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Traumatic amputations of the extremity are relatively common catastrophic injuries that adversely affect a patient’s physical function and wellbeing. This article reviews the current management of amputated limbs and discusses the role of ischemia and reperfusion processes in its future management. The decision to replant an extremity depends on numerous factors which include, but are not limited to, the time from injury, mechanism and site of injury, patient factors, and technic
Traumatic amputations of the extremity are relatively common catastrophic injuries that adversely affect a patient’s physical function and wellbeing. This article reviews the current management of amputated limbs and discusses the role of ischemia and the reperfusion processes in its future management. The decision to replant an extremity depends on numerous factors which include, but are not limited to, the time from injury, mechanism of injury, site of injury, patient factors and technical know-how of replantation surgery. Despite the significant progress in most of these aspects over the last decades, the management of the amputate has not significantly advanced. The outcomes of replantation are related to the amount of tissue injury incurred by the amputate and the time without blood supply. To further the optimisation of the amputated extremity and improve the success of replantation, the future of this field relies in the research into both pharmacological post-conditioning and ex vivo perfusion to overcome Ischemic Reperfusion Injury, particularly in proximal injuries.
al know-how of replantation surgery. Despite the significant progress in most of these aspects over the last decades, the management of the amputate has not significantly advanced. The outcomes of replantation are related to the amount of tissue injury incurred by the amputate and the time without blood supply. To further the optimization of the amputated extremity and improve replantation success, the future of this field relies on the research into both pharmacological post-conditioning and ex vivo perfusion to overcome Ischaemic Reperfusion Injury, particularly in proximal injuries.
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2. Reid DBC, Shah KN, Eltorai AEM, Got CC, Daniels AH. Epidemiology of Finger Amputations in the United States From 1997 to 2016. J Hand Surg Glob Online. 2019 Apr 1;1(2):45–51.
3. Malt RA, Mckhann CF. Replantation of Severed Arms. JAMA J Am Med Assoc. 1964 Sep 7;189(10):716–22.
4. Komatsu S, Tamai S. Successful replantation of a completely cut-off thumb. Plast Reconstr Surg. 1968;42(4):374–7.
5. Reavey PL, Stranix JT, Muresan H, Soares M, Thanik V. Disappearing digits: Analysis of national trends in amputation and replantation in the United States. Plast Reconstr Surg. 2018 Jun 1;141(6):857e-867e.
6. Chung KC, Kowalski CP, Walters MR. Finger replantation in the United States: Rates and resource use from the 1996 Healthcare Cost and Utilization Project. J Hand Surg Am. 2000 Nov 1;25(6):1038–42.
7. Hustedt JW, Bohl DD, Champagne L. The detrimental effect of decentralization in digital replantation in the United States: 15 years of evidence from the national inpatient sample. J Hand Surg Am [Internet]. 2016 May 1 [cited 2020 Mar 25];41(5):593–601. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27021636
8. Maroukis BL, Chung KC, Maceachern M, Mahmoudi E. Hand trauma care in the United States: A literature review. Vol. 137, Plastic and Reconstructive Surgery. Lippincott Williams and Wilkins; 2016. p. 100e-111e.
9. Brown M, Lu Y, Chung KC, Mahmoudi E. Annual Hospital Volume and Success of Digital Replantation. Plast Reconstr Surg. 2017 Mar 1;139(3):672–80.
10. Buncke H, Whitney T. Secondary reconstruction after replantation. In: Buncke H, editor. Microsurgery: Transplantation– Replantation. Philadelphia/London: Lea & Febiger Inc; 1991. p. 651–83.
11. Morrison W, O’Brien Bm, Macleod A. Digital replantation and revascularization. A long-term review of 100 cases. Hand. 1978;10:125–34.
12. Tamai S. Twenty years’ experience of limb replantation—Review of 293 upper extremity replants. J Hand Surg Am. 1982;7(6):549–56.
13. Wu Y, Chen L, Scott PG, Tredget EE. Mesenchymal Stem Cells Enhance Wound Healing Through Differentiation and Angiogenesis. Stem Cells [Internet]. 2007 Oct [cited 2018 Apr 5];25(10):2648–59. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17615264
14. Frey M, Mandl H, Holle J. Secondary operations after replantations. Chir Plast. 1980;5(4):235–41.
15. Pitzler D, Buck-Gramcko D. Secondary operations after replantation. Ann Chir Gynaecol [Internet]. 1982 [cited 2020 Mar 26];71(1):19–27. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7092123
16. Jupiter JB, Pess GM, Bour CJ. Results of flexor tendon tenolysis after replantation in the hand. J Hand Surg Am [Internet]. 1989 Jan [cited 2020 Mar 26];14(1):35–44. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2723366
17. Scott FA, Howar JW, Boswick JA. Recovery of function following replantation and revascularization of amputated hand parts. J Trauma - Inj Infect Crit Care. 1981;21(3):204–14.
