Bovine Surfactant Research Articles

Expression of the Carbohydrate Recognition Domain of Lung Surfactant Protein D and Demonstration of Its Binding to Lipopolysaccharides of Gram-Negative Bacteria

Surfactant protein D is a collagenous C-type lectin (collectin) that is found almost exclusively in the lung. A recombinant protein, composed of the neck-region and the carbohydrate binding domain of bovine lung surfactant protein D, has been overexpressed in E. coli. The recombinant protein showed the same sugar binding specificity as the native protein and was able to bind to the lipopolysaccharides of several strains of Gram-negative bacteria, such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli, which are known to cause lung infections. This binding was calcium-dependent and was inhibited by maltose. Native bovine surfactant protein D was also shown to be able to bind to these lipopolysaccharides in the same manner.

Reduction in lung injury after combined surfactant and high-frequency ventilation.

Previous studies demonstrated that high-frequency oscillatory ventilation (HFOV) begun at birth limits the development of alveolar proteinaceous edema in premature monkeys at risk for hyaline membrane disease (HMD). We hypothesized that exogenous surfactant combined with HFOV would lead to even further reductions in edema. Twenty Macaca nemestrina monkeys were delivered at 134 d gestation (term = 168 d) and treated with either HFOV or conventional mechanical ventilation (CMV) from the first breath; modified bovine surfactant (Survanta [beractant]) was introduced into the trachea over the first few minutes of life. These animals were compared with 20 animals treated with either CMV or HFOV but without surfactant. At 6 h the lung was rapidly frozen in situ during inflation for determination of the volume fraction of alveolar edema. The combined use of surfactant and HFOV from the first breath reduced alveolar proteinaceous edema (3 +/- 1%; mean +/- SEM) from that seen with CMV alone (27 +/- 3%, p < 0.0001), CMV after surfactant (21 +/- 3%, p < 0.0001), and HFOV alone (13 +/- 3%, p < 0.015). We conclude that the use of surfactant with HFOV after premature birth is superior to either surfactant or HFOV alone in reducing lung injury during the first few hours of life. We speculate that this reduction in lung injury may reduce the incidence or severity of bronchopulmonary dysplasia.

59 FACTORS ASSOCIATED WITH THE RESPONSE TO SURFACTANT REPLACEMENT THERAPY IN NEONATES WITH RDS

objective: Identification of factors associated with the response to surfactant replacement therapy in preterm neonates with RDS. Material - Methods: We prospectively studied 37 preterm neonates, 26 males and 11 females, ranging in GA from 23 to 34 weeks, with RDS. None neonate had received steroids prenatally and all had a score of radiographic severity >2. After initial stabilization they were treated with bovine surfactant (Alvofact*) at a dose of 100 mg/kg. Additional doses (each, 50mg/kg) were given if the neonate had an a/A PO2<20, 12 and 24 h later. Neonates were classified into responders (a/APO2 >30 or extubation at 24 h after the 1st dose and non responders (a/APO2 <30 or need for additional doses). This response pattern was analysed in relation to GA, BW, sex, perinatal ashyxia, pH on admission and at initiation of treatment, a/APO2, FiO2, ventilatory requirments and complications of RDS. Results: 20 neonates (GA=29.1±24 wk) were classified as responders and 17 (GA 29.8±20 wk) as non responders. Surfactant was given at a mean age of 7.7±8h and 11.3±6h to the two groups; respectively (>.05). The non responders had significantly lower mean pH on admission and mean a/APO2 before surfactant administration and higher incidence of PDA. There was also a trend for higher incidence of asphyxia, higher mean FiO2, mean airway pressure and peak inspiratory pressure in the group of the non responders. No difference was found with regard to GA, BW, sex, arterial pressure and pH at the time of surfactant administration. Conclusions: 1) The response is adversely affected by the low pH on admission, even when corrected before surfactant administration. 2) This response is also associated with the a/APO2, reflecting the severity of the disease, and the patency of ductus arteriosus.

