P042: Resuscitative endovascular balloon occlusion of the aorta (REBOA) in trauma: a systematic review

Introduction: Trauma leading to uncontrolled hemorrhage of the torso in the critically injured patient can rapidly progress to decreased cerebral and cardiovascular perfusion and carries a significant morbidity and mortality. Given the non-compressible nature and difficult anatomic access of these injuries, obtaining hemostasis is often a challenge and non-surgical options are sparse. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is a rapidly administered emergency department intervention that allows transient source control of caudal torso hemorrhage while arranging definitive surgical management. Although initially postulated in the 1950s, limited research regarding its therapeutic use in trauma has been available until recently. Here, we present a systematic review of the literature pertaining to the use of REBOA in severe trauma. Methods: An experienced medical librarian searched electronic databases for terms relating to REBOA, aortic balloon occlusion, hemorrhage, trauma and shock. Articles were identified, screened, retrieved and reviewed in accordance with PRISMA systematic review guidelines. English case reports, case series, cohort studies, randomized-controlled trials, systematic reviews and meta-analyses pertaining to the use of REBOA in human trauma patients were included. Customized inclusion and data extraction forms were created and used to form an electronic database of relevant studies. Results: After exclusion of duplicates, 2147 potentially relevant articles were identified and screened by title/abstract and 136 articles meeting inclusion criteria were retrieved for full-text review. Final analysis of 26 articles included 5 case reports, 13 case series, 7 observational cohort studies and 1 systematic review. Data spanning 771 patients undergoing REBOA were collected (weighted average age: 49.5, gender: 67.7% male, injury severity score: 35.1). Where data available, REBOA increased systolic blood pressure by a weighted average of 54.7mmhg and overall survival was 32.6%. Conclusion: Limited evidence pertaining to the use of REBOA in severe trauma exists with the majority of available data coming from individual case studies and case series. By extension, quantitative analysis regarding outcome data of this intervention requires further research in the form of larger studies with subgroup analysis to identify the subset of patients for which REBOA may benefit and to further delineate the risks of implementing this intervention

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Rituximab for Eosinophilic Granulomatosis with Polyangiitis: a Systematic Review of Observational Studies

Rheumatology ◽

10.1093/rheumatology/keab046 ◽

2021 ◽

Author(s):

Vincenzo G Menditto ◽

Giulia Rossetti ◽

Diletta Olivari ◽

Alessia Angeletti ◽

Marco Rocchi ◽

...

Keyword(s):

Systematic Review ◽

Cohort Studies ◽

Granulomatosis With Polyangiitis ◽

Case Reports ◽

Case Series ◽

Biologic Agents ◽

Cochrane Library ◽

Eosinophilic Granulomatosis With Polyangiitis ◽

Extensive Literature ◽

Eosinophilic Granulomatosis

Abstract Objective to analyze the available evidence about the use of rituximab (RTX) and other biologic agents in Eosinophilic Granulomatosis with Polyangiitis (EGPA) patients and to provide useful findings to inform the design of future, reliable clinical trials. Methods A systematic review was performed. A systematic search was conducted in PubMed/MEDLINE, Scopus, Web of Science and the Cochrane library databases and an extensive literature search on other biologic agents. Results 45 papers pertinent to our questions were found: 16 retrospective cohort studies, 8 case series, 3 prospective cohort studies and 18 single case reports, for a total of 368 EGPA patients. More than 80% of evaluable patients achieved complete or partial remission with a tendency towards a higher rate of complete response in pANCA positive subgroup. Conclusion Although the majority of the evaluable EGPA patients treated with RTX appears to achieve complete remission, we strongly believe that a number of sources of heterogeneity impairs a clear interpretation of results and limits their transferability in clinical practice. Differences in design, enrollment criteria, outcome definition and measurement make a comparison among data obtained from studies on RTX and other biologic agents unreliable.

