iloprost and Respiratory-Distress-Syndrome

Epoprostenol and the structurally related compounds treprostinil, iloprost, and beraprost are collectively referred to as prostanoids. The discovery of epoprostenol in 1976 and unequivocal demonstration of its efficacy in 1996 dramatically altered the approach to therapy for pulmonary arterial hypertension (PAH). Development of prostanoids available through multiple routes of administration and the discovery and development of other agents acting through alternative pathways continue to expand the array of therapeutic options. The use of prostanoids in combination with other PAH drugs and for treating pulmonary hypertensive disorders outside of the PAH classification are areas of ongoing research.

Topics: Antihypertensive Agents; Chronic Disease; Epoprostenol; Heart Defects, Congenital; Humans; Hypertension, Portal; Hypertension, Pulmonary; Iloprost; Prostaglandins; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome

Two prostacyclins (prostaglandin E(1) and prostaglandin I(2)) are potent vasodilators. Aerosolized prostacyclins reduce pulmonary artery pressure, improve right heart function, and increase arterial oxygenation by improving ventilation/perfusion matching. This report describes aerosolized prostacyclins and compares them to inhaled nitric oxide. I review the types of inhalable prostacyclins and their indications, evidence of efficacy, delivery, and adverse effects.

Topics: Administration, Inhalation; Aerosols; Alprostadil; Dose-Response Relationship, Drug; Epoprostenol; Equipment Design; Humans; Hypertension, Pulmonary; Iloprost; Nebulizers and Vaporizers; Nitric Oxide; Prostaglandins I; Respiratory Distress Syndrome; Respiratory Therapy; Treatment Outcome; Vasodilator Agents; Ventricular Dysfunction, Right

Topics: Administration, Inhalation; Alprostadil; Animals; Epoprostenol; Humans; Hypertension, Pulmonary; Iloprost; Nitric Oxide; Nitroglycerin; Nitroprusside; Phosphodiesterase Inhibitors; Pulmonary Circulation; Respiratory Distress Syndrome; Vasodilator Agents

We hypothesized that nebulized iloprost would improve ventilation-perfusion matching in patients with pulmonary hypertension and ARDS as reflected by an improved Pao2/Fio2 ratio and Pao2 without adversely affecting lung mechanics or systemic hemodynamics.. Patients with ARDS and pulmonary hypertension were enrolled. With constant ventilator settings, hemodynamics, airway pressures, and gas exchange measured at baseline were compared with values 30 min after administration of 10 μg nebulized iloprost, and again 30 min after a second, larger, 20 μg dose of iloprost, and then a final measurement 2 h after the second dose. The primary outcome variable was Pao2; secondary outcomes were Pao2/Fio2 ratio, mean arterial BP, and lung-compliance ventilatory equivalents for oxygen and CO2.. After informed consent was obtained, 20 patients (nine men, 11 women; median age, 59 years [interquartile range, 44-66 years]) with ARDS were enrolled. Baseline PaO2 improved from a mean (±SD) of 82 (13) mm Hg to 100 (25) mm Hg after both the first and second doses of iloprost, and the baseline mean (±SD) PaO2/FIO2 ratio of 177 (60) improved to 213 (67) and 212 (70) (all P<.01). PaCO2, peak and plateau airway pressures, systemic BP, and heart rate were not significantly changed after iloprost.. The improvement in gas exchange without any detrimental effects on pulmonary mechanics or systemic hemodynamics suggests nebulized iloprost may be a useful therapeutic agent to improve oxygenation in patients with ARDS.. ClinicalTrials.gov; No.: NCT01274481; URL: www.clinicaltrials.gov.

Topics: Administration, Inhalation; Adult; Aged; Comorbidity; Dose-Response Relationship, Drug; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Pulmonary Gas Exchange; Respiratory Distress Syndrome; Respiratory Mechanics; Treatment Outcome; Vasodilator Agents

