Bronchoalveolar lavage with a diluted surfactant suspension prior to surfactant instillation improves the effectiveness of surfactant therapy in experimental acute respiratory distress syndrome (ARDS).

OBJECTIVE: To assess whether bronchoalveolar lavage (BAL) with a diluted surfactant suspension prior to surfactant instillation prevents the only transient improvement in lung function as reported after surfactant instillation in severe acute respiratory distress syndrome (ARDS). DESIGN: Randomized, prospective, experimental study. SETTING: Laboratory and animal facility of a large university. MATERIALS: Adult male Sprague-Dawley rats (280 +/- 30 g). INTERVENTIONS: All animals underwent repetitive whole lung saline lavage to induce acute lung injury. Then, animals were randomly divided into seven study groups: the first group received surfactant (150 mg/ kg) within 10 min after the last lavage (early treatment), whereas in the other six groups mechanical ventilation was continued for 3 h before treatment (late treatment). Treatment consisted of: surfactant instillation at a dose of 150 mg/kg; at a dose of 250 mg/kg; BAL with saline; BAL with a diluted surfactant suspension (2.5 mg/ml); BAL with saline, immediately followed by surfactant instillation (150 mg/kg) and BAL with a diluted surfactant suspension (2.5 mg/kg), immediately followed by surfactant instillation (150 mg/kg). MEASUREMENTS AND RESULTS: Blood gases were measured for 6 h and then BAL was performed to measure the protein concentration and surface tension properties. Mean PaO2 values increased immediately after surfactant instillation to pre-lavage values but remained stable only in the group that received surfactant immediately after the lavage procedure and the group that underwent BAL with a diluted surfactant suspension prior to surfactant instillation. CONCLUSION: BAL with a diluted surfactant suspension prior to surfactant instillation at a later time point in lung injury resulted in a stable improvement of lung function. This improvement is comparable with the results seen after surfactant instillation immediately after lung lavage.

In vivo evaluation of the inhibitory capacity of human plasma on exogenous surfactant function.

OBJECTIVE: The adult respiratory distress syndrome (ARDS) and neonatal respiratory distress syndrome (RDS) are characterized by high permeability pulmonary edema which contains plasma-derived proteins inhibiting pulmonary surfactant function. Currently, discussion continues as to what dose of surfactant is required for treatment of these syndromes. DESIGN: The purpose of this study was to investigate the amount of exogenous surfactant needed to overcome the inhibitory components in human plasma. Male adult rats suffering from respiratory failure due to surfactant depletion after whole-lung lavage received human plasma (4 ml/kg body weight) mixed with surfactant at different concentrations, intratracheally. Rats receiving surfactant only at different concentrations served as controls. Blood gas analysis was performed. MEASUREMENTS AND RESULTS: It was demonstrated that plasma (4 ml/kg-273 mg plasma proteins/kg) mixed with surfactant at 300 mg/kg was able to increase and maintain PaO2 at normal values. Plasma mixed with surfactant at 100 mg/kg, after initial restoration of blood gases, showed deterioration of PaO2 values. Plasma mixed with surfactant at a dose of 50 mg/kg did not improve PaO2 whereas surfactant at 50 mg/kg, without plasma, restored blood gases to pre-lavage values. CONCLUSION: It is concluded that approximately 1 mg surfactant phospholipids is required to overcome the inhibitory effect of approximately 1 mg plasma proteins. For clinical practice this means that an excess of surfactant should be given, or repeatedly be substituted ("titrated") at low concentrations, until blood gases improve.

Surfactant treatment of respiratory failure induced by hydrochloric acid aspiration in rats.

BACKGROUND: The surfactant system seems to be involved in the pathophysiology of respiratory failure caused by hydrochloric acid (HCl) aspiration. This study was an investigation of the effect of different treatment strategies using an exogenous surfactant preparation on lung function of rats suffering from respiratory failure after intratracheal HCl instillation. METHODS: In rats anesthetized with halothane, nitrous oxide, and oxygen, tracheotomy was performed and the lungs were mechanically ventilated. Respiratory failure was induced by intratracheal instillation of HCl (0.1 N, 3 ml/kg). After the PaO2 decreased to < 200 mmHg, the animals were randomly divided into five groups. Group I received no treatment; group II received a natural surfactant preparation intratracheally (200 mg/kg); group III underwent bronchoalveolar lavage (BAL) with saline, followed by surfactant treatment (200 mg/kg); and groups IV and V underwent BAL with saline and a diluted surfactant suspension (3.3 mg/ml in 30 ml/kg), respectively. Groups IV and V received a second and third BAL 60 and 120 min after the first lavage. Blood gas analysis and protein measurements in BAL fluids were performed. RESULTS: Gas exchange improved in Groups III and V only. Protein concentrations were high in all BAL fluids. In the rats receiving BAL three times (groups IV and V), a decrease in protein concentration was observed. CONCLUSIONS: From these results, it was concluded that plasma-derived proteins (which are known to inhibit surfactant function) are washed out of the alveoli by BAL, resulting in improved efficacy of surfactant treatment.