336 Epidemiology and microbiology of congenital bacterial infections in VLBW-infants with respiratory failure

Background: Bacterial infections are considered to be a main factor for preterm birth. We analyzed the epidemiology of congenital bacterial infections on basis of data from three multicenter trials in VLBW-infants.Patients and Methods: Congenital bacterial infections were defined as clinical illness with positive blood culture (sepsis) or respiratory failure with positive bacteriological culture of the tracheal aspirate (congenital bacterial pneumonia), both samples taken within hour one following birth. VLBW-infants were enrolled in different trials of bovine surfactant (SF-RI1, Alveofact®) investigating efficacy, modifying factors, and dosing of the particular surfactant preparation.Results: A total of 453 VLBW-infants were enrolled (mean gestational age 27.9 ± 1 wks, mean birthweight 1022 ± 168 g; ± SD) all infants requiring intubation and mechanical ventilation during hour one following birth. Positive bacteriological cultures were obtained in 55 infants, (septicemia 20). The microbiologic data are given in table 1:Conclusion: The incidence of congenital bacterial infections was found in the range of 12%, with GBS and E. coli as the most frequently isolated germs. These findings have to be considered with respect to timing and selection of antimicrobial therapy.

Bovine conglutinin gene exon structure reveals its evolutionary relationship to surfactant protein-D.

Bovine conglutinin (BC), a member of the mammalian C-type collectin subfamily, is a serum protein synthesized in liver that is believed to play a role in natural host defense. Previously, we have characterized a full length BC cDNA and we now describe the partial characterization of a genomic clone that encodes for the BC gene (CGN1). BC is encoded by nine exons spanning > 11 kb and has been localized previously to band 18 of bovine (Bos taurus) chromosome 28. Genomic sequencing demonstrated that the signal peptide/amino-terminal domain, the carbohydrate recognition domain, and the linking peptide, a domain between the collagenous region and the carbohydrate recognition domain, are each encoded by a single exon. The collagenous domain is split into five exons, with the 5' most region being located within the exon that also encodes the signal peptide/amino terminus. The remaining four collagenous domain exons are tandemly arranged with lengths of 117, 108, 108, and 117 bp, respectively. Overall, the BC genomic organization is very similar to that of the human surfactant protein-D gene, SFTP4. On the basis of identical collagen domain structures, we suggest that conglutinin and bovine surfactant protein-D evolved from a gene duplication event occurring in Bovidae after divergence from other mammals.

Surface-area cycling of different surfactant preparations: SP-A and SP-B are essential for large-aggregate integrity.

Surface-area cycling is an in vitro procedure for the conversion of large into small surfactant aggregates. In this procedure a tube containing a surfactant suspension is rotated end-over-end at 37 degrees C so that the surface area of the suspension changes twice each cycle. We have utilized this method to study the mechanisms involved in aggregate conversion. Several different surfactant preparations were analysed: (1) bovine natural surfactant, a sucrose-gradient-purified material containing surfactant phospholipid and surfactant-associated proteins (SP-) SP-A, SP-B and SP-C; (2) bovine lipid-extract surfactant, which contains the surfactant phospholipids and SP-B and SP-C; (3) mixtures of dipalmitoyl phosphatidylcholine and phosphatidylglycerol (7:3, w/w) reconstituted with one or more surfactant proteins. Aggregate conversion was measured by phosphorus analysis of a 40,000 g supernatant (small aggregate) and pellet (large aggregates) before and after surface-area cycling. Surface-area cycling of lipid extract surfactant or lipids plus SP-B or SP-C resulted in rapid aggregate conversion. Lipids alone were not converted. Only a small percentage of purified natural surfactant was converted into small aggregates. Addition of SP-A to lipid extract surfactant could inhibit aggregate conversion of this material, but this was only observed when an additional 1% (w/w) of SP-B was added to the lipid extract. It is concluded that SP-A is important for large-aggregate integrity. It appears that SP-A acts in conjunction with SP-B. The presence of SP-B and/or SP-C is required for aggregate conversion; it is proposed that this reflects the necessity for lipid adsorption in aggregate conversion.

Two-year follow-up of infants treated for neonatal respiratory distress syndrome with bovine surfactant

In 1988 and 1989, a total of 1228 infants were studied in four double-blind, controlled, multidose clinical trials establishing the safety and efficacy of beractant (Survanta intratracheal suspension, Ross Products Division of Abbott Laboratories), a modified bovine lung extract, in prevention and treatment of neonatal respiratory distress syndrome in premature infants. Data on clinical status were collected for surviving infants at hospital discharge and at 6, 12, and 24 months of adjusted age. Significantly fewer beractant-treated infants required supplemental oxygen at discharge (p = 0.036). At 6 months of adjusted age, beractant-treated infants had more wheezing (p = 0.023) than control infants, a reduced need for supplemental oxygen (p = 0.019), and a lower incidence of cerebral palsy (p = 0.020). At 12 months of adjusted age, beractant-treated infants had less wheezing than control infants (p = 0.005), and this finding persisted at 24 months of adjusted age (p = 0.008). No circulating antibodies to the proteins present in beractant were found in serum samples at 6 and 12 months of age. These results suggest that the increased survival rate associated with beractant treatment is followed through 2 years of adjusted age by outcomes equivalent to those of untreated control infants.

