Iloprost Infusion Research Articles

Central Venous Catheter Infection with Brevibacterium sp. in an Immunocompetent Woman: Case Report and Review of the Literature

Brevibacterium spp. were considered apathogenic until a few reports of infections in immunocompromised patients were published. Herein, we present a case of a catheter-related septicemia with Brevibacterium casei in an immunocompetent patient receiving continuous iloprost infusion for pulmonary arterial hypertension and review the clinical presentation of this mainly emerging opportunistic pathogen.

Iloprost treatment in patients with Raynaud's phenomenon secondary to systemic sclerosis and the quality of life: a new therapeutic protocol

To evaluate the clinical efficacy and the effects on the quality of life of iloprost, a prostacyclin analogue, used according to a new protocol in patients with Raynaud's phenomenon secondary to systemic sclerosis. In this randomized study, we treated 30 patients with iloprost, given by intravenous infusion, at progressively increasing doses (from 0.5 to 2 ng/kg/min) over a period of 6 h each day for 10 days in two consecutive weeks, with repeated cycles at regular intervals of 3 months for 18 months. The results were compared with those obtained in 30 other patients who received the same drug but with different dosing schemes. The total average daily duration of the attacks, the average duration of a single attack and the average daily frequency of the attacks were reduced significantly in all treatment groups, but the comparison between the groups demonstrated significant differences between patients treated with the new protocol and the others at later times (12 and 18 months). The effects on the quality of life in the group treated with the new protocol, evaluated with the Short Form-36, demonstrated a marked improvement regarding both the scale relating to the physical aspect of the illness and, especially, the scale relating to the mental aspect. In patients with systemic sclerosis, cyclic intravenous iloprost infusion is efficacious in the treatment of Raynaud's phenomenon. The protocol that we used, compared with others, not only has favourable clinical effects but also leads to a marked improvement in the quality of life.

Evaluation of finger skin temperature in scleroderma patients cyclically treated with iloprost

Objectives. – To evaluate by computerized digital thermometry (CDT) the effect of cyclic iloprost infusions on finger skin temperature (FST) in scleroderma patients. Methods. – Twenty-two scleroderma outpatients (one man, 21 women, mean age 54.2 years) underwent three computerized digital thermometries, the first one 3 days before a 5-day cycle of iloprost infusion, the second the day of the fifth infusion soon after the end of the therapy and the third 1 month after. FST was evaluated under basal conditions, immediately after a cold test and after an 18 min recovery period. For comparison CDT was performed in 10 sex and age matched control subjects. Results. – FST was lower in scleroderma patients before iloprost infusion than in the control group either after cold test either at the end of the recovery period while no difference was found before the cold test. Soon after iloprost infusion and 1 month later the FST at the end of the recovery period increased from the pre-treatment value of 27.8 ± 5.3 to 30.4 ± 3.5 °C and to 30.0 ± 4.5 °C, respectively ( P < 0.05 for both values). No substantial differences were found concerning FST before and at the end of the cold test. Conclusion. – Iloprost administration for 5 days allows to normalize the FST value after cold exposition not only immediately after the infusions but even at 1 month distance from the therapy. Despite its short half-life the effect of the drug on endothelium is protracted.

Effect of prostaglandin I 2 analogues on left ventricular diastolic function in vivo

