FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Volume 334:1417-1422 May 30, 1996 Number 22 Next

	Full Text PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Patients with acute respiratory distress syndrome (ARDS) have a deficiency of surfactant. Surfactant replacement improves physiologic function in such patients, and preliminary data suggest that it may improve survival.

Methods We conducted a prospective, multicenter, double-blind, randomized, placebo-controlled trial involving 725 patients with sepsis-induced ARDS. Patients were stratified according to the risk of death at base line (indicated by their score on the Acute Physiologic and Chronic Health Evaluation [APACHE III] index) and randomly assigned to receive either continuously administered synthetic surfactant (13.5 mg of dipalmitoylphosphatidylcholine per milliliter; 364 patients) or placebo (0.45 percent saline; 361 patients) in aerosolized form for up to five days.

Results The demographic and physiologic characteristics of the two treatment groups were similar at base line. The mean (±SD) age was 50±17 years in the surfactant group and 53±18 years in the placebo group, and the mean APACHE III scores at randomization were 70.4±25 and 70.5±25, respectively. Hemodynamic measures, measures of oxygenation, duration of mechanical ventilation, and length of stay in the intensive care unit did not differ significantly in the two groups. Survival at 30 days was 60 percent for both groups. Survival was similar in the groups when analyzed according to APACHE III score, cause of death, time of onset and severity of ARDS, presence or absence of documented sepsis, underlying disease, whether or not there was a do-not-resuscitate order, and medical center. Increased secretions were significantly more frequent in the surfactant group; the rates of other complications were similar in the two groups.

Conclusions The continuous administration of aerosolized synthetic surfactant to patients with sepsis-induced ARDS had no significant effect on 30-day survival, length of stay in the intensive care unit, duration of mechanical ventilation, or physiologic function.

Source Information

From the University of Texas Health Science Center at San Antonio and the South Texas Veterans Health Care System, Audie L. Murphy Memorial Veterans Hospital Division, San Antonio (A.A.); the University of Ohio, Cincinnati (R.P.B.); Baylor College of Medicine, Houston (K.K.G.); the University of Michigan Medical Center, Ann Arbor (J.G.W.); the Cleveland Clinic, Cleveland (H.P. W.); Consorci Hospitalari del Parc Tavli, Sabadel, Spain (A.A.R.); Henri Mondor Hospital, Paris (F.L.); the University of North Carolina, Chapel Hill (W.L.); and Glaxo Wellcome, Research Triangle Park, N.C. (D.S.Z., E.N.P.).

Address reprint requests to Dr. Anzueto at the South Texas Veterans Health Care System, Audie L. Murphy Memorial Veterans Hospital Division, Pulmonary Disease Section (111E), 7400 Merton Minter Blvd., San Antonio, TX 78284.

Full Text of this Article

This article has been cited by other articles:

