Nitric oxide is a potent vasodilator which when inhaled causes dilatation in the pulmonary vasculature. It is this action that has been studied in intensive care medicine, especially in relation to hypoxic vasoconstriction associated with acute respiratory distress syndrome (ARDS). The use of inhaled nitric oxide has been shown to improve ventilation:perfusion matching, and thus to improve oxygenation. This article reviews the chemistry and clinical properties of nitric oxide as well as its potential uses, clinical effectiveness and side effects. The authors also surveyed UK intensive care units to review the current prevalence of the use of inhaled nitric oxide. It was found that while the majority do not currently use inhaled nitric oxide in ARDS patients, it had still been used in 27% (n=61) of the departments surveyed.
KoshlandDE. The molecule of the year. Science1992;258: 1861.
2.
LiuVWHuangPL. Cardiovascular roles of nitric oxide: a review of insights from nitric oxide synthase gene disrupted mice. Cardiovasc Res2008;77: 19–29.
3.
MoncadaSHiggsEA. The L-arginine-nitric oxide pathway. N Engl J Med1993;329: 2002–12.
4.
VincentJLSakrYRanieriVM. Epidemiology and outcome of acute respiratory failure in intensive care unit patients. Crit Care Med2003;31: S296–S299.
5.
InglessisIShinJTLeporeJJ. Hemodynamic effects of inhaled nitric oxide in right ventricular myocardial infarction and cardiogenic shock. J Am Coll Cardiol2004;44: 793–98.
6.
Al HajeriASerjeantGRFedorowiczZ. Inhaled nitric oxide for acute chest syndrome in people with sickle cell disease. Cochrane Database Syst Rev2008;(1):CD006957.
7.
SerghidesLKimHLuZKainDC. Inhaled nitric oxide reduces endothelial activation and parasite accumulation in the brain, and enhances survival in experimental cerebral malaria. PLos One2011;6: e27714.
8.
BellinganGJ. The pulmonary physician in critical care · c6: The pathogenesis of ALI/ARDS. Thorax2002;57: 540–46.
9.
LuceJM. Acute lung injury and the acute respiratory distress syndrome. Crit Care Med1998;26: 369–76.
10.
Deby-DupontGLamyM. Pathophysiology of acute respiratory distress syndrome and acute lung injury. In: WebbAShapiroMJSingerMSuterPM, eds. Oxford Textbook of Critical Care. Oxford: Oxford University Press; 1999: 55–59.
11.
CordingleyJJKeoghBF. The pulmonary physician in critical care. 8: Ventilatory management of ALI/ARDS. Thorax2002;57: 729–34.
12.
Brun-BuissonCMinelliCBertoliniG. Epidemiology and outcome of acute lung injury in European intensive care units. Results from the ALIVE study. Intensive Care Med2004;30: 51–61.
13.
ZambonMVincentJL. Mortality rates for patients with acute lung injury/ARDS have decreased over time. Chest2008;133: 1120–27.
14.
DellingerRPTrzeciakSWCrinerGJ. Association between inhaled nitric oxide treatment and long-term pulmonary function in survivors of acute respiratory distress syndrome. Crit Care2012;16: R36.
Pepke-ZabaJHigenbottamTWDinh-XuanAT. Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet1991;338: 1173–74.
17.
AfshariABrokJMøllerAMWetterslevJ. Inhaled nitric oxide for acute respiratory distress syndrome and acute lung injury in adults and children: a systematic review with meta-analysis and trial sequential analysis. Anesth Analg2011;112: 1411–21.
18.
MaxeyTSSmithCDKernJA. Beneficial effects of inhaled nitric oxide in adult cardiac surgical patients. Ann Thorac Surg2002;73: 529–33.
19.
GerlachHKehDSemmerowA. 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 Med2003;167: 1008–15.
20.
RossaintRFalkeKJLopezF. Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med1993;328: 399–405.
21.
AdhikariNKBurnsKEFriedrichJO. Effect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review and meta-analysis. BMJ2007;334: 779.
22.
ButlerARMegsonILWrightPG. Diffusion of nitric oxide and scavenging by blood in the vasculature. Biochim Biophys Acta1998;1425: 168–76.
23.
JoshiMSFergusonTBJrHanTH. Nitric oxide is consumed, rather than conserved, by reaction with oxyhemoglobin under physiological conditions. Proc Natl Acad Sci USA2002;99: 10341–46.
24.
CogginsMPBlochKD. Nitric oxide in the pulmonary vasculature. Arterioscler Thromb Vasc Biol2007;27: 1877–85.
25.
CranshawJGriffithsMJDEvansTW. The pulmonary physician in critical care – part 9: Non-ventilatory strategies in ARDSThorax2002;57: 823–29.
26.
VallancePCollierJMoncadaS. Nitric oxide synthesized from L-arginine mediates endothelium dependent dilatation in human veins in vivo. Cardiovasc Res1989;23: 1053–57.
27.
CosbyKPartoviKSCrawfordJH. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med2003;9: 1498–1505.
28.
HuangZShivaSKim-ShapiroDB. Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control. J Clin Invest2005;115: 2099–107.
29.
MehtaRLPascualMTSorokoS. Spectrum of acute renal failure in the intensive care unit: the PICARD experience. Kidney Int2004;66: 1613–21.
30.
GoldhillD. Evidence-based medicine in critical care. JICS2012;13: 14–16.
31.
MontgomeryABStagerMACarricoCJHudsonLD. Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Respir Dis1985;132: 485–89.
32.
FerringMVincentJL. Is outcome from ARDS related to the severity of respiratory failure?Eur Resp J1997;10: 1297–300.
33.
Del SorboLSlutskyAS. Acute respiratory distress syndrome and multiple organ failure. Curr Opin Crit Care2011;17: 1–6.
