Preoperative lactate, wound complications, and mortality following major amputation in patients with peripheral artery disease
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Abstract
Introduction: Peripheral Arterial Disease (PAD) is a leading cause of major lower-extremity amputation, particularly in patients with severe ischemia, gangrene, infection, or when revascularization is no longer feasible. Preoperative blood lactate is a biomarker reflecting tissue hypoperfusion and systemic metabolic stress, but its prognostic role in predicting postoperative wound complications and mortality after major amputation in PAD remains limited. Methods: This was an analytic observational study with a prospective cohort design conducted at Dr. Hasan Sadikin General Hospital between November 2024 and November 2025. Adult patients with PAD who underwent major amputation were enrolled using total sampling. Preoperative lactate levels were categorized into <2.5, 2.5–4, and >4 mmol/L, and associations with postoperative wound complications and mortality were analyzed using Fisher's Exact test. Results: A total of 51 patients met the study criteria; 60.8% were male and 52.9% were older than 60 years. Diabetes mellitus was the most common comorbidity (64.7%). Postoperative wound complications occurred in all patients with lactate >4 mmol/L, compared with 16 of 44 patients with lactate <2.5 mmol/L (p = 0.016). Mortality occurred in 4 of 5 patients with lactate >4 mmol/L, compared with 7 of 43 patients with lactate <2.5 mmol/L (p = 0.001). Discussion: Preoperative blood lactate is significantly associated with postoperative wound complications and mortality following major amputation in patients with PAD. Elevated lactate, particularly >4 mmol/L, identifies patients with worse postoperative outcomes, supporting its use as a simple, rapid, and accessible biomarker for perioperative risk stratification.
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How to Cite
Djajakusumah, T. M., Yarman, I. P., & Wibowo, A. S. (2026). Preoperative lactate, wound complications, and mortality following major amputation in patients with peripheral artery disease. International Journal on Health and Medical Sciences, 4(3), 155–163. https://doi.org/10.35335/healmed.v4i3.742
References
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Bucataru, A., Balasoiu, M., Ghenea, A. E., Zlatian, O. M., Vulcanescu, D. D., Horhat, F. G., Bagiu, I. C., Sorop, V. B., Sorop, M. I., Oprisoni, A., Boeriu, E., & Mogoanta, S. S. (2023). Factors Contributing to Surgical Site Infections: A Comprehensive Systematic Review of Etiology and Risk Factors. Clinics and Practice, 14(1), 52–68. https://doi.org/10.3390/clinpract14010006
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Criqui, M. H., & Aboyans, V. (2015). Epidemiology of Peripheral Artery Disease. Circulation Research, 116(9), 1509–1526. https://doi.org/10.1161/CIRCRESAHA.116.303849
Dutronc, H., Gobet, A., Dauchy, F.-A., Klotz, R., Cazanave, C., Garcia, G., Lafarie-Castet, S., Fabre, T., & Dupon, M. (2013). Stump infections after major lower-limb amputation: A 10-year retrospective study. Médecine et Maladies Infectieuses, 43(11–12), 456–460. https://doi.org/10.1016/j.medmal.2013.09.003
Farber, A., & Eberhardt, R. T. (2016). The Current State of Critical Limb Ischemia. JAMA Surgery, 151(11), 1070. https://doi.org/10.1001/jamasurg.2016.2018
Fortington, L. V., Geertzen, J. H. B., van Netten, J. J., Postema, K., Rommers, G. M., & Dijkstra, P. U. (2013). Short and Long Term Mortality Rates after a Lower Limb Amputation. European Journal of Vascular and Endovascular Surgery, 46(1), 124–131. https://doi.org/10.1016/j.ejvs.2013.03.024