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Resuscitative Endovascular Balloon Occlusion of the Aorta is a Risk Factor for Intestinal Necrosis: A Case Report

10.21203/rs.3.rs-102623/v1 ◽

2020 ◽

Author(s):

Keitaro Yajima ◽

Shokei Matsumoto ◽

Motoyasu Yamazaki

Keyword(s):

Case Reports ◽

Severe Trauma ◽

Balloon Occlusion ◽

Trauma Patients ◽

Occlusion Time ◽

Intestinal Necrosis ◽

Ischemic Complications ◽

Inappropriate Utilization ◽

Enhanced Computed Tomography ◽

Endovascular Balloon Occlusion

Abstract BackgroundResuscitative endovascular balloon occlusion of the aorta (REBOA) is effective for temporary hemorrhage control and resuscitative effort, as it enhances cerebral and coronary circulation in trauma patients. However, an inappropriate utilization of REBOA leads to critical complications. Placement of the balloon in Zone 2 of the aorta should be avoided as the occlusion restricts the intestinal blood supply leading to fatal complications. There is a scarcity of case reports on complications associated with endovascular balloon occlusion in the literature. Here, we have presented a rare case in which Zone 2 REBOA contributed to an ischemic complication in a trauma patient.Case presentationA 50-year-old man with severe trauma, who accidentally got buried under a fallen cement wall, was carried to the nearest hospital. Contrast-enhanced computed tomography showed an unstable pelvic fracture that required hemostatic intervention. Prior to being transferred to another hospital, the patient was treated with endovascular balloon placement. A Zone 2 endovascular balloon placement with resuscitative effort accidentally led to insufficient abdominal blood flow and he developed extensive intestinal necrosis. Following surgical intervention, the patient was resuscitated; however, he developed partial intestinal necrosis and was subsequently managed with surgical intestinal resection.ConclusionsBlood supply to the abdominal organs should be considered when deploying the balloon. Further, balloon positioning, aortic occlusion time, and inflation volume should be carefully considered to avoid ischemic complications.

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Neonates with Asymptomatic Central Venous Catheter-Related Thrombosis - a Systematic Review

Blood ◽

10.1182/blood-2020-133646 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 8-9

Author(s):

Bader Allahyani ◽

Abdullah Alanazi ◽

Joshua Feder ◽

Ewurabena Simpson

Keyword(s):

Systematic Review ◽

Cohort Studies ◽

Conflicts Of Interest ◽

Umbilical Vein ◽

Case Reports ◽

Anticoagulation Therapy ◽

Case Series ◽

Current Guideline ◽

Central Venous ◽

Randomized Controlled Studies

Background: Central venous catheters (CVCs) are the most frequent cause of thrombosis in acutely unwell neonates. The natural history CVC-RT remains unclear. The current guideline for symptomatic CVC-related thrombus suggests that anticoagulation likely leads to minimizing complications while the recommendation for pediatric patients with asymptomatic deep vein thrombosis (DVT) is equivocal. Objective: This systematic review was undertaken to summarize evidence from the pediatric literature on the prevalence of asymptomatic CVC-RT in the neonate and whether anticoagulation therapy (ACT) improves the outcomes of asymptomatic CVC-RT in the neonate. Methods: We searched CENTRAL, MEDLINE, Embase, CINAHL, the Web of Science, and clinical trial databases. We considered data from retrospective and prospective cohort studies, case series, and randomized controlled studies evaluating the prevalence and outcomes of CVC-RT following the use or non-use of ACT. Data were analyzed using Fisher exact and Chi-square statistics. Results: In total 762 articles were identified and screened, of which 16 articles included (1 RCT, 4 prospective studies and 8 retrospective cohort studies, and 3 case reports) that met inclusion criteria and contained extracted case data; these studies reported on a total of 1909 neonates with CVC have been screened for thrombosis. All studies were considered at moderate or high risk of bias. Tau2 and I2 suggested a high degree of heterogeneity. Ultimately, 309 cases were identified with the prevalence of asymptomatic CVC-RT was 16%. Notably, only 6.5% of neonates with symptomatic CVC-RT had undergone ultrasound (US) screening. The majority of the cases were premature neonates. 45% of the neonate had Umbilical Vein Catcher (UVC). 114 (41%) of the cases received ACT, of which none complicated with major bleeding. Overall there was no difference following the use or nonuse of ACT in patency of the asymptomatic CVC-RT, recurrence, and thrombosis related mortality. The frequency of each outcome according to therapy is shown in Table1. CONCLOSION: This systematic review has provided additional evidence supporting the favorable outcome of asymptomatic CVC-RT in the neonate regardless of the use of ACT. Further well-designed, prospective, multi-center clinical trials are needed to establish evidence-based treatment recommendations for neonates with asymptomatic CVC-RT. Figure Disclosures No relevant conflicts of interest to declare.

