PAPER Reduction of the Incidence of Amputation in Frostbite Injury With Thrombolytic Therapy Kevin J. Bruen, MD; James R. Ballard, BS; Stephen E. Morris, MD; Amalia Cochran, MD; Linda S. Edelman, MPhil, BSN; Jeffrey R. Saffle, MD Hypothesis: Thrombolytic therapy will decrease the in- gers or toes) and more proximal (ray, transmetatarsal, cidence of amputation when administered within 24 hours or below-knee) amputations. Resource utilization in- of exposure. cluding length of stay, total costs, cost per involved digit, and cost per saved digit were analyzed. Design: Single institution retrospective review of clini- cal outcomes and resource use. Results: Thirty-two patients with digital involvement (hands, 19%; feet, 62%; both, 19%) were identified. Seven Setting: Burn unit of a tertiary academic referral center. patients received tPA, 6 within 24 hours of injury. The incidence of digital amputation in patients who did not Patients: From 2001 to 2006, patients with severe frost- receive tPA was 41%. In those patients who received tPA bite admitted within 48 hours of injury underwent digi- within 24 hours of injury, the incidence of amputation tal angiography and treatment with intra-arterial tissue was reduced to 10% (PϽ.05). plasminogen activator (tPA) if abnormal perfusion was demonstrated. These patients were compared with those Conclusions: Tissue plasminogen activator improved tis- treated from 1995 to 2006 who did not receive tPA. sue perfusion and reduced amputations when adminis- tered within 24 hours of injury. This modality repre- Interventions: Tissue plasminogen activator vs tradi- tional management of frostbite injury. sents the first clinically significant advancement in the treatment of frostbite in more than 25 years. Main Outcome Measures: Number and type of sur- gery were recorded, along with amputations of digits (fin- Arch Surg. 2007;142:546-553 HE TREATMENT OF FROST- in 2001, we employed thrombolytic therapy bite has remained essen- for severe cases of frostbite at our regional tially unchanged for the last burn referral center. We hypothesized that 25 years. Today, tradi- our experience would demonstrate that tional therapy consists of tis- thrombolytic therapy decreased the inci- sue rewarming, prolonged watchful wait- dence of amputation when administered T 1 ing, and often delayed amputation. While within 24 hours of exposure. many other areas of burns, trauma, and critical care have advanced significantly in METHODS their treatment modalities, the saying “Frostbite in January, amputate in July” is still relevant today.2 A variety of maneu- PATIENT POPULATION vers aimed at advancing the care of pa- tients with frostbite have been attempted, The University of Utah Medical Center is a 425- including hyperbaric oxygen,3-7 surgical and bed tertiary care teaching facility. The Burn Author Affiliations: Division of medical sympathectomy,8-20 pharmaceuti- Center is an American College of Surgeons– and General Surgery (Drs Bruen, cal agents,21-25 and anticoagulation.26-36 None American Burn Association–verified regional Morris, Cochran, and Saffle, of these have resulted in alterations in the facility dedicated to the care of patients with and Mr Ballard and burn trauma. The 12-bed unit is staffed by 3 Ms Edelman), and the Burn management of this disorder. full-time burn surgeons and provides care for Center (Drs Morris, Cochran, Recent reports have described the use a wide range of burn, soft tissue, and trau- and Saffle, and Ms Edelman), of thrombolytic therapy using urokinase or matic injuries, including frostbite. Beginning University of Utah, tissue plasminogen activator (tPA) as a po- in 2001, we instituted a protocol in which pa- Salt Lake City. tential therapy for frostbite.37-40 Beginning tients with evidence of clinically significant (REPRINTED) ARCH SURG/ VOL 142, JUNE 2007 WWW.ARCHSURG.COM 546 ©2007 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 frostbite underwent assessment of extremity perfusion using 99 Tc-scintigraphy or digital angiography. Patients who dem- 2001-2006 1995-2000 onstrated perfusion defects were given a course of intra- 21 Patients 11 Patients arterial tPA (Alteplase; Genentech Inc, San Francisco, Calif). We reviewed all patients treated with this protocol from 2001 to 2006. Outcomes of patients who received tPA were com- 9 Patients Had Absent Doppler pared with a control group consisting of all patients with vary- or Deep Purple/ 12 Other Patients∗ ing degrees of injury severity who were not treated with throm- Black Digits bolytic therapy from 1995 to 2006. 9 Patients 2 Patients Had Normal 26 Patients Received Underwent Angiography Results Traditional Treatment STUDY DESIGN Angiography This retrospective study was approved by the institutional re- view board of the University of Utah Health Science Center. 