Thrombolytic Therapy Saves Frostbitten Limbs

WASHINGTON — Thrombolytic therapy resulted in limb salvage among 18 patients with severe frostbite treated at one Minnesota hospital in the last few years.

Thrombolytic therapy has been available for management of frostbite for 10 years and has the potential to reduce the need for some amputations. However, its use has not extended to rural northern areas.

Severe frostbite results in ischemia and blistering with subsequent demarcation and loss of tissue. Arterial thrombosis results from injury to endothelial cells that retract to expose subintimal collagen, subsequently triggering acute thrombosis after rewarming, according to Dr. George R. Edmonson of St. Paul (Minn.) Radiology.

At the annual meeting of the Society of Interventional Radiology, Dr. Edmonson described the patient care process at Regions Hospital, also in St. Paul. Patients are admitted from the emergency department to the burn unit, where surgeons assess the affected limb for severity of injury and blood flow. Diagnostic arteriography is done to assess small vessel occlusion and loss of “distal tuft blush” at the tips of digits. Catheters are positioned for simultaneous infusion of treatment drugs into each affected limb. Blisters and wounds are managed with debridement or amputation.

Since the mid-1990s, Dr. Edmonson and his associates have been treating frostbite of the extremities with a variety of combined antithrombotic, antiplatelet, and vasodilating agents. Initially, they used urokinase along with heparin and papaverine, then switched to reteplase, and now have moved to using tenecteplase (TNK) because of its superior plasma stability and higher fibrin specificity compared with reteplase. Tenecteplase is degraded more slowly in the bloodstream during infusion, and binds more firmly to the clot at the target than do similar agents. Because it also affects the normal clotting proteins to a lesser degree, it may therefore reduce the risk of bleeding, he explained.

Six patients aged 18–65 years with severe frostbite at risk for amputation were treated for up to 72 hours with intra-arterial TNK infusions at 0.25 mg/hour per limb, with coaxial papaverine at 30 mg/hour per limb, and intravenous heparin at 500 mcg/hour. They were managed in the burn unit with arteriography.

Of the 6 patients, 3 who had 16 involved digits responded well and required no amputations. The other 3 (6 limbs, 30 digits) had incomplete angiographic responses. Of those, 2 (with 4 limbs, 20 involved digits) improved noticeably following TNK infusion, but then developed infections and required partial amputations. One patient—who needed intubation for alcohol withdrawal—failed to respond and lost 8 fingers, but his thumbs were saved. There were no major bleeds or other periprocedural complications.

Those results were compared with data from 10 surviving patients (14–77 years) of 12 who were treated with the same protocol using various doses of reteplase and papaverine over a 2-year period. Six of the patients recovered with no amputations, 4 had lost 31 digits at 45 days, and 2 had amputations but more distally than would have been anticipated without treatment.

More recently, six more frostbite patients were treated with TNK. Five of these patients had complete response and one had no response. To date, 8 out of 12 TNK-treated patients have been saved from amputation.

These data are part of an ongoing FDA-approved prospective trial undertaken by Dr. Edmonson. The hope was that more scientific results might encourage others to use this type of treatment.

WASHINGTON — Thrombolytic therapy resulted in limb salvage among 18 patients with severe frostbite treated at one Minnesota hospital in the last few years.

Thrombolytic therapy has been available for management of frostbite for 10 years and has the potential to reduce the need for some amputations. However, its use has not extended to rural northern areas.

Severe frostbite results in ischemia and blistering with subsequent demarcation and loss of tissue. Arterial thrombosis results from injury to endothelial cells that retract to expose subintimal collagen, subsequently triggering acute thrombosis after rewarming, according to Dr. George R. Edmonson of St. Paul (Minn.) Radiology.

At the annual meeting of the Society of Interventional Radiology, Dr. Edmonson described the patient care process at Regions Hospital, also in St. Paul. Patients are admitted from the emergency department to the burn unit, where surgeons assess the affected limb for severity of injury and blood flow. Diagnostic arteriography is done to assess small vessel occlusion and loss of “distal tuft blush” at the tips of digits. Catheters are positioned for simultaneous infusion of treatment drugs into each affected limb. Blisters and wounds are managed with debridement or amputation.

Since the mid-1990s, Dr. Edmonson and his associates have been treating frostbite of the extremities with a variety of combined antithrombotic, antiplatelet, and vasodilating agents. Initially, they used urokinase along with heparin and papaverine, then switched to reteplase, and now have moved to using tenecteplase (TNK) because of its superior plasma stability and higher fibrin specificity compared with reteplase. Tenecteplase is degraded more slowly in the bloodstream during infusion, and binds more firmly to the clot at the target than do similar agents. Because it also affects the normal clotting proteins to a lesser degree, it may therefore reduce the risk of bleeding, he explained.

