CLINICAL STUDIES
Inhaled nitric oxide in primary pulmonary hypertension
A safe and effective agent for predicting response to nifedipine
Mark J. Ricciardi, MDa,
Bradley P. Knight, MDa,
Fernando J. Martinez, MDb and
Melvyn Rubenfire, MD, FACCa
a Division of Cardiology, University of Michigan, Ann Arbor, Michigan, USA
b Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA
Manuscript received March 3, 1998;
revised manuscript received May 29, 1998,
accepted June 12, 1998.
Address for correspondence: Melvyn Rubenfire, MD, University of Michigan Health System, 24 Frank Lloyd Wright Drive, Ann Arbor, MI 48106-0363
Mrubenfi{at}umich.edu
Objectives. 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  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.
|
Abbreviations and Acronyms
| | CO | = cardiac output | | mPA | = mean pulmonary artery pressure | | mRA | = mean right atrial pressure | | NO | = nitric oxide | | PPH | = primary pulmonary hypertension | | PVR | = pulmonary vascular resistance |
|
This article has been cited by other articles:
|
|
|
|
 
Z-C. Jing, X. Jiang, Z-Y. Han, X-Q. Xu, Y. Wang, Y. Wu, H. Lv, C-R. Ma, Y-J. Yang, and J-L. Pu
Iloprost for pulmonary vasodilator testing in idiopathic pulmonary arterial hypertension
Eur. Respir. J.,
June 1, 2009;
33(6):
1354 - 1360.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Skoro-Sajer, N. Hack, R. Sadushi-Kolici, D. Bonderman, J. Jakowitsch, W. Klepetko, M. A. R. Hoda, M. P. Kneussl, P. Fedullo, and I. M. Lang
Pulmonary Vascular Reactivity and Prognosis in Patients With Chronic Thromboembolic Pulmonary Hypertension: A Pilot Study
Circulation,
January 20, 2009;
119(2):
298 - 305.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. A. Ghofrani, M. W. Wilkins, and S. Rich
Uncertainties in the Diagnosis and Treatment of Pulmonary Arterial Hypertension
Circulation,
September 9, 2008;
118(11):
1195 - 1201.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. D. Bloch, F. Ichinose, J. D. Roberts Jr., and W. M. Zapol
Inhaled NO as a therapeutic agent
Cardiovasc Res,
July 15, 2007;
75(2):
339 - 348.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. M. Mourani, D. D. Ivy, D. Gao, and S. H. Abman
Pulmonary Vascular Effects of Inhaled Nitric Oxide and Oxygen Tension in Bronchopulmonary Dysplasia
Am. J. Respir. Crit. Care Med.,
November 1, 2004;
170(9):
1006 - 1013.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Ichinose, J. D. Roberts Jr, and W. M. Zapol
Inhaled Nitric Oxide: A Selective Pulmonary Vasodilator: Current Uses and Therapeutic Potential
Circulation,
June 29, 2004;
109(25):
3106 - 3111.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. H. Leuchte, M. Schwaiblmair, R. A. Baumgartner, C. F. Neurohr, T. Kolbe, and J. Behr
Hemodynamic Response to Sildenafil, Nitric Oxide, and Iloprost in Primary Pulmonary Hypertension
Chest,
February 1, 2004;
125(2):
580 - 586.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bhatia, R. P. Frantz, C. J. Severson, L. A. Durst, and M. D. McGoon
Immediate and Long-term Hemodynamic and Clinical Effects of Sildenafil in Patients With Pulmonary Arterial Hypertension Receiving Vasodilator Therapy
Mayo Clin. Proc.,
October 1, 2003;
78(10):
1207 - 1213.
