Abstract
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.
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References
Ennema JJ, Kobayashi T, Robertson B, Curstedt T (1988) Inactivation of exogenous surfactant in experimental respiratory failure induced by hyperoxia. Acta Anaesthesiol Scand 32:665–671
Ikegami M, Jacobs H, Jobe A (1983) Surfactant function in respiratory distress syndrome. J Pediatr 102:443–447
Johnson JWC, Permutt S, Sipple JH, Salem ES (1964) Effect of intra-alveolar fluid on pulmonary surface tension properties. J Appl Physiol 19:769–777
Kobayashi T, Ganzuka M, Tanigushi J, Nitta, K, Murakami S (1990) Lung lavage and surfactant replacement for hydrochloric acid aspiration in rabbits. Acta Anaesthesiol Scand 34:216–221
Kobayashi T, Nitta K, Ganzuka M, Inui S, Grossmann G, Robertson B (1991) Inactivation of exogenous surfactant by pulmonary edema fluid. Pediatr Res 29:353–356
Said SI, Avery ME, Davis RK, Banerjee CM, El-Cohary M (1965) Pulmonary surface activity in induced pulmonary edema. J Clin Invest 44:458–464
Seeger W, Stöhr, G, Wolf HRD, Neuhof H (1985) Alteration of surfactant function due to protein leakage: special interaction with fibrin monomer. J Appl Physiol 58:326–338
Guyton AC, Moffatt DS, Adair TH (1984) Role of alveolar, surface tension in transepithelial movement of fluid. In: Robertson B, Van Golde LMG, Batenburg JJ (eds) Pulmonary surfactant. Elsevier, Amsterdam, pp 171–185
Fujiwara T, Chida S, Watabe Y, Maeta H, Morita T, Abe T (1980) Artificial surfactant therapy in Hyaline-Membrane Disease. Lancet I:55–59
Hallman M, Merritt TA, Jarvenpaa A-L, Boynton B, Mannino F, Gluck L, Moore T, Edwards D (1985) Exogenous human surfactant for treatment of severe respiratory distress syndrome: a randomized clinical trial. J Pediatr 106:963–969
Konishi M, Fujiwara T, Naito T, Takeuchi Y, Ogawa Y, Inukai K, Fujimura M, Nakamura H, Hashimoto T (1988) Surfactant replacement therapy in neonatal respiratory distress syndrome: a multi-centre, randomized clinical trial: comparison of high-versus low-dose of surfactant TA. Eur J Pediatr 147:20–25
Collaborative European Multicenter Study Group (1988) Surfactant replacement therapy for severe neonatal, respiratory distress syndrome: an international randomized clinical trial. Pediatrics 82:683–691
Ten Centre Study Group (1987) Ten centre trial of artificial surfactant (artificial lung expanding compound) in very premature babies. Br Med J 294:991–996
Dunn MS, Shennan AT, Possmayer F (1990) Single-versus multipledose surfactant replacement therapy in neonates of 30 to 36 weeks' gestation with respiratory distress syndrome. Pediatrics 86:564–571
Lachmann B (1987) The role of pulmonary surfactant in the pathogenesis and therapy of ARDS. In: Vincent JL (ed) Update in intensive care and emergency medicine. Springer, berlin Heidelberg New York Tokyo, pp 123–134
Nosaka S, Sakai T, Yonekura M, Yoshikawa K (1990) Surfactant for adults with respiratory failure. Lancet I:947–948
Richman PS, Spragg RG, Robertson B, Merritt TA, Curstedt T (1989) The adult respiratory distress syndrome: first trials with surfactant replacement. Eur Respir J 2 [Suppl 3]:109s-111s
Marraro G (1991) Respiratory emergencies and supplementary surfactant in the treatment of severe RDS in leukaemic adolescents. In: Cosmi EV, Di Renzo GC, Anceschi MM (eds) The surfactant system of the lung: prevention and treatment of neonatal and adult respiratory distress syndrome. Macmillan, London, pp 198–206
