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Inhaled Nitric Oxide and Pulmonary Vasoreactivity

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Abstract

Inhaled nitric oxide is a ubiquitous molecule which is produced endogenously and is also found in air pollution and in cigarette smoke. After describing the chemistry of NO, we review its history from the first description in 1980 to the current clinical indications. The biosynthesis of NO, its effects on pulmonary vasoreactivity, and the administration of inhaled NO will be described. The indications, uses, and side effects of inhaled NO are discussed with an emphasis on withdrawal of NO therapy, specifically the “rebound” phenomenon. Possible drug interactions are listed. Inhaled nitric oxide is here to stay, and future studies will provide more information on its therapeutic dose, duration and potential toxicity.

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REFERENCES

  1. Mitchell HH, Shonle HA, Grindley HS. The origin of the nitrates in the urine. J Biol Chem 1916; 24: 461–490

    CAS  Google Scholar 

  2. Tannenbaum SR, Fett D, Young VR, Land PD, Bruce WR. Nitrite and nitrate are formed by endogenous synthesis in the human intestine. Science 1928; 200: 1487–1489

    Google Scholar 

  3. Furchgott RF, Zawadzki JV. The obligatory role of the endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980; 228: 373–376

    Article  Google Scholar 

  4. NIOSH recommendations for occupational safety and health standards. MMWR Morb Mortal Wklly Res 1988; 37: 1

    Google Scholar 

  5. Aranda M, Bradford KK, Pearl RG. Continuous therapy with inhaled nitric oxide and intravenous vasodilators during experimental pulmonary hypertension. Anesth Analg Jul 1999; 89: 152–158

    Article  PubMed  CAS  Google Scholar 

  6. Kuhlen R, Walbert E, Frankel P, Thaden S, Behrendt W, Rossaint R. Combination of inhaled nitric oxide and intravenous prostacyclin for successful treatment of severe pulmonary hypertension in a patient with acute respiratory distress syndrome. Intens Care Med Jul 1999; 25: 752–754

    Article  CAS  Google Scholar 

  7. Barst RJ. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (Editorial). Heart 1997; 77: 299–301

    PubMed  CAS  Google Scholar 

  8. Rosales AM, Bolivar J, Burke RP, Chang AC. Adverse hemodynamic effects observed with inhaled nitric oxide Aranda and Pearl: NitricOxide after surgical repair of total anomalous pulmonary venous return. Ped Cardiol May-Jun 1999; 20: 224–226

    Article  CAS  Google Scholar 

  9. Koleff MH. Inhaled nitric oxide for severe acute respiratory distress syndrome: A blessing or a curse? Heart Lung 1997; 26: 358–362

    Article  Google Scholar 

  10. Anonymous. Inhaled nitric oxide and hypoxic respiratory failure in infants with congenital diaphragmatic hernia. The Neonatal Inhaled Nitric Oxide Study Group (NINOS). Pediatrics Jun 1997; 99: 838–845

  11. Kinsella JP, Abman SH. Controversies in the use of inhaled nitric oxide therapy in the newborn. Clin Perinatology Mar 1998; 25: 203–217

    CAS  Google Scholar 

  12. Frostell C, Fratacci MD, Waine JC, Jones R, Zapol WM. Inhaled nitric oxide: A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction. Circulation 1991; 83: 2038–2047

    PubMed  CAS  Google Scholar 

  13. Higenbottam T, Pepke-Zaba J, Scott J, Woolman P, Coutts C, Wallwork J. Inhaled “endothelial derived-relaxing factor” (EDRF) in primary hypertension (PPH). Amer Rev Resp Dis 1988; 137 (Suppl): A107

    Google Scholar 

  14. Steudel W, Hurford WE, Zapol WM. Therapeutic uses of inhaled nitric oxide. Anesthesiol 1999; 91: 1090–1121

    Article  CAS  Google Scholar 

  15. Oka M, Ohnishi M, Takahashi H, Soma S, Hasunuma K, Satok K, Kira S. Altered vasoreactivity in lungs isolated from rats exposed to nitric oxide gas. Am J Physiol 1996; 271: L419-L424