7 Patients Had 1 Patient Underwent Abnormal tPA Therapy >24 h Patients with frostbite were identified by searching our Trauma Angiography After Exposure Registry, American College of Surgeons/American Burn Asso- Results ciation (TRACS/ABA) database. Data were extracted from pa- tient medical records. Admission history was used to identify 6 Patients exposure circumstance and duration. Physical examination data Underwent tPA were obtained from standardized burn diagrams and docu- Therapy <24 h mented soft tissue and vascular assessments. The number of After Exposure digits and proximal extremities involved were recorded. Time to admission, tPA therapy, and duration of tPA treatment was 13 Extremities 57 Extremities determined from documentation included in patient medical records. Figure 1. Evaluation and treatment groups of all patients with frostbite at the University of Utah admitted from 1995 to 2006. Asterisk indicates present EVALUATION AND TREATMENT REGIMEN Doppler/clinical findings were limited to bullae without significant discoloration or a delay in presentation. tPA indicates tissue plasminogen activator. All patients were evaluated by an attending burn surgeon at the time of their admission. Initial therapy consisted of immediate rewarming and fluid resuscitation as appropriate. Vascular ex- ANALYSIS amination included assessment of Doppler pulses, capillary re- fill, and skin color. Patients who appeared to have circulatory Primary end points were the number of digital amputations (fin- compromise, as evidenced by absence of pulses or black/deep gers or toes) and more proximal amputations (ray, transmeta- purple discoloration of digits, then underwent perfusion evalu- tarsal, or below the knee). Secondary end points included cu- ation by digital angiography. Patients with a history of concur- mulative length of stay (which included readmissions for surgery rent trauma, neurological impairment, recent surgery or hem- or rehabilitation), total costs, cost per involved digit, and cost orrhage, or bleeding diathesis were excluded. If significant per saved digits. Cost per involved digit was calculated by di- perfusion defects were demonstrated, tPA was administered at viding the total cost per individual patient by the number of an initial rate of 0.5 to 1.0 mg/h into the extremity via the fem- involved digits for each. Similarly, cost per saved digit was cal- oral or brachial arterial catheter sheath. Heparin was also ad- culated by dividing the total costs per individual patient by the ministered at 500 U/h into the intra-arterial catheter. Repeat number of digits that did not require amputation. Statistical analysis was performed using SPSS software, version 14.0 (SPSS angiograms were obtained every 8 to 12 hours to evaluate re- Ͻ sponse to therapy. Tissue plasminogen activator was discon- Inc, Chicago, Ill). A P value .05 using the Mann-Whitney U tinued when perfusion was restored to distal vessels or at an test was considered significant. absolute limit of 48 hours. Patients’ affected areas were then managed with local wound RESULTS care, which was identical to patients not treated with tPA. Fol- lowing admission and initial evaluation, extremities were washed From 1995 to 2006, 32 patients were treated for frost- gently. Intact blisters were left in place; ruptured blisters were carefully debrided, and the underlying wounds were evalu- bite injury at our regional burn center (Figure 1). Seven ated for evidence of perfusion. Extremities with intact blisters patients received tPA therapy, 6 of whom received therapy were dressed with dry gauze padding, which was changed daily. within 24 hours of exposure. The seventh patient re- Extremities that required debridement were dressed with an- ceived tPA after 48 hours of tissue thawing and was there- tibiotic ointment, nonadherent gauze (Adaptic; Johnson & fore included in the control group. Patient characteris- Johnson, New Brunswick, NJ), and dry gauze wraps, all of which tics are listed in Table 1 and Table 2. The majority of were changed twice daily. All involved extremities were el- patients were men and presented with lower extremity evated, and patients were assisted with gentle range of motion involvement. Study patients had a high incidence of sub- therapy twice daily. stance abuse, mental illness, and homelessness. Vehicle Injured extremities were maintained using local wound care breakdown was also a prominent risk factor for frost- until 1 of 2 end points was reached. Amputation was per- formed if areas of obvious necrosis or mummification devel- bite injury, found in 8 of the 32 cases. oped. Otherwise, wounds that appeared to be healing