• Engle, W. A., and the Committee on Fetus and Newborn, (2008). Surfactant-Replacement Therapy for Respiratory Distress in the Preterm and Term Neonate. Pediatrics 121: 419-432 [Abstract] [Full Text]  
• Schuster, K. M., Alouidor, R., Barquist, E. S. (2008). Nonventilatory Interventions in the Acute Respiratory Distress Syndrome. J Intensive Care Med 23: 19-32 [Abstract]  
• Benfield, R., DuBose, J., Demetriades, D. (2007). Prevention and treatment of post-traumatic acute respiratory distress syndrome. Trauma 9: 255-266 [Abstract]  
• Thompson, B. T., Schoenfeld, D. (2007). Usual Care as the Control Group in Clinical Trials of Nonpharmacologic Interventions. Proc Am Thorac Soc 4: 577-582 [Abstract] [Full Text]  
• Wang, Z., Chang, Y., Schwan, A. L., Notter, R. H. (2007). Activity and Inhibition Resistance of a Phospholipase-Resistant Synthetic Surfactant in Rat Lungs. Am. J. Respir. Cell Mol. Bio. 37: 387-394 [Abstract] [Full Text]  
• Stevens, T. P., Sinkin, R. A. (2007). Surfactant Replacement Therapy. Chest 131: 1577-1582 [Abstract] [Full Text]  
• Calfee, C. S., Matthay, M. A. (2007). Nonventilatory Treatments for Acute Lung Injury and ARDS. Chest 131: 913-920 [Abstract] [Full Text]  
• Cepkova, M., Matthay, M. A. (2006). Pharmacotherapy of acute lung injury and the acute respiratory distress syndrome.. J Intensive Care Med 21: 119-143 [Abstract]  
• Kacmarek, R. M., Wiedemann, H. P., Lavin, P. T., Wedel, M. K., Tutuncu, A. S., Slutsky, A. S. (2006). Partial Liquid Ventilation in Adult Patients with Acute Respiratory Distress Syndrome. Am. J. Respir. Crit. Care Med. 173: 882-889 [Abstract] [Full Text]  
• Huang, W., McCaig, L. A., Veldhuizen, R. A. W., Yao, L-J., Lewis, J. F. (2005). Mechanisms responsible for surfactant changes in sepsis-induced lung injury. Eur Respir J 26: 1074-1079 [Abstract] [Full Text]  
• Matthay, M. A., Calfee, C. S. (2005). Therapeutic Value of a Lung Protective Ventilation Strategy in Acute Lung Injury. Chest 128: 3089-3091 [Full Text]  
• Matthay, M. A., Zimmerman, G. A. (2005). Acute Lung Injury and the Acute Respiratory Distress Syndrome: Four Decades of Inquiry into Pathogenesis and Rational Management. Am. J. Respir. Cell Mol. Bio. 33: 319-327 [Full Text]  
• Bernard, G. R. (2005). Acute Respiratory Distress Syndrome: A Historical Perspective. Am. J. Respir. Crit. Care Med. 172: 798-806 [Abstract] [Full Text]  
• Burleson, B. S., Maki, E. D. (2005). Acute Respiratory Distress Syndrome. Journal of Pharmacy Practice 18: 118-131 [Abstract]  
• Willson, D. F., Thomas, N. J., Markovitz, B. P., Bauman, L. A., DiCarlo, J. V., Pon, S., Jacobs, B. R., Jefferson, L. S., Conaway, M. R., Egan, E. A., for the Pediatric Acute Lung Injury and Sepsis Inv, (2005). Effect of Exogenous Surfactant (Calfactant) in Pediatric Acute Lung Injury: A Randomized Controlled Trial. JAMA 293: 470-476 [Abstract] [Full Text]  
• McVerry, B. J., Peng, X., Hassoun, P. M., Sammani, S., Simon, B. A., Garcia, J. G. N. (2004). Sphingosine 1-Phosphate Reduces Vascular Leak in Murine and Canine Models of Acute Lung Injury. Am. J. Respir. Crit. Care Med. 170: 987-993 [Abstract] [Full Text]  
• Esteban, A., Fernandez-Segoviano, P., Frutos-Vivar, F., Aramburu, J. A., Najera, L., Ferguson, N. D., Alia, I., Gordo, F., Rios, F. (2004). Comparison of Clinical Criteria for the Acute Respiratory Distress Syndrome with Autopsy Findings. ANN INTERN MED 141: 440-445 [Abstract] [Full Text]  
• Baudouin, S. V. (2004). Exogenous Surfactant Replacement in ARDS -- One Day, Someday, or Never?. NEJM 351: 853-855 [Full Text]  
