Emergency Medicine

Fluorescence Microangiography

A new tool in the management of frostbite

BY Thomas Masters, MD

Naturally, depending on the temperatures seen in the winter, hospitals may see greater or fewer victims of cold. In an average winter though, I suspect that every hospital in the state/region will see patients with hypothermia and frostbite, of varying degrees of severity. While there are no “hypothermia centers,” the standard of care is that severe frostbite will be managed at a burn center. This means that each winter, the state’s two burn centers (Regions Hospital in St Paul and Hennepin County Medical Center) will see dozens (if not hundreds) of patients with frostbite. These volumes have allowed these hospitals to develop expertise in the management of frostbite victims and to refine the care provided. 

Frostbite is caused when skin is exposed to cold temperatures. Parts of the body such as hands, feet, nose, and ears that are most exposed to the cold environment are the most commonly afflicted areas. After a period of cold-induced vasoconstriction, ice crystals form in the tissues. This freezing process causes direct cellular damage and disrupts perfusion. 

Traditional descriptions of frostbite have been comparable to burn descriptions in that both describe depth of tissue involved. Patients presenting with first degree frostbite are described as having loss of sensation with reddened skin. Second degree frostbite victims have clear blistering. In third degree frostbite, victims have hemorrhagic blisters and skin darkening-to-necrosis. Finally, in forth degree frostbite, patients will have discolored skin and digits will be hard and frozen.

Invariably, we have our coldest days with the most victims of frostbite on weekend nights when staffing is tightest.

Unreliable diagnoses

First and second degrees of frostbite are considered superficial whereas third and fourth degrees are considered deep.  It is felt that the deeper the tissue involvement, the greater the threat of tissue and digit loss. Unfortunately, studies have shown that bedside evaluation of frostbite has proven unreliable.

Making the appropriate diagnosis of severity is important as it impacts the therapies given. Rewarming is the mainstay of all frostbite therapy, regardless of the depth of tissue involved. When a patient presents with suspected frostbite, affected extremities are placed in warm water baths until rewarmed. After rewarming, the challenge is then deciding if thrombolytic medication is needed.

Studies done in the early 2000s demonstrated that individuals with deep frostbite showed increased perfusion to digits using technetium (Tc)-99m agent through scintigraphy nuclear medicine bone scanning after receiving rTPA. Several additional subsequent studies have shown benefit of rTPA in improving patient outcomes and preventing amputations. At our facility, IV rTPA is the accepted therapy for individuals with deep frostbite when they present within 12 hours after rewarming.

The challenge though is making the diagnosis of deep frostbite. As noted earlier, determining deep frostbite is challenging when using clinical exam alone. As such, numerous other modalities have been used to confirm the involvement of deep tissues such as bones. These include angiography and bone scans. Unfortunately, studies like this that have shown the strongest correlation with eventual amputation are resource intensive. For example, nuclear medicine studies require specially trained technicians and nuclear material. Other more conventionally available studies such as x-rays have not shown to correlate well with clinical outcome.

Since the pioneering work on rTPA, our facility has used the bone scans to evaluate patients with suspected deep frostbite. Our burn service has long considered this the gold standard to make the diagnosis. However, even in a tertiary referral center such as ours with an exceptional radiology department, staffing and budgetary challenges have made continuous availability of bone scan challenging. Invariably, we have our coldest days with the most victims of frostbite on weekend nights when staffing is tightest. As such for the past two winters, we have been working to refine our approach to frostbite to optimize and expedite diagnosis of deep frostbite.

Combing technologies

In 2015, the department of hyperbaric medicine (as a part of HCMC’s limb preservation program) began using fluorescence microangiography (Luna; Stryker Corporation; Kalamazoo, Michigan) to monitor the status of nonhealing wounds, compromised flaps and grafts, crush injuries and other injuries effecting perfusion. This study involves injecting patients with an iodine-based dye (ICG) that binds to blood proteins. This dye will fluoresce under infra-red light and a camera on the device will allow a clinician to visualize perfusion 3 – 5 mm below the skin. Images range from a bright white (denoting robust perfusion or inflammation) to a gray (suggesting compromised perfusion) to black (fully ischemic).

Invariably, we have our coldest days with the most victims of frostbite on weekend nights when staffing is tightest.

Taking less than 5 minutes, the study is very well tolerated by the patients. The dye is metabolized by the liver and is therefore safe in patients with renal issues. There is no radiation involved. The only contra-indication is an iodine allergy. There have been multiple previous studies about the efficacy of fluorescence microangiography in plastic surgery patients and the device has been used intraoperatively evaluating bowel anastomoses.  We have found the device useful in monitoring a patient’s healing progress and helpful in assessing the efficacy of wound healing techniques.

After gaining multiple years of experience with fluorescence microangiography in wound patients, the hyperbaric and burn services began to collaborate to explore the role that hyperbaric medicine may play in patients who have been diagnosed with deep frostbite. The rationale behind this therapy was that arterial occlusion is a part of the pathophysiology of frostbite that leads to digit loss. Acute arterial occlusion is an approved indication for therapy with hyperbaric oxygen and it stood to reason that patients with severe deep frostbite might benefit from therapy with hyperbaric oxygen. However, knowing that patients do not always respond to therapies as expected, we utilized periodic microangiography as they were receiving therapies with hyperbaric oxygen to monitor patient’s response to therapy.

Improving decision-making.

While we are still evaluating whether hyperbaric oxygen has a role in treating patients with frostbite, we did find that fluorescence microangiography correlated at least as well as bone scan with anticipating eventual amputation sites. As the physicians who work in the hyperbaric department also work in the emergency department, we felt that there may be an opportunity to employ microangiography in the acute setting prior to receiving rTPA to evaluate patients for deep frostbite. The goal was to pair fluorescence microangiography (using a slightly different version of the Stryker device than we used in the subacute setting) with bone scans to help guide clinical decision making.

Given previous experience with microangiography and the importance of rewarming in the management of frostbite, the direction was to perform the study once the patient had been rewarmed. All emergency department physicians were oriented to the use of microangiography and the mechanics of the device itself. Hyperbaric physicians were available to provide real-time feedback, interpretations, and provided over-reads on each study. 

In addition to the relative-safety of the study, microangiography has the additional benefit of being a performed at the bedside by the provider. This allows the clinician to evaluate the patient promptly and determine the appropriate course of action as it pertains to therapies. We found many instances where there was frank ischemia (with complete absence of fluorescence despite rewarming) in which the clinician felt compelled to give rTPA without delay. Additionally, given the short half-life of ICG (about 3 minutes) there were occasions where the ICG could be re-dosed to track reperfusion. 

We continue to learn about the role of microangiography in the management of frostbite, but the initial results seem encouraging. Certainly, the ease of access has been a benefit in obtaining relevant clinical data faster than the historical methods. Also, keeping the machine in the ED allows for round- -the-clock availability. We are optimistic that microangiography may allow for more prompt appropriate administration of rTPA with benefit to patient morbidity. 

Many patients with frostbite also struggle with psychosocial and substance abuse issues, which makes long term evaluation and management challenging. However, the difficulties inherent with life in the upper Midwest will present an opportunity to provide excellent cutting edge care to a disease with significant consequences. 

Thomas Masters, MD, FACEP, FAAEM, specializes in Emergency Medicine and has a sub-specialty in Hyperbaric Medicine. His primary research interests include the use of hyperbaric oxygen for wound healing and limb preservation.