18. Tark KC, Kim YW, Lee YH, Lew JD. Replantation and revascularization of hands: Clinical analysis and functional results of 261 cases. J Hand Surg Am. 1989 Jan 1;14(1):17–27.
19. Tamai S. Digit replantation. Analysis of 163 replantations in an 11 year period. Clin Plast Surg [Internet]. 1978 Apr [cited 2020 Mar 26];5(2):195–209. Available from: http://www.ncbi.nlm.nih.gov/pubmed/679604
20. Chim H, Maricevich MA, Carlsen BT, Moran SL, Salgado CJ, Wei FC, et al. Challenges in replantation of complex amputations. Semin Plast Surg. 2013 Nov 20;27(4):182–9.
21. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell Biology of Ischemia/Reperfusion Injury. In: International Review of Cell and Molecular Biology. Elsevier Inc.; 2012. p. 229–317.
22. Atkins SE, Winterton RIS, Kay SP. MINI-SYMPOSIUM: HAND TRAUMA (v) Upper limb amputations: Where, when and how to replant. [cited 2020 Mar 25]; Available from: www.elsevier.com/locate/cuor
23. Sorensen K, Allison K. An overview of limb replantation. Trauma [Internet]. 2009 Oct 17 [cited 2020 Mar 25];11(4):209–20. Available from: http://journals.sagepub.com/doi/10.1177/1460408609349889
24. Graham T., Sapega A, Heppenstall B, Sokolow D, Graham T, Maris J, et al. Bioenergetics of Preservation of Limbs before Replantation. J Bone Jt Surg. 1988;70(10):1500–13.
25. Gold AH, Lee GW. Upper extremity replantation: current concepts and patient selection. J Trauma [Internet]. 1981 Jul [cited 2020 Mar 25];21(7):551–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7253053
26. Webb JB. Replantation in trauma. Trauma [Internet]. 2005 Jan 24 [cited 2020 Jun 6];7(1):1–9. Available from: http://journals.sagepub.com/doi/10.1191/1460408605ta325oa
27. Amillo S, Leyes M, Fernández J, Torres R. [Current indications for reimplantation of the upper extremity]. Rev Med Univ Navarra [Internet]. [cited 2020 Mar 26];40(4):34–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9499833
28. Zhong-Wei C, Meyer VE, Kleinert HE, Beasley RW. Present indications and contraindications for replantation as reflected by long-term functional results. Orthop Clin North Am [Internet]. 1981 Oct [cited 2020 Mar 26];12(4):849–70. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7322515
29. Chung KC, Yoon AP, Malay S, Shauver MJ, Wang L, Kaur S. Patient-Reported and Functional Outcomes after Revision Amputation and Replantation of Digit Amputations: The FRANCHISE Multicenter International Retrospective Cohort Study. JAMA Surg [Internet]. 2019 Jul 1 [cited 2020 Mar 24];154(7):637–46. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30994871
30. Janezic TF, Arnez ZM, Solinc M, Zaletel‐Kragelj L. One hundred sixty‐seven thumb replantations and revascularisations: Early microvascular results. Microsurgery. 1996 Jan 1;17(5):259–63.
31. Waikakul S, Sakkarnkosol S, Vanadurongwan V, Un-Nanuntana A. Results of 1018 digital replantations in 552 patients. Injury. 2000;31(1):33–40.
32. Koman; JURNG. The results of replantation after amputation of a single finger. J Bone Jt Surg. 1985;67(4):611–9.
33. Venkatramani H, Sabapathy S. Fingertip replantation: Technical considerations and outcome analysis of 24 consecutive fingertip replantations. Vol. 44, Indian Journal of Plastic Surgery. Thieme Medical Publishers; 2011. p. 237–45.
34. Brunelli G. Experimental studies of the effects of ischemia on devascularized limbs. Textbook of Microsurgery. Milan; 1988. 89–99 p.
35. Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol. 2000 Feb;190(3):255–66.
36. Zhang C. The role of inflammatory cytokines in endothelial dysfunction [Internet]. Vol. 103, Basic Research in Cardiology. NIH Public Access; 2008 [cited 2020 Jul 6]. p. 398–406. Available from: /pmc/articles/PMC2705866/?report=abstract
37. Wei FC, Chang YL, Chen HC, Chuang CC. Three successful digital replantations in a patient after 84, 86, and 94 hours of cold ischemia time. Plast Reconstr Surg [Internet]. 1988 Aug [cited 2020 Mar 25];82(2):346–50. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3399566
38. VanderWilde RS, Wood MB, Zeng-gui S. Hand replantation after 54 hours of cold ischemia: A case report. J Hand Surg Am. 1992;17(2):217–20.
