk population of very low birth weight infants. However, the widespread use of vancomycin in total parenteral nutrition solution is not recommended until better data on the emergence of vancomycin-resistant organisms are available.

TNF-alpha release in endotoxemia contributes to neutrophil-dependent pulmonary edema.

We examined whether the generation of tumor necrosis factor (TNF-alpha) after lipopolysaccharide (LPS) challenge contributes to increases in lung vascular permeability and water content. Guinea pig lungs perfused at constant flow with Ringer-albumin solution (0.5 g/100 ml) were challenged for 120 min with LPS (Escherichia coli; final concentration 33 ng/ml; n = 5). Lung effluent samples were assayed for TNF-alpha activity using the modified L-929 fibroblast cytolytic assay. TNF-alpha concentrations increased in a time-dependent manner with a peak value of 100 +/- 20 pg/ml noted 90-120 min after LPS. Human neutrophils [polymorphonuclear leukocytes (PMN; 2 x 10(7)] added to the perfusion solution after endotoxin challenge (n = 5) produced a threefold increase in lung tissue myeloperoxidase (MPO) activity over control values. PMN, added after LPS and activated using phorbol 12-myristate 13-acetate (PMA; 5 x 10(-9) M; n = 6), produced three- to sixfold increases in mean pulmonary arterial pressure (Ppa) and pulmonary capillary pressure (Pcap), wet weight-to-dry weight ratio (W/D), and the pulmonary capillary filtration coefficient (Kf,c) over control values (P < 0.05). Activation of PMN with PMA in non-LPS-challenged lungs produced only threefold increases in Ppa and Pcap and did not change W/D and Kf,c. Infusion of an anti-TNF-alpha antibody before the LPS challenge reduced by approximately 50% the increases in Ppa, Pcap, MPO content, Kf,c, and lung wet weight gain (P < 0.05). Therefore, endotoxin-induced TNF-alpha generation in lungs significantly contributes to pulmonary sequestration of PMN. Activation of the sequestered PMN increases pulmonary vascular permeability and tissue water content.

Release of tumor necrosis factor after pulmonary artery occlusion and reperfusion.

Cytokines may function as mediators of reperfusion tissue injury in lungs. Because the lung contains resident macrophages that can serve as potential sources of cytokines, we examined the possibility that pulmonary artery occlusion by reperfusion is a factor in mediating the release of cytokines. After left lung ischemia induced by a 24-h period of left pulmonary artery occlusion, we observed a transient increase in TNF-alpha concentration in lung effluent in rabbits during the period reperfusion. The peak TNF-alpha levels ranged from 55 to 335 pg/ml, and a mean peak time was at 45 to 60 min after the initiation of reperfusion. The TNF-alpha concentrations then decreased towards baseline. TNF-alpha was detected in control plasma or in plasma from sham-operated animals. Less than 10 pg/ml of endotoxin was detected in any samples. Lung tissue myeloperoxidase content, a measure of neutrophil infiltration, increased progressively during the 2-h reperfusion period. The time course of generation of TNF-alpha preceded the maximal rise in lung tissue myeloperoxidase activity. The data show that lung ischemia/reperfusion results in transient generation of TNF-alpha, which is known to mediate neutrophil sequestration. Neutrophil sequestration and resulting lung injury after reperfusion may be dependent on generation of TNF-alpha at the onset of reperfusion.

Generation of 5-lipoxygenase metabolites following pulmonary reperfusion in isolated rabbit lungs.

