Role of 99mTc MDP Bone Scan in Delineation of Ischaemic Zone in Cases of Severe Frostbite.

Frostbite or cold burn is the medical condition in which localized damage is caused to exposed skin and subcutaneous tissue due to freezing. Frostbite most likely involves body parts farthest from the heart and those with large exposed areas. At or below 0 °C (32 °F), blood vessels close to the skin start to constrict, and blood is shunted away from the extremities via the physiological feedback action of glomus bodies. This peripheral vasoconstriction helps to conserve core body temperature. In extreme cold, or when certain parts of the body are exposed to cold conditions for long periods, this protective mechanism can reduce blood flow in some areas of the body to dangerously low levels. This is followed by crystallisation of water in the tissue and subsequent death of tissues in the affected areas. In this case series, we highlight the importance of a 99mtechnetium methylene diphosphonate (99mTc MDP) triple phase bone scan in cases of severe frostbite to precisely delineate the ischaemic and reperfusion zones, so as to help the surgeons in carefully deciding if amputation is required and the level of amputation in such cases.

Introduction

Frostbite is a clinical situation where water molecules freeze and crystallize within biological tissue, causing cellular and tissue death. Frostbite occurs when skin is exposed to a temperature below −10°C, resulting in vasoconstriction. The resultant decrease in blood flow caused by the vasoconstriction does not deliver sufficient heat to the tissues to prevent the formation of ice crystals inside the tissues. The three distinct processes that occur in a frostbite injury are extracellular and intracellular ice crystallization, intracellular dehydration, and a vascular process of arterial insufficiency with intermittent spasm. The initial injury to the tissues is caused by formation of extracellular ice crystals, which damage the cell membranes, initiating a cascade of events that lead to cell death. As the tissues continue to freeze, osmolarity changes due to water shifting out of the cells into the extracellular spaces. The cells dehydrate and intracellular crystals are formed. These intracellular crystals expand and mechanically damage the cell, resulting in irreversible ischaemic changes. As the temperature gets colder, the vasoconstriction persists leading to hypoxia, acidosis, arteriolar and venular thrombosis, and ischemic necrosis. The last process of cold injury is the vascular process, which consists of arteriovenous shunting, coagulation, thrombus formation, hypoxia, anaerobic metabolism, and tissue death.[123] Objective clinical assessment of the viability of involved tissue in severe frostbite has always been ambiguous. It is well recognized that the appearance of superficial tissue is often an unreliable indicator of deep tissue viability. Early establishment of the prognosis for patients with frostbite is hampered by the lack of useful, early clinical guidelines. Furthermore, the current classification scheme does not allow gradation of lesions until long after the initial frostbite, when the definitive outcome has already become clear. For these reasons, the most appropriate treatment and treatment efficacy are difficult to determine.[4] Various methods have been proposed for the evaluation of frostbite, including thermography, capillaroscopy, laser Doppler, magnetic resonance imaging,[5] arteriography, and bone scanning. To date none of these methods has been fully validated; however, scintigraphic methods using technetium- 99mpertechnetate seem to hold much promise.[67] We present a case series of three severe frostbite patients whose management plan had been decided based on a triple phase bone scan. This series serves to highlight the role of 99mTc MDP triple phase bone scan in management of severe frostbite.

Case 1

A 42-year-old male patient with no known comorbidities presented with complaints of pain and numbness in his right great toe and medial aspect of both feet. He had been working in a high altitude location with extreme cold conditions. Patient noticed a blister in his right great toe and left fifth toe laterally after 4 hours of continuous work in severe cold conditions. The patient was treated at his post with rewarming of the limbs; pentoxyphylline, antibiotics, and NSAIDs was evacuated to a hospital at lower altitudes. After 1 month, the right great toe developed a blackish ulcer and the left fifth toe had healed completely [Figure 1]. The patient was then referred to our centre for management by a vascular surgeon. The patient was subjected to a triple phase bone scan after administration of 16mCi of 99mtechentium methylene diphosphonate (99mTc MDP). The perfusion and blood pool images revealed normal tracer distribution in both feet. The skeletal phase images obtained 3 hours after the injection of the radiopharmaceutical revealed relatively increased tracer concentration in the proximal and distal phalanges of right great toe. The triple phase bone scan findings were suggestive of reperfusion after frostbite injury [Figure 2]. The patient was, therefore, continued on medical management with instructions to avoid high altitude areas and areas of extreme cold climatic conditions. The patient gradually recovered with no functional deficits.