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A Systematic Review of the Protective Effect of Prior SARS-CoV-2 Infection on Repeat Infection

Evaluation & the Health Professions ◽

10.1177/01632787211047932 ◽

2021 ◽

pp. 016327872110479

Author(s):

N. Kojima ◽

N. K. Shrestha ◽

J. D. Klausner

Keyword(s):

Systematic Review ◽

Cohort Studies ◽

Protective Effect ◽

Case Series ◽

Weighted Average ◽

P Value ◽

Average Risk ◽

Search Term ◽

Scientific Publications ◽

The Impact

We systematically reviewed studies to estimate the risk of SARS-CoV-2 reinfection among those previously infected with SARS-CoV-2. For this systematic review, we searched scientific publications on PubMed and MedRxiv, a pre-print server, through August 18, 2021. Eligible studies were retrieved on August 18, 2021. The following search term was used on PubMed: (((“Cohort Studies”[Majr]) AND (“COVID-19”[Mesh] OR “SARS-CoV-2”[Mesh])) OR “Reinfection”[Majr]) OR “Reinfection”[Mesh]. The following search term was used on MedRxiv: “Cohort Studies” AND “COVID-19” OR “SARS-CoV-2” AND “Reinfection”. The search terms were broad to encompass all applicable studies. There were no restrictions on the date of publication. Studies that did not describe cohorts with estimates of the risk of SARS-CoV-2 reinfection among those with previous infection were excluded. Studies that included vaccinated participants were either excluded or limited to sub-groups of non-vaccinated individuals. To identify relevant studies with appropriate control groups, we developed the following criteria for studies to be included in the systematic analysis: (1) baseline polymerase chain reaction (PCR) testing, (2) a uninfected comparison group, (3) longitudinal follow-up, (4) a cohort of human participants, i.e. not a case report or case series, and (5) outcome determined by PCR. The review was conducted following PRISMA guidelines. We assessed for selection, information, and analysis bias, per PRISMA guidelines. We identified 1,392 reports. Of those, 10 studies were eligible for our systematic review. The weighted average risk reduction against reinfection was 90.4% with a standard deviation of 7.7% ( p-value: <0.01). Protection against SARS-CoV-2 reinfection was observed for up to 10 months. Studies had potential information, selection, and analysis biases. The protective effect of prior SARS-CoV-2 infection on re-infection is high and similar to the protective effect of vaccination. More research is needed to characterize the duration of protection and the impact of different SARS-CoV-2 variants.

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Spectrum of Neurologic Complications after Allogeneic Hematopoietic Cell Transplantation for Hematologic Diseases in Adults: Systematic Review and Meta-Analysis

Blood ◽

10.1182/blood-2019-128641 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5692-5692

Author(s):

Maria Gavriilaki ◽

Maria Mainou ◽

Eleni Gavriilaki ◽

Anna-Bettina Haidich ◽

Sotirios Papagiannopoulos ◽

...

Keyword(s):