The prostaglandin I 2 analogues epoprostenol and iloprost increase left ventricular contractility. Therefore, we hypothesize that the prostaglandin I 2 analogues epoprostenol and iloprost improve also left ventricular diastolic function. To test this hypothesis, the effects of epoprostenol and iloprost on left ventricular diastolic function were assessed in vivo and compared to two vasodilators sodium nitroprusside and adenosine, not formerly associated with changes of left ventricular contractility. Eleven pigs (25.9 ± 2.8 kg, balanced anaesthesia) were exposed to the short-acting intravenous vasodilators sodium nitroprusside, adenosine and epoprostenol in a randomized cross over design. The long-acting iloprost was administered at the end of the protocol. The drugs are titrated to achieve a 25% reduction of diastolic aortic pressure. Active isovolumic relaxation properties of the left ventricle were assessed by the maximum velocity of left ventricular pressure drop . Passive phase of relaxation and filling was assessed by the determination of end diastolic compliance during a preload reduction manoeuvre. The maximum velocity of left ventricular pressure drop worsened during the infusion of sodium nitroprusside (baseline: − 1950; sodium nitroprusside: − 1293 mm Hg/s, p < 0.05, Wilcoxon signed rank test versus vs. baseline) and adenosine (baseline: − 2015; adenosine: − 1345 mm Hg/s, p < 0.05), but remained stable during the infusion of the prostaglandins (baseline: − 1943; epoprostenol: − 1785 mm Hg/s; baseline: − 2042; iloprost: − 1923 mm Hg/s). End diastolic compliance was not altered significantly by any vasodilator. Interstitial myocardial cAMP increased during the infusion of epoprostenol (7.60 to 13.87 fmol/ml, p < 0.05) and tended to increase during the infusion of iloprost (7.56 to 11.66 fmol/ml, p = 0.21). The prostaglandin I 2 analogues epoprostenol and iloprost preserved the early phase of active isovolumic relaxation, presumably mediated by myocardial cAMP, whereas sodium nitroprusside and adenosine impaired early active isovolumic relaxation. Passive relaxation and filling properties remained stable during the infusion of each applied vasodilator in the intact left ventricle in vivo.

Ischémie subaiguë d’un membre inférieur révélant une hyperhomocystéinémie chez une femme jeune

A 51-year-old woman had no known cardiovascular risk factor. She presented with bilateral calf intermittent claudication from February. She was hospitalized in August for acute right leg ischemia without loss of sensorymotor functions, following angiography by one week. She had an occlusion of both superficial femoral arteries and abdominal aorta thrombus, plausible source for embolism. Her condition quickly improved with heparin and iloprost infusion. Since the aortic thrombus was removed on ultrasound, aortic surgery was not performed at this time. Investigations showed hyperhomocysteinemia (25 μg/L after overnight fasting and 115 after methionin load) and decrease in folic acid. This report highlights the occurrence of severe arterial disease in young women with high serum homocysteine levels. (J Mal Vasc 2005; 30: 178-180)

Treatment of Reflex Sympathetic Dystrophy in Children Using a Prostacyclin Analog

The aim of our study was to evaluate Iloprost, a prostacyclin analog, for treatment of reflex sympathetic dystrophy in children not responsive to conservative treatment. Seven female patients with a mean age of 9 years (range, 6-11 years) diagnosed with reflex sympathetic dystrophy Stage II were treated with infusions of Iloprost given on three consecutive days. Additionally, all patients had physiotherapy and were offered psychologic consultation. One day after the final infusion, all seven patients were free of pain and achieved full weightbearing. The side effects of Iloprost were headache in all patients and vomiting in two patients. Two patients experienced relapse--one patient at 3 months and the other patient 5 months after primary treatment--but both were free of pain by 5 days after a second series of infusions. During a mean followup of 30 months all patients remained asymptomatic. Our preliminary results suggest that temporary sympathicolysis with Iloprost, physiotherapy, and psychologic counseling is a safe and an effective treatment of reflex sympathetic dystrophy in children with a long history of symptoms or in those who do not respond to conservative treatment. Therapeutic study, Level IV (case series--no, or historical control group). See the Instructions for Authors for a complete description of levels of evidence.

MRI-controlled analysis of 104 patients with painful bone marrow edema in different joint localizations treated with the prostacyclin analogue iloprost

Bone marrow edema (BME) is a common cause of pain of the musculoskeletal system. The aim of the study was to assess the efficacy of iloprost in the treatment of BME of different localizations and etiologies. We reviewed 104 patients (54 male, 50 female) with BME. Their mean age was 52.8 +/- 14.7 years. BME was located 50 times in the knee, 19 times in the talus, 18 times in the femoral head and 17 times in other bones. Patients were allocated to three distinct etiological groups: 27 cases were estimated to have idiopathic BME, 16 post-traumatic BME and the other 61 BME secondary to activated osteoarthritis or mechanical stress. Therapy consisted of a series of five iloprost infusions with either 20, 25 or 50 microg of iloprost given over 6 hours on 5 consecutive days each. At the clinical follow-up four months after therapy, the pain level of the 104 patients at rest had diminished by a mean of 73% (p<0.0001): 64% of patients reported a reduction, 34% no change and 2% an increase in pain at rest. Pain under stress decreased by a mean of 59%, (p<0.0001): 76% of patients had less pain during activity, 22% no change from baseline and 2% an increased pain level. On MRI, 65% had significant reduction of BME size or complete normalization and 20% showed no change. Worsening of the MRI pattern was found in 2%. 13% were lost to MRI follow-up. Side effects were significantly reduced by lowering the daily dose from 50 to 20 microg, without impairment of therapeutic effect. The authors conclude that the use of parenteral iloprost might be a viable method in the treatment of BME of different etiologies.

