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CMAJ : Canadian Medical Association... Nov 2021
Topics: Fluorescence; Frostbite; Humans; Iloprost
PubMed: 34810170
DOI: 10.1503/cmaj.202258-f -
European Review For Medical and... Jan 2022Despite its low incidence, pulmonary hypertension in children places a substantial burden on families and society because survival can be shorter than 10 months and... (Review)
Review
OBJECTIVE
Despite its low incidence, pulmonary hypertension in children places a substantial burden on families and society because survival can be shorter than 10 months and treatment options are limited and ineffective. Drugs to treat pulmonary hypertension include endothelin antagonists, phosphodiesterase type 5 inhibitors and prostacyclin, which is the most widely used to treat pediatric pulmonary hypertension. The main aim of this study was to provide a comprehensive overview of the advantages and disadvantages of prostacyclin and its analogs for treating pulmonary hypertension in children.
MATERIALS AND METHODS
To retrieve a thorough collection of studies, we performed a search in PubMed using the following combination of keywords: (Prostacyclins) or (Epoprostenol) or (Iloprost) or (Treprostinil) or (Beraprost), (children) and (pulmonary arterial hypertension). The time limits used for the search were December 1983 to May 2021.
RESULTS
The search retrieved a total of 238 articles. Titles and abstracts of articles were screened for relevance, and all relevant articles published in English were included.
CONCLUSIONS
Epoprostenol can be effective against severe pulmonary hypertension. Iloprost can treat severe persistent pulmonary hypertension in newborns and inhaled iloprost can be used in pulmonary vasoreactivity testing. Treprostinil is a long-acting prostacyclin analog, and it shows the highest antiproliferative activity among prostacyclins. Beraprost may be effective in premature infants, but available evidence comes from only one patient, so more clinical testing is needed.
Topics: Antihypertensive Agents; Child; Endothelin Receptor Antagonists; Humans; Hypertension, Pulmonary; Iloprost; Infant, Newborn; Prostaglandins I; Pulmonary Arterial Hypertension
PubMed: 35049017
DOI: 10.26355/eurrev_202201_27745 -
Heart & Lung : the Journal of Critical... 2024The efficacy of iloprost in treating pulmonary arterial hypertension (PAH) is controversial. Adverse reactions such as hypotension may occur during treatment. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The efficacy of iloprost in treating pulmonary arterial hypertension (PAH) is controversial. Adverse reactions such as hypotension may occur during treatment.
OBJECTIVES
Aim to evaluate the efficacy and safety of iloprost for PAH.
METHODS
Studies were obtained from an electronic search of the CNKI, Wanfang, VIP, SinoMed, PubMed, Medline, Embase, and Cochrane Library databases up to May 18, 2023. A meta-analysis of each study was performed using RevMan 5.4 with a 95 % confidence interval (CI). A randomized or fixed-effects model was applied according to a heterogeneity test.
RESULTS
Twelve trials involving 718 participants were selected, including 433 in five randomized controlled trials (RCTs) and 285 in seven prospective clinical trials. All the patients received iloprost inhalation. The short- and prolonged treatment groups significantly improved the 6-minute walking distance (6 MWD). The mortality and clinical deterioration incidences in the iloprost group were not significantly different from those in the control group. The mean pulmonary arterial pressure (mPAP) was reduced after 3 months of iloprost RCTs and 12 months of prospective treatment. Iloprost decreased pulmonary vascular resistance (PVR) by approximately 231.29 units, significantly increased cardiac output (CO), and improved the quality of life (QoL). The main adverse reactions to iloprost treatment were cough (17 %), headache (16.4 %), and flushing (12.4 %).
CONCLUSION
Iloprost, either used alone or as adjuvant therapy, can enhance exercise capacity, lower hemodynamic parameters, and improve long-term outcomes. However, the risk of mortality and clinical deterioration remains unknown.