Systematic Review ◽

Cohort Studies ◽

Hematopoietic Cell Transplantation ◽

Case Reports ◽

Meta Analysis ◽

Case Series ◽

Neurologic Complications ◽

Hematologic Diseases ◽

Immune Mediated ◽

Impact On Survival

Introduction: Neurologic adverse events remain challenging complications with poor morbidity and mortality post adult allogeneic hematopoietic cell transplantation (alloHCT) for hematologic diseases. We conducted a systematic review and meta-analysis to determine their spectrum, incidence and impact on survival. Methods: We searched MEDLINE, COCHRANE, EMBASE through March 2019 for studies published in English. We deemed eligible all types of primary studies including randomized controlled trials (RCTs), controlled observational studies (both cohort and case control), case series and case reports. The eligibility criteria were: (a) adult population specified as patients fifteen years old or older, (b) alloHCT for hematologic diseases, (c) neurologic disorders' diagnosis. Two independent reviewers screened, extracted data and assessed risk of bias (RoB). The primary outcome being the incidence of neurologic complications was assessed in a form of a proportion of adult patients with the neurologic manifestation (n) from the total group of patients that received alloHCT for hematologic diseases (N). We performed a random-effects meta-analysis of proportions using the Freeman-Tukey double arcsine transformation, including only cohort studies. Secondary outcome was impact of neurologic complications on overall survival of patients presented with symptoms after allo-HCT. Pre-planned sensitivity analysis integrating the risk of bias assessment by excluding studies evaluated as high risk was performed as well as prespecified subgroup analyses according to the type of neurologic event. Results: We identified 552 eligible studies describing 57.972 patients; one randomized controlled trial, two case-control, 17 prospective, 86 retrospective cohort studies, 21 case-series and 425 case-reports (PRISMA flow diagram). RoB ranged from fair to high although case-series were of low-risk. The majority of studies traced infectious or drug-related neurologic manifestations. Incidence rates of neurologic complications varied, according to type of complications and studies, from 0.6% for immune-mediated disorders in retrospective cohorts to 13% for drug-related events in prospective cohorts. In meta-analysis of proportions, we included only cohort studies, retrospective or prospective, with homogenous population to estimate a proportion. Neurologic clinical signs or symptoms were detected in 1415 out of 37450 [6.2% (95%CI 4.8-7.7), Ι2= 96.1% (p<0.001)] patients described in 78 included cohort studies. Heterogeneity of results remained high, even after sensitivity analysis excluding studies of high RoB. Infectious complications were present in 2.7% (95%CI 1.9-3.6) and 3.3% (95%CI 0.8-7.1) of patients in retrospective and prospective cohort studies respectively. In retrospective studies, 3.4% (95%CI 2.1-4.9) of patients suffered from drug-related neurologic events. In prospective cohorts, the equivalent incidence was 13% (95%CI 4.2-24.8). Other neurologic complications included cerebrovascular events, thrombotic microangiopathy, immune-mediated complications, relapse and metabolic events. Regarding the severity of neurologic complications and death rate in patients with outcome of interest, data were too diverse to provide any safe conclusion. Neurologic complications had a detrimental impact on survival depending on type of complication in various studies. Based on study type, high RoB in most of the included studies, as well as significant heterogeneity in results from observational data, high imprecision and suspected publication bias, quality of evidence was very low applying the GRADE tool. Conclusion: Our study highlights the wide spectrum and significant impact of neurologic complications on survival post alloHCT. This systematic review summarizes existing data and provides the necessary background information for every physician involved in the management of these patients. Disclosures No relevant conflicts of interest to declare.

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The Use of tPA in the Treatment of Frostbite: A Systematic Review

Hand ◽

10.1177/1558944718800731 ◽

2018 ◽

Vol 14 (1) ◽

pp. 13-18 ◽

Cited By ~ 8

Author(s):

Richard L. Hutchison ◽

Hannah M. Miller ◽

Spencer K. Michalke

Keyword(s):

Systematic Review ◽

Cohort Studies ◽

Case Reports ◽

Case Series ◽

Scientific Quality ◽

Complication Rates ◽

Outcomes Measures ◽

Study Results

Background: The use of tissue plasminogen activator (tPA) for the treatment of frostbite has been reported and advocated, but its efficacy has not been well established. We conducted a systematic review to guide physicians on the role of tPA in the treatment of frostbite. Our hypothesis was that the use of tPA improves clinical outcomes, as measured by amputation rate. Methods: We searched MEDLINE (PubMed) and EMBASE for primary research articles on the use of tPA for the treatment of extremity frostbite. Information related to study design, outcomes, and complications was extracted. A total of 204 citations were screened, and then 35 abstracts and 24 reports were reviewed. Fifteen studies met the standard for final review. Results: One randomized, prospective study; 3 cohort studies; 8 case series; and 3 case reports were found. A total of 208 patients were treated. Differences in protocols, inclusion criteria, and outcomes measures prevented combining the study results. In all the studies, the authors reported that the use of tPA was or may have been useful in reducing amputation rates or increasing tissue salvage. Complication rates ranged from 0% to 100%, with a combined rate of 13%. The quality of the evidence was low. Conclusions: Due to the low scientific quality of the studies, the efficacy of tPA in reducing amputation rates cannot currently be established. Randomized, prospective trials or well-controlled cohort studies are needed to better assess the role of tPA. Consideration should be given to limiting its use to research protocols.