Behandlung therapieresistenter akraler Ulzera mit Iloprost

Patients with systemic sclerosis (SSc) develop often acral ulcers which are resistant to therapy and may result in gangrene and amputation. We investigated the effects of iloprost infusion on the acral ulcers and necrosis in patients with five patients with SSc and one with mixed connective tissue disease who had been previously treated with various modalities without improvement. All patients had Raynaud phenomenon, acral ulcers and necrosis. Iloprost 25 microg per day was administered intravenously daily over six hours for ten consecutive days. Eight weeks later all patients were treated with a second iloprost therapy cycle for five days. Two patients with severe ulceration received a third cycle until remission occurred. In all cases acral ulcers healed completely and no patient relapsed during an observation period of 6 months.

Iloprost: an adjunctive approach to chronic viral hepatitis treatment

Chronic viral liver disease may evolve to cirrhosis. The medical treatment to slow down this passage is based on anti-viral and anti-fibrotic properties of interferon. Recently, we evidenced significant increase of portal vein flow velocity and volume after a prostacyclin analog (iloprost) infusion in subjects without and with chronic viral hepatitis. On the basis of these results and considering both the pathophysiology of viral liver disease and the mechanism of action of iloprost in portal microcirculation, we hypothesize that it may be of some efficacy in chronic liver disease ameliorating the portal hemodynamics and producing an anti-oxidant liver effect.

Finger pricking

A 59-year-old man with diabetes mellitus and end-stage renal disease requiring peritoneal dialysis was admitted for amputation of the right lower leg because of severe arterial occlusive disease. During his recovery, he started glucose self-monitoring and a few days later, complained of pain and purple discolouration of the fourth finger of his left hand. Examination showed multiple small, well circumscribed areas of skin necrosis around recent finger pricking sites. Despite treatment with iloprost infusions, the lesions progressed to necrosis of the distal phalange.

Improved Hepatic Perfusion After Iloprost Infusion in Patients with HCV Chronic Infection: A Pilot Study with Possible Therapeutic Implications

We performed a pilot study to evaluate whether portal flow volume (PFV) changed in subjects with chronic hepatitis C virus (HCV) infection with respect to control patients after infusion of iloprost, a prostacyclin analog. Six subjects with chronic HCV infection and arteriopathy of the lower limbs (CHCVIA) and 4 control patients affected only by HCV infection (CHCV) were studied with color Doppler sonography. CHCVIA patients were examined before and after 3 days of iloprost infusion, and CHCV patients were examined before and after 3 days with no treatment. In each patient, PFV was obtained after calculating portal flow velocity (PV), portal diameter, and portal vein cross-sectional area. The mean difference between basal and final values of the PFV of CHCVIA patients was significant (p = 0.03), as was the difference in the PFV (final values expressed as percent of basal values) in CHCVIA patients compared with those obtained in the CHCV patients (p = 0.01). We have observed significant improvement in hepatic perfusion in CHCVIA patients compared with CHCV patients after iloprost infusion. In light of these results, we suggest some possible therapeutic implications in patients with HCV infection. Further studies are necessary to confirm this hypothesis.

