Pulmonary arterial hypertension (PAH) is characterized by progressive increases in pulmonary vascular resistance, leading to right heart failure and death. Guidelines recommend customization of treatment, necessitating the development of effective strategies for transitioning patients among treatments. In this study, we characterized our experience with patient transitions from parenteral prostacyclin to inhaled iloprost. We retrospectively assessed records from 11 centers of 37 consecutive patients with PAH aged ≥ 18 years who were treated with intravenous (IV) or subcutaneous (SC) prostacyclin analogues and transitioned to inhaled iloprost. The transition period began on the first day of inhaled iloprost with the intent of discontinuing parenteral prostacyclin and ended on the first day on inhaled iloprost free of parenteral prostacyclin. Persistence was defined as the absence of (1) parenteral prostacyclin while remaining on inhaled iloprost during post-transition Days 1-90 and (2) no reinitiation of parenteral prostacyclin during post-transition Days 90-365. All patients were clinically stable before transitioning to inhaled iloprost. The mean age was 46.5 years, 70.3% were female, 51.4% had idiopathic PAH, and 43.0% were in New York Heart Association Functional Class III. Among patients with an overlapping transition, the mean transition period was 10.5 days. A transition dosing algorithm was used in 10 patients (27.0%). At one year, 78.4% of the patients remained persistent on inhaled iloprost and 81.1% were free of clinical worsening. In selected patients on background oral PAH therapy, transitioning from parenteral prostacyclin to inhaled iloprost appears safe and feasible and is associated with long-term success. Further study is needed to define the optimal patient selection criteria and transition algorithm.
iloprost; persistence; prostacyclin; pulmonary arterial hypertension; transition; treatment strategy
Primary pulmonary hypertension is a rare disease in childhood associated with a poor prognosis. However, during the past 10 years, pulmonary vasodilator treatment has somewhat improved its prognosis. Long term continuous infusion of prostacyclin (epoprostenol) has been shown to improve physical capacity and to reduce mortality in primary and secondary pulmonary hypertension. It has been reported in adults that daily repetitive inhalation of iloprost, a prostacyclin analogue, seems also suitable for long term therapy of pulmonary hypertension. Repetitive inhalation of iloprost was administered to a 5 year old boy with severe primary pulmonary hypertension. He showed continuous clinical improvement without any side effects over the three years of treatment. This treatment may offer an alternative to continuous intravenous prostacyclin infusion and obviates the need for a permanent central venous catheter.
Keywords: iloprost; inhalation; prostacyclin; pulmonary hypertension
Case Pulmonary hypertension secondary to respiratory disease most often occurs as a complication of chronic obstructive pulmonary disease, which currently constitutes one of the leading causes of death. Some patients with hypoxaemia reveal “out of proportion” pulmonary hypertension with inappropriate increase of pulmonary artery pressure. Iloprost, analogue of prostacyclin, dilates systemic vessels and pulmonary vessels in particular if administered by inhalation. It appears to be important, life-saving, complementary therapy. However, there is no evidence for its routine use in out of proportion arterial pulmonary hypertension. This case study presents a 44-year old man with chronic obstructive pulmonary disease and “out of proportion” pulmonary hypertension. We present the results of his treatment with iloprost. Conclusion In a patient with “out of proportion” pulmonary hypertension due to chronic obstructive pulmonary disease, inhaled iloprost led to improvement in clinical status and echocardiographic parameters, including a reduction of right ventricular systolic pressure.
Chronic obstructive pulmonary disease; Heart failure; Iloprost; Prostanoids; Pulmonary hypertension
Inhalation of iloprost, a stable prostacyclin (PGI2) analog, is a well-accepted and safe treatment for pulmonary arterial hypertension. Although iloprost mainly acts as a vasodilator by binding to the I prostanoid (IP) receptor, recent evidence suggests that signaling via this receptor also has antiinflammatory effects through unclear mechanisms. Here we show in a murine model of asthma that iloprost inhalation suppressed the cardinal features of asthma when given during the priming or challenge phase. As a mechanism of action, iloprost interfered with the function of lung myeloid DCs, critical antigen-presenting cells of the airways. Iloprost treatment inhibited the maturation and migration of lung DCs to the mediastinal LNs, thereby abolishing the induction of an allergen-specific Th2 response in these nodes. The effect of iloprost was DC autonomous, as iloprost-treated DCs no longer induced Th2 differentiation from naive T cells or boosted effector cytokine production in primed Th2 cells. These data should pave the way for a clinical effectiveness study using inhaled iloprost for the treatment of asthma.