[Abstract]
[PDF]
|
|
|
|
|
|
|
D. Chemla, V. Castelain, P. Herve, Y. Lecarpentier, and S. Brimioulle
Haemodynamic evaluation of pulmonary hypertension
Eur. Respir. J.,
November 1, 2002;
20(5):
1314 - 1331.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Michelakis, W. Tymchak, D. Lien, L. Webster, K. Hashimoto, and S. Archer
Oral Sildenafil Is an Effective and Specific Pulmonary Vasodilator in Patients With Pulmonary Arterial Hypertension: Comparison With Inhaled Nitric Oxide
Circulation,
May 21, 2002;
105(20):
2398 - 2403.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.A. Ghofrani, R. Wiedemann, F. Rose, N. Weissmann, R.T. Schermuly, K. Quanz, F. Grimminger, W. Seeger, and H. Olschewski
Lung cGMP release subsequent to NO inhalation in pulmonary hypertension: responders versus nonresponders
Eur. Respir. J.,
April 1, 2002;
19(4):
664 - 671.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Bossone, G. Paciocco, D. Iarussi, A. Agretto, A. Iacono, B. W. Gillespie, and M. Rubenfire
The Prognostic Role of the ECG in Primary Pulmonary Hypertension
Chest,
February 1, 2002;
121(2):
513 - 518.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. M. Robbins, R. J. Barst, R. N. Channick, and L. J. Rubin
Pulmonary vasoreactivity in PPH
J. Am. Coll. Cardiol.,
October 1, 2001;
38(4):
1267 - 1267.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Paciocco, F.J. Martinez, E. Bossone, E. Pielsticker, B. Gillespie, and M. Rubenfire
Oxygen desaturation on the six-minute walk test and mortality in untreated primary pulmonary hypertension
Eur. Respir. J.,
April 1, 2001;
17(4):
647 - 652.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. G. Nielsen
Nitric Oxide Decreases Coagulation Protein Function in Rabbits as Assessed by Thromboelastography
Anesth. Analg.,
February 1, 2001;
92(2):
320 - 323.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Krasuski, J. J. Warner, A. Wang, J. K. Harrison, V. F. Tapson, and T. M. Bashore
Inhaled nitric oxide selectively dilates pulmonary vasculature in adult patients with pulmonary hypertension, irrespective of etiology
J. Am. Coll. Cardiol.,
December 1, 2000;
36(7):
2204 - 2211.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Archer and S. Rich
Primary Pulmonary Hypertension : A Vascular Biology and Translational Research "Work in Progress"
Circulation,
November 28, 2000;
102(22):
2781 - 2791.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. G. NIELSEN, M. S. BAIRD, L. CHEN, and S. MATALON
DETANONOate, a Nitric Oxide Donor, Decreases Amiloride-sensitive Alveolar Fluid Clearance in Rabbits
Am. J. Respir. Crit. Care Med.,
April 1, 2000;
161(4):
1154 - 1160.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
H. Olschewski, H. A. Ghofrani, T. Schmehl, J. Winkler, H. Wilkens, M. M. Hoper, J. Behr, F.-X. Kleber, W. Seeger, and for the German PPH Study Group*
Inhaled Iloprost To Treat Severe Pulmonary Hypertension: An Uncontrolled Trial
Ann Intern Med,
March 21, 2000;
132(6):
435 - 443.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Hoeper, H. Olschewski, H. A. Ghofrani, H. Wilkens, J. Winkler, M. M. Borst, J. Niedermeyer, H. Fabel, W. Seeger, and the German PPH Study Group
A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension
J. Am. Coll. Cardiol.,
January 1, 2000;
35(1):
176 - 182.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Ricciardi, E. Bossone, D. S. Bach, W. F. Armstrong, and M. Rubenfire
Echocardiographic Predictors of an Adverse Response to a Nifedipine Trial in Primary Pulmonary Hypertension: Diminished Left Ventricular Size and Leftward Ventricular Septal Bowing
Chest,
November 1, 1999;
116(5):
1218 - 1223.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. S Hayward, R. P Kelly, and P. S Macdonald
Inhaled nitric oxide in cardiology practice
Cardiovasc Res,
August 15, 1999;
43(3):
628 - 638.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