Prevention of respiratory failure after hydrochloric acid aspiration by intratracheal surfactant instillation in rats.

Because the surfactant system probably is involved in the pathophysiology of respiratory failure caused by hydrochloric acid (HCl) aspiration, we investigated the effects of different ventilation strategies and intratracheal surfactant instillation at different time intervals on the course of pulmonary gas exchange after HCl aspiration in rats. In this study rats were anesthetized and mechanically ventilated via a tracheostomy. Respiratory failure was induced by intratracheal instillation of 3 mL/kg 0.1 N HCl. Animals (n = 49) were divided into nine groups: Groups 1 and 2 through 9 were ventilated with peak airway pressure/positive end-expiratory pressure of 14/2 and 26/6 cm H2O, respectively; Groups 3 and 4 received surfactant (200 mg/kg) intratracheally, 1 and 10 min after HCl aspiration; Groups 5 and 6 received saline, 1 and 10 min after HCl aspiration; Groups 7 and 8 received surfactant, 60 and 90 min after HCl aspiration; Group 9 received saline instead of HCl. Gas exchange deteriorated in Groups 1, 2, 5, 6, 7, and 8, whereas respiratory failure could be prevented in Groups 3 and 4. After deterioration of gas exchange, surfactant treatment prevented further decrease of PaO2 values in Group 7, whereas no effect on gas exchange was observed in Group 8; intratracheal instillation of saline had no effect on gas exchange (Group 9). These results suggest that surfactant should be given as early as possible after aspiration of gastric contents to prevent development of respiratory failure.

Surfactant replacement therapy improves pulmonary mechanics in end-stage influenza A pneumonia in mice.

Surfactant replacement therapy may be a promising approach for treatment of respiratory failure caused by viral pneumonia. This study in mice demonstrates that during the development of lethal influenza A pneumonia, thorax-lung compliance (Ctl/kg) and lung volume at 5 cm H2O PEEP (V5/kg) significantly decrease (28 and 54%, respectively), whereas lung water content significantly increases (25%). Surfactant replacement therapy during the end stage of pneumonia significantly increases Ctl/kg (31%) and V5/kg (21%). Instillation of the vehicle for surfactant in control animals does not significantly affect Ctl/kg (5% decrease), but it significantly decreases V5/kg (25% decrease). Further, a new method for postmortem measurement of lung volumes in small laboratory animals based on Archimedes' principle is presented.

Improvement of pulmonary gas exchange after surfactant replacement in rats with Pneumocystis carinii pneumonia.

The effect of intratracheal surfactant instillation on pulmonary function in rats with pneumocystis carinii pneumonia (PCP) was investigated. In these animals which developed PCP with severe respiratory failure after s.c. administration of cortisone acetate over 8-12 weeks, pulmonary function could be improved by surfactant instillation, as measured by an increase in PaO2. Histological examination showed that alveoli of rats with PCP which received no surfactant treatment are filled with foamy edema, whereas after surfactant treatment alveoli are stabilized and well-aerated. These results indicate that surfactant therapy could be used in patients with severe PCP to overcome an acute stage of respiratory distress while at the same time surfactant could serve as a carrier substance for antimicrobial drugs to attain high intra-alveolar and low systemic antimicrobial drug concentrations.

A new catheter for quasi-continuous measurement of arterial partial oxygen pressure.

Recently a catheter has been developed based on amperometric measurement principle for in vivo monitoring of PaO2. A study in pigs was performed to compare the cell with a standard method for measuring PaO2. The results show that the cell is capable to accurately measure PaO2.

Acute respiratory failure during pneumonia induced by Sendai virus.

In this study a model of acute respiratory failure due to viral pneumonia in rats, closely resembling ARDS, is presented. Severe respiratory failure with lethal outcome in four days was induced by infection concentrated Sendai virus aerosol. This model permits evaluation of different therapeutical approaches for improving gas exchange during ARDS. Furthermore, preliminary results of surfactant substitution therapy in this model are presented.