In the pediatric population, pulmonary hypertension may present as an acute event in the setting of lung or cardiac pathology or as a chronic disease, mainly as idiopathic pulmonary hypertension or associated with congenital heart disease. Recently, new pharmacologic approaches have demonstrated significant efficacy in the management of adults with pulmonary arterial hypertension; these include intravenous epoprostenol, prostacyclin analogs, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors. The same treatment strategies are currently used in children. There are only few reports of the use of inhaled iloprost in pediatrics, only one of which reported the use of chronic inhaled iloprost in a significant number of children. This report showed that 1) the acute pulmonary vasodilator response to inhaled iloprost is equivalent to that of inhaled nitric oxide; 2) acute inhalation of iloprost can induce bronchoconstriction 3) the addition of inhaled iloprost can reduce the need for intravenous prostanoid therapy in some patients; 4) most children tolerated the combination of inhaled iloprost and endothelin receptor antagonist or phosphodiesterase inhibitors; 5) Several patients had clinical deterioration during chronic inhaled iloprost therapy and required rescue therapy with intravenous prostanoids. In this review we will discuss the role of inhaled iloprost in acute and chronic pulmonary hypertension in children.
pulmonary hypertension; children; iloprost
intravenous treatment with epoprostenol significantly improves
pulmonary haemodynamics and survival in patients with primary pulmonary
hypertension (PPH). Its beneficial effect, however, may be blunted
due to adverse effects such as catheter sepsis and systemic
hypotension. Recent investigations have shown that inhaled iloprost is
effective in the treatment of PPH. Based on their different
pharmacokinetics, we hypothesised that the combination of
intravenous epoprostenol and inhaled iloprost would be more efficacious
than epoprostenol alone during acute testing in patients with PPH.
METHODS—The effect of
a single dose of inhaled iloprost (30 µg total over 15 minutes) on
pulmonary haemodynamics was examined in eight patients with PPH
(initial non-responders to nitric oxide) who had considerable adverse
effects during treatment with epoprostenol.
combination of inhaled iloprost and intravenous epoprostenol
significantly improved mean pulmonary artery pressure (MPAP), cardiac
index (CI), mixed venous oxygen saturation
(SvO2), and systemic arterial oxygen pressure
(PaO2) compared with epoprostenol treatment
alone. Mean systemic arterial pressure (MSAP) and pulmonary capillary
wedge pressure (PCWP) remained unchanged.
pulmonary vasoreactivity shown by additional iloprost inhalation during
effective epoprostenol treatment suggests that an improvement of
treatment for pulmonary hypertension may be possible by combining
This is the case report of a pregnant woman who refused pregnancy termination when diagnosed with pulmonary arterial hypertension (PAH) functional class 2–3 at the 24th week of gestation and of her newborn. A pregnant woman with PAH functional class 2–3 was treated with inhaled prostacyclin analog (iloprost), oral sildenafil, oxygen, and low molecular weight heparin. She delivered at 32nd week by Cesarean section. The infant required oxygen up to 36th week postconceptional age and had a short steroid treatment. The mother needed close cardiovascular monitorization, intensive oxygen and pulmonary vasodilator therapy for 2 months and was discharged with oxygen and oral iloprost treatment. A multidisciplinary approach together with pulmonary vasodilator therapy may be succesful in such a high-risk pregnant woman.
