iloprost and Frostbite

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

Topics: Epoprostenol; Frostbite; Humans; Iloprost; Prospective Studies; Retrospective Studies

Cold Weather Injury (CWI) represents a spectrum of pathology, the two main divisions being Freezing Cold Injury (FCI) and Non-Freezing Cold Injury (NFCI). Both are disabling conditions associated with microvascular and nerve injury often treated hours after initial insult when presenting to a healthcarestablishment. Given that iloprost is used for the treatment of FCI, could it be used in a forward operating environment to mitigate treatment delay? Is there a role for its use in the forward treatment of NFCI? This review sought to evaluate the strength of evidence for the potential use of iloprost in a forward operating environment.. Literature searches were undertaken using the following question for both FCI and NFCI: in [patients with FCI/NFCI] does [the use of iloprost] compared to [standard care] reduce the incidence of [long-term complications]. Medline, CINAHL and EMBASE databases were searched using the above question and relevant alternative terminology. Abstracts were reviewed before full articles were requested.. The FCI search yielded 17 articles that were found to refer to the use of iloprost and FCI. Of the 17, one referred to pre-hospital treatment of frostbite at K2 base camp; however, this was utilising tPA. No articles referred to pre-hospital use in either FCI or NFCI.. Although evidence exists to support the use of iloprost in the treatment of FCI, its use to date has been in hospital. A common theme is delayed treatment due to the challenges of evacuating casualties from a remote location. There may be a role for iloprost in the treatment of FCI; however, further study is required to better understand the risk of its use.

Topics: Cold Injury; Cold Temperature; Frostbite; Humans; Iloprost; Military Personnel

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.. To assess the benefits and harms of the different management options for frostbite injuries.. 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.. 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.. 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.. 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.. 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

A short cut review was carried out to establish whether an infusion of iloprost can be used to treat frostbite to reduce the risk of needing an amputation. Three studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that iloprost may reduce the risk of amputation after frostbite.

Topics: Frostbite; Humans; Iloprost; Vasodilator Agents

Topics: Adult; Aspirin; Combined Modality Therapy; Drug Therapy, Combination; Female; Fibrinolytic Agents; Frostbite; Humans; Iloprost; Male; Platelet Aggregation Inhibitors; Pyrrolidines; Rewarming; Tissue Plasminogen Activator; Vasodilator Agents

Magnan, Dre Marie-Anne, Marco Gelsomino, Pierre Louge, and Rodrigue Pignel. Successful delayed hyperbaric oxygen therapy and iloprost treatment on severe frostbite at high altitude.

Topics: Adult; Altitude; Arthritis; Frostbite; Humans; Hyperbaric Oxygenation; Iloprost; Male

Nonfreezing cold injury (NFCI) is caused by prolonged exposure to cold, usually wet conditions and represents a separate pathological entity from frostbite. The pathophysiology of NFCI is characterized by vasoconstriction and microcirculatory disturbance. Iloprost, a synthetic prostaglandin analogue with vasodilatory properties is a recognized adjuvant treatment in frostbite; however, its role in NFCI is unclear. We present a case of a 29-y-old man with severe NFCI to both forefeet after prolonged immersion in cold seawater. Initial treatment with passive rewarming, analgesia and aspirin was initiated. Infusion of iloprost was used within 24 h from presentation and was well tolerated. This resulted in reduced tissue loss compared to the apparent tissue damage documented during the initial assessment. Delayed surgical intervention allowed minor debridement and minor toe amputations, maintaining the patient's ability to ambulate. This case demonstrates the safe use of iloprost in acute NFCI and highlights the importance of delayed surgical intervention in patients presenting with severe NFCI.

