Perioperative Pulmonary Hypertension (see Pulmonary Hypertension, [[Pulmonary Hypertension]])
General Comments: although early studies of iNO in the treatment of pulmonary hypertension used concentrations of 5-80 ppm, concentrations >20 ppm usually provide little additional hemodynamic benefit
Congenital Heart Disease
Cardiac Transplantation
Insertion of Ventricular Assist Device (VAD) (see Ventricular Assist Device, [[Ventricular Assist Device]])
Persistent Pulmonary Hypertension of the Newborn (see Pulmonary Hypertension, [[Pulmonary Hypertension]])
Pulmonary Vasoreactivity Testing in the Cardiac Catheterization Lab (see Pulmonary Hypertension, [[Pulmonary Hypertension]])
Pharmacology
Actions of Inhaled Nitric Oxide (iNO)
Selective Pulmonary Vasodilation with Improvement in Pulmonary V/Q Matching: due to increased perfusion to well-ventilated lung units and decreased shunt
In contrast, IV pulmonary vasodilators cause diffuse pulmonary vasodilation, resulting in worsening V/Q matching and increased shunt -> worsening pO2
Soluble guanylate cyclase converts GTP to cGMP -> intracellular cGMP relaxes smooth muscle via a number of different mechanisms
cGMP is hydrolyzed to GMP by cyclic nucleotide phosphodiesterases (PDE) or by export from the cell
PDE5 is the most active cGMP-hydrolyzing PDE in smooth muscle
PDE5 is selectively inhibited by zaprinast, sildenafil, and verdenafil
Inhaled Nitric Oxide Metabolism
After Diffusing into the Bloodstream, iNO is Scavenged by Hemoglobin and Rapidly Inactivated: prevents systemic vasodilation
In contrast, IV vasodilators can cause systemic vasodilation and systemic arterial hypotension
iNO Rapidly Reacts with Oxyhemoglobin: formation of methemoglobin + nitrate
About 70% of iNO is excreted within 48 hrs as nitrate in the urine
iNO Rapidly Reacts with Deoxyhemoglobin: formation of iron-nitrosyl-Hb
Administration
iNO Delivery Methods
Endotracheal Tube/Mechanical Ventilator: start at 10-20 ppm
Although early studies of iNO in the treatment of pulmonary hypertension used concentrations of 5-80 ppm, concentrations >20 ppm usually provide little additional hemodynamic benefit
Face Mask
Nasal Cannula
Weaning: gradual weaning is advised (to prevent rebound pulmonary hypertension)
Epidemiology: associated with rapid discontination of iNO
Physiology: likely related to downregulation of endogenous iNO or endothelin-1 synthesis
Clinical: consequently, gradual weaning of iNO is advised
Increased LV Filling Pressure
Epidemiology: may be observed in patients with LV dysfunction
Physiology: due to augmented LV filling of a stiff ventricle (rather than negative inotropy)
Toxicologic Adverse Effects
Formation of Nitrogen Dioxide
Physiology: iNO concentration-dependent
Clinical
Bronchospasm (see Obstructive Lung Disease, [[Obstructive Lung Disease]]): can occur with as little as 1.5 ppm of NO2
Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]]): occurs at higher NO doses, probably not clinically significant at 20 ppm of iNO