Topics: Humans; Iloprost; Hypertension, Pulmonary; Vasodilator Agents; Pulmonary Arterial Hypertension; Clinical Deterioration; Familial Primary Pulmonary Hypertension; Administration, Inhalation; Randomized Controlled Trials as Topic
PubMed: 37992575
DOI: 10.1016/j.hrtlng.2023.11.006 -
Respiratory Care Jun 2015The inhaled route has a number of attractive features for treatment of pulmonary hypertension, including delivery of drug directly to the target organ, thus enhancing... (Review)
Review
The inhaled route has a number of attractive features for treatment of pulmonary hypertension, including delivery of drug directly to the target organ, thus enhancing pulmonary specificity and reducing systemic adverse effects. It can also improve ventilation/perfusion matching by dilating vessels supplying ventilated regions, thus improving gas exchange. Furthermore, it can achieve higher local drug concentrations at a lower overall dose, potentially reducing drug cost. Accordingly, a number of inhaled agents have been developed to treat pulmonary hypertension. Most in current use are prostacyclins, including epoprostenol, which has been cleared for intravenous applications but is used off-label in acute care settings as a continuously nebulized medication. Aerosolized iloprost and treprostinil are both prostacyclins that have been cleared by the FDA to treat pulmonary arterial hypertension (PAH). Both require frequent administration (6 and 4 times daily, respectively), and both have a tendency to cause airway symptoms, including cough and wheeze, which can lead to intolerance. These agents cannot be used to substitute for the infused routes of prostacyclin because they do not permit delivery of medication at high doses. Inhaled nitric oxide (INO) is cleared for the treatment of primary pulmonary hypertension in newborns. It is also used off-label to test acute vasoreactivity in PAH during right-heart catheterization and to treat acute right-heart failure in hospitalized patients. In addition, some studies on long-term application of INO either have been recently completed with results pending or are under consideration. In the future, because of its inherent advantages in targeting the lung, the inhaled route is likely to be tested using a variety of small molecules that show promise as PAH therapies.
Topics: Administration, Inhalation; Adult; Antihypertensive Agents; Bronchodilator Agents; Epoprostenol; Humans; Hypertension, Pulmonary; Iloprost; Infant, Newborn; Nitric Oxide; Off-Label Use; Prostaglandins I; Vasodilator Agents
PubMed: 26070575
DOI: 10.4187/respcare.03927 -
International Journal of Circumpolar... Dec 2023We performed a scoping review to identify the extent of the literature describing the use of iloprost in the treatment of frostbite. Iloprost is a stable synthetic... (Review)
Review
We performed a scoping review to identify the extent of the literature describing the use of iloprost in the treatment of frostbite. Iloprost is a stable synthetic analog of prostaglandin I. As a potent inhibitor of platelet aggregation and vasodilator, it has been used to address the post-rewarming reperfusion injury in frostbite. The search using iloprost and frostbite as key words and MeSH terms yielded 200 articles. We included in our review the literature examining iloprost for the treatment of frostbite in humans in the form of primary research, conference proceedings and abstracts. Twenty studies published from 1994 to 2022 were selected for analysis. The majority were retrospective case series consisting of a homogeneous population of mountain sport enthusiasts. A total of 254 patients and over 1000 frostbitten digits were included among the 20 studies. The larger case series demonstrated a decrease in amputation rates relative to untreated patients. Primary gaps in the literature include a paucity of randomised trials and relatively limited study populations to date. While the case evidence is promising, a multi-centre collaboration would be crucial to adequately power prospective randomised studies to definitively determine if iloprost has a role in the treatment of frostbite.
Topics: Humans; Iloprost; Prospective Studies; Retrospective Studies; Epoprostenol; Frostbite
PubMed: 36966492
DOI: 10.1080/22423982.2023.2189552 -
The Cochrane Database of Systematic... Mar 2016Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The etiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularization to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain.
OBJECTIVES
To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease.