Six patients aged 18–65 years with severe frostbite at risk for amputation were treated for up to 72 hours with intra-arterial TNK infusions at 0.25 mg/hour per limb, with coaxial papaverine at 30 mg/hour per limb, and intravenous heparin at 500 mcg/hour. They were managed in the burn unit with arteriography.

Of the 6 patients, 3 who had 16 involved digits responded well and required no amputations. The other 3 (6 limbs, 30 digits) had incomplete angiographic responses. Of those, 2 (with 4 limbs, 20 involved digits) improved noticeably following TNK infusion, but then developed infections and required partial amputations. One patient—who needed intubation for alcohol withdrawal—failed to respond and lost 8 fingers, but his thumbs were saved. There were no major bleeds or other periprocedural complications.

Those results were compared with data from 10 surviving patients (14–77 years) of 12 who were treated with the same protocol using various doses of reteplase and papaverine over a 2-year period. Six of the patients recovered with no amputations, 4 had lost 31 digits at 45 days, and 2 had amputations but more distally than would have been anticipated without treatment.

More recently, six more frostbite patients were treated with TNK. Five of these patients had complete response and one had no response. To date, 8 out of 12 TNK-treated patients have been saved from amputation.

These data are part of an ongoing FDA-approved prospective trial undertaken by Dr. Edmonson. The hope was that more scientific results might encourage others to use this type of treatment.

WASHINGTON — Thrombolytic therapy resulted in limb salvage among 18 patients with severe frostbite treated at one Minnesota hospital in the last few years.

Thrombolytic therapy has been available for management of frostbite for 10 years and has the potential to reduce the need for some amputations. However, its use has not extended to rural northern areas.

Severe frostbite results in ischemia and blistering with subsequent demarcation and loss of tissue. Arterial thrombosis results from injury to endothelial cells that retract to expose subintimal collagen, subsequently triggering acute thrombosis after rewarming, according to Dr. George R. Edmonson of St. Paul (Minn.) Radiology.

At the annual meeting of the Society of Interventional Radiology, Dr. Edmonson described the patient care process at Regions Hospital, also in St. Paul. Patients are admitted from the emergency department to the burn unit, where surgeons assess the affected limb for severity of injury and blood flow. Diagnostic arteriography is done to assess small vessel occlusion and loss of “distal tuft blush” at the tips of digits. Catheters are positioned for simultaneous infusion of treatment drugs into each affected limb. Blisters and wounds are managed with debridement or amputation.

Since the mid-1990s, Dr. Edmonson and his associates have been treating frostbite of the extremities with a variety of combined antithrombotic, antiplatelet, and vasodilating agents. Initially, they used urokinase along with heparin and papaverine, then switched to reteplase, and now have moved to using tenecteplase (TNK) because of its superior plasma stability and higher fibrin specificity compared with reteplase. Tenecteplase is degraded more slowly in the bloodstream during infusion, and binds more firmly to the clot at the target than do similar agents. Because it also affects the normal clotting proteins to a lesser degree, it may therefore reduce the risk of bleeding, he explained.

Six patients aged 18–65 years with severe frostbite at risk for amputation were treated for up to 72 hours with intra-arterial TNK infusions at 0.25 mg/hour per limb, with coaxial papaverine at 30 mg/hour per limb, and intravenous heparin at 500 mcg/hour. They were managed in the burn unit with arteriography.

Of the 6 patients, 3 who had 16 involved digits responded well and required no amputations. The other 3 (6 limbs, 30 digits) had incomplete angiographic responses. Of those, 2 (with 4 limbs, 20 involved digits) improved noticeably following TNK infusion, but then developed infections and required partial amputations. One patient—who needed intubation for alcohol withdrawal—failed to respond and lost 8 fingers, but his thumbs were saved. There were no major bleeds or other periprocedural complications.

Those results were compared with data from 10 surviving patients (14–77 years) of 12 who were treated with the same protocol using various doses of reteplase and papaverine over a 2-year period. Six of the patients recovered with no amputations, 4 had lost 31 digits at 45 days, and 2 had amputations but more distally than would have been anticipated without treatment.

More recently, six more frostbite patients were treated with TNK. Five of these patients had complete response and one had no response. To date, 8 out of 12 TNK-treated patients have been saved from amputation.

These data are part of an ongoing FDA-approved prospective trial undertaken by Dr. Edmonson. The hope was that more scientific results might encourage others to use this type of treatment.