ICU management of Pulmonary Hypertension

Literature review for the use of inhaled Nitric Oxide (iNO)Farooq Khan MDCM

PGY2 FRCP-EMMcGill University

Dec 3rd 2010

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

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

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

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

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

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

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

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

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