SEARCH METHODS
The Cochrane Vascular Trials Search Co-ordinator searched their Specialised Register (last searched in April 2015) and the Cochrane Register of Studies (Issue 3, 2015). The review authors searched trial registers and the European grey literature; screened reference lists of relevant studies, and contacted study authors and major pharmaceutical companies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease.
DATA COLLECTION AND ANALYSIS
Two review authors, independently assessed the studies, extracted data and performed data analysis.
MAIN RESULTS
Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid.Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; one study; moderate quality evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; one study; moderate quality evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; one study; moderate quality evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; two studies; I² = 0%; very low quality evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; one study; low quality evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; one study; moderate quality evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; one study; moderate quality evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; one study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; one study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low quality evidence).Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study.Overall, the quality of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information regarding for example baseline tobacco exposure.
AUTHORS' CONCLUSIONS
Moderate quality evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Verylow and low quality evidence suggests there is no difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very-low quality evidence suggests there is no difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. High quality trials assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.
Topics: Adult; Alprostadil; Amputation, Surgical; Aspirin; Epoprostenol; Humans; Iloprost; Male; Middle Aged; Prostaglandins; Randomized Controlled Trials as Topic; Thromboangiitis Obliterans; Ulcer
PubMed: 26967103
DOI: 10.1002/14651858.CD011033.pub3 -
Scientific Reports Feb 2022Expression of Frizzled 9 (FZD9) is critical to the activity of the lung cancer chemoprevention agent and prostacyclin analogue, iloprost. FZD9 is required in lung...
Expression of Frizzled 9 (FZD9) is critical to the activity of the lung cancer chemoprevention agent and prostacyclin analogue, iloprost. FZD9 is required in lung epithelial cells for iloprost to activate peroxisome proliferator activated receptor gamma (PPARG) and related anti-tumor signaling. We aimed to investigate which miRNA regulate FZD9 in the context of cigarette smoke exposure and iloprost treatment. We found that miR-520a-5p binds the FZD9 3'UTR in lung cell lines and alters activity and expression of FZD9 downstream targets. Cigarette smoke condensate (CSC) increases expression of miR-520a-5p, while iloprost decreases expression. Cancer promoting effects of a miR-520a-5p mimic were rescued with iloprost treatment, and effects of cigarette smoke were partially rescued with a miR-520a-5p inhibitor. Here we confirm miR-520a-5p as a regulator of FZD9 activity and a mediator of CSC and iloprost effects in the lung. Targeting miR-520a-5p could be an approach to restoring FZD9 expression and improving response to iloprost lung cancer chemoprevention.
Topics: Cell Line, Tumor; Chemoprevention; Cigarette Smoking; Epithelial Cells; Frizzled Receptors; Humans; Iloprost; Lung Neoplasms; MicroRNAs; PPAR gamma; Protein Binding; Protein Domains
PubMed: 35149732
DOI: 10.1038/s41598-022-06292-7 -
ARP Rheumatology 2022Vasculopathy is a crucial feature of systemic sclerosis (SSc). It occurs in almost every patient with SSc, with Raynaud's phenomenon (RP) and digital ulcers (DU) having...
INTRODUCTION
Vasculopathy is a crucial feature of systemic sclerosis (SSc). It occurs in almost every patient with SSc, with Raynaud's phenomenon (RP) and digital ulcers (DU) having a great impact on the quality of patients' lives. Intravenous (IV) iloprost, a synthetic analogue of prostacyclin, is broadly used to treat RP and DU secondary to SSc. Currently, there is no standard protocol defined for the iloprost treatment of SSc-associated RP and DU, and, consequently, the management of this treatment is largely based on each centre's experience.
OBJECTIVE
The objective of this study is to evaluate the safety profile of a particular scheme of IV iloprost used in our centre as the standard treatment of SSc-related vascular complications.
