Ricciardi M J, Knight B P, Martinez F J, Rubenfire M
Department of Internal Medicine, University of Michigan, Ann Arbor, USA.
J Am Coll Cardiol. 1998 Oct;32(4):1068-73. doi: 10.1016/s0735-1097(98)00361-1.
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).
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.
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.
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).
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.
本研究旨在评估吸入一氧化氮（NO）这一选择性肺血管扩张剂，用于预测原发性肺动脉高压（PPH）患者对大剂量口服硝苯地平的安全性及急性血流动力学反应的效用。
口服硝苯地平激发试验导致肺血管阻力显著降低，预示着预后改善及PPH潜在的临床疗效。然而，所需的硝苯地平试验存在显著的首剂低血压风险。虽然已推荐吸入NO用于评估PPH患者的肺血管扩张储备，但尚不清楚它能否预测对硝苯地平的反应。
17例接受硝苯地平试验的PPH患者接受评估，吸入百万分之80的NO 5分钟，观察血流动力学反应。硝苯地平试验包括每小时口服20 mg硝苯地平，共8小时，除非因低血压或无法耐受的副作用而受限。患者分为反应者和无反应者，阳性反应定义为使用血管扩张剂后平均肺动脉压（mPA）或肺血管阻力（PVR）降低≥20%。
所有参与者均安全吸入NO。17例中有7例（41.2%）对NO有反应，17例中有8例（47.1%）对硝苯地平有反应。17例中有14例安全服用了硝苯地平。3例出现轻度或重度低血压，其中1例死亡。所有对NO有反应者对硝苯地平也有反应，10例对NO无反应者中有9例对硝苯地平无反应，敏感性为87.5%，特异性为100%，总体预测准确性为94%。所有对NO有反应者均耐受了完整的硝苯地平试验且未出现低血压。NO和硝苯地平对PVR的影响之间存在高度显著的相关性（r = 0.67，p = 0.003）。
吸入NO引起的肺血管反应可准确预测PPH患者对硝苯地平的急性血流动力学反应，对NO的阳性反应与安全的硝苯地平试验相关。在与所评估患者类似的患者中，对NO无反应者进行硝苯地平试验似乎没有必要且可能有危险。