Fowkes, F. G. R., Aboyans, V., Fowkes, F. J. I., McDermott, M. M., Sampson, U. K. A., & Criqui, M. H. (2017). Peripheral artery disease: epidemiology and global perspectives. Nature Reviews Cardiology, 14(3), 156–170. https://doi.org/10.1038/nrcardio.2016.179
He, L., Yang, D., Ding, Q., Su, Y., & Ding, N. (2023). Association Between Lactate and 28-Day Mortality in Elderly Patients with Sepsis: Results from MIMIC-IV Database. Infectious Diseases and Therapy, 12(2), 459–472. https://doi.org/10.1007/s40121-022-00736-3
Husain, F. A., Martin, M. J., Mullenix, P. S., Steele, S. R., & Elliott, D. C. (2017). Serum lactate as a predictor of outcomes in surgical patients. Journal of Trauma and Acute Care Surgery, 62(4), 934–938. https://doi.org/10.1097/TA.0b013e3180330c9e
Ivashkiv, L. B. (2020). The hypoxia–lactate axis tempers inflammation. Nature Reviews Immunology, 20(2), 85–86. https://doi.org/10.1038/s41577-019-0259-8
Khalil, A. A., Aziz, F. A., & Hall, J. C. (2006). Reperfusion Injury. Plastic and Reconstructive Surgery, 117(3), 1024–1033. https://doi.org/10.1097/01.prs.0000204766.17127.54
Kolasiński, W. (2018). Surgical site infections- review of current knowledge, methods of prevention. Polish Journal of Surgery, 90(5), 1–7. https://doi.org/10.5604/01.3001.0012.7253
Kong, V., Ko, J., Narayanan, A., Hassan, S., Leow, P., Lim, J., Bruce, J., Laing, G., & Clarke, D. (2023). Serum lactate level is an independent predictor of mortality in cardiac stab wounds – A South African experience. Surgery in Practice and Science, 12, 100157. https://doi.org/10.1016/j.sipas.2023.100157
Krähenbühl, N. (1980). Blood Lactate Measurement in Peripheral Arterial Disease. In Lactate (pp. 174–180). Springer Berlin Heidelberg. https://doi.org/10.1007/978-3-642-67525-6_20
Kruse, O., Grunnet, N., & Barfod, C. (2011). Blood lactate as a predictor for in-hospital mortality in patients admitted acutely to hospital: a systematic review. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 19(1), 74. https://doi.org/10.1186/1757-7241-19-74
Kullo, I. J., & Rooke, T. W. (2016). Peripheral Artery Disease. New England Journal of Medicine, 374(9), 861–871. https://doi.org/10.1056/NEJMcp1507631
Kushimoto, S., Akaishi, S., Sato, T., Nomura, R., Fujita, M., Kudo, D., Kawazoe, Y., Yoshida, Y., & Miyagawa, N. (2016). Lactate, a useful marker for disease mortality and severity but an unreliable marker of tissue hypoxia/hypoperfusion in critically ill patients. Acute Medicine & Surgery, 3(4), 293–297. https://doi.org/10.1002/ams2.207
Li, X., Yang, Y., Zhang, B., Lin, X., Fu, X., An, Y., Zou, Y., Wang, J.-X., Wang, Z., & Yu, T. (2022). Lactate metabolism in human health and disease. Signal Transduction and Targeted Therapy, 7(1), 305. https://doi.org/10.1038/s41392-022-01151-3
Marcarelli, M., Trovato, L., Novarese, E., Riccio, M., & Graziano, A. (2017). Rigenera protocol in the treatment of surgical wound dehiscence. International Wound Journal, 14(1), 277–281. https://doi.org/10.1111/iwj.12601
Moxey, P. W., Gogalniceanu, P., Hinchliffe, R. J., Loftus, I. M., Jones, K. J., Thompson, M. M., & Holt, P. J. (2011). Lower extremity amputations - a review of global variability in incidence. Diabetic Medicine, 28(10), 1144–1153. https://doi.org/10.1111/j.1464-5491.2011.03279.x
Muller-Sloof, E., de Laat, E., Zwanenburg, P., Wijlens, A., Vermeulen, H., Hummelink, S., & Ulrich, D. (2024). Exploring the definition of surgical wound dehiscence in literature: a Scoping Review. Journal of Tissue Viability, 33(4), 923–929. https://doi.org/10.1016/j.jtv.2024.09.006
Nair, P., Arunagiri, K., Tan, W., Suresh, R., & Lee, C. (2020). Preoperative lactate levels and risk of postoperative complications in peripheral arterial disease. Annals of Vascular Surgery, 66, 326–333.