Iloprost; newborn; pregnancy; pulmonary hypertension; sildenafil; survival; therapy
Pulmonary artery hypertension is a common cardiovascular complication in preterm infants with bronchopulmonary dysplasia which is associated with increased morbidity and mortality. Inhaled iloprost is used as a therapeutic option in pulmonary hypertension, especially in adults. There have been but a few reports on the use of iloprost for neonates and infants. We report the case of a 5 month-old-male infant who received neonatal intensive care for 4 months due to respiratory distress syndrome and prematurity, during which he developed bronchopulmonary dysplasia. Echocardiography showed severe pulmonary hypertension. The initial treatment included respiratory support with high frequency oscillatory ventilation (HFOV); however, his clinical condition did not improve. Inhaled iloprost with sildenafil, an oral phosphodiesterase-5 inhibitor, was thus used. With the administration of iloprost and sildenafil, his condition improved and he was weaned from oxygen. Our clinical experience suggests that iloprost is a promising therapy for pulmonary hypertension, especially when inhaled nitric oxide is unavailable.
Pulmonary hypertension; Bronchopulmonary dysplasia; Iloprost
Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by an elevated pulmonary arterial pressure and vascular resistance with a poor prognosis. Various pulmonary and extrapulmonary causes are now recognized to exist separately from the idiopathic form of pulmonary hypertension. An imbalance in the presence of vasoconstrictors and vasodilators plays an important role in the pathophysiology of the disease, one example being the lack of prostacyclin. Prostacyclin and its analogues are potent vasodilators with antithrombotic, antiproliferative and anti-inflammatory qualities, all of which are important factors in the pathogenesis of precapillary pulmonary hypertension. Iloprost is a stable prostacyclin analogue available for intravenous and aerosolized application. Due to the severe side effects of intravenous administration, the use of inhaled iloprost has become a mainstay in PAH therapy. However, owing to the necessity for 6 to 9 inhalations a day, oral treatment is often preferred as a first-line therapy. Numerous studies proving the efficacy and safety of inhaled iloprost have been performed. It is therefore available for a first-line therapy for PAH. The combination with endothelin-receptor antagonists or sildenafil has shown encouraging effects. Further studies with larger patient populations will have to demonstrate the use of combination therapy for long-term treatment of pulmonary hypertension.
pulmonary arterial hypertension; prostacyclin; iloprost; inhaled
Inhaled treprostinil is a prostacyclin analog approved for the treatment of pulmonary arterial hypertension (PAH) that may provide a more convenient treatment option for patients receiving inhaled iloprost while maintaining the clinical benefit of inhaled prostacyclin therapy.
In this open-label safety study, 73 PAH patients were enrolled with primarily World Health Organization Class II (56%) or III (42%) symptoms. At baseline, most patients (93%) were receiving 5 μg of iloprost per dose but 38% of patients reported a dosing frequency below the labeled rate of 6–9 times daily. Patients initiated inhaled treprostinil at 3 breaths four times daily (qid) at the immediate next scheduled iloprost dose. The primary objective was to assess the safety of rapid transition from iloprost to inhaled treprostinil; clinical status and quality of life were also assessed.
Most patients (84%) achieved the target treprostinil dose of 9 breaths qid and remained on study until transition to commercial therapy (89%). The most frequent adverse events (AEs) were cough (74%), headache (44%), and nausea (30%), and five patients prematurely discontinued study drug due to AE (n = 3), disease progression (n = 1), or death (n = 1). At week 12, the time spent on daily treatment activities was reduced compared to baseline, with a mean total savings of 1.4 h per day. Improvements were also observed at week 12 for 6-min walk distance (+16.0; P < 0.001), N-terminal pro-B-type natriuretic peptide (−74 pg/mL; P = 0.001), and the Cambridge Pulmonary Hypertension Outcome Review (all domains P < 0.001).
Pulmonary arterial hypertension patients can be safely transitioned from inhaled iloprost to inhaled treprostinil while maintaining clinical status.
Iloprost; Inhaled; Pulmonary arterial hypertension; Quality of life; Treprostinil
Reactive pulmonary hypertension is frequent in children with high pulmonary flow and pressure. Inhaled iloprost and nitric oxide are the only substances approved as selective pulmonary vasodilators, but data about the effectiveness and safety of inhaled iloprost during cardiac surgery in infants and children are limited.
