Current Insights On The Pathophysiology And Management Of Frostbite Blisters

There is a wide spectrum of frostbite injuries, ranging from those with minimal soft tissue loss and no long-term sequelae to disastrous injuries with severe necrosis resulting in major amputations. Several factors influence the severity of frostbite injuries and these factors include temperature, humidity, wind chill factor and length of exposure.

Researchers have shown the pathophysiology of frostbite to be similar to the inflammatory processes of burn and ischemia/reperfusion injuries. Tissue injury due to cold exposure results from several mechanisms including cellular injury, vascular impairment and the release of inflammatory mediators.^1,2 Cold-induced cellular injury results from both intracellular and extracellular processes. Mechanisms of intracellular injury include intracellular water crystallization, temperature-induced protein changes and membrane damage.³ Mechanisms of extracellular injury include crystallization of extracellular water, which decreases interstitial water and draws water out of cells; decreased intracellular water, which changes electrolyte concentration; and modified protein structures.⁴  

Vascular impairment from cold injury results from several mechanisms including vasoconstriction, endothelial injury and thromboembolism.⁵ These pathologic processes lead to vascular insufficiency and ischemia. Vasoconstriction leads to inadequate perfusion of tissues as well as stasis. Endothelial injury results in thrombosis and a loss of vascular integrity.⁵ Thromboembolism can result from vasoconstriction or endothelial injury as well as hemoconcentration and hyperviscosity.⁵ Cold injury can also lead to bleeding through cold-induced inhibition of coagulation cascade enzymes and platelet dysfunction.^6,7 

An inflammatory process with excess prostaglandin and thromboxane production also contributes to the pathogenesis of frostbite injury. Robson and Heggers found elevated levels of prostaglandin F2 alpha (PGF2a) and thromboxane B2 (TXA2) in frostbite blister fluid.⁸ Research has found that both PGF2a and TXA2 cause platelet aggregation, thrombosis and resulting progressive ischemia in burns, frostbite and ischemia/reperfusion injuries.⁹ Both animal and clinical studies have shown that inhibition of the arachidonic acid cascade and these inflammatory mediators improves tissue survival in frostbite injuries.^9,10

The classification of frostbite is based on the depth of tissue injury and the amount of tissue loss.¹¹ The appearance of frostbite blisters can aid in determining the depth of tissue injury. Superficial frostbite involves the skin and subcutaneous tissues while deep frostbite extends to bone, joints and tendon.¹¹ Rewarming of skin with superficial frostbite can result in clear blister formation while rewarmed skin with deep frostbite often results in hemorrhagic blisters.⁵ Frostbite blister appearance can also be an indicator of long-term prognosis of frostbite injuries. Favorable prognostic factors in frostbite injuries include retained sensation, normal skin color and clear blister fluid.⁵ Poor prognostic factors include non-blanching cyanosis, firm skin and hemorrhagic blister formation.⁵

The management of frostbite blisters is controversial and no definitive evidence exists in regard to the optimal treatment course. Some practitioners and researchers recommend the removal of blisters due to the high concentration of inflammatory mediators, specifically prostaglandin F2 and thromboxane A2, in the blister exudate.⁸ Others recommend leaving blisters intact as removal can lead to desiccation of the underlying tissues.^5,12 Several authors recommend leaving small, clear blisters that do not limit the range of motion and debriding or aspirating blisters that are large, hemorrhagic and/or interfere with range of motion.^5,12-14

Researchers have shown the pathophysiology of frostbite injury is similar to the inflammatory processes that occur in burn wounds. Two clinical trials examining the healing of superficial burns found that intact blisters healed faster and were less likely to become infected than blisters that were ruptured.^14,15 Animal studies have shown similar results with debridement of the epidermis leading to slower re-epithelialization, an increased rate of infection and increased scarring.¹⁶

Due to the role of inflammatory mediators and the arachidonic acid cascade in the pathogenesis of frostbite, authors have recommended treating blister sites with aloe vera every six hours.¹² Aloe vera is a potent inhibitor of the arachidonic acid cascade, blocking prostaglandin and thromboxane synthesis. Aloe vera is a successful adjunct for treating frostbite injuries in both animal studies and clinical practice.^3,17

In Conclusion

Frostbite injuries have a wide range of severity ranging from superficial injuries with minimal sequelae to deep injuries, leading to extensive tissue loss and possible amputation. Tissue injury secondary to frostbite results from cellular injury, vascular impairment and the release of inflammatory mediators. Blisters, serous or hemorrhagic, are common findings in frostbite injuries. Debate exists regarding the appropriate management of frostbite blisters with treatment recommendations ranging from leaving blisters intact to rapid debridement to decrease the presence of inflammatory mediators. Aloe vera is a successful adjunct in the treatment of frostbite injury due to its ability to inhibit the arachidonic acid cascade and prostaglandin and thromboxane synthesis.

References

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2. Murphy JV, Banwell PE, Roberts AHN, et al. Frostbite pathogenesis and treatment. J Trauma. 2000;48(1):171-8.

3. Heggers JP, Robson MC, Manavalen K, Weingarten MD, Carethers JM, Boerman JA, et al. Experimental and clinical observations on frostbite. Ann Emerg Med.  1987;16(9):1056-62.

4. Bracker MD. Environmental and thermal injury. Clin Sports Med.  1992;11(2):419-36.

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9. Raine TJ et al. Antiprostaglandis and antithromboxanes in the treatment of frostbite. Surg Forum. 1980;31:557-8.

10. Marsigny B. Mountain frostbite. ISSM Newsletter. 1998;8:8-10.

11. Vogel JE, Dellon AL. Frostbite injuries of the hand. Clin Plast Surg.  1989;16(3):565-76.

12. Grieve AW, Davis P, Dhillon S, Richards P, Hillebrandt D, Imray CHE. A clinical review of the management of frostbite. J R Army Med Corps. 2011;157(1):73-8.

13. Singer AJ, Dagum AB. Current management of acute and cutaneous wounds. N Engl J Med. 2008;359(10):1037-46.

14. Swain AH, Azadian BS, Wakeley CJ, Shakespeare PG. Management of blisters in minor burns. BMJ. 1987;295:181.

15. Gimbel NS, Kapetansky DI, Weissman F, Pinkus HKB. A study of epithelization in blistered burns. AMA Arch Surg. 1957;74:800-3.

16. Singer AJ, Thode HC Jr, McClain SA. The effects of epidermal debridement of partial-thickness burns on infection and reepithelialization in swine. Acad Emerg Med. 2000;7:114-29.

17. Miller MB, Koltai PJ. Treatment of experimental frostbite with pentoxifylline and aloe vera cream. Arch Otolaryngol Head Neck Surg. 1995;121(6):678-680.