Figure 1

Third degree frostbite of right great toe showing blackish ulceration

Figure 2

The perfusion and blood pool images reveal normal tracer distribution in both feet. The skeletal phase images reveal relatively increased tracer concentration in the proximal and distal phalanges of right great toe. The triple phase bone scan findings were suggestive of reperfusion after frostbite injury

Case 2

A 30-year-old male patient was air evacuated from Mt. Everest base camp post a successful mountaineering expedition after developed pain and swelling in both his feet. The patient initially noticed bluish discoloration of toes with mild pain during the expedition. He continued with the expedition after rewarming the area with water and some analgesics. The symptoms gradually increased over a 3-day period and the patient developed swelling and redness in the dorsum of both feet along with blackish discoloration and blister formation in all his toes [Figure 3]. The patient was initially evaluated at a hospital in Nepal where he was started on pentoxyphylline along with antibiotics and NSAIDs and was transferred to our centre for further management. The patient was subjected to a triple phase bone scan after administration of 15mCi of 99mTc MDP. The perfusion phase revealed relatively increased flow of tracer in the right foot localizing at the proximal phalanges along with decreased tracer flow in the region of distal phalanges. The left foot showed a uniform tracer flow. The blood pool phase images revealed intense tracer distribution in the soft tissue of right great toe in the proximal phalangeal area. Rest of the toes in the right foot also showed uniformly increased tracer distribution in the proximal phalangeal region along with abrupt cut off and photopenia in the region of distal phalanges. The left foot showed mildly increased tracer distribution in soft tissue around proximal and distal phalanges of all toes. The skeletal phase images obtained 3 hours after the injection of the radiopharmaceutical revealed the intense tracer uptake in the proximal phalanx of right great toe and the increased tracer uptake in proximal phalanges in rest of the toes of right foot along with a relative photopenia in the region of mid and distal phalanges. The left foot revealed the intense tracer uptake in the proximal and distal phalanges of great toe. The triple phase bone scan findings were suggestive of distal phalanx of right great toe, mid and distal phalanges of rest of toes in right foot in ischaemic zone and the proximal phalanges of all toes in right foot, proximal and distal phalanges of left foot undergoing reperfusion hyperemia [Figure 4]. The patient had developed dry gangrene in the distal phalange of right great toe and mid and distal phalanges of rest of toes in the right foot, which autoamputated on its own without any active intervention. The patient had no residual neurovascular deficit in the left foot and right proximal phalanges.

Figure 3

Fourth degree frostbite with swelling and blackish discolouration of all toes of both feet

Figure 4

The triple phase bone scan findings reveal the distal phalanx of right great toe, mid and distal phalanges of rest of toes in the right foot to be in the ischaemic zone and the proximal phalanges of all toes in the right foot, proximal and distal phalanges of left foot undergoing reperfusion hyperemia

Case 3

A 29-year-old male was air evacuated from Mt. Everest base camp after he had developed blackish discoloration of toes of both feet. The patient noticed decreased sensation and discolouration of right great toe during descending from Mt. Everest summit. The discolouration then gradually extended to all toes with blister formation [Figure 5]. The patient was initially treated with rewarming, antibiotics, pentoxyphylline and NSAIDs and transferred to our centre. The patient was subjected to a triple phase bone scan after administration of 15mCi of 99mTc MDP. The perfusion phase revealed relatively increased tracer flow in the right foot region. The blood pool images revealed a mildly increased tracer distribution in the soft tissues around proximal phalanges of right first to third toe along with abrupt photopenia in the soft tissues around distal phalanges. The left foot revealed mildly increased tracer distribution in the soft tissue of great toe. The skeletal phase images obtained 3 hours after the injection of the radiopharmaceutical revealed absent tracer distribution in the region of distal phalanges of right great toe and middle and distal phalanges of right second and third toes. The triple phase bone scan findings were suggestive of ischaemic zone in distal phalanges of right great toe and middle and distal phalanges of right second and third toes and reperfusion hyperemia in the respective proximal phalanges [Figure 6]. The patient underwent amputation of distal phalanges of right first to third toes due to the development of local infection. The patient had an uneventful recovery period with no residual neurovascular deficit.

Figure 5

Fourth degree frostbite with swelling and blackish discolouration of all toes of both feet, predominantly on the right side

Figure 6

The triple phase bone scan findings reveal distal phalanges of right great toe and middle and distal phalanges of right second and third toes to be in the ischaemic zone and reperfusion hyperemia in the respective proximal phalanges

Discussion

Although frostbite is classified into four groups, based on its severity [Table 1], it is difficult to assess actual tissue damage and its extent. There is no gold standard for assessment of the damage, and studies such as CT angiography, digital subtraction angiography and thermography provide limited information about the microcirculation. The levels of tissue markers such as alkaline phosphatase and creatine phosphokinase do not rise due to relatively small amount of tissue involved.[8]

Table 1

Clinical Grades of Frost Bite

The tissue injury of frostbite can be divided into three zones.