We retrospectively analysed the effects of inhaled iloprost after cardiopulmonary bypass weaning on the ratio of mean pulmonary artery to mean arterial pressure. The effectiveness of the inhalation set up was tested in an in vitro study.
Thirty-one patients received inhaled iloprost during surgery. The clinically used inhalation set up for inhaled iloprost delivered 20% to 30% (500 to 750 ng * kg-1) of the nebulizer dose and caused a decrease in the ratio of mean pulmonary artery to mean arterial pressure from 0.6±0.2 to 0.4±0.1 and 0.4±0.1 (30 and 60 minutes after)p <0.05. In eleven (35%) patients norepinephrine infusion was started.
Our data suggest that a single dose of inhaled iloprost significantly decreases the ratio of mean pulmonary artery to mean arterial pressure for at least 60 min. Vasopressor support may be indicated to avoid systemic hypotension. The filled dose in the nebulizer should be high enough to compensate for the high depletion rate of the pediatric inhalation system. However, our study allows no final decision about beneficial or detrimental effects of the off label use of inhaled iloprost to reduce pulmonary artery pressure during congenital heart surgery.
pediatric heart surgery; pulmonary hypertension; iloprost; inhalation therapy
Objective—To compare prostacyclin with an analogue, iloprost, in treatment of severe pulmonary hypertension.
Patients—Eight patients with severe pulmonary hypertension: primary in five, thromboembolic pulmonary hypertension in three.
Methods—All patients underwent right heart catheterisation. Mean (SEM) right atrial pressure was 9.9 (2.2) mm Hg, mean pulmonary artery pressure 67.4 (3.0) mm Hg, cardiac index 1.75 (0.13) l/min/m2 and mixed venous oxygen saturation 59.1(3.1)%. Continuous intravenous epoprostenol (prostacyclin, PGI2) or iloprost was given for phase I (three to six weeks); the patients were then crossed over to receive the alternate drug in an equivalent phase II.
Main outcome measures—Exercise tolerance was measured at baseline and at the end of phase I and II with a 12 minute walk; distance covered, rest period, percentage drop in arterial oxygen saturation (ΔSaO2%) and percentage rise in heart rate (ΔHR%).
Results—Walking distance covered rose from (mean (SEM)) 407.5 (73) to 591 (46) m with PGI2 (p = 0.004) and to 602.5 (60) m while on iloprost (p = 0.008). Rest period decreased from 192 (73) seconds at baseline to 16 (16) seconds with PGI2 (p = 0.01) and to 58 (34) seconds with iloprost (p = 0.008). ΔHR% was 37.5(6)% at baseline, 35(3)% on PGI2, and 24(6)% on iloprost (p = 0.04).
Conclusions—Both intravenous PGI2 and iloprost caused significant improvement in exercise tolerance. Iloprost offers an alternative to PGI2 treatment of severe pulmonary hypertension.
Keywords: prostacyclin; vasodilatation; iloprost; pulmonary hypertension
The rapid desensitization of the human prostacyclin (IP) in response to agonist binding has been shown in cell culture. Phosphorylation of the IP receptor by protein kinase C (PKC) has been suggested to be involved in this process.
Methods and results
In this study we investigated the vasodilatory effects of iloprost, a stable prostacyclin analogue, in perfused rabbit lungs. Continuous infusion of the thromboxane mimetic U46619 was employed to establish stable pulmonary hypertension. A complete loss of the vasodilatory response to iloprost was observed in experiments with continuous iloprost perfusion, maintaining the intravascular concentration of this prostanoid over a 180 min period. When lungs under chronic iloprost infusion were acutely challenged with inhaled iloprost, a corresponding complete loss of vasoreactivity was observed. This desensitization was not dependent on upregulation of cAMP-specific phosphodiesterases or changes in adenylate cyclase activity, as suggested by unaltered dose-response curves to agents directly affecting these enzymes. Application of a prostaglandin E1 receptor antagonist 6-isopropoxy-9-oxoxanthene-2-carboxylic acid (AH 6809) or the PKC inhibitor bisindolylmaleimide I (BIM) enhanced the vasodilatory response to infused iloprost and partially prevented tachyphylaxis.