Evaluation of lung function changes before and after surfactant application during artificial ventilation in newborn rats with congenital diaphragmatic hernia

Patients with congenital diaphragmatic hernia (CDH) have unilateral or bilateral hypoplasia of the lungs including delayed maturation of the terminal air sacs. Because these lungs are highly susceptible to barotrauma and oxygen toxicity, even in full-term newborns, continued research into optimal ventilatory regimen is essential to improve survival rate and to prevent ongoing lung damage. Against this background, the effect of exogenous surfactant application is evaluated. In newborn rats, CDH was induced after a single dose of 2,4 dichloro-4′-nitrophenyl (Nitrofen) (400 mg/kg) on day 10 of gestation. The newborn rats were intubated immediately after hysterotomy, transferred to a heated multichambered body plethysmograph, and artificially ventilated. Inspiratory peak pressures were initially set at 17 cm H 2O, with positive end-expiratory pressure at 0 cm H 2O and Fio 2 at 1.0. The pressure was raised in steps of 5 cm H 2O, from 5 to 30 cm H 2O, to obtain pressure-volume diagrams at 0, 1, and 6 hours of artifical ventilation. These measurements were obtained in controls and in CDH rats with and without endotracheal installation of bovine surfactant (n = 4 to 10 in each group). Significant differences in lung volume between CDH and control rats were observed at all time-points. Surfactant application had a positive effect on lung volume, especially in control rats at t = 1 hour. No significant differences were observed between the CDH groups at t = 1 or t = 6 hours. In this animal model, the effect of artificial ventilation as well as the beneficial short-term effect of exogenous surfactant application have been evaluated. A continued positive effect on lung volume in CDH lungs could not be determined. Routine administration of exogenous surfactant in human CDH patients is not supported by these experimental results.

Effect of a Bovine Lung Surfactant Protein Isolate (SP-B/C) on Egg Phosphatidylglycerol Acyl Chain Order in a Lipid Mixture with Dipalmitoylphosphatidylcholine and Palmitic Acid

Dynamic surface tension measurements of films of a d621,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine:L-α-phosphatidyl-DL-glycerol:d31palmitic acid (d62-DPPC:EggPG:d31-PA) lipid matrix in the presence of a bovine pulmonary surfactant protein isolate (SP-B/C) demonstrate the improved surface activity over that of the lipids alone. Thus, significant interaction of the proteins with the lipid matrix is demonstrated. The effect of SP-B/C on the acyl chain order of the negatively charged EggPG within a d62-DPPC:EggPG:d31-PA lipid matrix in D2O saline was investigated in thermal perturbation Fourier transform IR spectroscopic studies. The EggPG thermotropic phase behavior was determined independently of the other lipid components with perdeuterated lipids and D2O. The data demonstrate the high degree of EggPG acyl chain disorder in the absence of the protein isolate. A broad transition occurs between 30 and 40 °C. The addition of the protein isolate did not alter the acyl chain order at 0.281 and 1.46 mg/mL of protein. However, alterations in the lipid carbonyl vibrational mode were observed.

Primary structure of bovine collectin-43 (CL-43). Comparison with conglutinin and lung surfactant protein-D.

Collectin-43 (CL-43) is a bovine serum protein that is composed of subunits of three identical chains, each of which contains a collagen region and a C-type carbohydrate recognition domain; thus, CL-43 belongs to the collectins (group III of the C-type lectins). We have derived the complete primary sequence of CL-43 using partial protein sequencing, cDNA cloning, and reverse transcription-polymerase chain reaction techniques. The primary sequence of CL-43 shows that it contains an N-terminal region of 28 residues, followed by a collagenous domain of 38 repeats of Gly-Xaa-Yaa and then a C-terminal section of 159 residues, containing a short "neck" region and the carbohydrate recognition domain with the conserved residues found in all C-type lectins. The amino acid sequence of CL-43 showed 74% identity to bovine conglutinin and 70% identity to bovine lung surfactant protein D (SP-D), but the collagen region is considerably shorter than the 57 Gly-Xaa-Yaa triplets found in conglutinin and SP-D. Northern blot analysis showed that CL-43 was only synthesized in bovine liver, with no detectable signal in a variety of other bovine tissues, including lung. No cross-hybridizing signals were detected in mRNA from sheep, human, rat, or mouse liver. Since CL-43 and conglutinin have only been detected in members of bovidae, it is probable that an ancestral gene of these two proteins was first derived from a SP-D-like gene, and that this ancestral gene duplicated during evolution.