Sandy‐Hodgetts, K., Carville, K., & Leslie, G. D. (2015). Determining risk factors for surgical wound dehiscence: a literature review. International Wound Journal, 12(3), 265–275. https://doi.org/10.1111/iwj.12088
Septiani, A. E., Rahardjo, S. S., & Prasetya, H. (2021). Meta-Analysis of Risk Factors for Lower Extremity Amputation in Diabetes Mellitus Patients with Foot Ulcers. Indonesian Journal of Medicine, 5(4), 343–355. https://doi.org/10.26911/theijmed.2020.5.4.355
ter Avest, E., Griggs, J., Wijesuriya, J., Russell, M. Q., & Lyon, R. M. (2020). Determinants of prehospital lactate in trauma patients: a retrospective cohort study. BMC Emergency Medicine, 20(1), 18. https://doi.org/10.1186/s12873-020-00314-1
Thorud, J. C., Plemmons, B., Buckley, C. J., Shibuya, N., & Jupiter, D. C. (2016). Mortality After Nontraumatic Major Amputation Among Patients With Diabetes and Peripheral Vascular Disease: A Systematic Review. The Journal of Foot and Ankle Surgery, 55(3), 591–599. https://doi.org/10.1053/j.jfas.2016.01.012
Yunir, E., Hidayah, C. D., Harimurti, K., & Kshanti, I. A. M. (2022). Three Years Survival and Factor Predicting Amputation or Mortality in Patients with High Risk for Diabetic Foot Ulcer in Fatmawati General Hospital, Jakarta. Journal of Primary Care & Community Health, 13, 21501319211063708. https://doi.org/10.1177/21501319211063707
Zhang, Y., Jordan, A., Schaffer, J. V., Brown, K., & Karim, R. (2021). Risk factors for wound complications after lower extremity amputations: A systematic review. Wound Repair and Regeneration, 29(2), 159–169.
Al‐Saadi, N., Al‐Hashimi, K., Popplewell, M., Fabre, I., Gwilym, B. L., Hitchman, L., Chetter, I., Bosanquet, D. C., & Wall, M. L. (2024). The incidence of surgical site infection following major lower limb amputation: A systematic review. International Wound Journal, 21(7), e14946. https://doi.org/10.1111/iwj.14946
Blaisdell, F. W. (2002). The Pathophysiology of Skeletal Muscle Ischemia and the Reperfusion Syndrome: A Review. Cardiovascular Surgery, 10(6), 620–630. https://doi.org/10.1177/096721090201000620
Bucataru, A., Balasoiu, M., Ghenea, A. E., Zlatian, O. M., Vulcanescu, D. D., Horhat, F. G., Bagiu, I. C., Sorop, V. B., Sorop, M. I., Oprisoni, A., Boeriu, E., & Mogoanta, S. S. (2023). Factors Contributing to Surgical Site Infections: A Comprehensive Systematic Review of Etiology and Risk Factors. Clinics and Practice, 14(1), 52–68. https://doi.org/10.3390/clinpract14010006
Campia, U., Gerhard-Herman, M., Piazza, G., & Goldhaber, S. Z. (2019). Peripheral Artery Disease: Past, Present, and Future. The American Journal of Medicine, 132(10), 1133–1141. https://doi.org/10.1016/j.amjmed.2019.04.043
Criqui, M. H., & Aboyans, V. (2015). Epidemiology of Peripheral Artery Disease. Circulation Research, 116(9), 1509–1526. https://doi.org/10.1161/CIRCRESAHA.116.303849
Dutronc, H., Gobet, A., Dauchy, F.-A., Klotz, R., Cazanave, C., Garcia, G., Lafarie-Castet, S., Fabre, T., & Dupon, M. (2013). Stump infections after major lower-limb amputation: A 10-year retrospective study. Médecine et Maladies Infectieuses, 43(11–12), 456–460. https://doi.org/10.1016/j.medmal.2013.09.003