METHODS
We retrospectively evaluated the clinical records of SSc patients, classified according to the 2013 European Alliance of Associations for Rheumatology (EULAR) criteria (31) with SSc-related DU and/or severe RP not responsive to CCB, receiving or who have received IV iloprost infusions from January 1st 2011 to March 31st 2021 Results: Within this time frame, 60 patients (n=44 for DU; n=16 for severe RP) were treated with a monthly 10-hour IV iloprost perfusion with a dosing regimen adapted to individual tolerance. Forty-nine of these 60 patients (81.7%) were on iloprost for more than one year. Within 12 months of therapy, 40 patients have healed the DUs (90.9%), with only 4 patients maintaining active DUs. A significant clinical improvement in RP at 12 months was observed in 87.5% (n=14/16) of SSc patients with severe RP. Eleven AE implying treatment dose/frequency adjustments or suspension were recorded (18.3% of patients): severe headache (n=5), hypotension (n=3), tachycardia (n=1), flushing (n=1) and generalised erythroderma (n=1). In all patients, the perfusion rate was reduced in the following treatment sessions with good tolerance, with the exception of the patient with the generalised erythroderma reaction, who suspended the perfusion and was later switched to bosentan. After a mean follow-up time of 6.9 (+/-) 4.0 years of treatment (range 0.06-22), 24 patients (40%) stopped the therapy, 14 (58.3%) of whom due to clinical improvement. The overall 5-, and 10-year survival rates of IV iloprost were 68.2% and 55.6%, respectively.
CONCLUSION
SSc patients who received this flexible IV iloprost regimen achieved clinical improvement, reflected in the high persistence rate of the drug, with a good tolerability profile. In addition, most side effects were mild and easily managed.
Topics: Dermatitis, Exfoliative; Humans; Iloprost; Raynaud Disease; Retrospective Studies; Scleroderma, Systemic; Skin Ulcer
PubMed: 35810370
DOI: No ID Found -
Scandinavian Journal of Trauma,... Dec 2023Our objective was to perform a systematic review of the outcomes of various frostbite treatments to determine which treatments are effective. We also planned to perform... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Our objective was to perform a systematic review of the outcomes of various frostbite treatments to determine which treatments are effective. We also planned to perform meta-analyses of the outcomes of individual treatments for which suitable data were available.
MAIN BODY
We performed a systematic review and meta-analyses in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We searched PubMed, Cochrane Trials, and EMBase to identify primary references from January 1, 1900, to June 18, 2022. After eliminating duplicates, we screened abstracts to identify eligible studies containing information on treatment and outcomes of Grade 2 to 4 frostbite. We performed meta-analyses of groups of articles that provided sufficient data. We registered our review in the prospective registry of systematic reviews PROSPERO (Nr. 293,693). We identified 4,835 potentially relevant studies. We excluded 4,610 studies after abstract screening. We evaluated the full text of the remaining 225 studies, excluding 154. Ultimately, we included 71 articles with 978 cases of frostbite originating from 1 randomized controlled trial, 20 cohort studies and 51 case reports. We found wide variations in classifications of treatments and outcomes. The two meta-analyses we performed both found that patients treated with thrombolytics within 24 h had better outcomes than patients treated with other modalities. The one randomized controlled trial found that the prostacyclin analog iloprost was beneficial in severe frostbite if administered within 48 h.
CONCLUSIONS
Iloprost and thrombolysis may be beneficial for treating frostbite. The effectiveness of other commonly used treatments has not been validated. More prospective data from clinical trials or an international registry may help to inform optimal treatment.
Topics: Humans; Iloprost; Cohort Studies
PubMed: 38072923
DOI: 10.1186/s13049-023-01160-3 -
The Cochrane Database of Systematic... Dec 2020Frostbite is a thermal injury caused when tissue is exposed to sub-zero temperatures (in degrees Celsius) long enough for ice crystals to form in the affected tissue....