A three-hour infusion of iloprost in pulmonary hypertensive rabbit lungs results in complete loss of the lung vasodilatory response to this prostanoid. This rapid desensitization is apparently not linked to changes in adenylate cyclase and phosphodiesterase activation, but may involve PKC function and co-stimulation of the EP1 receptor in addition to the IP receptor by this prostacyclin analogue.
Inhaled iloprost potentially improves hemodynamics and gas exchange in patients with chronic obstructive pulmonary disease (COPD) and secondary pulmonary hypertension (PH).
To evaluate acute effects of aerosolized iloprost in patients with COPD-associated PH.
A randomized, double blind, crossover study was conducted in 16 COPD patients with invasively confirmed PH in a single tertiary care center. Each patient received a single dose of 10 µg iloprost (low dose), 20 µg iloprost (high dose) and placebo during distinct study-visits. The primary end-point of the study was exercise capacity as assessed by the six minute walking distance.
Both iloprost doses failed to improve six-minute walking distance (p = 0.36). Low dose iloprost (estimated difference of the means −1.0%, p = 0.035) as well as high dose iloprost (−2.2%, p<0.001) significantly impaired oxygenation at rest. Peak oxygen consumption and carbon dioxide production differed significantly over the three study days (p = 0.002 and p = 0.003, accordingly). As compared to placebo, low dose iloprost was associated with reduced peak oxygen consumption (−76 ml/min, p = 0.002), elevated partial pressure of carbon dioxide (0.27 kPa, p = 0.040) and impaired ventilation during exercise (−3.0l/min, p<0.001).
Improvement of the exercise capacity after iloprost inhalation in patients with COPD-associated mild to moderate PH is very unlikely.
One hundred and twenty seven patients who had Raynaud's attacks secondary to connective tissue disease received intravenous infusions of iloprost in controlled clinical trials. Results of previous treatments for Raynaud's attacks had been recorded by clinicians in 84 of these cases, allowing a comparison to be made with the response to iloprost treatment. Iloprost was reported by the patients as beneficial in 49 (58%) of 84 cases, whereas only 36 (43%) of the 84 patients had previously found any other treatment to be useful. Twenty four of 48 (50%) patients who had not responded to any previous treatment found iloprost to be of benefit. Success or failure of treatment with iloprost was not accurately predicted by the result of treatment with any other drug, except prostacyclin. This survey suggests that iloprost is a useful treatment for patients with severe secondary Raynaud's phenomenon and can be effective in patients unresponsive to other treatments.
Pulmonary hypertension is a major reason for elevated perioperative morbidity and mortality, even in noncardiac surgical procedures. Patients should be thoroughly prepared for the intervention and allowed plenty of time for consideration. All specialty units involved in treatment should play a role in these preparations. After selecting each of the suitable individual anesthetic and surgical procedures, intraoperative management should focus on avoiding all circumstances that could contribute to exacerbating pulmonary hypertension (hypoxemia, hypercapnia, acidosis, hypothermia, hypervolemia, and insufficient anesthesia and analgesia). Due to possible induction of hypotonic blood circulation, intravenous vasodilators (milrinone, dobutamine, prostacyclin, Na-nitroprusside, and nitroglycerine) should be administered with the greatest care. A method of treating elevations in pulmonary pressure with selective pulmonary vasodilation by inhalation should be available intraoperatively (iloprost, nitrogen monoxide, prostacyclin, and milrinone) in addition to invasive hemodynamic monitoring. During the postoperative phase, patients must be monitored continuously and receive sufficient analgesic therapy over an adequate period of time. All in all, perioperative management of patients with pulmonary hypertension presents an interdisciplinary challenge that requires the adequate involvement of anesthetists, surgeons, pulmonologists, and cardiologists alike.
Bone marrow oedema (BME) and avascular osteonecrosis (AVN) are disorders of unclear origin. Although there are numerous operative and non-operative treatments for AVN, pain management in patients with AVN remains challenging. Prostaglandins play an important role in inflammatory responses and cell differentiation. It is thought that prostaglandin I2 ([PGI2] or synonoma prostacyclin) and its analogues promote bone regeneration on a cellular or systemic level. The purpose of this study was to assess the curative and symptomatic efficacy of the prostacyclin analogue iloprost in BME and AVN patients.
