Editor’s note: This article is part two in a series about frostbite. Part one is available online at www.aaosnow.org.
Frostbite is a severe soft tissue injury secondary to prolonged cold exposure and can result in a wide range of ischemic injuries. In a previous article (“Prevention and Early Treatment of Frostbite Injuries of the Hand—2019 Update,” AAOS Now, March 2019), we addressed the physiology, prevention, and early treatment of frostbite injury, including the dangers of rewarming when a second freeze is possible, keys to central body warming, the benefits of rehydration, the importance of waiting until the limb is fully warmed for full injury assessment, tips on prevention, and additional risk factors (e.g., alcohol use).
It is well accepted that determination of depth of injury is important in long-term treatment and limb salvage. Recent advances in imaging and treatment protocols for frostbite injury and its sequelae will help practitioners mitigate some of the potentially devastating long-term consequences of more severe frostbite injuries.
Upon presentation to the emergency room, patients with known frostbite injuries should undergo initial angiography after rapid rewarming of the extremity. This will provide a detailed view of perfusion deficits and allow for monitoring of thrombolysis efficacy. In patients in whom thrombolysis is indicated, angiography should be repeated every 12 to 24 hours during tissue plasminogen activator (tPA) administration. Plain radiographs may be useful if concomitant fracture is suspected.
A technetium bone scan provides a functional view of bony perfusion. This traditionally has helped determine level of amputation in the weeks following frostbite injury. Bone scan for limb salvage attempts can be performed as early as two days post-injury. Cauchy et al., found that early bone scan at 48 hours predicted eventual level of amputation in 84 percent of cases, and serial scans between days two and seven were even more sensitive (99 percent). Single-photon emission CT (SPECT)/CT is emerging as another potential option for early limb salvage and has become more cost-effective than the previously mentioned options. Conducting SPECT/CT several days after arrival for severe frostbite injuries provides both functional and detailed anatomic information and leads to more distal amputations than clinically expected with bone scan alone or via intraoperative SPY System. Current recommendations support the use of either bone scan or SPECT/CT during initial admission to predict the level of amputation.
MRI and magnetic resonance angiography are not well validated in the literature. Thermography (a test that uses an infrared camera to detect heat patterns and blood flow in body tissues) is not acutely useful but could help monitor the effects of treatment on frostbite sequelae.
After initial rewarming, thrombolysis is initiated in patients presenting within 24 hours of injury with evidence of decreased perfusion on angiography or bone scan. This is thought to interrupt the ongoing cascade of thrombosis that continues after the rewarming process. Patients undergoing thrombolytic treatment will require admission to the intensive care unit for frequent laboratory monitoring. Thrombolysis may be administered with tPA as a catheter-directed infusion or systemically via the intravenous route (Fig. 1). Catheter-directed tPA may be provided either anterograde via the brachial artery or retrograde via the femoral artery; treatment should consist of a 2 mg to 4 mg bolus of tPA followed by a maximum 1 mg/hour of tPA plus heparin 500 µ/hour. Systemic therapy should consist of tPA 0.15mg/kg/hour for six hours, followed by heparin drip.
- Catheter placed into brachial or femoral artery
- Tissue plasminogen activator (tPA) bolus: 2–4 mg
- tPA administered at 1 mg/hr
- Heparin administered at doses to achieve partial thromboplastin time (PTT) 50–70 seconds
- Complete blood count/Platelets/Fibrinogen/prothrombin time/PTT assessed:
- q6h until tPA discontinued
- q12h until Heparin discontinued
- Daily until discharge
- If Fibrinogen < 150 mg/dL, tPA infusion is discontinued
- Repeat angiography at every 12 hours for a maximum treatment time of 48 hours
- If reperfusion is complete evidenced by angiography:
- Discontinue tPA
- Continue Heparin for 72–96 hours at doses to achieve PTT 50–70 seconds
- If reperfusion is not complete:
- Continue tPA
- Continue Heparin
- If reperfusion is complete evidenced by angiography:
- The tPA is discontinued at 48 hours whether or not reperfusion has been achieved.
Fig. 1 Thrombolytic therapy administration protocol
Adapted from Ibrahim AE, Goverman J, Sarhane KA, et al: The emerging role of tissue plasminogen activator in the management of severe frostbite. J Burn Care Res 2015;36:e62-6.
At three to five days post-injury, patients may transition to warfarin for as long as four weeks. With either protocol, angiography should be repeated every 12 to 24 hours to assess the efficacy of thrombolysis. Caution should be taken if the cold injury was associated with severe dehydration and/or renal failure, as angiography use usually assumes the kidneys can excrete the dye. Early administration of tPA can salvage 80 percent of at-risk digits if provided within 24 hours of injury. Contraindications may include hemorrhage, recent surgery, trauma, or neurologic impairment.
A prostacyclin analogue like iloprost may be used as an alternative to tPA. Although it is not currently approved by the Food and Drug Administration for intravenous use, its efficacy has been demonstrated in European populations. It is purported to possess vasodilatory properties and prevent platelet aggregation. A randomized, controlled trial demonstrated that iloprost alone or in combination with tPA was superior to other vasodilatory agents. Iloprost significantly decreases the risk of amputation and may provide an alternative when tPA is contraindicated.