Comparison of captive and pulsating bubble surfactometers with use of lung surfactants

We compared surface tension measures of surfactants with various surface activities by using a pulsating bubble surfactometer (PBS) and a captive bubble surfactometer (CBS). Rabbit lung lavage surfactant (60,000 x average g for 60 min), bovine surfactant extract (Survanta), and a synthetic lipid surfactant mixture (dipalmitoylphosphatidylcholine-egg phosphatidylglycerol-palmitic acid) were studied at 1.25 mg phospholipid/ml. The PBS was used either unmodified according to manufacturer's instructions or with the sample chamber capillary kept dry and the sample adsorbing at maximum bubble size (5 min). The CBS was used in a manner that imitated the unmodified PBS. We found that all three techniques indicated low surface tension on the first cycle for 60K. For Survanta, the CBS and the modified PBS reported low surface tension on the first cycle, whereas the unmodified PBS did not achieve this within 10 cycles. For the synthetic lipid surfactant mixture, only the CBS measured low surface tension within 10 cycles. Video observations indicate that the modified PBS performs better than the unmodified PBS because keeping the capillary dry prevents surface film from occupying this large surface during cycling, thereby allowing larger area compressions.

Characterization of exosurf (surfactant)-mediated suppression of stimulated human alveolar macrophage cytokine responses.

Previous studies in our laboratory demonstrated that the synthetic surfactant Exosurf (Burroughs Wellcome Co.) inhibited endotoxin-stimulated cytokine secretion from human alveolar macrophages in vitro. The purpose of the present study was to further characterize the suppressive effects of Exosurf, which consists of dipalmitoylphosphatidylcholine (DPPC), cetyl alcohol (spreading agent), and tyloxapol (nonionic dispersing agent). Suppression was not stimulus specific in that Exosurf also significantly reduced cytokine production elicited by either Staphylococcus aureus or recombinant interleukin-1. Suppression was also mediated by a modified bovine surfactant (Survanta), which, in contrast to Exosurf, contains the surfactant-associated proteins B and C, and several different phospholipids, but no cetyl alcohol or tyloxapol. This suggests that suppression of macrophage cytokines is not specific to Exosurf. Both cell associated and secreted tumor necrosis factor and interleukin-1 were reduced by Exosurf, indicating that Exosurf is not simply blocking cytokine release. At 3 h, cytokine mRNA levels were not different between Exosurf-treated and untreated cells. However, at 8 and 24 h, cytokine mRNA levels were lower in Exosurf-treated cells. The observations that mRNA levels were decreased at 8 and 24 h and that cellular cytokine release was not blocked suggest that Exosurf's effect may in part be pretranslationally mediated. Collectively, these data add to previous work indicating that pulmonary surfactant may play a critical role in reducing inflammatory cytokine production associated with the adult respiratory distress syndrome and similar disorders.

Bovine conglutinin (BC) mRNA expressed in liver: cloning and characterization of the BC cDNA reveals strong homology to surfactant protein-D.

Bovine conglutinin (BC) is a C-type lectin isolated from bovine serum that appears to play a role in first-line host defense. The BC cDNA was cloned from a bovine liver library and the nucleotide (nt) sequence of 1519 bp was determined. The longest open reading frame encoded a 20-amino-acid (aa) signal sequence and a mature protein of 351 aa. Analysis of the nt and deduced aa sequences revealed 87 and 78% identity, respectively, with the sequences of another vertebrate lectin: bovine surfactant protein-D (SP-D). Of interest, the expression of the BC mRNA, as determined by RNase protection assay, is restricted to liver, unlike bovine SP-D, a lung-surfactant protein.

Bovine Surfactant in Full-Term Neonates With Adult Respiratory Distress Syndrome-like Disorders

Kammash and co-workers described the effects of natural surfactant (BLSE) in full-term neonates1 suffering from adult respiratory distress syndrome (ARDS)-like disorders.2 Due to paucity of further published data,3 we would like to confirm the aforementioned studies by our observations in neonates. Full-term newborns were eligible for the pilot trial, if severe ARDS-like disorder was diagnosed: Fio2 0.9 to 1.0 for Pao2 &amp;gt;50 mm Hg; peak inspiratory pressure (PIP) 35 cm H2O for Paco2 50 mm Hg.

