Prostacyclin in the intensive care setting

Abstract

The prostacyclins-prostanoids were one of the first medications used to treat pulmonary arterial hypertension (PAH). Three prostanoids have been developed to treat PAH: epoprostenol, treprostinil, and iloprost. In the acute setting, experience is growing, using the inhaled forms of these three medications. Inhalation may improve ventilation/perfusion matching, whereas in the intravenous form these medications may cause nonselective pulmonary vasodilation and may worsen ventilation/perfusion matching. Currently, there are no universal recommendations for dosing delivery of inhaled prostanoids to intubated patients in the intensive care unit setting.

Figure 1

Signal transduction pathway of the prostacyclin (PGI₂)–cyclic adenosine monophosphate (cAMP) pathway. Both PGI₂ and milrinone, a PDE3 inhibitor, increase cAMP by different mechanisms. COX, cyclooxygenase; AC, adenylate cyclase; ATP, adenosine triphosphate. Reprinted with permission from Rashid et al (7).

Figure 2

Prostacyclin I₂ (PGI₂) given intravenously nonselectively dilates the pulmonary vasculature and may worsen ventilation/perfusion matching. In contrast, inhaled PGI₂ may improve ventilation/perfusion matching by improving pulmonary blood flow to well-ventilated regions of the lung. PAP, pulmonary artery pressure; MAP, mean arterial pressure; Qs/Qt, intrapulmonary shunt. Reprinted with permission from Max and Rossaint (23).

Figure 3

Effect of inhaled prostacyclin I₂ (PGI₂) on oxygenation index (OI) in term neonates with persistent pulmonary hypertension of the newborn receiving inhaled nitric oxide. Inhaled PGI₂ decreased OI within 2 hrs except in one patient (patient 4) who was later found to have alveolar capillary dysplasia. Reprinted with permission from Kelly et al (25).

Figure 4

In children with pulmonary arterial hypertension associated with congenital heart disease, inhaled nitric oxide (iNO), and inhaled iloprost lowered the pulmonary vascular resistance/systemic vascular resistance ratio (Rp/Rs) compared with baseline. There was no additive effect of iNO to inhaled iloprost. Reprinted with permission from Rimensberger et al (46).

Figure 5

Effects of acute inhalation of iloprost in 13 children with pulmonary arterial hypertension. At baseline, mean mid-volume forced expiratory flow (FEF, 25–75%) was 82% of predicted (range, 32%–119%). After iloprost inhalation, mean FEF 25% to 75% decreased to 72% of predicted (p = .03). In five (38%) of 14 patients, FEF 25% to 75% decreased by >15% (range, −53% to −17%). Reprinted with permission from Ivy et al (40).

Figure 6

Effect of inhaled iloprost in 12 children with postoperative congenital heart disease. Iloprost lowered mean pulmonary artery pressure (mPAP) without lowering mean systemic blood pressure (mSBP). Reprinted with permission from Limsuwan et al (48).