In vivo and in vitro inactivation of bovine surfactant by an anti-surfactant monoclonal antibody.

In this study the importance of a low-weight surfactant protein (11 kDa) is demonstrated by selectively blocking this protein with a monoclonal antibody. In adult rats respiratory failure was induced by repeated bronchoalveolar lavage to remove all pulmonary surfactant. It was shown that surfactant mixed with the antibody was not capable of restoring lung function when compared with surfactant alone or surfactant mixed with control serum. Using the pulsating bubble surfactometer, it could be demonstrated that surfactant mixed with this antibody had a significant higher minimum surface tension when compared with surfactant alone, or surfactant mixed with an unrelated mouse immunoglobulin G (IgG). The inhibition of surfactant function by the monoclonal antibody suggests the importance of the 11 kDa protein for normal surfactant function.

Intratracheal surfactant administration restores gas exchange in experimental adult respiratory distress syndrome associated with viral pneumonia.

The effect of intratracheal surfactant administration was studied in rats with adult respiratory distress syndrome associated with infection with nebulized Sendai virus. Thirty-six hours after infection, animals (n = 7) showed severely impaired gas exchange and acidosis during artificial ventilation (PaO2 = 152.2 +/- 18.7, PaCO2 = 65.3 +/- 19.2, pH = 7.26 +/- 0.11) with a pressure-controlled mode, standard frequency of 35/min, peak airway pressure of 15 cm H2O (15/0), inspiratory/expiratory ratio of 1:2, and F1O2 = 1. Gas exchange improved (P = 0.02) with increased ventilator pressures with PEEP (25/4). Forty-eight hours after infection, blood gas tensions could no longer be significantly improved by these same ventilator settings (PaO2 = 123.8 +/- 31.0, PaCO2 = 95.1 +/- 43.6, pH = 7.12 +/- 0.16, n = 9). At this time, surfactant replacement dramatically increased arterial oxygenation within 5 min (PaO2 = 389.4 +/- 79.9) and resulted in a fourfold increase in PaO2 within 2 h. It is concluded that intratracheal surfactant administration is a promising approach in the treatment of respiratory failure during adult respiratory distress syndrome associated with viral pneumonia.

Effects of antisurfactant antibodies on the course of mild respiratory distress syndrome.

The role of surfactant-associated proteins in surfactant function was studied by selectively blocking these proteins with monoclonal antibodies. Four monoclonal antibodies, M1, M2, M3, and M4 were identified and their reactivities examined by Western blot analysis. M1, M2, and M4 bind, respectively, 8-, 10- and both 10- and 34-kD proteins. M3 antibody did not recognize a protein as assayed by this technique. These antibodies were then administered intratracheally to adult rats that had been partially depleted of lung surfactant by broncholavage. None of these antibodies had any deleterious effect on pulmonary function. On the other hand, M4 antibody significantly improved gas exchange. Possible mechanisms by which antibody may effect such improvement are discussed.

Effect of surfactant replacement on Pneumocystis carinii pneumonia in rats.

The effect of intratracheal surfactant instillation on pulmonary function in rats with Pneumocystis carinii pneumonia (PCP) was investigated. In those animals which developed PCP with severe respiratory failure after administration of cortisone acetate s.c. over 8-12 weeks, pulmonary function was improved by surfactant instillation. PaO2 values 30 min after surfactant instillation were significantly higher compared to pretreatment values and also compared to PaO2 values of rats 30 min after receiving saline (482.9 mmHg +/- 44.7, 170.7 mmHg +/- 39.3 and 67.2 mmHg +/- 17.4, respectively). Histological examination showed that alveoli of rats with PCP which received no exogenous surfactant are filled with foamy edema, whereas after exogenous surfactant alveoli are stabilized and well-aerated. These results indicate that exogenous surfactant may help patients with severe PCP to overcome an acute stage of respiratory distress.

Online measurements of SaO2, Ht and Hb using a micro transmission cell.

Recently a Micro Transmission Cell has been developed based on spectrophotometry for in vivo monitoring of SaO2 together with Hb. A study in pigs was performed to compare the cell with standard methods for measuring SaO2, Hb and Ht. The results show that the cell is capable of following the trends of SaO2, Hb and Ht at different Hb concentrations and/or O2 saturations.