    PubMed  CAS  Google Scholar 

  16. Ream RS, Hauver JG, Lynch RE, Kountzman B, Gale GB, and Mink RB. Low-dose inhaled nitric oxide improves the oxygenation and ventilation of infants and children with acute, hypoxemic respiratory failure. Crit Care Med 1999; 27: 989–996

    Article  PubMed  CAS  Google Scholar 

  17. Kinsella JP, Truog WE, Walsh WF, Goldberg RN, Bancalari E, Mayock DE, Redding GJ, deLemos RA, Sardesai S, McCurnin DC, Moreland SG, Cutter GR, Abman SH. Randomized multicenter trial of inhaled nitric oxide and high-frequency oscillatory ventilation in severe, persistent pulmonary hypertension of the newborn. J Pediatrics 1997; 131: 55–62

    Article  CAS  Google Scholar 

  18. Sheridan RL, Zapol WM, Ritz RH, Tompkins RG. Low-dose inhaled nitric oxide in acutely burned children with profound respiratory failure. Surgery 1999; 126: 856–862

    PubMed  CAS  Google Scholar 

  19. Day RW, Guarin M, Lynch JM, Vernon DD, Dean MJ. Inhaled nitric oxide in children with severe lung disease: Results of acute and prolonged therapy with two concentrations. Crit Care Med 1996; 24: 215–221

    Article  PubMed  CAS  Google Scholar 

  20. Puybasset L, Rouby JJ, Mourgeon E, Cluzel P, Souhil Z, Law-Koune JD, Stewart T, Devilliers C, Lu Q, Roche S. Factors influencing cardiopulmonary effects of inhaled nitric oxide in acute respiratory failure. Am J Respir Crit Care Med 1995; 152: 318–328

    PubMed  CAS  Google Scholar 

  21. Leeman M. Pulmonary hypertension in acute respiratory distress syndrome. Mon Arch Chest Dis 1999; 54: 146–149

    CAS  Google Scholar 

  22. Rossaint R, Falke KJ, Lopez FA, Slama K, Pison U, Zapol WM. Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl JMed 1993; 328: 399

    Article  CAS  Google Scholar 

  23. Lundin S, Mang H, Smithies M, Stenqvist O, Frostell C. Inhalation of nitric oxide in acute lung injury: Results of a European multicentre study. The European Study Group of Inhaled Nitric Oxide. Inten Care Med 1999; 25: 911–919

    Article  CAS  Google Scholar 

  24. Michael JR, Barton RG, Saffle JR, Mone M, Markewitz BA, Hillier K, Elstad MR, Campbell EJ, Troyer BE, Whatley RE, Liou TG, Samuelson WM, Carveth HJ, Hinson DM, Morris SE, Davis BL, Day RW. Inhaled nitric oxide versus conventional therapy. Effect on oxygenation in ARDS. Am J Respir Crit Care Med 1998; 157: 1372–1380

    PubMed  CAS  Google Scholar 

  25. Dupont H, Le Corre F, Fierobe L, Cheval C, Moine P, Timsit JF. Efficiency of inhaled nitric oxide as rescue therapy during severe ARDS: Survival and factors associated with the first response. J Crit Care 1999; 14: 107–113

    Article  PubMed  CAS  Google Scholar 

  26. Treggiari-Venzi M, Ricou B, Romand JA, Suter PM. The response to repeated nitric oxide inhalation is inconsistent in patients with acute respiratory distress syndrome. Anesthesiol 1998; 88: 634–641

    Article  CAS  Google Scholar 

  27. Dellinger RP, Zimmerman JL, Taylor RW, Straube RC, Hauser DL, Criner GJ, Davis K Jr, Hyers TM, Papadakos P. Effects of inhaled nitric oxide in patients with acute respiratory distress: Results of a randomized phase II trial. Crit Care Med 1998; 1: 15–23

    Article  Google Scholar 

  28. Turnage WS, Lunn JJ. Post pneumonectomy pulmonary edema. A retrospective analysis of associated variables. Chest 1993; 103: 1646–1650

    PubMed  CAS  Google Scholar 

  29. Mathisen DJ, Kuo EY, Hahn C, Moncure AC, Wayne JC, Grillo HC, Hurford WE, Wright CD. Inhaled nitric oxide for adult respiratory distress syndrome after pulmonary resection. AnnThorac Surg 1998; 66: 1894–1902

