LIMB REPLANTATION: SURGICAL STRATEGY AND THE PROPHYLAXIS OF ACUTE RENAL FAILURE IN ISCHEMIA REPERFUSION INJURY – A REPORT OF TWO CASES

Introduction. The arm replantation is extremely rare and challenging procedure. The recognised risk is myoglobinuria and ischemia reperfusion induced renal failure. Case report. Two patients aged 24 and 46-years were admitted after traumatic arm amputation. Ischemia time was two hours and six hours. Postoperative intensive care treatment with assisted ventilation, sedation and obtaining sufficient urine output prevents myoglobin induced renal injury. In case where ischemia time was shorter, there was only one delayed reconstruction of skin defects after fasciotomy, but in the case where ischemia lasted longer, patient had two secondary look procedures with acceptable definitive results. Conclusion. Arm replantation is safe procedure even in cases with longer ischemia time. Postoperative control of urine output and correction of acidosis, preventing myoglobin induced tubular injury is crucial for stable postoperative recovery.


Introduction
Reconstruction of upper extremity injuries is challenging especially after traumatic amputation. There is a lack of knowledge about the impact of ischemia duration on the development of possible complications, as myoglobinuria and acute renal failure.
Rhabdomyolysis is a clinical syndrome characterised by acute damage of the sarcolemma of the skeletal muscle leading to release in circulation: myoglobin, creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), etc. (1).
During rhabdomyolysis the necroptosis and ferroptosis occur as the form of the nonapoptotic cell death resulting in accumulation of reactive oxygen species (ROS) (2), that could lead to skeletal muscle cell death (3). Due to the toxic effects of free radicals tubular necrosis occurs resulting in acute renal failure (4). The aims in intensive therapy after replantation are addressed on prevention of ischemia reperfusion injury.

Case 1
A 46-year-old male patient was admitted with traumatic amputation of right upper extremity happened one hour before admission. The injury was caused by a wood cutting machine.
He underwent emergency surgery and revascularization was achieved after two hours from injury time. External skeletal fixation was applied, followed by debridement of the wound edges, arterial and venous anastomosis by the technique of running suture. Immediately after creation of vascular anastomoses heparin single dose 10000 I.U. was administered.
Neuroraphy of median, radial and ulnar nerves and musculoraphy were performed. The skin is closed with interrupted stitches. Longitudinal fasciotomies are performed on the forearm. During surgery the blood transfusion started in overall amount of 1400 ml of red blood cells (RBC) and 1100 ml of fresh frozen plasma.
During the first two days in Intensive Care Unit (ICU), he was intubated on bilevel positive airway pressure (BiPAP) ventilation mode, using midazolam sedation. Renal excretory function was controlled by monitoring of hourly diuresis that was reaching 200 ml/h in first two days. Muscle damage was controlled through myoglobin and CK concentrations. C-reactive protein (CRP) reached pick in fourth day measuring 164 I.U. The high doses of bicarbonate were used for correction of negative blood base excess (BE). Daily urine output was sufficient during recovery. The parameters of the renal function were in normal reference values at all times. Fifth day a second look procedure was performed and additional debridement on distal wound edge was performed and wound was closed. The second surgery was performed on the fifteenth day when skin defects at the site of fasciotomy was skin grafted. The patient was discharged on twenty seventh day.

Case 2
A 24-year-old male patient was admitted after traumatic amputation of a right upper extremity, accompanying with fractures of lower jaw, left clavicle and left fibula, that happened four hours before admission. The injury was caused when a huge rock from ceiling in mining shaft fell on patient. Revascularization was achieved one and a half hours after admission, but total ischemia time was six hours. Debridement of devitalised bone tissue was made proximal and distal cc 2.5 cm in length converting irregular fracture line in sharp cut and obtaining bone fragments covered by the periosteum. All steps of surgery were same as in case 1 but after performing an arterial anastomosis, bleeding from the brachial vein was uncontrolled for 20 seconds in order to eliminate the initial products of anaerobic metabolism, as well as ROS. A drain was placed into the amputation line and fasciotomies were performed. Because of unstable double lower jaw fracture, temporary Risdon ligature was applied. Intraoperative blood transfusion was administered in amount 1700 ml of resuspended RBC and 880 ml of fresh frozen plasma.
First two days in ICU, he was on BiPAP ventilation mode, with proper sedation. Diuresis was stimulated with 10% Mannitol 125 ml/h during first two days. Renal function was controlled by monitoring hourly diuresis that was 245 ml/h in first two days. The high doses of bicarbonate were used for correction of the acid-base status. Muscle damage was monitored by myoglobin and CK concentrations. Anticoagulant therapy was administered intraoperatively by administering 10.000 I.U. of heparin, and postoperatively ten days was given low-molecular-weight heparin (LMWH). Anti-aggregation therapy was started on the seventh day by administering acetylsalicylic acid at a dose of 500 mg daily. The parameters of the renal function were in reference values all time.
He was operated for the second time on the seventh day when lower jaw, left clavicle and left fibula was stabilised by plates. Skin defects at the site of forearm fasciotomy covered with a skin graft at seventeenth day. Due to the pseudoarthrosis of humerus after nine months, a bone graft of lyophilised bone was inserted and humerus was healed properly.
Two years after surgery, the patient has full range of motion in the elbow and wrist, but hand muscles are atrophic and functionless (Figure 1.). The patient is not motivated for further treatment.
[Insert Figure 1  Rhabdomyolysis can be caused by a variety of factors, including muscular trauma after surgery (6), lower extremity exercise training (7), undifferentiated connective tissue disease (8), as well as non-traumatic muscle breakdown, including chemical (9) and biologic agents (10, 11). However, the highest incidence of rhabdomyolysis is associated with the onset of compartment syndrome in the extremity injuries. Diagnosis of rhabdomyolysis is confirmed by elevated plasma myoglobin levels and increased CK levels. The CK usually rises within two to twelve hours of muscle injury, reaching maximum values at 24-72 hours (12).
In both presented cases, we found markable changes in serum CK and myoglobin after arm replantation (Fig.2, Fig.3).
Creatine kinase activity was above 2800 U/L (reference value up to 195 U/L) in case 1 and above 3400 U/L in case 2. It is important to point out that patient in case 2, who had multiple injuries and a longer ischemia time, had higher values of CK on tenth day compared to case 1.
In case 1 myoglobin level was up to 2973 µg/L (reference value up to 92 µg/L) compared to patient in case 2 were the myoglobin level was up to 7035 µg/L. In our review of the literature, we found that duration of surgery (about five and a half hours) had crucial risk factors for developing rhabdomyolysis and acute renal failure (13), but our two cases had not developed any sign of it.
Activity of AST and ALT, as markers of liver injury, were transitory elevated in case 2 (Tab.5). Liver dysfunction molecular mechanisms have not yet been clarified. Literature data state that released proteases from injured muscles can be significant causes of liver damage (14).
Although the surgical requirement itself was more demanding, multiple injuries as well as a longer period of ischemia in case 2 compared to case 1, we can conclude that rapid