We characterized the release of arachidonic acid (AA) metabolites in lung effluent following lung ischemia-reperfusion since they may contribute to the pathophysiology of reperfusion lung injury. The left pulmonary artery of rabbits (N = 5) was occluded for 24 hrs with a surgically implanted vascular clip. At 24 hrs, the heart and lungs were removed en bloc and perfused with Ringers-albumin (0.5 gm%) at 60 ml/min while statically inflated with 95% O2-5% CO2. The lipid fraction of the lung effluent was concentrated using the Bligh-Dyer extraction and analyzed by gradient RP-HPLC. Samples obtained in the first minute of reperfusion showed significant increases in LTB4 (+180%), LTC4 (+3600%), 15-HETE (+370%), 5-HPETE (+270%), PGE2 (+140%), 6-keto-PGF1 alpha (+110%) and 12-HHT (+160%) compared to the effluent from the right control lung. The reperfusion-induced increases in LTB4, LTC4, LTD4 and 15-HETE were inhibited greater than or equal to 70% by pretreatment with the 5-LO inhibitors L663,536 or L651,392. The increases in lipid concentrations corresponded to significantly increased pulmonary arterial pressure from a baseline value of 9.5 +/- 0.3 to 29.3 +/- 2.9 (cmH2O) during the first min of reperfusion. The pulmonary arterial pressure remained elevated for at least 20 min of reperfusion. Reperfusion also resulted in PMN uptake (assessed by lung tissue myeloperoxidase content) in the reperfused lung versus control lung (25.0 +/- 2.4 vs. 10.5 +/- 2.5 units). The generation of lipoxygenase metabolites during the initial phase of reperfusion may contribute to post-reperfusion PMN uptake and pulmonary vasoconstriction.

Role of ICAM-1 in neutrophil-mediated lung vascular injury after occlusion and reperfusion.

We examined the role of intracellular adhesion molecule 1 (ICAM-1 or CD54) in the development of pulmonary edema in rabbits after pulmonary artery occlusion and reperfusion using a monoclonal antibody (MAb) RR1/1 directed against ICAM-1, a ligand for the CD18 leukocyte adhesion glycoprotein complex. A vascular clamp was placed around the left pulmonary artery for 24 h and then released to allow reperfusion for 2 h. Lungs subjected to 24 h of unilateral pulmonary artery occlusion showed increased binding of 125I-labeled RR1/1 and immunocytochemical evidence of ICAM-1 expression in pulmonary vascular endothelial cells compared with the contralateral lung. MAbs RR1/1 (0.5 mg/kg) or IB4 (1.0 mg/kg) (MAb directed against an epitope on the CD18 adhesion glycoprotein) was infused 45-60 min before the start of reperfusion to assess the roles of ICAM-1 and CD18 in the response. After reperfusion, the lungs were removed, suspended from one end of a weighing balance, and perfused with Ringer-albumin (0.5 g/100 ml), and the changes in lung weight were monitored for 60 min. Lung tissue myeloperoxidase (MPO) content (a marker of neutrophil sequestration) was determined after reperfusion. The increases in lung weight gain in the RR1/1- and IB4-treated groups of 960 +/- 100 and 865 +/- 110 mg, respectively, were less (P less than 0.05) than in untreated controls (3,550 +/- 725 mg).(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of endothelin-1-induced pulmonary vasoconstriction.

Endothelins are endothelial cell-derived peptides with potent vasoconstrictor properties. We investigated the actions of porcine/human endothelin-1 (ET-1) on the microvasculature of the guinea pig lung perfused at constant flow with Ringers-albumin. We measured the perfusion pressure, distribution of pulmonary vascular resistance (using the double occlusion method), lung weight change, and the pulmonary capillary filtration coefficient. At concentrations of greater than or equal to 10(-10) M, ET-1 produced dose-dependent increases in mean pulmonary artery pressure (EC50, approximately 10(-9.5) M), which were rapid in onset and biphasic (first phase peaking at 1-2 minutes; second phase peaking at 10-15 minutes) up to 60 minutes of the perfusion period. The vasoconstrictor response was sustained for the 60-minute perfusion period. The pulmonary vasoconstriction was inhibited by pretreatment with indomethacin (10(-5) M), the thromboxane A2 receptor antagonist SQ-29,548 (4 x 10(-6) M), or papaverine (10(-5) M). Nifedipine (10(-5) or 10(-7) M) had no effect on the first phase but prevented the second phase of the vasoconstriction. The vasoconstriction was primarily the result of a 10-fold increase in pulmonary venous resistance. Pulmonary edema developed after ET-1 challenge because of the venoconstriction and the resultant pulmonary capillary hypertension. However, the pulmonary capillary filtration coefficient was unchanged, indicating that pulmonary vascular permeability did not increase. ET-1 also had no effect on transendothelial 125I-albumin flux. The results indicate that ET-1 is a potent thromboxane-dependent venoconstrictor in the guinea pig lung.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of surfactant as immediate prophylaxis and as rescue therapy in newborns of less than 30 weeks' gestation.