    CAS  Google Scholar 

  30. Beck JR, Mongero LB, Kroslowitz RM, Choudhri AF, Chen JM, DeRose JJ, Argenziano M, Smerling AJ, Oz MC. Inhaled nitric oxide improves hemodynamics in patients with acute pulmonary hypertension after high-risk cardiac surgery. Perfusion 1999; 14: 37–42

    PubMed  CAS  Google Scholar 

  31. Yahagi N, Kumon K, Tanigami H, Watanabe Y, Haruna M, Hayashi H, Imanaka H, Takeuchi M, Takamoto S. Cardiac surgery and inhaled nitric oxide: Indication and follow-up (2–4 years). Artificial Organs 1998; 22: 886–891

    Article  PubMed  CAS  Google Scholar 

  32. Carrier M, Blaise G, Belisle S, Perrault LP, Pellerin M, Petitclerc R, Pelletier LC. Nitric oxide inhalation in the treatment of primary graft failure following heart transplantation. J Heart LungTransplant 1999; 18: 664–667

    Article  CAS  Google Scholar 

  33. Argenziano M, Choudhri AF, Moazami N, Rose EA, Smith CR, Levin HR, Smerling AJ, Oz MC. Randomized, double-blind trial of inhaled nitric oxide in LVAD recipients with pulmonary hypertension (see comment in: Ann Thorac Surg 1998; 66: 1862–1863). Ann Thorac Surg 1998; 65: 340–345

    Article  PubMed  CAS  Google Scholar 

  34. Schenk P, Pernerstorfer T, Mittermayer C, Kranz A, Frommel M, Birsan T, Ratheiser K. Inhalation of nitric oxide as a life-saving therapy in a patient after pulmonary embolectomy. Br J Anaesth 1999; 82: 444–447

    PubMed  CAS  Google Scholar 

  35. Christie JD, Bavaria JE, Palevsky HI, Litzky L, Blumenthal NP, Kaiser LR, Kotloff RM. Primary graft failure following lung transplantation. Chest 1998; 114: 51–60

    PubMed  CAS  Google Scholar 

  36. Meyer KC, Love RB, Zimmerman JJ. The therapeutic potential of nitric oxide in lung transplantation. Chest 1998; 113: 1360–71

    PubMed  CAS  Google Scholar 

  37. Date H, Triantafillou AN, Trulock EP, Pohl MS, Cooper JD, Patterson GA. Inhaled nitric oxide reduces human 400 Journal of ClinicalMonitoring and Computing Vol 16 Nos 5–6 2000 lung allograft dysfunction. J Thorac Cardiovasc Surg 1996; 111: 913–919

    Article  PubMed  CAS  Google Scholar 

  38. Adatia I, Lillehei C, Arnold JH, Thompson JE, Palazzo R, Fackler JC, Wessel DL. Inhaled nitric oxide in the treatment of postoperative graft dysfunction after lung transplantation. AnnThorac Surg 1994; 57: 1311–1318

    Article  CAS  Google Scholar 

  39. Adatia I, Perry S, Landzberg M, Moore P, Thompson JE, Wessel DL. Inhaled nitric oxide and hemodynamic evaluation of patients with pulmonary hypertension before transplantation. J Am Coll Cardiol 1995; 25: 1656

    Article  PubMed  CAS  Google Scholar 

  40. Bocchi EA, Bacal F. Auler JOJ, Carmone MJ, Bellotti G, Pileggi F. Inhaled nitric oxide leading to pulmonary edema in stable severe heart failure. Am J Cardiol 1994; 74: 70

    Article  PubMed  CAS  Google Scholar 

  41. Rasmussen TR, Kjaergaard SK, Tarp U, Pedersen OF. Delayed effects of NO2 exposure in alveolar permeability and glutathione peroxidase in healthy humans. Am Rev Respir Dis 1992; 146: 654–659