Epithelial damage together with endothelitis and microvascular thrombi are responsible for COVID-19 associated acute respiratory distress syndrome (ARDS). Iloprost, improves endothelial damage and reduces thrombotic complications with its vasodilator, anti-platelet, anti-inflammatory, and anti-fibrotic effects. In our study, we aimed to determine the effect of iloprost on oxygenation, hemodynamics, weaning, and mortality in severe COVID-19 ARDS.. This was a retrospective study conducted in a pandemic hospital in the city of Istanbul, Turkey. Patients, with severe COVID-19 ARDS, who were receiving iloprost for seven days were included in the study. The demographic data, APACHE II, and SOFA (Sequential Organ Failure Assessment score) scores (at admission and discharge), pH, PaO2, PCO2, SatO2, lactate, PaO2/FiO2 (inspiratory fractionated oxygen), respiratory rate-oxygenation (ROX) index (peripheral oxygen saturation/fraction of inhaled oxygen), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressures (MAP), heart rate (HR) values were recorded before starting iloprost (T0), and on days of iloprost administration (2.0 nanograms/kg/minute/6 hours/day) (T1, T2, T3, T4, T5, T6, T7), and the day after last day of iloprost administration (Tfinal). Also, mortality was recorded in a retrospective manner. Two groups were formed according to mortality (Group M) and discharge (Group D).. A total of 22 patients (16 men, 6 women) were evaluated. Age, APACHE II, SOFA scores were higher in Group M. The lactate value at T1-3-4-5-7 was lower than T0 in both groups. PaO2 value between T2-Tfinal was higher than T0. A statistically significant increase was found in PaO2/FiO2 levels in both groups. The PaO2/FiO2value between T5-Tfinal was significantly lower in Group M compared to Group D. ROX index was significantly higher between T4-Tfinal when compared with T0.. Iloprost improves oxygenation but has no effect on mortality in COVID-19 ARDS.

Topics: COVID-19; Female; Humans; Iloprost; Male; Prognosis; Respiratory Distress Syndrome; Retrospective Studies

In acute respiratory distress syndrome (ARDS), pulmonary hypertension is associated with a poor prognosis. Prone position is effective to improve oxygenation whereas inhaled iloprost can treat pulmonary hypertension. However, combination of these interventions has not been examined before. The hypothesis was that this combination had additive effects on oxygenation and pulmonary hemodynamics as compared with each intervention alone.. In a prospective, randomized cross-over study, ten pigs were anesthetized, intubated and ventilated with volume controlled ventilation. Carotid, jugular venous and pulmonary artery catheters were inserted. ARDS was induced with oleic acid (0.20 mL/kg). Measurements were repeated in randomized different sequences of prone or supine positions with or without iloprost inhalation (220 ng/kg/min) (four combinations). Systemic and pulmonary arterial pressures; arterial and mixed venous blood gases; and Qs/Qt and the resistances were recorded.. Iloprost decreased pulmonary artery pressures (for MPAP: P=0.034) in both supine (37±10 vs. 31±8 mmHg; P<0.05) and prone positions (38±9 vs. 29±8 mmHg; P<0.05); but did not obtain a significant improvement in oxygenation in both positions. Prone position improved the oxygenation (p<0.0001) compared to supine position in both with (361±140 vs. 183±158 mmHg, P<0.05) or without iloprost application (331±112 vs. 167±117 mmHg, P<0.05); but did not achieve a significant decrease in MPAP.. Although iloprost reduced pulmonary arterial pressures, and prone positioning improved oxygenation; there are no additive effects of the combination of both interventions on both parameters. To treat both pulmonary hypertension and hypoxemia, application of iloprost in prone position is suggested.

Topics: Administration, Inhalation; Animals; Blood Pressure; Carotid Arteries; Cross-Over Studies; Drug Evaluation, Preclinical; Hypertension, Pulmonary; Hypoxia; Iloprost; Jugular Veins; Male; Oleic Acid; Oxygen; Prognosis; Prone Position; Prospective Studies; Pulmonary Artery; Random Allocation; Respiration, Artificial; Respiratory Distress Syndrome; Sus scrofa; Swine

Topics: Animals; Hypertension, Pulmonary; Iloprost; Male; Oxygen; Prone Position; Respiratory Distress Syndrome

Young infants with measles requiring respiratory support have a significant risk for death and long-term complications. Even in developed countries, the occurrence of spontaneous air-leaks and acute respiratory distress syndrome (ARDS) still represent the most severe clinical presentation in early childhood, with a high fatality rate. A clinical series review from a tertiary university paediatric intensive care unit (PICU) was undertaken. During the 2006-2007 outbreak in Rome, Italy, a young infant presented with ARDS/spontaneous air-leak and needed aggressive ventilatory management and haemodynamic support. Both nebulised iloprost and intravenous pentoxifylline were administered during the acute hypoxaemic phase; the role of this pharmacologic approach in critically ill patients is still under debate. We observed four further cases of respiratory impairment requiring a non-invasive approach. Clinical-radiological findings ranged from interstitial pneumonia to bronchiolitis-like pictures. All patients were imported cases, representing an important epidemiological factor and future medical issue, though they were not malnourished nor affected by chronic diseases. We conclude that early respiratory assessment and timely PICU referral is of mainstem importance in the youngest infants with measles-induced respiratory failure. The protean nature of clinical presentation and the possibility of rapid respiratory deterioration should be highlighted, and infants from immigrant families may represent a susceptible high-risk group.