Efficacy of a novel method of intravenous infusion of the prostaglandin analogue iloprost for the treatment of lower-limb critical ischemia: An open-label, nonrandomized study in two cohorts

BackgroundPatients with advanced peripheral atherosclerotic occlusive disease who are no longer candidates for either surgical or intravascular treatment or who have undergone unsuccessful surgical revascularization may be treated with IV prostanoids. ObjectiveThe aim of this study was to assess the efficacy, tolerability, compliance, and cost of a new system of prostanoid administration that provides a constant plasma concentration of iloprost and maintains the efficacy of the drug while reducing the risk for adverse effects (AEs) and the overall cost of treatment compared with the actually adopted infusion system. MethodsThis open-label, nonrandomized study was conducted at the University Hospital of Catania (Catania, Italy). Patients with chronic critical ischemia who were not candidates for surgical revascularization were observed. The study population was divided into 2 groups: patients in group A were treated with a continuous 6-hour IV infusion of iloprost 0.5 to 2.0 ng/kg.min once daily for at least 14 consecutive days, and patients in group B were treated with a 20-day iloprost continuous IV infusion at a mean dosage of 25 μg/d by means of a portable elastomeric infusion system. Every 5 days the patient was admitted to the day-hospital setting to replenish the drug. Primary end points were rates of major and minor amputations and death; secondary end points were complete relief or a marked reduction of pain at rest, as reflected by discontinuation of analgesic therapy and by a decrease in the patients' complaints of pain, as well as by the satisfactory healing of ulcerations. Tolerability, compliance, and cost also were assessed. ResultsFifty-six patients (34 men, 22 women; mean [SD] age, 67 [11] years) entered the study. Group A comprised 25 patients; group B, 31 patients. The rate of major amputation in patients at Fontaine stage IV was higher in group A (33.3%) compared with group B (20.0%). The death rate was higher in group A (4.0%) than in group B (3.2%). Pain at rest completely subsided in 37.5% of patients in group A and 68.8% of patients in group B. Trophic lesions healed in 44.4% and 73.3% of patients in groups A and B, respectively. In group A, 40.0% of patients experienced AEs (ie, hyperemia, headache, flushing) that required a reduction in dose. In group B, 6.5% of patients had hyperemia at the injection site that required a reduction in dose. Total cost wasin group B wasd €1995.60, with a mean hospital stay of 6 days. Overall, patients' quality of life, assessed as the ability to resume their normal social activities, improved. ConclusionsIn this study of patients with chronic lower-limb critical ischemia, due to the consistent blood level achieved with iloprost, 20-day iloprost continuous IV infusion at a mean dosage of 25 μg/d administered by means of a portable elastomeric infusion system was shown to be similarly or more effective than the Methods used by the most important European trials (ie, iloprost 0.5–2.0 ng/kg·min once daily for at least 14 consecutive days). Furthermore, the patients were more compliant and the cost of treatment and the length of hospitalization were reduced compared with iloprost 0.5 to 2.0 ng/kg·min once daily for at least 14 consecutive days.

Preoperative detection and management of immune heparin-induced thrombocytopenia in patients undergoing heart surgery with iloprost

Objective The objective of this study was to evaluate our protocol for the identification and management of patients with immune heparin-induced thrombocytopenia undergoing cardiac surgery. Methods Among 1518 patients who underwent cardiac surgery between June 1998 and May 2001, 32 (2.1%) presented with platelet counts less than 150,000/mm 3 preoperatively or a history of prolonged (>3 days) intravenous exposure to heparin or both. These 32 patients were evaluated with an enzyme-linked immunosorbent assay for antibodies against heparin-platelet factor 4 complex. Platelets of patients with detected antibodies were tested with the prostacyclin analog iloprost for inhibition of heparin aggregation and determination of the inhibiting concentration and corresponding intravenous infusion rate of iloprost. Patients with antibodies received heparin after complete platelet inhibition with iloprost infusion. Hypotension was prevented or treated with intravenous noradrenaline. Ten randomly selected patients with similar preoperative characteristics, no previous extended exposure to heparin, and normal platelet counts served as controls. Results Ten of the 32 patients (group A, 31.3%) and none of the controls had antibodies against heparin-platelet factor 4 complex. Patients in group A underwent surgery with iloprost (6-24 ng · kg −1 · min −1) and had their blood pressure maintained at greater than 95 mm Hg with norepinephrine infusion (1-4 μg · kg −1 · min −1). Operative mortality was zero. There were no thrombotic complications or bleeding requiring exploration. One patient in group A bled 1310 mL/6 hours but did not need exploration. There was no difference in postoperative blood loss and morbidity between groups. Platelet counts were reduced by 12.5% ± 8.7% (group A) and 38.1% ± 15.2% (control) ( P < .001) 1 hour postoperatively and reached preoperative values by the fifth postoperative day. Conclusions Immune heparin-induced thrombocytopenia can be detected preoperatively among patients with a low platelet count or a history of prolonged heparin exposure or both. Cardiac surgery can be safely undertaken using iloprost-induced platelet inhibition during heparinization.