A variety of other proposed treatment modalities have been explored in the literature without conclusive evidence. Historically, hyperbaric oxygen was thought to increase angiogenesis and downregulate inflammation; however, its utility is mostly anecdotal, and evidence of efficacy is mixed in the literature. Acute sympathectomy is discouraged and may increase edema. Reserpine and other vasodilators are not superior to rapid rewarming. There is very little information on the use of negative pressure therapy.
An excellent resource summarizing the current treatment options and algorithms is provided by the Helsinki Burn Center (Fig. 2). The protocol allows for thrombolysis within 48 hours of injury and employs adjuvant options, including aspirin, a statin, and enoxaparin for two weeks after thrombolysis. With adherence to this protocol, the digital salvage rate is 75 percent.
After severe frostbite injuries, debilitating sequelae are prevalent. Common complaints include cold sensitivity (75 percent), hyperhidrosis (75 percent), chronic pain (67 percent), and sensory loss (68 percent). Other sequelae include growth plate disturbances in children, focal osteoporosis and subchondral bone loss, contractures, chronic ulcerations, and carpal tunnel syndrome.
Neuropathic symptoms may be addressed with neuropathic agents such as gabapentin or pregabalin. Carpal tunnel release may alleviate pressure from chronic edema. Digital artery sympathectomy has been performed for other vascular conditions, such as Raynaud’s disease. Although discouraged in the acute phase, surgical sympathectomy for chronic frostbite sequelae leads to decreased cold sensitivity, increased ambient finger temperature, and healing of chronic ulcerations.
Chemical sympathectomy with botulinum toxin also may be an emerging treatment option. In one case study, an individual with severe bilateral cold intolerance after frostbite received 60 units of botulinum toxin per hand (12 units at each A1 pulley). After several months, the patient had improved cold tolerance, improved performance on sensory testing, and increased blood flow on angiography and thermography.
After diagnosis and rapid rewarming, early imaging and thrombolysis are essential for digital or limb salvage. When possible and if there are no contraindications, thrombolysis with tPA and heparin should be administered within 24 hours. Early bone scan or SPECT/CT can predict amputation level. Frostbite sequelae are common and devastating, but new treatment options are promising.
Erin Cravez, MD, is an orthopaedic surgery resident at Yale New Haven Health. Born and raised in Anchorage, Alaska, and an avid participant in winter sports, Dr. Cravez takes special interest in the prevention of cold injuries.
Alan M. Reznik, MD, MBA, FAAOS, specializes in sports medicine and arthroscopic surgery and serves on the AAOS Now Editorial Board, AAOS Communications Cabinet, and Committee on Research and Quality. Dr. Reznik is chief medical officer of Connecticut Orthopaedic Specialists, associate professor of orthopaedics at Yale University School of Medicine, and a consultant.
- Greenwald D, Cooper B, Gottlieb L: An algorithm for early aggressive treatment of frostbite with limb salvage directed by triple-phase scanning. Plast Reconstr Surg 1998;102:1069-74.
- Kraft C, Millet JD, Agarwal S, et al: SPECT/CT in the evaluation of frostbite. J Burn Care Res. 2017;38:e227-34.
- Ljungberg M, Pretorius PH: SPECT/CT: an update on technological developments and clinical applications. Br J Radiol 2018;91:20160402.
- Shenaq DS, Gottlieb LJ: Cold injuries. Hand Clin 2017;33:257-67.
- Bruen KJ, Gowski WF: Treatment of digital frostbite: current concepts. J Hand Surg 2009;34:553-4.
- Ibrahim AE, Goverman J, Sarhane KA, et al: The emerging role of tissue plasminogen activator in the management of severe frostbite. J Burn Care Res 2015;36:e62-6.
- Lindford A, Valtonen J, Hult M, et al: The evolution of the Helsinki frostbite management protocol. Burns 2017;43:1455-63.
- 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;59:1350-4.
- Hutchison RL: Frostbite of the hand. J Hand Surg 2014;39:1863-8.
- Cauchy E, Cheguillaume B, Chetaille E: A controlled trial of a prostacyclin and rt-PA in the treatment of severe frostbite. N Engl J Med 2011;364:189-90.
- Kaller M: BET 2: Treatment of frostbite with iloprost. Emerg Med J 2017;34:689-90.
- Handford C, Thomas O, Imray CHE: Frostbite. Emerg Med Clin North Am 2017;35:281-99.
- Blair JR, Schatzki R, Orr KD: Sequelae to cold injury in one hundred patients; follow-up study four years after occurrence of cold injury. J Am Med Assoc 1957;163:1203-8.
- Norheim AJ, Mercer J, Musial F, et al: A new treatment for frostbite sequelae; botulinum toxin. Int J Circumpolar Health 2017;76:1273677.
- Flatt AE: Digital artery sympathectomy. J Hand Surg 1980;5:550-6.