Topics: Bronchiolitis; Child, Preschool; Disease Outbreaks; Female; Humans; Iloprost; Infant; Intensive Care Units, Pediatric; Lung Diseases, Interstitial; Male; Measles; Pentoxifylline; Platelet Aggregation Inhibitors; Radiography, Thoracic; Respiratory Distress Syndrome; Rome

Meconium aspiration induces acute lung injury (ALI) and subsequent pulmonary arterial hypertension (PAH) which may lead to right ventricular failure. Increase of endothelin-1, thromboxane-A, and phosphodiesterases are discussed molecular mechanisms. We investigated the intrapulmonary and hemodynamic effects of the intravenous dual endothelin A and B receptor blocker tezosentan and inhalational iloprost in a model of ALI due to meconium aspiration.. Animal study.. University-affiliated research laboratory.. White farm pigs.. Acute lung injury was induced in 24 pigs by instillation of meconium. Animals were randomly assigned to four groups to receive either intravenous tezosentan, inhalational iloprost, or combined tezosentan and iloprost, or to serve as controls.. After meconium aspiration-induced lung injury each treatment increased oxyhemoglobin saturations (TEZO: 88 +/- 6% (p = 0.02), ILO: 85 +/- 13% (p = 0.05), TEZO-ILO: 89 +/- 6% (p = 0.02), control: 70 +/- 18%). TEZO but not ILO significantly decreased pulmonary arterial pressure and pulmonary vascular resistance (both p < 0.01). ILO alone decreased intrapulmonary shunt blood flow (p < 0.01). Compared with control, TEZO-ILO yielded the highest arterial partial pressure of oxygen (70 +/- 6 torr vs.49 +/- 9 torr, p = 0.04), although it decreased arterial blood pressure (change from 71 +/- 13 mmHg to 62 +/- 12 mmHg vs.85 +/- 14 mmHg to 80 +/- 11 mmHg (p = 0.01).. Intravenous TEZO improves pulmonary gas exchange and hemodynamics in experimental acute lung injury secondary to meconium aspiration. Inhaled ILO improves gas exchange only, thereby reducing intrapulmonary shunt blood flow. Combination of TEZO and ILO marginally improves pulmonary gas exchange at the disadvantage of pulmonary selectivity.

Topics: Analysis of Variance; Animals; Hemodynamics; Humans; Iloprost; Infant, Newborn; Injections, Intravenous; Meconium Aspiration Syndrome; Pulmonary Gas Exchange; Pyridines; Respiratory Distress Syndrome; Swine; Tetrazoles

Ischemia-reperfusion (I/R) injury of the lung involves increased pulmonary vascular resistance. Prostaglandins are thought to have a beneficial effect in lung transplantation, but their mechanism in I/R injury is unknown. We investigated whether iloprost, a stable prostacyclin analogue, prevents I/R-associated pulmonary vascular dysfunction and whether it affects endothelin-1 (ET-1) balance.. In an isolated blood-perfusion model, we subjected lungs of Lewis rats to 45 minutes of ischemia at 37 degrees C and randomly allocated the lungs to 3 groups (n = 6 each): iloprost (33.3 nmol/liter) added to the perfusate before ischemia and reperfusion (ILO+IR), iloprost (33.3 nmol/liter) given only before reperfusion (ILO+R), and controls without iloprost treatment (ILO-).. Reperfusion induced marked pulmonary edema in non-treated controls (ILO-), which was attenuated in ILO+R lungs and completely prevented in ILO+IR lungs. At 60 minutes reperfusion, arterial oxygen tension was significantly greater in both ILO+R and ILO+IR lungs compared with ILO- controls. Mean pulmonary artery pressure and pulmonary vascular resistance were slightly decreased in the ILO+R and significantly decreased in the ILO+IR group compared with the ILO- controls. Plasma levels of big ET-1, measured in both afferent and efferent blood, showed that I/R results in increased pulmonary venous levels of big ET-1. Interestingly, the increased venoarterial ET-1 gradient in ILO- lungs decreased significantly in the ILO+IR group.. We demonstrated in an isolated lung perfusion model that iloprost ameliorates post-ischemic lung reperfusion injury and maintains an appropriate pulmonary ET-1 balance.