• Spragg, R. G., Lewis, J. F., Walmrath, H.-D., Johannigman, J., Bellingan, G., Laterre, P.-F., Witte, M. C., Richards, G. A., Rippin, G., Rathgeb, F., Hafner, D., Taut, F. J.H., Seeger, W. (2004). Effect of Recombinant Surfactant Protein C-Based Surfactant on the Acute Respiratory Distress Syndrome. NEJM 351: 884-892 [Abstract] [Full Text]  
• Vincent, J.-L. (2004). Evidence-Based Medicine in the ICU: Important Advances and Limitations. Chest 126: 592-600 [Abstract] [Full Text]  
• The National Heart, Lung, and Blood Institute ARDS, (2004). Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome. NEJM 351: 327-336 [Abstract] [Full Text]  
• Prodhan, P., Noviski, N. (2004). Pediatric Acute Hypoxemic Respiratory Failure: Management of Oxygenation. J Intensive Care Med 19: 140-153 [Abstract]  
• Moloney, E. D., Griffiths, M. J. D. (2004). Protective ventilation of patients with acute respiratory distress syndrome. Br J Anaesth 92: 261-270 [Abstract] [Full Text]  
• Dhand, R. (2003). Aerosol Therapy during Mechanical Ventilation: Getting Ready for Prime Time. Am. J. Respir. Crit. Care Med. 168: 1148-1149 [Full Text]  
• Wu, Y.-Z., Medjane, S., Chabot, S., Kubrusly, F. S., Raw, I., Chignard, M., Touqui, L. (2003). Surfactant Protein-A and Phosphatidylglycerol Suppress Type IIA Phospholipase A2 Synthesis via Nuclear Factor-{kappa}B. Am. J. Respir. Crit. Care Med. 168: 692-699 [Abstract] [Full Text]  
• Cole, F. S. (2003). Surfactant protein B: unambiguously necessary for adult pulmonary function. Am. J. Physiol. Lung Cell. Mol. Physiol. 285: L540-L542 [Full Text]  
• Spragg, R. G., Lewis, J. F., Wurst, W., Hafner, D., Baughman, R. P., Wewers, M. D., Marsh, J. J. (2003). Treatment of Acute Respiratory Distress Syndrome with Recombinant Surfactant Protein C Surfactant. Am. J. Respir. Crit. Care Med. 167: 1562-1566 [Abstract] [Full Text]  
• Steinbrook, R. (2003). How Best to Ventilate? Trial Design and Patient Safety in Studies of the Acute Respiratory Distress Syndrome. NEJM 348: 1393-1401 [Full Text]  
• Brower, R. G., Matthay, M., Schoenfeld, D. (2002). Meta-analysis of acute lung injury and acute respiratory distress syndrome trials. Am. J. Respir. Crit. Care Med. 166: 1515-1517 [Full Text]  
• Hattler, B. G., Lund, L. W., Golob, J., Russian, H., Lann, M. F., Merrill, T. L., Frankowski, B., Federspiel, W. J. (2002). A respiratory gas exchange catheter: In vitro and in vivo tests in large animals. J. Thorac. Cardiovasc. Surg. 124: 520-530 [Abstract] [Full Text]  
• Topulos, G. P., Brown, R. E., Butler, J. P. (2002). Increased surface tension decreases pulmonary capillary volume and compliance. J. Appl. Physiol. 93: 1023-1029 [Abstract] [Full Text]  
• Cranshaw, J, Griffiths, M J D, Evans, T W (2002). The pulmonary physician in critical care c 9: Non-ventilatory strategies in ARDS. Thorax 57: 823-829 [Abstract] [Full Text]  
• Tomlinson, L, Bellingan, G. (2002). Trauma and acute lung injury. Trauma 4: 147-157 [Abstract]  
• Whitehead, T, Slutsky, A S (2002). The pulmonary physician in critical care * 7: Ventilator induced lung injury. Thorax 57: 635-642 [Abstract] [Full Text]  
• Murray, T. A., Patterson, L. A. (2002). Prone Positioning of Trauma Patients With Acute Respiratory Distress Syndrome and Open Abdominal Incisions. Crit Care Nurse 22: 52-56 [Full Text]  
• Anzueto, A. (2002). Exogenous surfactant in acute respiratory distress syndrome: more is better. Eur Respir J 19: 787-789 [Full Text]  
• Walmrath, D., Grimminger, F., Pappert, D., Knothe, C., Obertacke, U., Benzing, A., Gunther, A., Schmehl, T., Leuchte, H., Seeger, W. (2002). Bronchoscopic administration of bovine natural surfactant in ARDS and septic shock: impact on gas exchange and haemodynamics. Eur Respir J 19: 805-810 [Abstract] [Full Text]  
