Department of Pharmacy, Banner Good Samaritan Medical Center, Phoenix, Arizona 85006, USA.
Pharmacotherapy. 2010 Jul;30(7):728-40. doi: 10.1592/phco.30.7.728.
Pulmonary arterial hypertension (PAH) is a progressive disease without a cure. The primary treatment goal for patients with this disease is improving pulmonary blood flow through vasodilation of the pulmonary arteries. Several drugs are available that ameliorate walk distance and hemodynamics, but their maximum tolerated doses are limited in critically ill patients with PAH because of systemic vasodilation resulting in hypotension. The ideal vasodilator would be cost-effective, safe, and selective to the pulmonary vasculature; no such agent currently exists. Inhaled nitric oxide selectively reduces pulmonary pressures without systemic hypotension. However, it is expensive, potentially toxic, and requires complex technology for monitoring and administration. Inhaled epoprostenol may be an alternative therapy to minimize systemic hypotension, which often accompanies rapid intravenous titration. To evaluate the safety and efficacy of inhaled epoprostenol in critically ill patients with PAH, we conducted a literature search by using the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases (1966-August 2009) for relevant studies. Case reports and in vitro studies were excluded. Overall, 11 studies met the inclusion criteria. The PAH population included patients requiring cardiac surgery, lung or heart transplantation, or nonspecific intensive care. All trials showed that inhaled epoprostenol significantly decreased pulmonary pressures without lowering systemic blood pressure. The duration of therapy in most studies was 10-15 minutes, with one study evaluating its effects up to an average of 45.6 hours. Pulmonary pressures returned to baseline soon after drug discontinuation. Minimal adverse events were reported. Thus, inhaled epoprostenol in various subgroups of critically ill patients was effective in reducing pulmonary pressures. However, the significance of these effects on improving clinical outcomes remains unknown. Further studies are needed to determine the role of inhaled epoprostenol in critically ill patients with PAH.
肺动脉高压(PAH)是一种无法治愈的进行性疾病。该病患者的主要治疗目标是通过肺动脉扩张来改善肺血流量。有几种药物可改善步行距离和血液动力学,但在患有 PAH 的重症患者中,由于全身血管扩张导致低血压,其最大耐受剂量有限。理想的血管扩张剂应该具有成本效益、安全且对肺血管具有选择性;目前尚无此类药物。吸入性一氧化氮选择性降低肺动脉压而不引起全身低血压。然而,它昂贵、潜在毒性且需要复杂的监测和给药技术。吸入性前列环素可能是一种替代疗法,可以最大限度地减少经常伴随快速静脉滴定出现的全身低血压。为了评估吸入性前列环素在患有 PAH 的重症患者中的安全性和疗效,我们使用 MEDLINE、EMBASE 和 Cochrane 对照试验中心注册数据库(1966 年-2009 年 8 月)进行了文献检索,以查找相关研究。排除了病例报告和体外研究。共有 11 项研究符合纳入标准。PAH 患者人群包括需要心脏手术、肺或心脏移植或非特异性重症监护的患者。所有试验均表明,吸入性前列环素可显著降低肺动脉压而不降低全身血压。大多数研究的治疗持续时间为 10-15 分钟,有一项研究评估了其长达平均 45.6 小时的效果。停药后不久,肺压即恢复到基线水平。报告的不良事件很少。因此,吸入性前列环素在各种重症患者亚组中可有效降低肺压。然而,这些效果对改善临床结局的意义尚不清楚。需要进一步研究以确定吸入性前列环素在患有 PAH 的重症患者中的作用。