Topics: Animals; Body Weight; Disease Models, Animal; Endothelin-1; Iloprost; Lung; Male; Models, Cardiovascular; Oxygen; Pulmonary Circulation; Pulmonary Edema; Pulmonary Gas Exchange; Pulmonary Wedge Pressure; Rats; Rats, Inbred Lew; Reperfusion Injury; Respiratory Distress Syndrome; Severity of Illness Index; Statistics as Topic; Vascular Resistance; Vasodilator Agents

In this study, the impact of aerosolised prostacyclin (PGI2) and iloprost in the absence or presence of subthreshold intravascular doses of the dual-selective phosphodiesterase-3/4 inhibitor zardaverine was investigated in an experimental model of acute respiratory failure. In perfused rabbit lungs, continuous infusion of the thromboxane-A2-mimetic U46619 provoked pulmonary hypertension, accompanied by progressive lung oedema formation and severe ventilation-perfusion mismatch with predominance of shunt flow (increasing from approximately 2 to 58%, as assessed by the multiple inert gas elimination technique). Aerosolisation of PGI2 (in total 1.05 microg x kg(-1) for 15 min caused a decrease in pulmonary artery pressure (Ppa) and a limitation of maximum shunt flow to approximately 37%. When nebulised PGI2 was combined with subthreshold intravascular zardaverine, which did not affect pulmonary haemodynamics per se, the duration of the PGI2 effect was increased. Aerosolisation of 3 microg x kg(-1) PGI2 resulted in a transient decrease in Ppa and a reduction in shunt flow. In the presence of subthreshold zardaverine, the effects of this PGI2 dose were only marginally increased. Aerosolisation of iloprost (in total 0.7 microg x kg(-1)) for 15 min caused a more sustained decrease in Ppa, some enhanced reduction of oedema formation as compared with PGI2 and a decrease in shunt flow to approximately 32%. Most impressively, when combined with subthreshold zardaverine, iloprost suppressed oedema formation to <15% and shunt flow to approximately 8%. In conclusion, combined use of aerosolised iloprost and subthreshold systemic phosphodiesterase-3/4 inhibitor may result in selective intrapulmonary vasodilation, a reduction in oedema formation and an improvement in ventilation-perfusion matching in acute respiratory failure.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Administration, Inhalation; Animals; Antihypertensive Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epoprostenol; Female; Iloprost; Infusions, Intravenous; Male; Phosphodiesterase Inhibitors; Pyridazines; Rabbits; Respiratory Distress Syndrome; Vasodilator Agents

We hypothesized that Iloprost, a long-acting prostacyclin analog, would inhibit neutrophil (PMN)-induced lung injury and decrease PMN adherence to vascular endothelium. Human PMNs infused into isolated buffer-perfused rat lungs subsequently stimulated with phorbol myristate acetate (PMA) resulted in lung injury as assessed by the accumulation of [125I]bovine serum albumin (125I-BSA) in lung parenchyma and alveolar lavage fluid. Addition of Iloprost to the lung perfusate, prior to activation of the PMNs, reduced lung injury as assessed by a decrease in the accumulation of 125I-BSA in the lung. This protective effect was not due to the vasodilatory effect of Iloprost. Protection by Iloprost was not linked to a reduction in PMA-induced PMN superoxide production since Iloprost did not reduce the amount of superoxide released into lung perfusate. In vitro, Iloprost caused a dose-dependent inhibition of PMA-stimulated PMN adherence to endothelial cells. Iloprost did not affect the number of Mo1 adhesion molecules constitutively expressed or the number of receptors expressed on the PMNs following PMA. Addition of cAMP or dibutyryl cAMP to the endothelial cells mimicked the effects of Iloprost, diminishing PMA-stimulated PMN adhesion. In separate experiments, addition of the phosphodiesterase inhibitor IBMX to Iloprost resulted in a greater inhibition of PMA-stimulated PMN adherence, while addition of an adenylate cyclase inhibitor, SQ 22,536, or cAMP antibodies with the Iloprost abolished Iloprost's inhibitory effect on PMN adhesion. Thus, Iloprost inhibits PMA-activated PMN-induced lung injury despite continued superoxide production. Iloprost inhibition of PMN adhesion is dependent on cAMP.

Topics: 1-Methyl-3-isobutylxanthine; Adenine; Adenylyl Cyclase Inhibitors; Animals; Cell Adhesion; Cyclic AMP; Iloprost; In Vitro Techniques; Macrophage-1 Antigen; Male; Neutrophils; Nifedipine; Permeability; Phosphodiesterase Inhibitors; Rats; Respiratory Distress Syndrome; Superoxides; Tetradecanoylphorbol Acetate