Effect of pulmonary surfactant protein A (SP-A) and calcium on the adsorption of cholesterol and film stability

The effect of exogenous cholesterol on the stability of surface films at 37°C from various surfactants was studied with the pulsating bubble surfactometer. Addition of cholesterol (5%, w/w) to bovine lipid extract surfactant (bLES) or mixtures of dipalmitoylphosphatidylcholine/1-palmitoyl-2-oleoyl-phosphatidylglycerol/SP-B (7:3:1%) dispersed in 1.5 mM CaCl 2/0.9% NaCl resulted in unstable surface films. Although 10% cholesterol only partially impaired the surface activity of bLES, it virtually abolished that of the reconstituted surfactant. The inhibitory effects of cholesterol were significantly repressed by SP-A (10%, w/w of lipid) and 3 mM CaCl 2 or 5 mM CaCl 2 without SP-A. Adsorption of cholesterol from various surfactants into the air/water interface was examined by measuring the surface radioactivity of [ 14C]cholesterol. Cholesterol alone dispersed in 1.5 mM CaCl 2/0.9% NaCl could not adsorb to the interface, but it adsorbed readily when mixed with bLES. Cholesterol adsorption was markedly suppressed by SP-A in 3 mM CaCl 2/0.9% NaCl or 5 mM CaCl 2/0.9% NaCl without SP-A. Electron microscopy revealed striking ultrastructural differences between bLES/5% cholesterol/10% SP-A in 3 mM CaCl 2/0.9% NaCl and bLES/5% cholesterol in 3 or 5 mM CaCl 2/0.9% NaCl. The former exhibited large multilayer and small unilamellar vesicles, while the latter displayed condensed patches of aggregates. Adsorption studies showed aggregated patches adsorbed more rapidly than vesicles but attained lower equilibrium surface pressures. These results indicate SP-A and calcium limit the adsorption of surfactant cholesterol to the air-water interface.

Surfactant (beractant) therapy for infants with congenital diaphragmatic hernia on ECMO: Evidence of persistent surfactant deficiency

Infants with congenital diaphragmatic hernia (CDH) on extracorporeal membrane oxygenation (ECMO) can have initial lung atelectasis which, in survivors, gradually improves over time. To test the hypothesis that these patients could benefit from surfactant therapy, infants with CDH (born at >34 weeks' gestation) on ECMO received either four doses of modified bovine lung surfactant extract (beractant) (surfactant group, n = 9) or an equal volume of air (control group, n = 8). Tracheal aspirate surfactant protein-A (SP-A) concentrations were initially low, and then increased over time in both CDH groups ( P = .0021); however, levels remained low when compared with those of infants on ECMO who had other diagnoses ( P = .04). Lung compliance (C L), time to extubation, time on oxygen, and total no. of hospital days were not different between the two groups. Infants with CDH had persistently elevated right ventricular pressure (RVP) at cessation of bypass when compared with non-CDH infants on ECMO (RVP = 53.25 mm Hg ± 19.52 in the CDH group, 32.90 ± 10.63 in the non-CDH group; P = .0121). The findings suggest that the postnatal surfactant deficiency may be more persistent in CDH infants than in non-CDH infants on ECMO. However, CDH remains a multifactorial condition, with delayed improvement, because of persistence of pulmonary hypertension, difficulties with vascular remodeling, degree of lung hypoplasia, or compromised respiratory mechanics.

Inhibition of Trimeresurus flavoviridis phospholipase A 2 by lung surfactant protein A (SP-A)

A marked sequence homology has been noted between lung surfactant protein A (SP-A) and an inhibitor of phospholipase A 2 (PLA 2) isolated from the serum of Trimeresurus flavoviridis (Habu snake). This study evaluated the effect of SP-A on PLA 2 activity from several sources. SP-A was isolated from bovine or rat lung surfactant by extraction with 1-butanol and octyl β- d-glucopyranoside. The addition of SP-A produced a concentration-dependent inhibition of T. flavoviridis PLA 2 that indicated non-competitive kinetics with K i 5 μg/ml. Inhibition was reversed by heat inactivation, disulfide bond reduction or alkylation of SP-A, or by the presence of anti-SP-A antibody. Treatment of SP-A with endoglycosidase F or the presence of various monosaccharides or lectins did not alter SP-A inhibition. Binding of PLA 2 to SP-A was shown by ultrafiltration and was abolished by SP-A alkylation or the presence of SDS. The SP-A/PLA 2 complex recovered from the ultrafilter had essentially no enzymatic activity, but activity was restored by treatment with mercaptoethanol. SP-A had no effect on activity of PLA 2 from Naja naja, Crotalus atrox, or bovine pancreas. These results indicate that surfactant protein A selectively inhibits Trimeresurus phospholipase A 2 activity and suggest that binding to the enzyme is the mechanism for inhibition.