Topics: Aspirin; Cold Injury; Cold Temperature; Frostbite; Humans; Iloprost; Male; Microcirculation

We assessed the effectiveness and safety of a 5-day intravenous prostaglandin (iloprost) protocol at reducing digital amputation for patients with severe frostbite injuries at urban emergency departments.. This retrospective study examines consecutive patients who presented to Calgary emergency departments from April 2017 to April 2020 with Grade 2-4 frostbite injuries. Patients from February 2019 onward were managed using a 5-day iloprost infusion protocol, whereas patients prior to this time were managed with standard care (local best practice without iloprost as a therapeutic option). The primary effectiveness outcome was rate of affected digits amputated, stratified by frostbite severity. The secondary safety outcome was the incidence of serious adverse events associated with iloprost (allergic reactions or symptomatic hypotension requiring treatment or discontinuation of the infusion).. 90 patients were included, 26 were treated with iloprost, compared to 64 patients who received usual care. Both the treatment and usual care groups experienced substantial rates of homelessness and substance use. No digital amputations were required for patients with Grade 2 injuries in either group, but significantly lower digital amputation rates were observed for patients with more severe frostbite injuries treated with iloprost versus usual care: Grade 3 (18% vs 44%, p < 0.001), Grade 4 (46% vs 95%, p < 0.001). No serious adverse events were associated with iloprost.. In this unselected socially complex urban population, administration of iloprost for patients with frostbite was shown to be safe and was associated with lower digital amputation rates, particularly for those with more severe injuries.. RéSUMé: OBJECTIF: Nous avons évalué l'efficacité et la sécurité d'un protocole de 5 jours de prostaglandine intraveineuse (iloprost) pour réduire l'amputation digitale chez les patients souffrant d'engelures graves dans les services d'urgence urbains. MéTHODES: Cette étude rétrospective examine des patients consécutifs qui se sont présentés aux services d’urgence de Calgary d’avril 2017 à avril 2020 avec des engelures de niveau 2 à 4. À compter de février 2019, les patients ont été traités au moyen d’un protocole de perfusion d’iloprost de 5 jours, tandis que les patients avant cette période ont été pris en charge avec des soins standard (meilleures pratiques locales sans iloprost comme option thérapeutique). Le principal résultat d'efficacité était le taux de doigts affectés amputés, stratifié selon la gravité des gelures. Le critère secondaire de sécurité était l'incidence des événements indésirables graves associés à l'iloprost (réactions allergiques ou hypotension symptomatique nécessitant un traitement ou l'arrêt de la perfusion). RéSULTATS: 90 patients ont été inclus, 26 ont été traités avec de l'iloprost, contre 64 patients qui ont reçu les soins habituels. Les groupes de traitement et de soins habituels ont tous deux connu des taux importants de sans-abrisme et de consommation de substances. Aucune amputation digitale n'a été nécessaire pour les patients présentant des lésions de grade 2 dans l'un ou l'autre groupe, mais des taux d'amputation digitale significativement plus faibles ont été observés pour les patients présentant des lésions de gelures plus sévères traités par iloprost par rapport aux soins habituels : Grade 3 (18 % contre 44 %, p < 0,001), Grade 4 (46 % contre 95 %, p < 0,001). Aucun événement indésirable grave n'a été associé à l'iloprost. CONCLUSION: Dans cette population urbaine non sélectionnée et socialement complexe, l'administration d'iloprost pour les patients souffrant d'engelures s'est avérée sûre et a été associée à des taux d'amputation digitale plus faibles, en particulier pour ceux présentant des blessures plus graves.

Topics: Amputation, Surgical; Frostbite; Humans; Iloprost; Prostaglandins; Retrospective Studies

Topics: Fluorescence; Frostbite; Humans; Iloprost

Topics: Fibrinolytic Agents; Frostbite; Humans; Hyperbaric Oxygenation; Iloprost; Prospective Studies

Topics: Coloring Agents; Fluorescence; Frostbite; Humans; Iloprost; Indocyanine Green; Male; Middle Aged; Optical Imaging; Treatment Outcome; Vasodilator Agents

Topics: Aspirin; Athletic Injuries; Betamethasone; Drug Therapy, Combination; Enoxaparin; Frostbite; Hand Injuries; Humans; Iloprost; Male; Treatment Outcome

Severe frostbite occurs frequently at extreme altitude in the Himalayas, often resulting in amputations. Recent advances in treatment of frostbite injuries with either intravenous or intra-arterial tissue plasminogen activator, or with iloprost, have improved outcomes in frostbite injuries, but only if the patient has access to these within 24 to 48 h postinjury, and ideally even sooner. Frostbitten Himalayan climbers are seldom able to reach medical care in this time frame. We wished to see if delayed iloprost use (up to 72 h) would help reduce tissue loss in grade 3 to 4 frostbite. In a series of 5 consecutive climbers with severe frostbite in whom we used iloprost, 4 of whom received treatment between 48 and 72 h from injury, 2 had excellent results with minimal tissue loss, and 2 had good results with tissue loss less than expected. The 1 patient with a poor outcome likely experienced a freeze-thaw-refreeze injury. This small series suggests that iloprost can be beneficial for severe frostbite, even after the standard 48-h window and perhaps for up to 72 h.

