Inhaled nitric oxide in primary pulmonary hypertension: a safe and effective agent for predicting response to nifedipine.
OBJECTIVE
The purpose of this study was to assess the utility of inhaled nitric oxide (NO), a selective pulmonary vasodilator, for predicting the safety and acute hemodynamic response to high-dose oral nifedipine in primary pulmonary hypertension (PPH).


BACKGROUND
A significant decrease in pulmonary vascular resistance with an oral nifedipine challenge is predictive of an improved prognosis, and potential clinical efficacy in PPH. However, the required nifedipine trial carries significant first-dose risk of hypotension. While inhaled NO has been recommended for assessing pulmonary vasodilator reserve in PPH, it is not known whether it predicts the response to nifedipine.


METHODS
Seventeen patients with PPH undergoing a nifedipine trial were assessed for hemodynamic response to inhaled NO at 80 parts per million for 5 minutes. The nifedipine trial consisted of 20 mg of nifedipine hourly for 8 hours unless limited by hypotension or intolerable side effects. Patients were classified as responders and nonresponders with positive response defined as > or =20% reduction in mean pulmonary artery pressure (mPA) or pulmonary vascular resistance (PVR) with the vasodilator administration.


RESULTS
NO was safely administered to all participants. Seven of 17 (41.2%) responded to NO, and 8 of the 17 to nifedipine (47.1%). Nifedipine was safely administered in 14 of the 17. Three suffered either mild or severe hypotension, including one death. All NO responders also responded to nifedipine, and 9 of the 10 NO nonresponders were nifedipine nonresponders, representing a sensitivity of 87.5%, specificity of 100%, and overall predictive accuracy of 94%. All NO responders tolerated a full nifedipine trial without hypotension. There was a highly significant correlation between the effects of NO and nifedipine on PVR (r=0.67, p=0.003).


CONCLUSIONS
The pulmonary vascular response to inhaled NO accurately predicts the acute hemodynamic response to nifedipine in PPH, and a positive response to NO is associated with a safe nifedipine trial. In patients comparable with those evaluated, a trial of nifedipine in NO nonresponders appears unwarranted and potentially dangerous.
Department of Internal Medicine, University of Michigan, Ann Arbor, USA.
M J
MJ
Ricciardi
B P
BP
Knight
F J
FJ
Martinez
M
M
Rubenfire
D000280:Administration, Inhalation; D000284:Administration, Oral; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000009:adverse effects / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000008:administration & dosage*; D011652:Pulmonary Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D009569:Nitric Oxide; D009543:Nifedipine