• Sayeed, S., Koniaris, L. G., Papadakos, P. J. (2002). Image of the Month. Arch Surg 137: 491-492 [Full Text]  
• Brower, R. G., Ware, L. B., Berthiaume, Y., Matthay, M. A. (2001). Treatment of ARDS. Chest 120: 1347-1367 [Abstract] [Full Text]  
• Tashiro, K., Yamada, K., Konzaki, T., Yamamoto, K., Ohmura, S., Kobayashi, T., Suzuki, Y. (2001). Aerosolized surfactant therapy for endotoxin-induced experimental acute respiratory distress syndrome in rats. Br J Anaesth 87: 266-271 [Abstract] [Full Text]  
• Weiner, R. E., Sasso, D. E., Gionfriddo, M. A., Thrall, R. S., Syrbu, S., Smilowitz, H. M., Vento, J. (2001). Early Detection of Oleic Acid-Induced Lung Injury in Rats Using 111In-Labeled Anti-Rat Intercellular Adhesion Molecule-1. JNM 42: 1109-1115 [Abstract] [Full Text]  
• BRACKENBURY, A. M., PULIGANDLA, P. S., McCAIG, L. A., NIKORE, V., YAO, L.-J., VELDHUIZEN, R. A. W., LEWIS, J. F. (2001). Evaluation of Exogenous Surfactant in HCl-induced Lung Injury. Am. J. Respir. Crit. Care Med. 163: 1135-1142 [Abstract] [Full Text]  
• Zwischenberger, J. B., Alpard, S. K., Bidani, A. (2001). Severe respiratory failure. Ann. Thorac. Surg. 71: 394-396 [Full Text]  
• Laffey, J. G., Kavanagh, B. P., Ney, L., Kuebler, W. M., Oba, Y., Salzman, G. A., Brower, R. G., Matthay, M. A., Wheeler, A. (2000). Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury. NEJM 343: 812-814 [Full Text]  
• Mora, R., Arold, S., Marzan, Y., Suki, B., Ingenito, E. P. (2000). Determinants of surfactant function in acute lung injury and early recovery. Am. J. Physiol. Lung Cell. Mol. Physiol. 279: L342-L349 [Abstract] [Full Text]  
• Ware, L. B., Matthay, M. A. (2000). The Acute Respiratory Distress Syndrome. NEJM 342: 1334-1349 [Full Text]  
• Puligandla, P. S., Gill, T., McCaig, L. A., Yao, L.-J., Veldhuizen, R. A. W., Possmayer, F., Lewis, J. F. (2000). Alveolar environment influences the metabolic and biophysical properties of exogenous surfactants. J. Appl. Physiol. 88: 1061-1071 [Abstract] [Full Text]  
• Spragg, R. G., Smith, R. M., Harris, K., Lewis, J., Hafner, D., Germann, P. (2000). Effect of recombinant SP-C surfactant in a porcine lavage model of acute lung injury. J. Appl. Physiol. 88: 674-681 [Abstract] [Full Text]  
• Iribarren, C., Jacobs, D. R. Jr., Sidney, S., Gross, M. D., Eisner, M. D. (2000). Cigarette Smoking, Alcohol Consumption, and Risk of ARDS* : A 15-Year Cohort Study in a Managed Care Setting. Chest 117: 163-168 [Abstract] [Full Text]  
• WISWELL, T. E., SMITH, R. M., KATZ, L. B., MASTROIANNI, L., WONG, D. Y., WILLMS, D., HEARD, S., WILSON, M., HITE, R. D., ANZUETO, A., REVAK, S. D., COCHRANE, C. G. (1999). Bronchopulmonary Segmental Lavage with Surfaxin (KL4-Surfactant) for Acute Respiratory Distress Syndrome. Am. J. Respir. Crit. Care Med. 160: 1188-1195 [Abstract] [Full Text]  
• Elhalwagi, B. M., Zhang, M., Ikegami, M., Iwamoto, H. S., Morris, R. E., Miller, M. L., Dienger, K., McCormack, F. X. (1999). Normal Surfactant Pool Sizes and Inhibition-Resistant Surfactant from Mice That Overexpress Surfactant Protein A. Am. J. Respir. Cell Mol. Bio. 21: 380-387 [Abstract] [Full Text]  
• Matthay, M. A. (1999). Conference Summary: Acute Lung Injury. Chest 116: 119S-126S [Full Text]  
• DREYFUSS, D., MARTIN-LEFÈVRE, L., SAUMON, G. (1999). Hyperinflation-Induced Lung Injury during Alveolar Flooding in Rats . Effect of Perfluorocarbon Instillation. Am. J. Respir. Crit. Care Med. 159: 1752-1757 [Abstract] [Full Text]  
• LEWIS, J., MCCAIG, L., HÄFNER, D., SPRAGG, R., VELDHUIZEN, R., KERR, C. (1999). Dosing and Delivery of a Recombinant Surfactant in Lung-injured Adult Sheep. Am. J. Respir. Crit. Care Med. 159: 741-747 [Abstract] [Full Text]  
