Search for a command to run...
Limb transplantation is divided into replantation and allotransplantation. Replantation is the direct or indirect in replantation of a severed limb, whereas allotransplantation refers to the transplantation of limbs between individuals of different genotypes of the same species. Static cold storage (SCS) remains the gold standard for in vitro limb preservation. This hypothermic (0–4°C) storage method using ice packs is simple, cost-effective, and easy to implement. However, it is limited by a short preservation window of 4–6 hours, after which tissue viability and functional integrity decline.[1,2] SCS also fails to preserve muscle architecture and strength, and induces cold ischemic injury, compromising long-term graft survival.[3,4] Mechanical perfusion, though capable of relieving vasospasm and maintaining basic metabolism, still can not fully preserve tissue function and requires specialized equipment and protocols.[4,5] Temporary intravascular shunting (TIVS) and temporary ectopic implantation offer alternative approaches, but both present significant challenges.[6,7] IVS may cause toxin reflux and worsen the spread of infection in severely damaged patients.[8] Temporary ectopic implantation helps in limb salvage under special circumstances but poses challenges in the second-stage replantation due to the increased risk of infection.[7] Xenogeneic cross-circulation can initiate the self-repair mechanism of the limb by connecting it to the host’s circulation, promoting physiological function and tissue recovery, thereby prolonging the preservation time. However, it faces the critical challenge of immunological rejection.[9] To safely and effectively improve the preservation and repair of severed limbs, the Microsurgery Branch of the Chinese Medical Association and the National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation developed this guideline. (The complete guidelines and information are provided in the Supplementary File, https://links.lww.com/CM9/C613). Definition of amputation preservation and transplantation Replantation is the most effective method to treat a severed limb. Allogeneic limb transplantation is another potential method. The preservation and repair techniques for amputated and allograft limbs can significantly extend preservation time, a critical technology in clinical practice. Limb tissue, as a type of vascularized composite allograft (VCA), is composed of structures derived from different germ layers. It possesses distinct anatomical structures, tissue morphologies, and functions. Hypothermia, preservation liquid, and other preservation methods can extend the time limit for reimplantation of the severed limb. Recommendation strength The recommendation strength is based on a combination of the Grading of Recommendations Assessment, Development, and Evaluation system and the characteristics of clinical practice in China. Experts scored the recommendations individually. The final recommendation grade was determined by calculating the weighted average of individual scores, considering both the evidence and the clinical practice context in China, to ensure a balanced and appropriate final decision. [Supplementary Tables 1–3, https://links.lww.com/CM9/C614]. Technology for Static Hypothermic Preservation Optimal temperature range for SCS. Research indicates that cellular metabolism is reduced by 50% for every 10 °C decrease in temperature, and at standard SCS storage temperatures between 0 °C and 4 °C, cellular metabolism occurs at 10–12% of baseline function. Lowering the temperature below the freezing point of water leads to ice formation, which causes cell damage and destroys tissues. Numerous studies indicate that the optimal temperature range for SCS is between 0 °C and 4 °C (Grade 1A). Optimal preservation time for SCS. SCS reduces tissue cell metabolism and extends the preservation time for severed limbs, but as ischemia time increases, the success rate of limb replantation and limb function gradually decrease. Therefore, ischemia time remains a critical factor in limb preservation. Most studies suggest that SCS preservation should ideally be limited to 6 hours (Grade 1A). Cold storage immersion technique and preservation solution selection. SCS has been the gold standard for limb preservation, but a growing body of research indicates that hypothermic isotonic fluid immersion is superior. Hypothermic isotonic immersion preservation solutions include hypothermic isotonic fluids with metabolic energy and antibiotics such as Euro-Collins solution, University of Wisconsin (UW) solution, and histidine tryptophan ketoglutarate (HTK) solution. Hypothermic isotonic immersion preservation allows for a lower metabolic rate, provides nutrients to the limb, and offers anti-inflammatory and antimicrobial effects, thus extending the preservation time of amputated limbs (Grade 2A). Clinical applications and optimization of cryopreservation of amputated limbs at ultra-low temperatures. Cryopreservation refers to the preservation of biological materials or substances at temperatures below −196°C. At this temperature, all biological activity is theoretically terminated, including biochemical processes that could be lethal to cells. The process of cryopreservation mitigates metabolic processes and retards tissue degeneration, thereby extending the preservation time for limb transplantation. This technology has demonstrated successful clinical application in finger replantation and continues to be optimized for potential expansion to larger limb preservation, highlighting its broad translational prospects (Grade 2C). Mechanical Perfusion Technology The effectiveness of mechanical perfusion in preserving amputated limbs. Mechanical perfusion preserves amputated limbs by dynamically circulating a specialized solution through the vascular system, mimicking physiological blood flow to deliver nutrients, remove waste, and reduce ischemia-reperfusion injury. The technique demonstrates marked superiority over SCS by enabling precise control of perfusate parameters, which enhances tissue preservation, functional assessment, and damage repair (Grade 2A). Optimum temperature and pressure for mechanical perfusion technique. Mechanical perfusion techniques use various temperatures for preservation, including normothermic (35–38°C), sub-normothermic (25–34°C), and hypothermic (0–12°C), with the appropriate pressure adjusted based on temperature to achieve optimal physiological simulation. The pressure of hypothermic, sub-normothermic, and normothermic mechanical perfusion should be maintained at approximately 30, 50, and 70 mmHg, respectively. Selecting the right pressure requires precision—too high and it may cause tissue edema and increase stress on the limb; too low and it can compromise the delivery of nutrients and oxygen. Since perfusion pressure and tissue temperature interact dynamically, both must be carefully balanced to maintain the metabolic needs of the amputated limb (Grade 2A). Selection of the preservation solution for mechanical perfusion. An ideal mechanical perfusion fluid should mimic the physiological environment by delivering oxygen and nutrients, removing waste, and providing cytoprotective, anti-inflammatory, and antibacterial effects to extend preservation time. Commonly used solutions include UW solution, a high-potassium, high viscosity fluid that minimizes edema; HTK solution, which has a strong histidine buffer to reduce edema; and hemoglobin-based fluids, which use oxygen carriers to mimic erythrocyte function without the risks associated with blood perfusion (Grade 2A). TIVS Technique Indications and contraindications for TIVS. TIVS rapidly restores the blood supply to severed limbs by bridging a temporary vascular pathway through damaged vessels and decreases limb ischemia time. This technology is particularly useful in specialized settings for incomplete limb amputations or vascular injuries, especially those involving major limb vessels such as the brachial and popliteal arteries. Contraindications include severe shock, prolonged ischemia, and severely contaminated or damaged limbs (Grade 2B). Critical techniques for TIVS. The efficacy of TIVS is contingent upon the successful execution of several pivotal technical aspects. These include the selection of an appropriate shunting device, the implementation of efficacious anticoagulation strategies, thrombus removal, and the assurance of secure vessel fixation. These factors are of paramount importance for optimizing treatment outcomes and minimizing complications (Grade 1B). Temporary Ectopic Implantation Indications and complications of temporary ectopic implantation. Temporary ectopic implantation of a severed limb is an innovative procedure for salvaging the limb under special circumstances. Although this procedure is very demanding, it does deserve special consideration in reconstructive microsurgery because it offers the possibility of salvaging severed limbs with extensive soft tissue loss by preserving their anatomy and function. It is indicated for the treatment of severe trauma, hemodynamic instability, and segmental destruction of the limb. Temporary ectopic implantation represents an optimal treatment option for children with traumatic amputation of the upper extremity. The most common complications include infection at the recipient site, sepsis, and vascular injury at the recipient site (Grade 2B). Recipient sites for temporary ectopic implantation. Temporary ectopic implantation before subsequent replantation is an innovative and valuable surgical technique for patients who would otherwise be poor candidates for replantation. The recipient sites are selected at a distance from the injured area, always considering the availability and size of appropriate recipient vessels, and the safety of the surgical procedure. A contralateral healthy extremity is an ideal recipient site. The selection is based on the anatomy of the amputated limb and the donor site. For amputation injuries of the forearm and lower leg, temporary ectopic implantation on the medial side of the healthy lower leg is often chosen. For upper extremity amputations, the contralateral medial tibia or palmar distal forearm is often selected (Grade 2B). Critical techniques for temporary ectopic implantation. Preoperative planning for temporary ectopic implantation is of great benefit to the patient in terms of their recovery. Critical techniques such as bone fixation, anastomotic vascularization of the recipient area, and soft tissue coverage are important. Motor or sensory nerve anastomosis can address severed nerves and facilitate the restoration of sensory and neuromuscular functions. Anastomosing as many blood vessels as possible, with an arteriovenous ratio greater than 1:2, and preventing limb swelling, thrombosis, and vascular crises are the basis for ensuring limb survival and functional recovery. It is desirable to preserve healthy soft tissues as much as possible to increase coverage and avoid anastomotic infection. The optimal timing for reimplantation surgery is when the patient’s general condition has recovered, the ectopic implanted limb is viable, the stump wound is free of contamination, and the severed limb can be shortened and reimplanted or undergo tissue flap transplantation to rebuild the limb’s shape and function (Grade 2B). Xenogeneic Cross-Circulation Technology Critical technique of xenogeneic cross-circulation. Xenogeneic cross-circulation is a method of connecting the major arteries and veins of the severed limb to the host circulatory system based on extracorporeal membrane oxygenation (ECMO) and mechanical perfusion techniques. With the severed limb connected to the host’s circulatory system, recovery of physiological function and tissue injury may occur. The cross-circulation technique fully uses the self-repair mechanism of the limb and might represent a new technology for limb preservation in the future. This method is in the preclinical stage and has demonstrated promising applications. Mechanical perfusion in combination with xenogeneic cross-circulation technology integrates recent advancements in ECMO, genetic engineering, and transplantation immunology, and will bring about a revolutionary change in limb reimplantation and transplantation. In the xenogeneic cross-circulation system, the host animal can support the nutrient metabolism of the parasite limb by removing metabolic wastes through the liver and kidneys. ECMO can provide oxygen metabolism to the severed limb, prolonging the preservation time and enabling the limb to be repaired (Grade 3C). Conflicts of interest None.