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Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in the Management of Trauma Patients: A Systematic Literature Review

The American Surgeon ◽

10.1177/000313481908500631 ◽

2019 ◽

Vol 85 (6) ◽

pp. 654-662 ◽

Cited By ~ 2

Author(s):

Patrizio Petrone ◽

Aida PÉRez-JimÉNez ◽

Martín Rodríguez-Perdomo ◽

Collin E. M. Brathwaite ◽

D'andrea K. Joseph

Keyword(s):

Blood Pressure ◽

Systolic Blood Pressure ◽

Single Case ◽

Case Reports ◽

Balloon Occlusion ◽

Definitive Treatment ◽

Trauma Patients ◽

Aortic Balloon Occlusion ◽

Number Of Patients ◽

Endovascular Balloon Occlusion

Resuscitative endovascular balloon occlusion of the aorta (REBOA) represents an innovative method by which noncompressible bleeding in the torso can be mitigated until definitive treatment can be obtained. To perform a systematic review of the literature on the use of the REBOA in trauma patients. An English and Spanish literature search was performed using MEDLINE, PubMed, and Scopus, from 1948 to 2018. Keywords used were aortic balloon occlusion, resuscitative endovascular balloon, REBOA, hemorrhage, and resuscitative endovascular balloon occlusion of the aorta. The eligilibility criteria included only original and human subject articles. Nontrauma patients, nonbleeding pathology, letters, single case reports, reviews, and pediatric patients were excluded. Two hundred forty-six articles were identified, of which 17 articles were included in this review. The total number of patients was 1340; 69 per cent were men and 31 per cent women. In 465 patients, the aortic zone location was described: 83 per cent the balloon was placed in aortic zone I and 16 per cent in zone III. Systolic blood pressure increased at an average of 52 mmHg before and after aortic occlusion. Although 32 patients (2.4%) presented clinical complications derived from the procedure, no mortality was reported. The trauma-related mortality rate was 58 per cent (776/1340). REBOA is a useful resource for the management of non-compressive torso hemorrhage with promising results in systolic blood pressure and morbidity. Indications for its use include injuries in zones 1 and 3, whereas it is not clear for zone 2 injuries. Additional studies are needed to define the benefits of this procedure.

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Post-Thrombotic Syndrome (PTS) in Children: A Systematic Review of Prevalence, Validity of Outcome Measures, and Prognostic Factors.

Blood ◽

10.1182/blood.v114.22.2978.2978 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2978-2978 ◽

Cited By ~ 1

Author(s):

Neil A Goldenberg ◽

Susan Kahn ◽

Mark A. Crowther ◽

Gili Kenet ◽

Ulrike Nowak-Gottl ◽

...

Keyword(s):

Systematic Review ◽

Prognostic Factors ◽

Cohort Studies ◽

Conflicts Of Interest ◽

Single Case ◽

Case Reports ◽

Case Series ◽

Cross Sectional ◽

Medline Search ◽

Post Thrombotic Syndrome

Abstract 2978 Poster Board II-949 BACKGROUND: Post-thrombotic syndrome (PTS) is a condition of chronic venous insufficiency following deep venous thrombosis (DVT) that affects both adults and children. Nevertheless, investigation of PTS in children has lagged behind that in adults. OBJECTIVE: This systematic review was undertaken to summarize evidence from the pediatric literature on the prevalence of PTS, the validity of proposed measures of PTS, and prognostic factors for PTS in children. METHODS: A comprehensive Medline search was performed employing the following terms: “[pediatric OR children] AND [post-thrombotic syndrome OR post-phlebitic syndrome]”. Single case reports, narrative reviews, and commentaries were excluded. RESULTS: Seven case series and cross-sectional studies, nine registries and cohort studies, and one uncontrolled clinical trial were identified that met inclusion criteria; these studies reported on a total of 1316 children with DVT (Table 1). The prevalence of PTS differed substantially between observational and non-observational studies: 15% of 1042 children versus 46% of 274 children, respectively. No pediatric studies have evaluated quality of life (QOL) associated with PTS. Two reports from a single-institutional cohort have identified elevated levels of factor VIII and D-dimer and non-use of thrombolytic therapies as potentially prognostic of PTS in children, particularly among those with veno-occlusive thrombi; these are the only reports employing a PTS outcome measure that has been validated in children (the Manco-Johnson instrument). CONCLUSIONS: Overall, high-quality evidence on pediatric PTS is lacking. Collaborative prospective cohort studies and trials that use validated measures of pediatric PTS are needed to assess the incidence of, prognostic factors for, and QOL impact of PTS in children. Disclosures: No relevant conflicts of interest to declare.