Zone 1: Zone of Coagulation: This is the area of most severe tissue damage. It is the most distal region of damage. There is irreversible tissue death.

Zone 2: Zone of Stasis: This is the middle region. It is characterized by severe tissue damage that may be reversible.

Zone 3: Zone of Hyperaemia: This is the most proximal zone with the least amount of tissue damage.

A triple phase bone scan has three principal uses in frostbite injuries:

As early as the first few days after injury, bone scan provides precise prognostic information on the future evolution of lesions. Previously such information could not be obtained prior to 7 days post-injury.

Bone scan helps in delineating the zones of injury, helping the clinician to take early and appropriate steps in management. Patients with ischaemic but viable bone can be subjected to medical management involving on the use of one or more of the following agents: platelet aggregation inhibitor (aspirin), peripheral vasodilators (ketanserine, chlorhydrate of buflomedil),[9] prostacycline analogues (iloprost)[10] and fibrinolytics [streptokinase, urokinase, recombinant tissue plasminogen activator (r-TPA)].[1112]

In cases of severe sepsis, which require emergency amputation and for which clinical criteria are inapplicable because of the imprecise demarcation of the lesions, a triple phase bone scan is the only potential test or imaging modality that objectively determines the appropriate level of amputation.

A retrospective study of the results of two-phase 99mTc hydroxymethylene diphosphate (HMDP) bone scans in 88 patients with severe frostbite of the extremities was performed by Cauchy et al. All patients were evaluated within 48 hours after rewarming and all underwent a first bone scan (dual phase 99mTc HMDP) within 5 days after rewarming. An excellent correlation was found between the absence of tracer uptake in the phalanges and later amputation; this correlation was especially strong during the skeletal phase of the scans (specificity = 0.99, sensitivity = 0.96, positive predictive value = 0.92). Normal or high uptake in the phalanges was a reliable indicator of cold injury in the reperfusion/healing phase (negative predictive value = 0.99). The sensitivity of the examination was enhanced by performing a second scan more than 5 days after rewarming. A comparative analysis of both the bone scans demonstrated that some of the lesions continued to evolve between day 2 and day 8. This suggested that those lesions could still be modified during this period with effective management including reperfusion therapy. Based on these findings, they recommended that bone scan be performed close to day 2 in all patients who present with lesions extending proximally to include the entire part of one or more phalanges. They also recommended that in the case of severe sepsis, the results of the first bone scan can serve as an indication for emergency amputation. A second bone scan should be performed close to day 8 only if there is an area of low or absent uptake on the first bone scan. They concluded that bone scintigraphy is an excellent means of evaluating patients with severe frostbite of the extremities: as early as day 2 after the injury as it can indicate whether amputation is necessary, and between days 2 and 8, it provides valuable information on the efficacy of treatment.[4] A study by Bhatnagar et al on 20 patients with mild to moderately severe frostbite injury undergoing 99mTc pertechnetate scintigraphy also revealed that moderate to severe frostbite lesions can be classified as having infarcted, ischaemic or hibernating tissue. They also subjected the characterised “ischaemic” lesions to vasodilatory therapy. In contrast to the previous study by Cauchy et al., they also reported that the absence of uptake does not necessarily indicate infarction as many such lesions retain potential for vasodilation and recovery.[8] Despite the controversy, both the studies agree that the ischaemic zone in severe frostbite can be characterised by scintigraphic methods and can be subjected to appropriate management. In our case series, the three patients with severe frostbite of toes were subjected to 99mTc MDP scan; the ischaemic zone was detected in the toe lesions of two patients, of which one patient was subjected to early amputation due to infection and the other underwent autoamputation of the ischaemic zone as characterised in the scan. Both the patients had uneventful recovery with no residual neurovascular deficit in the viable areas as characterised by the bone scan. The patient with no ischaemic zone also had an uneventful recovery with no residual neurovascular deficit. This approach of using a 99mTc MDP bone in cases of severe frostbite can lead to efficient prognostication along with early initiation of appropriate treatment.

Conclusion

Triple phase bone scan imaging distinguishes viable from the nonviable tissue in frostbite in a simple, non-invasive manner with easily interpretable findings. Viable but hyperemic tissue shows increased perfusion and soft tissue uptake. Nonviable tissue appears as a perfusion defect in all three phases that is persistent on follow-up scans. In all our patients, scintigraphy provided more specific information than the clinical examination. This case series serves to highlight the value of a triple phase bone scan in the prognostication and management of severe frostbite patients by precisely delineating the ischaemic and reperfusion zones, to help the clinician in taking appropriate decision regarding management. This evidence-based approach to management of severe frostbite cases would lead to decrease in morbidity and improve the quality of life in such patients.

Financial support and sponsorship

Nil.

Conflicts of Interest

There are no conflicts of interest.