Inhaled Aerosolized Prostacyclin for Pulmonary Hypertension Requiring Inhaled Nitric Oxide

Acute secondary pulmonary hypertension (PH) often leads to dysfunction of the right ventricle (RV) and can be a significant cause of patient morbidity and mortality. Selective pulmonary vasodilation with inhaled nitric oxide (INO) has become the treatment of choice for this condition. The evidence supporting INO safety and efficacy under these circumstances is sparse, however, and is largely extrapolated from the use of INO in neonatal pulmonary hypertension. Moreover, the high cost and potential toxicity of INO makes the therapy far from ideal. Emerging evidence suggests that inhaled aerosolized prostacyclins such as iloprost may be a favorable alternative therapy.

Phase 1- In the original study, 3 doses of Iloprost were given. This was revised after 5 subjects were enrolled in order to study the effects of continuous delivery over a longer period of time. Phase 2 - All remaining subjects received Iloprost as a continuous treatment. The study was designed for an enrollment of 200 subjects and was ended early.

Each subject will have a stable dose of INO therapy as established by the attending physicians for at least one hour. Initial baseline data collection will then be made. A 20 mcg dose of Iloprost will be given initially. During this treatment there will be a nitric oxide titration to 0. Iloprost will be aerosolized continuously at a dose of 5-30mcg/hour for as long as the attending physician deems it necessary to deliver vasodilator therapy.

Each subject will have a stable dose of INO therapy as established by the attending physicians for at least one hour. Initial baseline data collection will then be made. A 20 mcg dose of Iloprost will be given initially. During this treatment there will be a nitric oxide titration to 0. Iloprost will be aerosolized three different times on hour apart. Thirty minutes after the last iloprost dose, INO will be added back at the previous (baseline) dose.

Readings were taken from the medical record and the data may not have been present at the exact time frames.

30 mins after initial dose, every 2 hours as long as subject was on drug up to approximately 24 hours

dose 1 (1 hour), dose 2 (2 hour), dose 3 (3 hour), combined therapy (4.5 - 5 hour), end INO (6 - 7 hour)

30 mins after initial dose, every 2 hours as long as subject was on drug up to approximately 24 hours

dose 1 (1 hour), dose 2 (2 hour), dose 3 (3 hour), combined therapy (4.5 - 5 hour), end INO (6 - 7 hour)

Treatment failure is defined as Central venous pressure (CVP) ≥ 20 mm Hg and any one of the following: Cardiac Index (CI) >/= 1.8 L/min/m2 Administration of >/=0.1 ug/kg/min Epinephrine or Norepinephrine MAP </= 50 mmHg (or as appropriate for age in pediatrics). SvO2</= 55% (or < 45% for patients with R to L intracardiac shunting and, thus, cyanosis at baseline.}

30 mins after initial dose, every 2 hours as long as subject was on drug up to approximately 24 hours

dose 1 (1 hour), dose 2 (2 hour), dose 3 (3 hour), combined therapy (4.5 - 5 hour), end INO (6 - 7 hour)

30 mins after initial dose, every 2 hours as long as subject was on drug up to approximately 24 hours

dose 1 (1 hour), dose 2 (2 hour), dose 3 (3 hour), combined therapy (4.5 - 5 hour), end INO (6 - 7 hour)

30 mins after initial dose, every 2 hours as long as subject was on drug up to approximately 24 hours

dose 1 (1 hour), dose 2 (2 hour), dose 3 (3 hour), combined therapy (4.5 - 5 hour), end INO (6 - 7 hour)

Inclusion Criteria: Clinical evidence of pulmonary hypertension (PH) requiring INO therapy as prescribed by the attending physician. Indwelling arterial catheter. Signed informed consent Exclusion Criteria: Clinically unstable circulatory condition requiring epinephrine > 0.1 mcg/kg/min or levophed, or already meeting treatment failure criteria (see section 5.3 below) Known hypersensitivity to prostacyclin compounds Patients receiving sildenafil or bosentan Refusal by the attending physician