We are reporting on 50 patients (117 bones) affected by BME/AVN who were treated with iloprost. Pain levels before, during and 3 and 6 months after iloprost application were evaluated by a visual analogue scale (VAS). The short form(SF)-36 health survey served to judge general health status before and after treatment. Harris Hip Score (HHS) and Knee Society Score (KSS) were performed as functional scores and MRI and X-rays before and 3 and 6 months after iloprost application served as objective parameters for morphological changes of the affected bones.
We found a significant improvement in pain, functional and radiological outcome in BME and early AVN stages after iloprost application, whereas patients with advanced AVN stages did not benefit from iloprost infusions. Mean pain level decreased from 5.26 (day 0) to 1.63 (6 months) and both HHS and KSS increased during follow-up. Moreover, the SF-36 increased from 353.2 (day 0) to 560.5 points (6 months). We found a significant decrease in BME on MRI scans after iloprost application.
In addition to other drugs, iloprost may be an alternative substance which should be considered in the treatment of BME/AVN-associated pain.
The case of a 14 month old girl with primary pulmonary hypertension treated with domiciliary oxygen is described. After invasive evaluation and testing of nitric oxide with very good response, the testing was repeated to study the effect of inhaled iloprost on pulmonary vascular resistance (PVR). An unexpected and severe increase of PVR was observed, rising from 392 dynes·s·cm−5 with oxygen to a maximum of 1192 dynes·s·cm−5 with oxygen and iloprost. Underlying ventilatory and technical problems were excluded. While inhaled iloprost has been described to be highly effective in the treatment of primary pulmonary hypertension, the possibility of contrary “paradoxical” reactions in isolated patients is emphasised, with a dramatic increase of PVR and a possible adverse outcome.
pulmonary hypertension; pulmonary vascular resistance; iloprost; inhalation; vasodilator
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.
epoprostenol; treprostinil; iloprost; pulmonary arterial hypertension; congenital heart disease; critical care
Insufficient osseous blood supply results in bone marrow oedema (BMO) and/or avascular necrosis (AVN). One treatment option to support osseous perfusion is the application of stable prostacycline analog iloprost. In this clinical study, 95 patients were treated with iloprost for BMO/AVN. One hundred eighty-six bones were affected by BMO/AVN before treatment. Average follow-up was 33.0 ± 17.6 months. Pain levels could be reduced (e.g. visual analogue scale, 5.0 ± 2.2 points reduced to 1.7± 2.2 points) and functional scores improved (Harris hip score, 52±21 points to 79±17 points) in the course of treatment. According to current data, healing of advanced stages of osteonecrosis is not possible. However, the results of this case series confirm previous findings that in early stages of insufficient osseous blood flow iloprost can contribute to the relief of pain and improve joint function.
Metabolites of arachidonic acid such as prostacyclin (PGI2) have been shown to participate in the pathogenesis of pulmonary fibrosis by inhibiting the expression of pro-inflammatory and pro-fibrotic mediators. In this investigation, we examined whether iloprost, a stable PGI2 analogue, could prevent bleomycin-induced pulmonary inflammation and fibrosis in a mouse model.
Mice received a single intratracheal injection of bleomycin with or without intraperitoneal iloprost. Pulmonary inflammation and fibrosis were analysed by histological evaluation, cellular composition of bronchoalveolar lavage (BAL) fluid, and hydroxyproline content. Lung mechanics were measured. We also analysed the expression of inflammatory mediators in BAL fluid and lung tissue.
Administration of iloprost significantly improved survival rate and reduced weight loss in the mice induced by bleomycin. The severe inflammatory response and fibrotic changes were significantly attenuated in the mice treated with iloprost as shown by reduction in infiltration of inflammatory cells into the airways and pulmonary parenchyma, diminution in interstitial collagen deposition, and lung hydroxyproline content. Iloprost significantly improved lung static compliance and tissue elastance. It increased the expression of IFNγ and CXCL10 in lung tissue measured by RT-PCR and their levels in BAL fluid as measured by ELISA. Levels of TNFα, IL-6 and TGFβ1 were lowered by iloprost.
