The trauma surgeons at my hospital have asked me to develop a protocol for catheter-directed therapy of severe frostbite injuries (tPA and vasodilator). The published protocols vary substantially in thrombolytic bolus (yes/no, dose, route . . . some IV?), thrombolytic infusion dose rate, choice and bolus dose/dose rate of vasodilator (if used at all), and degree of heparinization (full vs low dose, PTT monitoring vs no monitoring).
I would greatly appreciate guidance/suggestions from those of you with experience in this area. Any protocols you can share would also be greatly appreciated. Thank you.
—Ezana Azene, MD, PhD
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Residency and IR fellowship at Johns Hopkins. Five years in clinical IR practice.
What are your current practice preferences for managing severe frostbite injury?
Frostbite is common in the Upper Midwest and we have been sending severe frostbite patients to a burn center 2 hours away. After consulting with this burn center, our trauma surgeons approached our group about helping them develop a protocol for treating frostbite patients locally with thrombolytic agents and catheter-based techniques.
What prompted you to reach out on SIR Connect about the topic?
We were developing a protocol from scratch and after reviewing the literature, I discovered there were many different published techniques for treating severe frostbite. Although it appears that early intervention can help preserve digit function and reduce tissue loss, the magnitude of benefit and the approach that one should take are unclear. Options in the literature include systemic thrombolysis, catheter-directed thrombolysis and an intra-arterial vasodilator. Patient selection criteria are also variable. I sought the advice of my colleagues on SIR Connect to benefit from their experience.
What post(s) were most valuable to you?
Dr. Michael Braun’s post was helpful. He described his experience with systemic thrombolysis using the Hennepin County Medical Center (MN) protocol.1,2 Although HCMC has a lot of experience safely treating severe frostbite injuries with systemic thrombolysis, I was still a little hesitant to include systemic thrombolysis as an option in our protocol. Dr. Braun’s comments helped to reassure me. Although our protocol doesn’t include systemic thrombolysis as the first-line option, we include it as an option for patients who are unable to undergo CDT within a certain amount of time after initial cold injury or thawing.
How would you have approached this case in the absence of SIR Connect?
In addition to reviewing the literature, I would have contacted friends in the IR community and the authors of the most important papers in this area.
Did you collaborate with the trauma service members on the protocol? If so, how did collaboration guide the process?
The protocol was created with collaboration from our trauma surgeons, who provided input on selection criteria.
Do you find that the new protocol will make the outcome easier to achieve or lead you to an outcome that you did not think could have been achieved otherwise?
My IR partners and I have limited experience treating patients with severe frostbite injuries. Creating this protocol in collaboration with our more “frostbite-experienced” trauma surgeons, along with the input from our IR colleagues on SIR Connect, has allowed us to quickly learn about this disease and feel comfortable treating it.
Frostbite, or cold thermal injury, occurs when tissue is exposed to temperatures below its freezing point for a long duration, resulting in progression through sequential stages of pre-freezing (vasoconstriction and ischemia), freeze-thawing (after which cell damage promotes cycles of vasodilation and vasoconstriction), vascular stasis (hypoxia, acidosis, interstitial edema), and both early and late ischemia (a culmination of inflammatory and thrombotic cascades).3 When severe injury is observed, angiography offers both a diagnostic and therapeutic approach which moves beyond standard rewarming techniques to alleviate microvascular thrombosis.
Historically, data on intra-arterial (IA) or intravenous (IV) therapy has involved retrospective studies with small cohort sizes. For instance, Twomey et al. observed a reduction in predicted amputations1 while Bruen et al. demonstrated a significantly lower incidence of amputation (10 percent vs. 41 percent) in patients suffering from severe frostbite.4 A randomized controlled trial by Cauchy et al.5 observed amputation rates as low as 3 percent when combination IA thrombolysis and iloprost (a prostacyclin analogue with vasodilator properties) were utilized. This study joined a small body of retrospective series and case reports/series6–10 suggesting that iloprost may serve a role in the treatment of severe frostbite. Recent retrospective studies are better powered and observe digit salvage rates of 69–83 percent8,11–13 utilizing protocols incorporating combinations of an IA thrombolytic (tPA; tenecteplase), anticoagulation (heparin; aspirin), and a vasodilator (alprostadil; nicardipine; nitroglycerin; papervine). Thus, the algorithm developed by Dr. Azene and his colleagues reflects current trends in patient selection and multidisciplinary management of frostbite injuries.
- Twomey JA, Peltier GL, Zera RT. An open-label study to evaluate the safety and efficacy of tissue plasminogen activator in treatment of severe frostbite. J Trauma. 2005;59(6):1350–1354; discussion 1354–1355.
- Johnson AR, Jensen HL, Peltier G, DelaCruz E. Efficacy of intravenous tissue plasminogen activator in frostbite patients and presentation of a treatment protocol for frostbite patients. Foot & Ankle Specialist. 2011;4(6):344–348.
- Millet JD, Brown RK, Levi B, et al. Frostbite: Spectrum of imaging findings and guidelines for management. Radiographics. 2016;36(7):2154–2169.
- Bruen KJ, Ballard JR, Morris SE, Cochran A, Edelman LS, Saffle JR. Reduction of the incidence of amputation in frostbite injury with thrombolytic therapy. Arch Surg. 2007;142(6):546–551; discussion, 551–543.
- Cauchy E, Cheguillaume B, Chetaille E. A controlled trial of a prostacyclin and rt-PA in the treatment of severe frostbite. New England Journal of Medicine. 2011;364(2):189–190.
- Groechenig E. Treatment of frostbite with iloprost. Lancet. 1994;344(8930):1152–1153.
- Poole A, Gauthier J. Treatment of severe frostbite with iloprost in northern Canada. CMAJ : Canadian Medical Association journal = journal de l’Association medicale canadienne. 2016;188(17–18):1255–1258.
- Lindford A, Valtonen J, Hult M, et al. The evolution of the Helsinki frostbite management protocol. Burns. 2017;43(7):1455–1463.
- Pandey P, Vadlamudi R, Pradhan R, Pandey KR, Kumar A, Hackett P. Case report: Severe frostbite in extreme altitude climbers—The Kathmandu iloprost experience. Wilderness & Environmental Medicine. 2018;29(3):366–374.
- Cauchy E, Davis CB, Pasquier M, Meyer EF, Hackett PH. A new proposal for management of severe frostbite in the austere environment. Wilderness Environ Med. 2016;27(1):92–99.
- Gonzaga T, Jenabzadeh K, Anderson CP, Mohr WJ, Endorf FW, Ahrenholz DH. Use of intra-arterial thrombolytic therapy for acute treatment of frostbite in 62 patients with review of thrombolytic therapy in frostbite. J Burn Care Res. 2016;37(4):e323–334.
- Tavri S, Ganguli S, Bryan RG, et al. Catheter-directed intraarterial thrombolysis as part of a multidisciplinary management protocol of frostbite injury. J Vasc Interv Radiol. 2016;27(8):1228–1235.
- Patel N, Srinivasa DR, Srinivasa RN, et al. Intra-arterial thrombolysis for extremity frostbite decreases digital amputation rates and hospital length of stay. Cardiovasc Intervent Radiol. 2017;40(12):1824–1831.