Joka Th, Obertacke U (1989) Neue medikamentöse Behandlung im ARDS: Effekt einer intrabronchialen xenogenen Surfactantapplikation. Z Herz Thorax Gefäßchir 3 [Suppl 1]: 21s-24s
Lachmann B, Robertson B, Vogel J (1980) In vivo lung lavage as an experimental model of the respiratory distress syndrome. Acta Anaesthesiol Scand 24:231–236
Berggren P, Lachmann B, Curstedt T, Grossmann G, Robertson B (1986) Gas exchange and lung morphology after surfactant replacement in experimental adult respiratory distress syndrome induced by repeated lung lavage. Acta Anaesthesiol Scand 30:321–328
Robertson B, Lachmann B (1988) Experimental evaluation of surfactants for replacement therapy. Exp Lung Res 14:279–310
Lachmann B, Jonson B, Lindroth M, Robertson B (1982) Modes of artificial ventilation in severe respiratory distress syndrome. Lung function and morphology in rabbits after wash-out of alveolar surfactant. Crit Care Med 10:724–732
Metcalfe IL, Enhorning G, Possmayer F (1980) Pulmonary surfactant-associated proteins: their role in the expression of surface activity. J Appl Physiol 49:34–41
Van Daal GJ, So KL, Gommers D, Eijking EP, Fiévez RB, Sprenger MJ, Van Dam DW, Lachmann B (1991) Intratracheal surfactant administration restores gas exchange in experimental adult respiratory distress syndrome associated with viral pneumonia. Anesth Analg 72:589–595
Eijking EP, Van Daal GJ, Tenbrinck R, Luijendijk A, Sluiters JF, Hannappel E, Lachmann B (1991) Effect of surfactant replacement on pneumocystis carinii pneumonia in rats. Intensive Care Med 17:475–478
Van Daal GJ, Bos JAH, Eijking EP, Gommers D, Hannappel E, Lachmann B (1992) Surfactant replacement therapy improves pulmonary mechanics in end-stage influenza A pneumonia in mice. Am Rev Respir Dis 145:859–863
Bos AP, Tibboel D, Hazebroek FWJ, Molenaar JC, Lachmann B, Gommers D (1991) Surfactant replacement therapy in high-risk congenital diaphragmatic hernia. Lancet I:1279
Markwell MAK, Haas SM, Bieber LL, Tolbert NE (1978). A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal Biochem 87:206–210
Robertson B, Berry D, Curstedt T, Grossmann G, Ikegami M, Jacobs H, Jobe A, Jones (1985). Leakage of protein in the immature rabbit lung; effect of surfactant replacement. Respir Physiol 61:365–276
Hallman M, Spragg R, Harrell JH, Moser KM, Gluck L (1982) Evidence of lung function abnormality in respiratory failure. Study of bronchoalveolar lavage phospholipids, surface activity phospholipase activity, and plasma myoinositol. J Clin Invest 70:673–683
Gregory TJ, Longmore WJ, Moxley MA, Whitsett JA, Reed CR, Fowler AA, Hudson LD, Maunder RJ, Crim C, Hyers TM (1991) Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome. J Clin Invest 88:1976–1981
Petty TL, Reiss OK, Paul GW, Silvers GW, Elkins ND (1977) Characteristics of pulmonary surfactant in adult respiratory distress syndrome associated with trauma and shock. Am Rev Respir Dis 115:531–536
Pison U, Seeger W, Buchhorn R, Joka T, Brand M, Obertacke U, Neuhof H, Schmit-Neuerburg KP (1989) Surfactant abnormalities in patients with respiratory failure after multiple trauma. Am Rev Respir Dis 140:1033–1039
Von Wichert P, Kohl FV (1977) Decreased dipalmitoyllecithin, content found in lung specimens from patients with so-called shocklung. Intensive Care Med 3:27–30
Avery ME, Mead J (1959) Surface properties in relation to atelectasis and hyaline membrane disease. Am J Dis Child 97:517–523