Einfluss von Dopexamin und Iloprost auf die Plasma-Disappearance-Rate von Indozyaningr�n bei Patienten im septischen Schock

To evaluate the effect of dopexamine and iloprost on the plasma disappearance rate (PDR) of indocyanine green (ICG) in patients in septic shock in a prospective clinical trial. In 40 consecutive patients in septic shock, a femoral arterial fiberoptic catheter (COLD system) and a gastrotonometric probe were placed. Patients received either dopexamine infusion (0.5 microgram/kg body weight/min) or iloprost (1 ng/kg body weight/min) for 24 h i.v. PDR, intramucosal pH of stomach wall (pHi), cardiac index (HI) and intrathoracic blood volume (ITBV) were determined before, 1, 6, and 24 h after dopexamine or iloprost infusion and 1 h after end of infusion. PDR was significantly increased 24 h after starting dopexamine infusion from 12.2 +/- 1.8%/min to 17.8 +/- 2.2%/min (+45.9%) and 1 h after the end of infusion PDR decreased to baseline values. PDR increased to 16.4 +/- 2.1%/min, 1 h after starting iloprost infusion and increased to a maximum value of 18.6 +/- 2.2%/min (+33.8%, p < 0.05) 24 h after start of infusion compared to the baseline (13.9 +/- 1.7%/min). After the end of infusion PDR decreased to baseline values. Baseline values of pHi were in normal ranges in all groups and there was no change during the observation period. Cardiac index and ITBV were stable during the study. Dosage of norepinephrine could be reduced by dopexamine infusion. Dopexamine and iloprost have a positive effect on the plasma disappearance rate of ICG and therefore have a protective effect on splanchnic perfusion and liver function, respectively.

Comparison of acute hemodynamic effects of aerosolized and intravenous iloprost in secondary pulmonary hypertension in children with congenital heart disease

Both aerosolized and intravenous infusion of iloprost caused a significant decrease in mean pulmonary artery pressure and pulmonary vascular resistance. Although intravenous infusion caused a large decrease in mean systemic arterial pressure, this was only slightly affected by aerosolized iloprost. Aerosolized iloprost caused a significant decrease in the pulmonary-to-systemic vascular resistance ratio; however, intravenous infusion did not cause a prominent decrease in this ratio.

Hypotonicity-induced increases in duodenal mucosal permeability facilitates adjustment of luminal osmolality.

The integrated response to hypotonic NaCl solutions (100, 50, 25, and 0 mM NaCl) in proximal duodenum of anesthetized rats was examined. Luminal alkalinization, fluid flux, duodenal contractions, blood-to-lumen clearance of 51Cr-labeled EDTA (mucosal permeability), and perfusate osmolality were studied in the absence and presence of the cyclooxygenase inhibitor indomethacin. In response to hypotonic solutions net fluid absorption, increases in permeability and perfusate osmolality were markedly higher in indomethacin-treated animals than in controls, and these effects were diminished by the nicotinic-receptor antagonist hexamethonium. Infusion of iloprost, a stable PGI2 analog, to indomethacin-treated animals markedly reduced the hypotonicity-induced increase in mucosal permeability and diminished the rise in perfusate osmolality. Lowering the NaCl concentration in the perfusion solution but maintaining isotonicity with mannitol had no effect on mucosal permeability. Very good linear correlations were obtained between the degree of luminal hypotonicity and the increase in permeability and between increases in permeability and perfusate osmolality. It is concluded that luminal hypotonicity increases duodenal mucosal permeability. The hypotonicity-induced increase in permeability modulated by prostaglandins and nicotinic receptors fulfills the function of increasing blood-to-lumen transport of Na+ facilitating adjustment of luminal osmolality.

