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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