Iloprost prevents bleomycin-induced pulmonary fibrosis, possibly by upregulating antifibrotic mediators (IFNγ and CXCL10) and downregulating pro-inflammatory and pro-fibrotic cytokines (TNFα, IL-6, and TGFβ1). Prostacyclin may represent a novel pharmacological agent for treating pulmonary fibrotic diseases.
Iloprost, a stable prostacyclin analogue, was given by intravenous infusion to 29 patients with severe Raynaud's phenomenon, 26 of whom had systemic sclerosis (SS), and compared with placebo infusion in a double blind crossover trial. Iloprost significantly lessened the number and the severity of attacks compared with placebo. Nine patients expressed a preference for effectiveness of treatment, eight of these in favour of Iloprost. Thermography failed to show any long term effect of Iloprost. Side effects of headache, flushing, nausea, and vomiting were common, and the inconvenience of intravenous administration may limit its routine use.
Doppler echocardiography is useful in the initial evaluation and long-term follow-up of patients with pulmonary artery hypertension. Aerosolised iloprost has been shown to reduce pulmonary pressure immediately after inhalation. We report the echocardiographic findings in a patient with severe pulmonary hypertension, before and after the inhalation of aerosolized iloprost. These findings illustrate the acute influence of iloprost in right and left ventricular hemodynamics and morphology. These findings were reproduced in subsequent echocardiographic evaluations.
This study investigated the short- and long-term outcome of children with pulmonary arterial hypertension (PAH) treated with inhaled iloprost.
Inhaled iloprost has been approved for the treatment of adults with PAH, but little is known about the effects in children with PAH.
We evaluated the acute effects of inhaled iloprost on hemodynamic status and lung function and the response to long-term therapy in 22 children (range 4.5 to 17.7 years) with PAH (idiopathic, n = 12; congenital heart disease, n = 10). Cardiac catheterization, standard lung function testing before and after iloprost inhalation, 6-min walk test, World Health Organization functional class, and hemodynamic parameters were monitored.
Acute administration of inhaled iloprost lowered mean pulmonary artery pressure equivalent to the response to inhaled nitric oxide with oxygen. Acute iloprost inhalation reduced forced expiratory volume in 1 s and mid-volume forced expiratory flow by 5% and 10%, respectively, consistent with acute bronchoconstriction. At 6 months, functional class improved in 35%, decreased in 15%, and remained unchanged in 50% of children. Sixty-four percent of patients continued receiving long-term iloprost therapy, 36% stopped iloprost, due to lower airway reactivity, clinical deterioration, or death. In 9 patients on chronic intravenous prostanoids, 8 transitioned from intravenous prostanoids to inhaled iloprost, which continued during follow-up.
Inhaled iloprost caused sustained functional improvement in some children with PAH, although inhaled iloprost occasionally induced bronchoconstriction. Most patients tolerated the transition from intravenous to inhaled prostanoid therapy. Clinical deterioration, side effects, and poor compliance, owing to the frequency of treatments, could limit chronic treatment in children.
Major pulmonary embolism occurring insidiously over several weeks (subacute massive pulmonary embolism) has a high mortality and may not respond well to standard anticoagulant or thrombolytic treatment. A priming dose of plasminogen was used to enhance thrombolysis produced by a streptokinase infusion in five consecutive patients with subacute massive pulmonary embolism. In each patient a dramatic clinical improvement occurred with a substantial increase in pulmonary blood flow. All five patients survived to leave hospital. Malignant disease was the underlying cause of embolism in three patients, two of whom died of their malignant disease in the six months after treatment of their pulmonary embolism. The third patient with malignant disease had a choriocarcinoma; at least some of the pulmonary obstruction may have been tumour tissue but this obstruction was dramatically cleared by the treatment. The use of a combination of plasminogen with streptokinase should be considered in severely ill patients with subacute massive pulmonary embolism, particularly if other treatment, including streptokinase alone, has failed.