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ICU Management of Pulmonary Hypertension


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Brief literature review for the use of inhaled Nitric Oxide (iNO) to treat pulmonary hypertension in the critical care setting

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ICU Management of Pulmonary Hypertension

  1. 1. ICU management of Pulmonary Hypertension Literature review for the use of inhaled Nitric Oxide (iNO) Farooq Khan MDCM PGY2 FRCP-EM McGill University Dec 3rd 2010
  2. 2. Mechanism of action of nitric oxide • Potent inhaled vasodilator • Dilates pulmonary vasculature in ventilated lung units – improves oxygenation – reverses hypoxic pulmonary vasoconstriction – reduces PAP • Quickly inactivated by reaction with hemoglobin in the pulmonary capillaries – no significant systemic vasodilatory effects
  3. 3. Current WHO indications for therapy • Group 1 – Stabilization of PAH crisis – Hemodynamic support in OB patients – Treatment of porto-pulmonary hypertension • Groups 2-5 – PVH post cardiac surgery – Rescue from refractory hypoxemia in acute lung disease – Hemodynamic support in acute thromboembolic disease
  4. 4. Human physiological study • Pepke-Zaba J, Higenbottam TW, Dinh-Xuan AT, et al: Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet 1991; 338: 1173–1174 – Inhaled NO vs prostacyclin in severe PAH patients and control patients – Predictable drop in PAP without concomitant drop in SVR in both groups compared to placebo and compared to prostacyclin
  5. 5. Clinical studies of effect on chronic PAH • Cockrill BA, Kacmarek RM, Fifer MA, et al: Comparison of the effects of nitric oxide, nitroprusside, and nifedipine on hemodynamics and right ventricular contractility in patients with chronic pulmonary hypertension. Chest 2001; 119:128–136 – Decreased PAP, PVR and RVEDP – MAP unchanged, RV contractility unchanged – SVI increased
  6. 6. Effect of iNO in RH syndrome • Bhorade S, Christenson J, O’Connor M, et al: Response to inhaled nitric oxide in patients with acute right heart syndrome. Am J Respir Crit Care Med 1999; 159: 571–579 – Increase in CO (36%), SV and MVO2 sat – 38% decrease in PVR – 28% increase in PaO2/FiO2 – Not designed to study mortality
  7. 7. iNO in other disease states • iNO as treatment for severe ARDS – Kaisers U, Busch T, Deja M, et al: Selective pulmonary vasodilation in acute respiratory distress syndrome. Crit Care Med 2003; 31: S337–S342 • reduce pulmonary hypertension • improve matching of ventilation to perfusion and thus, hypoxemia – Taylor RW, Zimmerman JL, Dellinger RP, et al: Low- dose inhaled nitric oxide in patients with acute lung injury: A randomized controlled trial. JAMA 2004; 291:1603–1609 • Short term effect on increasing PaO2 • No effect on mortality or days spent off vent
  8. 8. iNO in other disease states • iNO in severe heart failure – Semigran MJ, Cockrill BA, Kacmarek R, et al: Hemodynamic effects of inhaled nitric oxide in heart failure. J Am Coll Cardiol 1994; 24:982–988 • Decrease in PAH caused by LV failure • Identify patients with reversible pulmonary vasocontriction where nipride can cause systemic hypotension
  9. 9. iNO in other disease states • iNO post MVR in chronic PAH patients – Girard C, Lehot JJ, Pannetier JC, et al: Inhaled nitric oxide after mitral valve replacementin patients with chronic pulmonary artery hypertension. Anesthesiology 1992;77:880–883 • Decrease in PAP, PVR • Increase in MVO2 Sat, no change in MAP or PCWP
  10. 10. Adverse effects • Methemoglobinemia – Weinberger B, Laskin DL, Heck DE, et al: The toxicology of inhaled nitric oxide. Toxicol Sci 2001; 59:5–16 • Oxidative stress due to combination with O2 creating NO2 – Wang T, El Kebir D, Blaise G: Inhaled nitric oxide in 2003: A review of its mechanisms of action. Can J Anaesth 2003; 50:839–846 • Abrupt withdrawal can cause rebound Pah and cardiovascular collapse – Christenson J, Lavoie A, O’Connor M, et al: The incidence and pathogenesis of cardiopulmonary deterioration after abrupt withdrawal of inhaled nitric oxide. Am J Respir Crit Care Med 2000; 161:1443–1449