    PubMed  CAS  Google Scholar 

  42. Morrow PE, Utell MJ, Bauer MA, Smeglin AM, Frampton MW, Cox C, Speers DM, Gibb RF. Pulmonary performance of elderly normal subjects and subjects with chronic obstructive pulmonary disease exposed to 0.3 ppm nitrogen dioxide. Am Rev Respir Dis 1992; 145: 291–300

    PubMed  CAS  Google Scholar 

  43. Haddad IY, Pataki G, Hu P, Galliani C, Beckman JS, Matalon S. Quantitation of nitrotyrosine levels in lung sections of patients and animals with acute lung injury. J Clin Invest 1994; 94: 2407–2413

    Article  PubMed  CAS  Google Scholar 

  44. Hopkins RA, Bull C, Haworth SG, deLevel MR, Stark J. Pulmonary hypertensive crises following surgery for congenital heart defects in young children. Eur J Cardiothorac Surg 1991; 5: 628–634

    Article  PubMed  CAS  Google Scholar 

  45. Grover R, Murdoch I, Smithies M, Mitchell I, Bihari D. Nitric oxide during hand ventilation in patient with acute respiratory failure (Letter). Lancet 1992; 340: 1038–1039

    Article  PubMed  CAS  Google Scholar 

  46. Beghetti M, Habre W, Friedli B, Berner M. Continuous low dose inhaled nitric oxide for treatment of severe pulmonary hypertension after cardiac surgery in paediatric patients. Br Heart J 1995; 73: 65–68

    PubMed  CAS  Google Scholar 

  47. al-Alaiyan SS, al-Omran A, Dyer D. The use of phosphodiesterase inhibitor (dipyridamole) to wean from inhaled nitric oxide. Intens Care Med 1996; 22: 1093–1095

    CAS  Google Scholar 

  48. Atz AM, Adatia I, Wessel DL. Rebound pulmonary hypertension after inhalation of inhaled nitric oxide. AnnThorac Surg 1996; 62: 1759–1764

    Article  CAS  Google Scholar 

  49. Lavoie A, Hall JB, Olson DM, Wylan ME. Life-threatening effects of discontinuing inhaled nitric oxide in severe respiratory failure. Am J Respir Crit Care Med 1996; 153: 1985–1987

    PubMed  CAS  Google Scholar 

  50. Koleff MH. Inhaled nitric oxide for severe acute respiratory distress syndrome: A blessing or a curse? Heart Lung 1997; 26: 358–362

    Article  Google Scholar 

  51. Kennaugh JM, Kinsella JP, Abman SH, Hernandez JA, Moreland SG, Rosenberg AA. Impact of new treatments for neonatal pulmonary hypertension on extracorporeal membrane oxygenation use and outcome. J Perinat 1997; 17: 366–369

    CAS  Google Scholar 

  52. Wessel DL, Adatia I, Van Marter LJ, Thompson JE, Kane JW, Stark AR, Kourembanas S. Improved oxygenation in a randomized trial of inhaled nitric oxide for persistent pulmonary hypertension of the newborn. Pediatrics 1997; 100: E7

    Article  PubMed  CAS  Google Scholar 

  53. Davidson D, Barefield ES, Kattwinkel J, Dudell G, Damask M, Straube R, Rhines J, Chang CT. Inhaled nitric oxide for the early treatment of persistent pulmonary hypertension of the term newborn: A randomized, double-masked, placebo-controlled, dose-response, multicenter study. The I-NO/PPHN Study Group. Pediatrics 1998; 101: 325–334

    Article  PubMed  CAS  Google Scholar 

  54. Aranda M, Pearl RG. The pharmacology and physiology of nitric oxide: Understanding its use in anesthesia and critical care medicine. Anesth Clin No Amer Mar 1998; 16: 235–257

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Anesthesia, University of Pennsylvania, Philadelphia, PA, U.S.A.

    Margaret Aranda

  2. Department of Anesthesia, Stanford University School of Medicine, Stanford, CA, U.S.A.

    Ronald G. Pearl

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  1. Margaret Aranda
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  2. Ronald G. Pearl
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Aranda, M., Pearl, R.G. Inhaled Nitric Oxide and Pulmonary Vasoreactivity. J Clin Monit Comput 16, 393–401 (2000). https://doi.org/10.1023/A:1011468005527

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