Inhaled nitric oxide in infants referred for extracorporeal membrane oxygenation: Dose response

To determine the role of inhaled nitric oxide (NO) in a population of critically ill hypoxic near-term infants and to determine the dose response to inhaled NO, we examined a consecutive group of 23 infants referred for neonatal extracorporeal membrane oxygenation (ECMO) who had an oxygen index of 20 or greater after treatment with bovine surfactant. Inhaled NO was administered in concentrations from 5 to 80 ppm in random order to 23 infants. Overall, 13 infants had a significant response (an improvement in arterial oxygen pressure > 10 mm Hg or arterial oxygen saturation > 10%) to the first administration of inhaled NO, and one infant had a late response. There was no significant difference in the response to inhaled NO as measured by changes in arterial oxygen pressure or in the alveolar-arterial difference in partial pressure of oxygen, for any of the doses from 5 to 80 ppm. Thirteen infants had echocardiographic evidence of persistent pulmonary hypertension; 11 of these infants responded, compared with 3 responders among the 10 infants without persistent pulmonary hypertension of the newborn ( p < 0.01). Overall, 11 infants required ECMO; there were two deaths in this group. Seven infants had congenital diaphragmatic hernia; five of those had a response to NO inhalation and four required ECMO. Our study demonstrates that there is no significant difference in response between low and high doses of inhaled NO and that this treatment may prevent the need for ECMO in some infants referred for this therapy, especially in infants with pulmonary hypertension. Prospective, controlled, randomized, and blinded trials of low doses of inhaled NO are needed to determine the clinical role of this potentially useful therapy. (J P EDIATR 1994;124:302-8)

High‐dose versus low‐dose bovine surfactant treatment in very premature infants

The aim of the study was to determine if high-dose bovine surfactant (Alveofact, initially 100 mg/kg birth weight) would improve oxygenation compared with low-dose surfactant (50 mg/kg birth weight) administered intratracheally within 1 h after birth. Inclusion criteria included gestational age 24-29 weeks and birth weight 500-1500 g, intubation and mechanical ventilation, absence of congenital malformations and bacterial infections. Retreatment was considered if the fraction of inspired oxygen (FiO2) was > 0.4 (dose 50 mg/kg birth weight). The primary endpoint was level of oxygenation (PaO2/FiO2) 2 h after treatment. The study design was a sequential analysis using a triangular test with alpha = 0.05 and 95% power to detect a 25% improvement in the endpoint. Oxygenation was improved significantly with high-dose (n = 42) compared to low-dose treatment (n = 48): 30.9 +/- 15.0 kPa (231.5 +/- 112.7 mmHg) versus 24.1 +/- 15.7 kPa (180.6 +/- 118.0 mmHg) (mean +/- SD). The survival rate was 83% in both groups and the incidence of pulmonary interstitial emphysema was 33% versus 14% with the high-dose treatment. We conclude that high-dose surfactant significantly improved oxygenation and reduced lung barotrauma. An initial dose greater than 50 mg/kg birth weight of surfactant is required for optimal acute response.

Successful Surfactant Replacement Therapy in Two Infants with ARDS due to Chlamydial Pneumonia

We report two cases of adult respiratory distress syndrome (ARDS) treated successfully with repeated doses of a bovine natural surfactant (Survanta). Two former premature infants developed severe respiratory failure as a consequence of a chlamydial pneumonia at the age of 3 or 12 weeks, respectively. As both patients were threatened by hypoxia in spite of mechanical ventilation with maximal pressures using 100% O2 and as the X-rays were compatible with the diagnosis of ARDS, we decided to perform rescue surfactant treatment. Following surfactant instillation, marked improvement in oxygenation and ventilatory requirements was observed. Within 2 h after surfactant replacement, the PaO2/FiO2 ratio increased from 52 to 84 (case 1) and from 35 to 94 (case 2), and the peak inspiratory pressure could be reduced from 47 to 40 cm H2O and from 35 to 28 cm H2O, respectively. Both infants received a second surfactant dose about 10 h after the initial treatment and survived without developing chronic lung disease.