Effectiveness of Nitric Oxide Inhalation in Septic ARDS

¹ From the Department of Anesthesiology and Intensive Care Medicine, University of Vienna, Vienna, Austria

Study objective: To evaluate the percentage of nitric oxide (NO) responders in septic shock patients with ARDS. Additionally, to investigate long-term NO effects on cardiac performance and oxygen kinetic paterns in NO responders vs nonresponders.

Design: Prospective cohort study.

Setting: ICU of a university hospital.

Patients: Twenty-five consecutive patients with a diagnosis of septic shock and established ARDS requiring inotropic and vasopressor support.

Interventions: After diagnosis of ARDS, NO was administered at 18 or 36 ppm. Patients demonstrating a NO-induced rise of arterial oxygen tension of 20% or more and/or a fall in mean pulmonary artery pressure of 15% or more were grouped as NO responders; others were grouped as nonresponders.

Measurements and results: Ten patients (40%) were NO responders, while 15 patients (60%) were nonresponders. Mortality was 40% in NO responders and 67% in nonresponders (NS). NO responders developed a significantly lower mean pulmonary artery pressure (28±6 vs 33±6 mm Hg; p<0.05), lower pulmonary vascular resistance (PVR: 258±73 vs 377±163 dyne·s·cm⁵·m²; p<0.05), and higher PaO₂/FIO₂ ratio (192±85 vs 144±74 mm Hg; p<0.05) within the study period. In responders, NO-induced afterload reduction resulted in increased right ventricular ejection fraction (RVEF: 40±7 vs 35±9%; p<0.05), significandy higher cardiac index (CI: 4.5±1.1 vs 4.0±1.2 L·min¹·m²; p<0.05) and oxygen delivery (DO₂: 681±141 vs 599±160 mL·min¹·m²; p<0.05) compared with nonresponders. In NO nonresponders, RVEF was correlated with PVR, CI, DO₂, mixed venous oxygen saturation (SvO₂), and oxygen extraction ratio (O₂ER) (r=±0.60 to ±0.69; p<0.05). No significant correlation between RVEF and any of these parameters was observed in responders. SvO₂ (75±7 vs 69±8%; p<0.05) and O₂ER (0.24±0.06 vs 0.27±0.06; p<0.05) were significantly different between responders and nonresponders, while no difference in oxygen consumption was observed (161±41 vs 153±43 mL·min·m²).

Conclusions: Inhaled NO is effective in only a subgroup of septic ARDS patients, with a higher, but insignificantly different percentage of survivors in the responder group. NO responders were characterized by increased RVEF accompanied by higher CI, DO₂, and lower O₂ER. In nonresponders, RVEF remained depressed, with a close correlation between RVEF and CO as well as DO₂ and O₂ER. Thus, nonresponders seem to suffer from impaired cardiac reserves and correspondingly lower oxygen transport variables.

Key Words: ARDS • arterial oxygenation • nitric oxide inhalation • pulmonary artery hypertension • right ventricular function • septic shock

Submitted on March 7, 1995
Accepted on September 6, 2007

This article has been cited by other articles:

				R. W. Taylor, J. L. Zimmerman, R. P. Dellinger, R. C. Straube, G. J. Criner, K. Davis Jr, K. M. Kelly, T. C. Smith, and R. J. Small Low-Dose Inhaled Nitric Oxide in Patients With Acute Lung Injury: A Randomized Controlled Trial JAMA, April 7, 2004; 291(13): 1603 - 1609. [Abstract] [Full Text] [PDF]

				H. Gerlach, D. Keh, A. Semmerow, T. Busch, K. Lewandowski, D. M. Pappert, R. Rossaint, and K. J. Falke Dose-Response Characteristics during Long-Term Inhalation of Nitric Oxide in Patients with Severe Acute Respiratory Distress Syndrome: A Prospective, Randomized, Controlled Study Am. J. Respir. Crit. Care Med., April 1, 2003; 167(7): 1008 - 1015. [Abstract] [Full Text] [PDF]

				H. Maurenbrecher, M. Lamy, G. Deby-Dupont, P. Frascarolo, and G. Hedenstierna An Animal Model of Response and Nonresponse to Inhaled Nitric Oxide in Endotoxin-Induced Lung Injury Chest, August 1, 2001; 120(2): 573 - 581. [Abstract] [Full Text] [PDF]

				M. Baldauf, P. Silver, and M. Sagy Evaluating the Validity of Responsiveness to Inhaled Nitric Oxide in Pediatric Patients With ARDS : An Analytic Tool Chest, April 1, 2001; 119(4): 1166 - 1172. [Abstract] [Full Text] [PDF]

				S. R. Kleeberger, S. P. M. Reddy, L.-Y. Zhang, H.-Y. Cho, and A. E. Jedlicka Toll-like receptor 4 mediates ozone-induced murine lung hyperpermeability via inducible nitric oxide synthase Am J Physiol Lung Cell Mol Physiol, February 1, 2001; 280(2): L326 - L333. [Abstract] [Full Text] [PDF]

				P. T. Murray, M. E. Wylam, and J. G. Umans Nitric Oxide and Septic Vascular Dysfunction Anesth. Analg., January 1, 2000; 90(1): 89 - 89. [Full Text] [PDF]

				L. PAPAZIAN, A. ROCH, F. BREGEON, X. THIRION, F. GAILLAT, P. SAUX, V. FULACHIER, Y. JAMMES, and J.-P. AUFFRAY Inhaled Nitric Oxide and Vasoconstrictors in Acute Respiratory Distress Syndrome Am. J. Respir. Crit. Care Med., August 1, 1999; 160(2): 473 - 479. [Abstract] [Full Text]

				M. Aranda, K. K. Bradford, and R. G. Pearl Combined Therapy with Inhaled Nitric Oxide and Intravenous Vasodilators During Acute and Chronic Experimental Pulmonary Hypertension Anesth. Analg., July 1, 1999; 89(1): 152 - 152. [Abstract] [Full Text] [PDF]

				C. M. Hart Nitric Oxide in Adult Lung Disease Chest, May 1, 1999; 115(5): 1407 - 1417. [Abstract] [Full Text] [PDF]

				G. F. ZHU, B. SUN, S. F. NIU, Y. Y. CAI, K. LIN, R. LINDWALL, and B. ROBERTSON Combined Surfactant Therapy and Inhaled Nitric Oxide in Rabbits with Oleic Acid-induced Acute Respiratory Distress Syndrome Am. J. Respir. Crit. Care Med., August 1, 1998; 158(2): 437 - 443. [Abstract] [Full Text] [PDF]

				C. S. Rayhrer, T. D. Edmisten, G. A. Cephas, C. G. Tribble, I. L. Kron, and J. S. Young Nitric Oxide Potentiates Acute Lung Injury in an Isolated Rabbit Lung Model Ann. Thorac. Surg., April 1, 1998; 65(4): 935 - 938. [Abstract] [Full Text] [PDF]

				J. R. MICHAEL, R. G. BARTON, J. R. SAFFLE, M. MONE, B. A. MARKEWITZ, K. HILLIER, M. R. ELSTAD, E. J. CAMPBELL, B. E. TROYER, R. E. WHATLEY, et al. Inhaled Nitric Oxide Versus Conventional Therapy . Effect on Oxygenation in ARDS Am. J. Respir. Crit. Care Med., May 1, 1997; 157(5): 1372 - 1380. [Abstract] [Full Text]