BACKGROUND
Frostbite is a thermal injury caused when tissue is exposed to sub-zero temperatures (in degrees Celsius) long enough for ice crystals to form in the affected tissue. Depending on the degree of tissue damage, thrombosis, ischaemia, necrosis (tissue death), gangrene and ultimately amputation may occur. Several interventions for frostbite injuries have been proposed, such as hyperbaric oxygen therapy, sympathectomy (nerve block), thrombolytic (blood-thinning) therapy and vasodilating agents such as iloprost, reserpine, pentoxifylline and buflomedil, but the benefits and harms of these interventions are unclear.
OBJECTIVES
To assess the benefits and harms of the different management options for frostbite injuries.
SEARCH METHODS
On 25 February 2020, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase (OvidSP), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), Conference Proceedings Citation Index-Science (CPCI-S), as well as trials registers. Shortly before publication, we searched Clinicaltrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform, OpenGrey and GreyLit (9 November 2020) again. We investigated references from relevant articles, and corresponded with a trial author.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared any medical intervention, e.g. pharmacological therapy, topical treatments or rewarming techniques, for frostbite injuries to another treatment, placebo or no treatment.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data. We used Review Manager 5 for statistical analysis of dichotomous data with risk ratio (RR) with 95% confidence intervals (CIs). We used the Cochrane 'Risk of bias' tool to assess bias in the included trial. We assessed incidence of amputations, rates of serious and non-serious adverse events, acute pain, chronic pain, ability to perform activities of daily living, quality of life, withdrawal rate from medical therapy due to adverse events, occupational effects and mortality. We used GRADE to assess the quality of the evidence.
MAIN RESULTS
We included one, open-label randomised trial involving 47 participants with severe frostbite injuries. We judged this trial to be at high risk of bias for performance bias, and uncertain risk for attrition bias; all other risk of bias domains we judged as low. All participants underwent rapid rewarming, received 250 mg of aspirin and 400 mg intravascular (IV) buflomedil (since withdrawn from practice), and were then randomised to one of three treatment groups for the following eight days. Group 1 received additional IV buflomedil 400 mg for one hour per day. Group 2 received the prostacyclin, iloprost, 0.5 ng to 2 ng/kg/min IV for six hours per day. Group 3 received IV iloprost 2 ng/kg/min for six hours per day plus fibrinolysis with 100 mg recombinant tissue plasminogen activator (rtPA) for the first day only. The results suggest that iloprost and iloprost plus rtPA may reduce the rate of amputations in people with severe frostbite compared to buflomedil alone, RR 0.05 (95% CI 0.00 to 0.78; P = 0.03; very low-quality evidence) and RR 0.31 (95% CI 0.10 to 0.94; P = 0.04; very low-quality evidence), respectively. Iloprost may be as effective as iloprost plus rtPA at reducing the amputation rate, RR 0.14 (95% CI 0.01 to 2.56; P = 0.19; very low-quality evidence). There were no reported deaths or withdrawals due to adverse events in any of the groups; we assessed evidence for both outcomes as being of very low quality. Adverse events (including flushing, nausea, palpitations and vomiting) were common, but not reported separately by comparator arm (very low-quality evidence). The included study did not measure the outcomes of acute pain, chronic pain, ability to perform activities of daily living, quality of life or occupational effects.
AUTHORS' CONCLUSIONS
There is a paucity of evidence regarding interventions for frostbite injuries. Very low-quality evidence from a single small trial indicates that iloprost, and iloprost plus rtPA, in combination with buflomedil may reduce the need for amputation in people with severe frostbite compared to buflomedil alone. However, buflomedil has been withdrawn from use. High quality randomised trials are needed to establish firm evidence for the treatment of frostbite injuries.
Topics: Amputation, Surgical; Aspirin; Bias; Drug Therapy, Combination; Epoprostenol; Fibrinolytic Agents; Frostbite; Humans; Iloprost; Platelet Aggregation Inhibitors; Pyrrolidines; Recombinant Proteins; Rewarming; Tissue Plasminogen Activator; Vasodilator Agents
PubMed: 33341943
DOI: 10.1002/14651858.CD012980.pub2