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A Systematic Review of the Protective Effect of Prior SARS-CoV-2 Infection on Repeat Infection

10.1101/2021.08.27.21262741 ◽

2021 ◽

Author(s):

Noah Kojima ◽

Nabin Shrestha ◽

Jeffrey D Klausner

Keyword(s):

Systematic Review ◽

Cohort Studies ◽

Protective Effect ◽

Case Series ◽

Weighted Average ◽

Average Risk ◽

Search Term ◽

Scientific Publications ◽

Systematic Analysis ◽

The Impact

Introduction: We systematically reviewed studies to estimate the risk of SARS-CoV-2 reinfection among those previously infected with SARS-CoV-2. Methods: For this systematic review, we searched scientific publications on PubMed and, the pre-print server, MedRxiv through August 18, 2021. Eligible studies were retrieved on August 18, 2021. We used the following search term on PubMed: (((Cohort Studies [Majr]) AND (COVID-19 [Mesh] OR SARS-CoV-2 [Mesh])) OR Reinfection [Majr]) OR Reinfection [Mesh]. We used the following search term on MedRxiv: Cohort Studies AND COVID-19 OR SARS-CoV-2 AND Reinfection. The search terms were broad to encompass all possibilities for applicable studies. There were no restrictions on the date of publication. Studies that did not describe cohorts with estimates of the risk of SARS-CoV-2 reinfection among those with previous infection were excluded. Studies that included vaccinated participants were either excluded or limited to sub-groups of non-vaccinated individuals. To identify relevant studies with appropriate control groups, we developed the following criteria for studies to be included in the systematic analysis: (1) baseline polymerase chain reaction (PCR) testing, (2) a negative comparison group, (3) longitudinal follow-up, (4) a cohort of human participants, i.e., not a case report or case series, and (5) outcome determined by PCR. The review was conducted following PRISMA guidelines. We assessed for selection, information, and analysis bias, per PRISMA guidelines. Results: We identified 1,392 reports. Of those, 10 studies were eligible for our systematic review. The weighted average risk reduction against reinfection was 90.4% with a standard deviation of 7.7%. Protection against SARS-CoV-2 reinfection was observed for up to 10 months. Studies had potential information, selection, and analysis biases. Conclusions: The protective effect of prior SARS-CoV-2 infection on re-infection is high and similar to the protective effect of vaccination. More research is needed to characterize the duration of protection and the impact of different SARS-CoV-2 variants.

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Thrombolytic Salvage of Threatened Frostbitten Extremities and Digits: A Systematic Review

Journal of Burn Care & Research ◽

10.1093/jbcr/irz097 ◽

2019 ◽

Vol 40 (5) ◽

pp. 541-549 ◽

Cited By ~ 2

Author(s):

James Drinane ◽

Vasanth S Kotamarti ◽

Casey O’Connor ◽

Lakshmi Nair ◽

Alex Divanyan ◽

...

Keyword(s):

Systematic Review ◽

Thrombolytic Therapy ◽

Animal Studies ◽

English Language ◽

Case Reports ◽

Case Series ◽

Weighted Average ◽

Tissue Loss ◽

Ischemic Tissue ◽

Soft Tissue Loss

Abstract Frostbite is a cold injury that results in soft tissue loss and can lead to amputation. Vascular thrombosis following injury causes ischemic tissue damage. Despite understanding the pathology, its treatment has remained largely unchanged for over 30 years. Threatened extremities may be salvaged with thrombolytics to restore perfusion. The authors performed a systematic review to determine whether thrombolytic therapy is effective and to identify patients who may benefit from this treatment. The Pubmed, EBSCO, and Google Scholar databases were queried using the key words “thrombolytics,” “frostbite,” “fibrinolytics,” and “tPA.” Studies written after 1990 in English met inclusion criteria. Exclusion criteria were failure to delineate anatomic parts injured, failure to report number of limbs salvaged, animal studies, and non-English language publications. Thrombolytic therapy was defined as administration of tPA, alteplase, urokinase, or streptokinase. Forty-two studies were identified and 17 included. Included were 1 randomized trial, 10 retrospective studies, 2 case series, and 4 case reports. One thousand eight hundred and forty-four limbs and digits in 325 patients were studied and 216 patients treated with thrombolytics and 346 amputations performed. The most common means of thrombolysis was intra-arterial tPA. The most common duration of therapy was 48 hours. Limb salvage rates ranged from 0% to 100% with a weighted average of 78.7%. Thrombolytics are a safe and effective treatment of severe frostbite. They represent the first significant advancement in frostbite treatment by preventing otherwise inevitable amputations warranting both greater utilization and further research to clarify the ideal thrombolytic protocol.

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