90 Individual and Injury Characteristics of Response to Thrombolytic Therapy Following Severe Frostbite Injury

TL;DR

This study examines how patients with severe frostbite respond to tPA treatment, finding that early administration improves outcomes and that imaging can help predict amputation risks.

Contribution

The study introduces a novel method to assess tPA efficacy using perfusion imaging and stratifies patients into response categories.

Findings

71.4% of patients were full responders to tPA, with significantly smaller initial perfusion deficits.

Early tPA administration (within 5–7 hours of warming) was associated with the best outcomes.

Imaging outcomes showed that 37.7% of partial responders and 40% of non-responders had amputations.

Abstract

Approximately 30% of severe frostbite injuries result in amputation. Thrombolytic therapy (tPA) is used to reduce tissue loss following severe frostbite injury. This study evaluates factors impacting the tPA effectiveness using post-tPA perfusion imaging and amputation level as outcome measures. We hypothesize that stratifying tPA-treated patients into full, partial, and non-responders will allow for a more nuanced assessment of treatment efficacy.

We reviewed a prospectively maintained frostbite database (2013–2020) for patients with post-rewarming perfusion deficits measured by Tc99 scan who were treated with IV tPA. Descriptive statistics and multinomial logistic regression assessed differences in responder categories (full, partial, non-responders), adjusting for time to tPA, pre-treatment tissue perfusion deficits, and infection.

Of 133 patients, 71.4% were full responders, 23.3% partial responders, and 5.3% non-responders for surgical outcome (Fig 1). The median time to tPA was 5.5 hours (range 3.5-14 for full responder); 7 hours (range 1.5-14 for partial responder); and 10 hours (range 1-10 for non-responder). Full responders had significantly smaller initial perfusion deficits than partial and non-responders (Fig 2 A-C). There were no significant differences in psychosocial or comorbid factors observed across responder groups. Time to tPA, amount of tissue with post-rewarming perfusion deficit, and cellulitis or infection significantly increased the risk of non-response relative to amputation in multinominal regression.

Since cellulitis/infection significantly impacts final amputation level, we used post-tPA imaging as an outcome measure less impacted by confounding factors. Imaging outcomes were available for 95 patients, 28.4% full responders, 55.8% partial responders, and 15.8% non-responders (Fig 1). Similar findings were observed regarding time to tPA and tissue impacted influencing response groups (Fig 2 D-F). Interestingly, significantly fewer imaging non-responders had a history of alcohol abuse. Full responders for imaging outcome corresponded with surgical outcomes and had no amputations, while 37.7% of partial responders and 40% of non-responders on imaging outcome had amputations (Fig 1). Of partial and non-responders for imaging outcomes that had amputations, all but 1 had predicted amputation needed on discharge planning.

This study is the largest to evaluate tPA outcomes in severe frostbite injured patients, provides new insight into tPA responses, and offers a novel assessment of tPA treatment efficacy. These findings underscore the importance of timely tPA administration and demonstrate benefits for patients treated outside the standard tPA treatment windows.

Early administration of tPA, within 5–7 hours of warming, was associated with the best outcomes, however tPA response was observed in a wide range of treatment times.

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