• López-Herce, J., de Lucas, N., Carrillo, A., Bustinza, A., Moral, R. (1999). Surfactant treatment for acute respiratory distress syndrome. Arch. Dis. Child. 80: 248-252 [Abstract] [Full Text]  
• Wheeler, A. P., Bernard, G. R. (1999). Treating Patients with Severe Sepsis. NEJM 340: 207-214 [Full Text]  
• LUTZ, C., CARNEY, D., FINCK, C., PICONE, A., GATTO, L. A., PASKANIK, A., LANGENBACK, E., NIEMAN, G. (1998). Aerosolized Surfactant Improves Pulmonary Function in Endotoxin-induced Lung Injury. Am. J. Respir. Crit. Care Med. 158: 840-845 [Abstract] [Full Text]  
• Kerr, C. L., Ito, Y., Manwell, S. E. E., Veldhuizen, R. A. W., Yao, L.-J., McCaig, L. A., Lewis, J. F. (1998). Effects of surfactant distribution and ventilation strategies on efficacy of exogenous surfactant. J. Appl. Physiol. 85: 676-684 [Abstract] [Full Text]  
• Halpern, D., Jensen, O. E., Grotberg, J. B. (1998). A theoretical study of surfactant and liquid delivery into the lung. J. Appl. Physiol. 85: 333-352 [Abstract] [Full Text]  
• BALARAMAN, V., MEISTER, J., KU, T. L., SOOD, S. L., TAM, E., KILLEEN, J., UYEHARA, C. F. T., EGAN, E., EASA, D. (1998). Lavage Administration of Dilute Surfactants after Acute Lung Injury in Neonatal Piglets. Am. J. Respir. Crit. Care Med. 158: 12-17 [Abstract] [Full Text]  
• HAFNER, D., GERMANN, P.-G., HAUSCHKE, D. (1998). Effects of rSP-C Surfactant on Oxygenation and Histology in a Rat-Lung-Lavage Model of Acute Lung Injury. Am. J. Respir. Crit. Care Med. 158: 270-278 [Abstract] [Full Text]  
• ZILBERBERG, M. D., EPSTEIN, S. K. (1998). Acute Lung Injury in the Medical ICU . Comorbid Conditions, Age, Etiology, and Hospital Outcome. Am. J. Respir. Crit. Care Med. 157: 1159-1164 [Abstract] [Full Text]  
• ARTIGAS, A., BERNARD, G. R., CARLET, J., DREYFUSS, D., GATTINONI, L., HUDSON, L., LAMY, M., MARINI, J. J., MATTHAY, M. A., PINSKY, M. R., SPRAGG, R., SUTER, P. M., the Consensus Committee, (1998). The American-European Consensus Conference on ARDS, Part 2 . Ventilatory, Pharmacologic, Supportive Therapy, Study Design Strategies, and Issues Related to Recovery and Remodeling. Am. J. Respir. Crit. Care Med. 157: 1332-1347 [Abstract] [Full Text]  
• Hudson, L. D. (1998). Protective Ventilation for Patients with Acute Respiratory Distress Syndrome. NEJM 338: 385-387 [Full Text]  
• Fok, T. F., Al-Essa, M., Dolovich, M., Rasid, F., Kirpalani, H. (1998). Nebulisation of surfactants in an animal model of neonatal respiratory distress. Arch. Dis. Child. Fetal Neonatal Ed. 78: 3F-9 [Abstract] [Full Text]  
• CHESNUTT, A. N., MATTHAY, M. A., TIBAYAN, F. A., CLARK, J. G. (1997). Early Detection of Type III Procollagen Peptide in Acute Lung Injury . Pathogenetic and Prognostic Significance. Am. J. Respir. Crit. Care Med. 156: 840-845 [Abstract] [Full Text]  
• SCHERMULY, R., SCHMEHL, T., GÜNTHER, A., GRIMMINGER, F., SEEGER, W., WALMRATH, D. (1997). Ultrasonic Nebulization for Efficient Delivery of Surfactant in a Model of Acute Lung Injury . Impact on Gas Exchange. Am. J. Respir. Crit. Care Med. 156: 445-453 [Abstract] [Full Text]  
• ITO, Y., MANWELL, S. E. E., KERR, C. L., VELDHUIZEN, R. A. W., YAO, L.-J., BJARNESON, D., MCCAIG, L. A., BARTLETT, A. J., LEWIS, J. F. (1997). Effects of Ventilation Strategies on the Efficacy of Exogenous Surfactant Therapy in a Rabbit Model of Acute Lung Injury. Am. J. Respir. Crit. Care Med. 157: 149-155 [Abstract] [Full Text]  
• DREYFUSS, D., SAUMON, G. (1997). Ventilator-induced Lung Injury . Lessons from Experimental Studies. Am. J. Respir. Crit. Care Med. 157: 294-323 [Full Text]  
• Matthay, M. A. (1996). The Acute Respiratory Distress Syndrome. NEJM 334: 1469-1470 [Full Text]