Ikegami M, Jobe A, Glatz T (1981) Surface activity following natural surfactant treatment of premature lambs. J Appl Physiol 51:306–312
Ikegami M, Jobe A, Jacobs H, Lam R (1984) A protein from airways of premature lambs that inhibits surfactant function. J Appl Physiol 57:1134–1142
Ikegami M, Jobe A, Berry D (1986) A protein that inhibits surfactant in respiratory distress syndrome. Biol Neonate 50:121–129
Kobayashi T, Curstedt T, Grossmann G, Robertson B (1989) Inhibition of exogenous surfactant in ventilated immature newborn rabbits. Respir Physiol 76:1–12
Tierney DF, Johnson RP (1965) Altered surface tension of lung extracts and lung mechanics. J Appl Physiol 20:1253–1260
Fuchimukai T, Fujiwara T, Takahashi A, Enhorning G (1987) Artificial pulmonary surfactant inhibited by proteins. J Appl Physiol 62:429–437
Holm BA, Notter RH, Finkelstein JN (1985) Surface property changes from interactions of albumin with natural lung surfactant and extracted lung lipids. Chem Phys. Lipids 38:287–298
Holm BA, Notter RH (1987) Effects of hemoglobin and cell membrane lipids on pulmonary surfactant activity. J Appl Physiol 63:1434–1442
Holm BA, Enhorning G, Notter RH (1988) A biophysical mechanism by which plasma proteins inhibit lung surfactant activity. Chem Phys Lipids 49:49–55
Keough KMW, Parsons CS, Phang PT, Tweedale MG (1988) Interactions between plasma proteins and pulmonary surfactant: surface balance studies. Can J Physiol Pharmacol 66:1166–1173
Taylor Jr FB, Abrams ME (1966) Effect of surface active lipoprotein on clotting and fibrinolysis, and of fibrinogen on surface tension of surface active lipoprotein (with a hypothesis on the pathogenesis of pulmonary atelectasis and hyaline membrane in respiratory distress syndrome of the newborn). Am J Med 40:346–350
Holm BA, Venkitaraman AR, Enhorning G, Notter RH (1990) Biophysical inhibition of synthetic lung surfactants. Chem Phys. Lipids 52:243–250
Ikegami M, Jobe A, Jacobs H, Jones S (1981) Sequential treatments of premature lambs with an artificial surfactant and natural surfactant. J Clin Invest 68:491–496
Ikegami M, Agata Y, Elkady T, Hallman M, Berry D, Jobe A (1987) Comparison of four surfactants: in vitro surface properties and responses of preterm lambs to treatment at birth. Pediatrics 79:38–46
Cockshutt AM, Weitz J, Possmayer F (1990) Pulmonary surfactant-associated protein A enhances the surface activity of lipid extract surfactant and reverses inhibition by blood proteins in vitro. Biochemistry 29:8424–8429
Seeger W, Günther A, Thede C (1992) Differential sensitivity to fibrinogen inhibition of SP-C-vs. SP-B-based surfactants. Am J Physiol (Lung Cell Mol Physiol) 5:L286-L291
Balis JU, Shelley SA, McCue MJ, Rappaport ES (1971) Mechanisms of damage to the lung surfactant system. Ultrastructure and quantitation of normal and in vitro inactivated lung surfactant. Exp Mol Pathol 14:243–262
Lachmann B, Hallman M, Bergmann KC (1987) Respiratory failure following anti-lung serum: study on mechanisms associated with surfactant system damage. Exp Lung Res 12:163–180
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This work was financially supported by the Dutch Foundation for Medical Research
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Lachmann, B., Eijking, E.P., So, K.L. et al. In vivo evaluation of the inhibitory capacity of human plasma on exogenous surfactant function. Intensive Care Med 20, 6–11 (1994). https://doi.org/10.1007/BF02425047
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DOI: https://doi.org/10.1007/BF02425047