BACKGROUND: Exogenous pulmonary surfactants are administered into the trachea either to prevent respiratory distress syndrome in premature infants or to treat it. In a randomized, multicenter trial, we compared the results of surfactant therapy initiated as prophylaxis with the results of rescue therapy with surfactant. METHODS: Before birth, 479 infants with an estimated gestational age of less than 30 weeks were randomly assigned to receive surfactant as prophylaxis (n = 235) or rescue therapy (n = 244). The infants in the prophylaxis group received a 90-mg intratracheal dose of an exogenous calf-lung surfactant extract at the time of delivery, whereas the infants in the rescue-therapy group received 90 mg of the surfactant several hours after delivery if the fractional inspiratory oxygen concentration was at least 0.40 or if the mean airway pressure was at least 0.686 kPa (7 cm of water), or both. Infants in both groups received additional doses of surfactant at intervals of 12 to 24 hours if these criteria were met. RESULTS: The proportion of infants surviving until discharge to their homes was significantly higher in the prophylaxis group than in the rescue-therapy group (88 vs. 80 percent, P = 0.028). This difference was due primarily to the longer survival of very premature infants (less than or equal to 26 weeks' gestation) in the prophylaxis group than in the rescue-therapy group (75 vs. 54 percent, P = 0.006). According to proportional-hazards regression analysis, the distribution of survival times was better for all infants in the prophylaxis group (P = 0.007) and for the subgroup of infants in the prophylaxis group who were delivered at 26 weeks' gestation or earlier (P = 0.0048). Infants in the prophylaxis group who were delivered at 26 weeks' gestation or earlier had a lower incidence of pneumothorax than similar infants in the rescue-therapy group (7 vs. 18 percent, P = 0.03). CONCLUSIONS: We found a significant advantage to the administration of the initial dose of surfactant as prophylaxis rather than as rescue therapy in very premature infants.

Antibody against leukocyte integrin (CD18) prevents reperfusion-induced lung vascular injury.

We studied the effects of pretreatment of rabbits with a monoclonal antibody (MoAb) IB4 directed against an epitope on the common beta-chain of leukocyte adhesion glycoprotein CD18 on the development of pulmonary edema following pulmonary artery occlusion and reperfusion. A balloon catheter occluded the right pulmonary artery in rabbits for 24 h, and the balloon was then deflated to allow reperfusion for 2 h. The lungs were removed, attached to a weighing balance, and perfused with Ringer-albumin solution (0.5 g/100 ml). IB4 (0.5 mg/kg) was infused 45 min before the start of reperfusion. In another experiment, we infused OKM-1 (0.5 mg/kg), a control MoAb directed against an irrelevant epitope on the alpha-chain of CD11b/CD18. IB4 prevented rabbit neutrophil adherence to pulmonary artery endothelial cells in vitro in response to a variety of stimuli, whereas OKM-1 was ineffective. Pulmonary artery occlusion and reperfusion increased the lung myeloperoxidase (MPO) content, whereas IB4 prevented the increase in MPO content. The increase in lung weight in the IB4-treated group (400 +/- 40 mg from baseline) was less (P less than 0.001) than in the untreated control group (1,400 +/- 90 mg) and the OKM-1-treated control group (1,320 +/- 125 mg). IB4 pretreatment also prevented the increase in pulmonary capillary filtration coefficient (a measure of capillary permeability to water) occurring in control and OKM-1-treated groups. The results indicate that neutrophil sequestration in the pulmonary microcirculation mediated by CD18 glycoprotein is a major determinant of reperfusion-induced lung vascular injury.