39. Lin CH, Aydyn N, Lin Y Te, Hsu CT, Lin CH, Yeh JT. Hand and finger replantation after protracted ischemia (more than 24 hours). Ann Plast Surg. 2010 Mar;64(3):286–90.
40. Wilhelmi BJ, Lee WPA, Pagenstert GI, Pagensteert GI, May JW. Replantation in the mutilated hand. Hand Clin [Internet]. 2003 Feb [cited 2020 Mar 25];19(1):89–120. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12683449
41. Prucz RB, Friedrich JB. Upper extremity replantation: Current concepts. Plast Reconstr Surg. 2014 Feb;133(2):333–42.
42. Battiston B, Tos P, Clemente A, Pontini I. Actualities in big segments replantation surgery. J Plast Reconstr Aesthetic Surg. 2007 Jul 1;60(7):849–55.
43. Quiñones-Baldrich WJ, Chervu A, Hernandez JJ, Colburn M, Moore WS. Skeletal muscle function after ischemia: “no reflow” versus reperfusion injury. J Surg Res [Internet]. 1991 Jul [cited 2020 Mar 25];51(1):5–12. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2067359
44. Eiken O, Nabseth DC, Mayer RF, Deterling RA. Limb Replantation: II. The Pathophysiological Effects. Arch Surg [Internet]. 1964 Jan 1 [cited 2020 Jul 6];88(1):54–65. Available from: https://jamanetwork.com/journals/jamasurgery/fullarticle/561743
45. Korthuis RJ, Granger DN, Townsley MI, Taylor AE. The role of oxygen-derived free radicals in ischemia-induced increases in canine skeletal muscle vascular permeability. Circ Res [Internet]. 1985 Oct [cited 2020 Mar 25];57(4):599–609. Available from: http://www.ncbi.nlm.nih.gov/pubmed/4042285
46. Yassin MMI, Harkin DW, Barros D’Sa AAB, Halliday MI, Rowlands BJ. Lower limb ischemia-reperfusion injury triggers a systemic inflammatory response and multiple organ dysfunction. In: World Journal of Surgery [Internet]. World J Surg; 2002 [cited 2020 Jul 6]. p. 115–21. Available from: https://pubmed.ncbi.nlm.nih.gov/11898044/
47. VanBenthuysen KM, McMurtry IF, Horwitz LD. Reperfusion after acute coronary occlusion in dogs impairs endothelium-dependent relaxation to acetylcholine and augments contractile reactivity in vitro. J Clin Invest [Internet]. 1987 Jan [cited 2020 Mar 25];79(1):265–74. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3793926
48. Davies MG, Hagen PO. The vascular endothelium: A new horizon [Internet]. Vol. 218, Annals of Surgery. Lippincott Williams and Wilkins; 1993 [cited 2020 Mar 25]. p. 593–609. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8239773
49. Münzel T, Afanas’ev IB, Kleschyov AL, Harrison DG. Detection of superoxide in vascular tissue. Vol. 22, Arteriosclerosis, Thrombosis, and Vascular Biology. 2002. p. 1761–8.
50. Frangogiannis NG, Youker KA, Rossen RD, Gwechenberger M, Lindsey MH, Mendoza LH, et al. Cytokines and the microcirculation in ischemia and reperfusion. In: Journal of Molecular and Cellular Cardiology. Academic Press; 1998. p. 2567–76.
51. Buncke H, Jackson R, Buncke G. The surgical and rehabilitative aspects of replanation and revascularization of the hand. 4th editio. Hunter J, Mackin E, Callahan A, editors. Mosby; 1995. 1075–1083 p.
