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more points indicating greater body involvement. To deter- TABLE 5 Protocol for Administration of Intravenous Recombinant
mine outcomes after management, an amputation score is Tissue Plasminogen Activator by Training Medical Personnel for
calculated using the same point system described above for Individuals With Severe Frostbite in Austere Environments 67
segments that are amputated after treatment. The salvage rate Areas of Concern Protocol and Considerations
quantifies the effectiveness of the treatment and is calculated • Weight <67 kg: 15 mg IV bolus, then
as (at-risk score – amputated score)/at-risk score =100%. Us- 0.75mg/kg over 30 min, then 0.35mg/kg
ing this system, ratings among three independent scorers was Administration* over next 60 min.
very high (i.e., intraclass correlation = 0.93). 62 • Weight >67kg: 15 mg IV bolus, then 50mg
over 30 min, then 35mg over next 60 min.
Total not to exceed 100mg.
Thrombolytic Therapy • Recent trauma, bleeding diathesis, stroke
Thrombolytics are drugs that break up thrombi and emboli in within 3 months, on anticoagulants,
the vasculature and microvasculature. The use of thrombolyt- Contraindications hypersensitivity; blood pressure
ics in treating frostbite was first reported in 1992 at Hennepin >180mmHg systolic or 110mmHg
County Hospital, Minnesota. The report provided preliminary diastolic.
results of a pilot study using recombinant tissue plasminogen • High altitude: high altitude pulmonary
activator (tr-PA) in frostbite treatment. Since that time, there Precautions or cerebral edema, retinal hemorrhage,
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gastritis.
has been one randomized controlled trial and several obser-
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vational studies, case studies, and case series examining the • Bleeding: stop infusion, hemostasis if
possible (consider tranexamic acid)
effectiveness of this therapy. In the randomized controlled Complications • Angioedema: stop infusion, antihistamine,
and management
study, 47 individuals with second- to fourth-degree frostbite corticosteroids.
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were either administered intravenous iloprost (0.5–2 ng/kg *Ideally given with a portable syringe pump.
body weight, 6 h/day) for 8 days plus tr-PA on the first day IV = intravenous
only (n = 32), or did not receive this treatment (n = 15). Pa-
tients administered iloprost had 2% of digits amputated com-
pared with 40% in the group not receiving iloprost (relative Imaging
risk [no iloprost / iloprost] = 24.75, 95% CI = 9.69–58.69). Various imaging techniques can assist in defining the severity,
depth, and range of frostbite tissue injury and determining the
Two systematic reviews 65,66 examined the effectiveness of viability of soft tissue and bone. Plain radiographs are often
thrombolytics for the treatment of frostbite. One review the first imaging technique used and can be useful in identify-
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examined 15 studies that included 208 patients treated with ing soft-tissue swelling and tissue loss, especially at the distal
tr-PA and 94 untreated patients, all with frostbite of the ex- phalanges. Osteopenia and periostitis may be observed weeks
tremities. The reviewers concluded that because of differences to months after the initial injury. 22,68
in treatment protocols, inclusion criteria, outcome measures,
and methodologic quality, the efficacy of tr-PA for reducing Laser Doppler ultrasound devices are often available in the field
amputation rates could not be established. They recommended and can assist in making the initial frostbite diagnosis, includ-
more randomized prospective trials, even though virtually all ing severity. 69–71 This technique uses a laser beam that reflects
investigations reported that tr-PA was or may have been useful off circulating red blood cells and uses the Doppler effect to
in reducing amputation rates. image the movement of blood through tissues. When blood is
moving away from the transducer head, the return signal has
The second review included 18 studies using any type of a lower Doppler-shifted frequency; when the blood is moving
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thrombolytics, including tr-PA, alteplase, urokinase, strepto- toward the transducer, the signal has a higher Doppler-shifted
kinase, or any other tr-PA derivative. In this review, 216 of 325 frequency. Some commercial devices also provide measures of
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patients were treated with thrombolytics. Combining all stud- hemoglobin oxygenation and relative amount of hemoglobin,
ies, the weighted average salvage rate for patients treated with which may also be useful. One study using a swine model
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thrombolytic infusion was 79%. This suggested that thrombo- showed that 3 hours after frostbite injury, there was a graded
lytics were a promising standard treatment for severe frostbite. response dependent on the severity of the injury: in super ficial
Similar limb salvage rates were achieved with intravenous or frostbite injury, there was an increase in Doppler-detected blood
intra-arterial administration. Complication rates were 3% for flow and no change in hemoglobin oxygenation; in deep partial
intravenous and 4% for intra-arterial administration. Factors frostbite, there was a decrease in Doppler-detected blood flow
associated with failed salvage after thrombolytic therapy in- and no change in hemoglobin oxygenation; and in deep frost-
cluded presentation >24 h, multiple freeze-thaw cycles, and bite (i.e., full-thickness injury), there was a decrease in Dop-
>24 h of warm ischemia. pler-detected blood flow and in hemoglobin oxygenation.

Cauchy et al proposed that rt-PA administration be included Thermography is another noninvasive technique that detects
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in the management of severe frostbite in austere environ- and images heat radiating from the skin in the infrared portion
ments when there is little doubt of amputation if the injury of the electromagnetic spectrum (i.e., wavelengths of approxi-
is untreated (i.e., fourth-degree frostbite) and trained medical mately 8 to 15μm). Variations in skin temperature are affected
personnel are available for treatment. The suggested adminis- by variations in blood flow. The images (called thermo-
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tration protocol is shown in Table 5. The Wilderness Medical grams) are displayed in various colors, with a color reference
Society Guidelines for the Prevention and Treatment of Frost- scale showing the temperature of the skin surface. Human re-
bite recommends that “for deep frostbite injury with potential search of thermography in frostbite injury is limited, although
significant morbidity, angiography and use of either [intrave- studies have been conducted on animal models. 74–78 The most
nous] or intra-arterial rt-PA within 25h of thawing may sal- recent study using a rat paw model showed that in super-
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vage some or all of tissue at risk.” 57 ficial frostbite, skin temperature determined by thermography
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