Hemodynamic effects of a prostacyclin analog (iloprost) on portal flow velocity and volume and visceral artery circulation in patients with lower limb arteriopathy

Previous studies demonstrated that iloprost improves the peripheral circulation. In this study, we examined, by Doppler sonography, portal flow velocity (cm/s) and volume (mL/min), and resistance index (RI) of visceral arteries in 23 patients before and after 7 days of iloprost infusion. Statistically significant hemodynamic changes were only seen in portal vein (pre-iloprost vs. post-iloprost treatment mean portal flow velocity and volume values: 23.9 cm/s vs. 29.0 cm/s, p < 0.001 and 1824.6 mL/min vs. 2294.4 mL/min, p < 0.001, respectively). On the other hand, the interlobar renal artery RI, reduced after iloprost treatment in most patients, was not statistically significant; conflicting results were obtained on the hepatic and mesenteric arteries. Our results indicate that iloprost significantly increases portal flow velocity and volume. The understanding of the mechanism through which iloprost plays a role in portal microcirculation could be useful for its new medical indications in liver hemodynamic disorders. (E-mail: e.zardi@unicampus.it)

Juvenile bone-marrow oedema of the acetabulum treated by iloprost

The bone-marrow oedema syndrome is associated with local vascular disturbances and may be treated either conservatively or by core decompression after which recovery may take several weeks. We describe a 15-year-old girl with bone-marrow oedema of the left acetabulum which was confirmed by MRI. She presented with a four-week history of severe constant pain. Routine blood tests and plain radiographs were normal. She was treated with intravenous infusions of iloprost on five consecutive days (20 μg administered in 500 ml of sodium chloride). Iloprost causes vasodilatation with reduction of capillary permeability and it inhibits platelet aggregation. She had relief from pain at rest after three days of treatment and was completely free from symptoms after two weeks. MRI after six weeks showed almost complete resolution of the marrow oedema and was normal after four months. This is the first report of the pharmacological treatment of the bone-marrow oedema syndrome in children.

Effect of a Prostacyclin Analogue, Iloprost, on Urinary Aquaporin-2 Excretion in Humans

The regulation of aquaporin-2 (AQP2) water channel excretion in the collecting duct depends mainly on the action of vasopressin (AVP). Recently, however, other regulatory factors have been identified: atrial natriuretic factor, oxytocin and prostaglandins. In healthy volunteers (5 males, 5 females; mean age 23 ± 3 years) we therefore evaluated the effect of a stable analogue of prostacyclin-2 (PGI₂), iloprost, on renal function and on the urinary excretion of AQP2 (U-AQP2). After 6 h of iloprost infusion, U-AQP2 increased from 0.8 ± 0.15 to 1.8 ± 0.2 pmol/mg creatinine (p < 0.001), while the urinary flow rate increased from 1.4 ± 0.2 to 1.8 ± 4 (p < 0.01). No significant change was found in the AVP serum concentration, with a basal value of 3.17 ± 0.12 vs. 3.15 ± 0.12 pg/ml after 6 h of prostacyclin infusion. All the values returned to pre-study levels after a recovery period of 6 h. In conclusion, the PGI₂ analogue, iloprost, can induce U-AQP2 excretion independent of AVP.

Sustained normalization of cerebral blood-flow after iloprost therapy in a patient with neuropsychiatric systemic lupus erythematosus

We report the case of a 30-year-old caucasian woman affected by SLE who developed neurological symptoms (prosopagnosia and visual-spatial agnosia) after nine years of disease. Brain MRI showed no abnormalities while a brain SPECT scan showed diffuse uptake defects and hypoperfusion areas in the right and left frontal-parietal regions. At that time the patient was on hydroxychloroquine (400 mg/day) and oral prednisolone (0.5 mg/kg/day) as maintenance therapy. One year later the patient showed worsening of Raynaud's phenomenon with digital dystrophic lesions and was therefore treated with an intravenous infusion of Iloprost (1.5 ng/kg/min per 6h/day for 10 days consecutively), while baseline treatment remained unchanged. One month later the patient showed a dramatic improvement in her cognitive function and subsequent SPECT scans showed the gradual disappearance of perfusion abnormalities. This first report of Iloprost treatment in CNS lupus suggests the potential therapeutic usefulness of this drug in patients with SLE and functional CNS involvement.