What is the role of inhaled nitric oxide (iNO) in managing right ventricular (RV) failure without pulmonary arterial hypertension (PAH)?

Inhaled Nitric Oxide in RV Failure Without PAH

Inhaled nitric oxide (iNO) can be used as salvage therapy in acute right ventricular failure without pulmonary arterial hypertension, particularly when RV dysfunction causes hemodynamic instability, as it selectively reduces pulmonary vascular resistance and improves cardiac output without compromising systemic blood pressure. 1, 2

Primary Indication: Acute RV Failure with Hemodynamic Compromise

Use iNO at 20 ppm when RV failure causes hemodynamic instability despite conventional inotropic support. 3 The evidence supports this approach specifically in critically ill patients with acute right heart syndrome, where iNO significantly increases cardiac output (5.5 to 6.4 L/min), stroke volume (54 to 65 ml), and mixed-venous oxygen saturation (69% to 73%). 2

Key Advantages in Non-PAH RV Failure

• No detrimental effect on systemic vascular resistance (SVR), which is critical since maintaining SVR > PVR prevents right ventricular ischemia. 3
• Rapid onset and short half-life allow for quick titration and immediate reversal if ineffective. 3
• Improves oxygenation through ventilation-perfusion matching while simultaneously unloading the failing RV. 3

Specific Clinical Scenarios

Post-Cardiac Surgery RV Failure

iNO has demonstrated efficacy in reducing PVR and improving cardiac output in patients following coronary bypass surgery or valve replacement who develop acute RV dysfunction. 3

Acute Pulmonary Embolism with RV Dysfunction

Consider iNO as a bridge to definitive therapy (thrombolysis or thrombectomy) in submassive PE with severe hypoxemia and RV dysfunction. 3, 4 In one case series, iNO improved oxygenation from PaO2 52 mmHg to 81 mmHg within one hour, allowing successful thrombolysis. 4

LVAD-Associated RV Failure

iNO improves RV function in patients with dilated cardiomyopathy on LVAD support by reducing RV afterload, improving LV filling, and increasing LVAD flow. 5, 6 This prevents the need for RVAD placement in select patients. 5

Dosing Strategy

Start at 20 ppm and titrate in 10 ppm increments based on hemodynamic response. 3, 2

• 85% of responders achieve maximal benefit at ≤40 ppm. 2
• Mean effective concentration is 35 ppm. 2
• For RV dysfunction specifically, the Intensive Care Medicine consensus suggests 5-10 ppm may be sufficient. 1

Hemodynamic Response Patterns

Approximately 50% of patients show substantial improvement (>20% increase in hemodynamic parameters), and 25% improve enough to allow reduction of other vasoactive medications. 2

Predictors of Response

• Alpha-agonist catecholamine use predicts response to iNO. 2
• Baseline hemodynamics and underlying cause of RV failure do NOT predict response. 2
• Always perform a trial since response cannot be predicted from clinical parameters alone. 2

Critical Management Considerations

Weaning Protocol

Upon discontinuation, rebound pulmonary hypertension can occur, particularly without replacement pulmonary vasodilator therapy. 3 Start or restart a phosphodiesterase inhibitor (e.g., sildenafil) before weaning iNO. 3

Combination with Inotropes

Use iNO alongside inotropes that have neutral or beneficial effects on PVR:

• Dobutamine (preferred due to shorter half-life) 3
• Milrinone 3
• Epinephrine 3

Offset potential SVR drops with replacement-dose vasopressin, especially in septic patients where vasopressin deficiency is common. 3

Ventilator Management During iNO

• Limit peak pressures to <30 cmH2O to minimize increases in RV afterload. 3
• Keep PEEP ≤10 cmH2O if oxygenation allows. 3
• Avoid permissive hypercapnea as acidosis and hypercapnia acutely increase PVR. 3
• Target SpO2 >90% since hypoxia increases PVR. 3

Important Caveats

Adverse Effects

• Methemoglobinemia at sustained high doses (monitor levels). 3
• Tachyphylaxis can develop with prolonged use. 3
• Significant cost compared to other therapies. 3

When NOT to Use

Do not use iNO routinely or prophylactically in RV dysfunction. 1 Reserve for acute hemodynamic compromise where conventional therapies have failed or as a bridge to definitive intervention. 1, 2

Distinction from ARDS Management

Unlike ARDS where iNO improves oxygenation but not mortality and should be restricted to salvage therapy only after all evidence-based interventions fail 1, in acute RV failure without PAH, iNO has a more established role as it directly addresses the pathophysiology by reducing RV afterload and improving cardiac output. 2