52. Fantini GA, Conte MS. Pulmonary failure following lower torso ischemia: Clinical evidence for a remote effect of reperfusion injury. Am Surg [Internet]. 1995 Apr 1 [cited 2020 Jul 6];61(4):316–9. Available from: https://europepmc.org/article/med/7893094
53. Gadaleta D, Fantini GA, Silane MF, Davis JM. Leukotriene Generation and Pulmonary Dysfunction following Aortic Cross Clamp in Humans. Ann N Y Acad Sci [Internet]. 1994 [cited 2020 Jul 6];723(1):470–2. Available from: https://pubmed.ncbi.nlm.nih.gov/8030915/
54. Goldman G, Welbourn R, Klausner JM, Kobzik L, Valeri CR, Shepro D, et al. Mast cells and leukotrienes mediate neutrophil sequestration and lung edema after remote ischemia in rodents. Surgery [Internet]. 1992 Sep 1 [cited 2020 Jul 6];112(3):578–86. Available from: http://www.surgjournal.com/article/003960609290263Y/fulltext
55. Welbourn R, Goldman G, Kobzik L, Paterson IS, Valeri CR, Shepro D, et al. Role of neutrophil adherence receptors (CD 18) in lung permeability following lower torso ischemia. Circ Res [Internet]. 1992 [cited 2020 Jul 6];71(1):82–6. Available from: https://pubmed.ncbi.nlm.nih.gov/1351425/
56. Neary P, Redmond HP. Ischaemia-Reperfusion Injury and the Systemic Inflammatory Response Syndrome. In: Grace PA, Mathie RT, editors. Ischaemia-Reperfusion Injury [Internet]. Oxford: Blackwell Science; 1999 [cited 2020 Jul 6]. p. 123–36. Available from: https://www.scirp.org/(S(351jmbntvnsjt1aadkposzje))/reference/ReferencesPapers.aspx?ReferenceID=2066230
57. Maxwell SRJ, Lip GYH. Reperfusion injury: A review of the pathophysiology, clinical manifestations and therapeutic options. Int J Cardiol [Internet]. 1997 Jan 31 [cited 2020 Jul 6];58(2):95–117. Available from: https://pubmed.ncbi.nlm.nih.gov/9049675/
58. Dhalla NS, Elmoselhi AB, Hata T, Makino N. Status of myocardial antioxidants in ischemia-reperfusion injury [Internet]. Vol. 47, Cardiovascular Research. Oxford Academic; 2000 [cited 2020 Jul 6]. p. 446–56. Available from: https://academic.oup.com/cardiovascres/article-lookup/doi/10.1016/S0008-6363(00)00078-X
59. Panés J, Perry M, Granger DN. Leukocyte-endothelial cell adhesion: Avenues for therapeutic intervention [Internet]. Vol. 126, British Journal of Pharmacology. Wiley-Blackwell; 1999 [cited 2020 Jul 6]. p. 537–50. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1565837/
60. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: A delay of lethal cell injury in ischemic myocardium. Circulation. 1986;74(5):1124–36.
61. Wang WZ, Anderson G, Firrell JC, Tsai TM. Ischemic preconditioning versus intermittent reperfusion to improve blood flow to a vascular isolated skeletal muscle flap of rats. In: Journal of Trauma - Injury, Infection and Critical Care [Internet]. Lippincott Williams and Wilkins; 1998 [cited 2020 Mar 26]. p. 953–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9820708
62. Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA, et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: Comparison with ischemic preconditioning. Am J Physiol - Hear Circ Physiol. 2003 Aug 1;285(2 54-2).
63. Loukogeorgakis SP, Panagiotidou AT, Yellon DM, Deanfield JE, MacAllister RJ. Postconditioning protects against endothelial ischemia-reperfusion injury in the human forearm. Circulation. 2006 Feb;113(7):1015–9.
64. McAllister SE, Ashrafpour H, Cahoon N, Huang N, Moses MA, Neligan PC, et al. Postconditioning for salvage of ischemic skeletal muscle from reperfusion injury: Efficacy and mechanism. Am J Physiol - Regul Integr Comp Physiol [Internet]. 2008 Aug [cited 2020 Mar 26];295(2):R681-9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18509099
65. Moon JG, Lim HC, Gye MR, Oh JS, Park JW. Postconditioning attenuates ischemia-reperfusion injury in rat skin flap. Microsurgery [Internet]. 2008 Jan 1 [cited 2020 Mar 26];28(7):531–7. Available from: http://doi.wiley.com/10.1002/micr.20530
66. Cavadas PC, Landín L, Ibáñez J. Temporary catheter perfusion and artery-last sequence of repair in macroreplantations. J Plast Reconstr Aesthetic Surg [Internet]. 2009 Oct [cited 2020 Mar 25];62(10):1321–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18650139
67. Cunha MS, da Silva JCF, Nakamoto HA, Ferreira MC. Study of warm ischemia followed by reperfusion on a lower limb model in rats: effect of allopurinol and streptokinase. Clinics (Sao Paulo). 2005;60(3):213–20.
68. Li X, Cooley BC, Gould JS. Ex vivo perfusion with anticoagulated blood decreases ischemia/reperfusion injury. J Hand Surg Am [Internet]. 1993 Jul [cited 2020 Mar 25];18(4):629–34. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8349970
69. Beyersdorf F, Matheis G, Krüger S, Hanselmann A, Freisleben HG, Zimmer G, et al. Avoiding reperfusion injury after limb revascularization: Experimental observations and recommendations for clinical application. J Vasc Surg. 1989 Jun 1;9(6):757–66.
70. Heilmann C, Schmoor C, Siepe M, Schlensak C, Hoh A, Fraedrich G, et al. Controlled reperfusion versus conventional treatment of the acutely ischemic limb: results of a randomized, open-label, multicenter trial. Circ Cardiovasc Interv [Internet]. 2013 Aug [cited 2020 Mar 26];6(4):417–27. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23881815