Topics: Adult; Altitude; Amputation, Surgical; Frostbite; Humans; Iloprost; Male; Middle Aged; Mountaineering; Nepal; Platelet Aggregation Inhibitors; Time Factors; Toes; Treatment Outcome; Young Adult

Frostbite is a common injury in high altitude medicine. Intravenous vasodilators have a proven efficacy and, recently, have been proposed as a safe outpatient treatment. Nevertheless, the lack of availability and consequently delayed application of this treatment option can result in poor clinical outcomes for patients. We present the case of a 60-year-old Chilean man with severe frostbite injuries suffered while climbing Mount Everest. The patient was initially given field treatment to the extent permitted by conditions and consensus guidelines. Unfortunately, advanced management was delayed, with iloprost administered 75 hours after the initial injury. The patient also underwent 5 days of hyperbaric and analgesic/antibiotic therapies. An early bone scan predicted a poor clinical outcome, and five of the patient's fingers, between both hands, were incompletely amputated. We present this case to exemplify the importance of advanced in-field management of frostbite injuries.

Topics: Amputation, Surgical; Finger Injuries; Frostbite; Humans; Iloprost; Male; Middle Aged; Mountaineering; Time-to-Treatment; Vasodilator Agents

Severe frostbite can result in devastating injuries leading to significant morbidity and loss of function from distal extremity amputation. The modern day management approach to frostbite injuries is evolving from a historically very conservative approach to the increasingly reported use of early interventional angiography and fibrinolysis with tPA. The aim of this study was to evaluate the results of our frostbite treatment protocol introduced 3 years ago.. All frostbite patients underwent first clinical and then Doppler ultrasound examination. Angiography was conducted if certain clinical criteria indicated a severe frostbite injury and if there were no contraindications to fibrinolysis. Intra-arterial tissue plasminogen activator (tPA) was then administered at 0.5-1mg/h proximal to the antecubital fossa (brachial artery) or popliteal fossa (femoral artery) if angiography confirmed thrombosis, as well as unfractionated intravenous heparin at 500 units/h. The vasodilator iloprost was administered intravenously (0.5-2.0ng/kg/min) in selected cases.. 20 patients with frostbite were diagnosed between 2013-2016. Fourteen patients had a severe injury and angiography was performed in 10 cases. The total number of digits at risk was 111. Nine patients underwent fibrinolytic treatment with tPA (including one patient who received iloprost after initial non response to tPA), 3 patients were treated with iloprost alone and 2 patients received neither treatment modality (due to contraindications). The overall digital salvage rate was 74.8% and the Hennepin tissue salvage rate was 81.1%. One patient developed a catheter-site pseudoaneurysm that resolved after conservative treatment.. Prompt referral to a facility where interventional radiology and 24/7 laboratory services are available, and the combined use of tPA and iloprost, may improve outcome after severe frostbite.

Topics: Adult; Aged; Angiography; Clinical Protocols; Disease Management; Female; Fibrinolytic Agents; Frostbite; Humans; Iloprost; Infusions, Intra-Arterial; Ischemia; Male; Middle Aged; Radiology, Interventional; Referral and Consultation; Thrombosis; Tissue Plasminogen Activator; Ultrasonography, Doppler; Vasodilator Agents; Young Adult

Topics: Adult; Canada; Facial Injuries; Foot Injuries; Frostbite; Hand Injuries; Humans; Iloprost; Male; Middle Aged; Nose; Severity of Illness Index; Vasodilator Agents

Topics: Adult; Frostbite; Humans; Iloprost; Infusions, Intravenous; Male