Farber, A., & Eberhardt, R. T. (2016). The Current State of Critical Limb Ischemia. JAMA Surgery, 151(11), 1070. https://doi.org/10.1001/jamasurg.2016.2018
Fortington, L. V., Geertzen, J. H. B., van Netten, J. J., Postema, K., Rommers, G. M., & Dijkstra, P. U. (2013). Short and Long Term Mortality Rates after a Lower Limb Amputation. European Journal of Vascular and Endovascular Surgery, 46(1), 124–131. https://doi.org/10.1016/j.ejvs.2013.03.024
Fowkes, F. G. R., Aboyans, V., Fowkes, F. J. I., McDermott, M. M., Sampson, U. K. A., & Criqui, M. H. (2017). Peripheral artery disease: epidemiology and global perspectives. Nature Reviews Cardiology, 14(3), 156–170. https://doi.org/10.1038/nrcardio.2016.179
He, L., Yang, D., Ding, Q., Su, Y., & Ding, N. (2023). Association Between Lactate and 28-Day Mortality in Elderly Patients with Sepsis: Results from MIMIC-IV Database. Infectious Diseases and Therapy, 12(2), 459–472. https://doi.org/10.1007/s40121-022-00736-3
Husain, F. A., Martin, M. J., Mullenix, P. S., Steele, S. R., & Elliott, D. C. (2017). Serum lactate as a predictor of outcomes in surgical patients. Journal of Trauma and Acute Care Surgery, 62(4), 934–938. https://doi.org/10.1097/TA.0b013e3180330c9e
Ivashkiv, L. B. (2020). The hypoxia–lactate axis tempers inflammation. Nature Reviews Immunology, 20(2), 85–86. https://doi.org/10.1038/s41577-019-0259-8
Khalil, A. A., Aziz, F. A., & Hall, J. C. (2006). Reperfusion Injury. Plastic and Reconstructive Surgery, 117(3), 1024–1033. https://doi.org/10.1097/01.prs.0000204766.17127.54
Kolasiński, W. (2018). Surgical site infections- review of current knowledge, methods of prevention. Polish Journal of Surgery, 90(5), 1–7. https://doi.org/10.5604/01.3001.0012.7253
Kong, V., Ko, J., Narayanan, A., Hassan, S., Leow, P., Lim, J., Bruce, J., Laing, G., & Clarke, D. (2023). Serum lactate level is an independent predictor of mortality in cardiac stab wounds – A South African experience. Surgery in Practice and Science, 12, 100157. https://doi.org/10.1016/j.sipas.2023.100157
Krähenbühl, N. (1980). Blood Lactate Measurement in Peripheral Arterial Disease. In Lactate (pp. 174–180). Springer Berlin Heidelberg. https://doi.org/10.1007/978-3-642-67525-6_20
Kruse, O., Grunnet, N., & Barfod, C. (2011). Blood lactate as a predictor for in-hospital mortality in patients admitted acutely to hospital: a systematic review. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 19(1), 74. https://doi.org/10.1186/1757-7241-19-74
Kullo, I. J., & Rooke, T. W. (2016). Peripheral Artery Disease. New England Journal of Medicine, 374(9), 861–871. https://doi.org/10.1056/NEJMcp1507631
Kushimoto, S., Akaishi, S., Sato, T., Nomura, R., Fujita, M., Kudo, D., Kawazoe, Y., Yoshida, Y., & Miyagawa, N. (2016). Lactate, a useful marker for disease mortality and severity but an unreliable marker of tissue hypoxia/hypoperfusion in critically ill patients. Acute Medicine & Surgery, 3(4), 293–297. https://doi.org/10.1002/ams2.207
Li, X., Yang, Y., Zhang, B., Lin, X., Fu, X., An, Y., Zou, Y., Wang, J.-X., Wang, Z., & Yu, T. (2022). Lactate metabolism in human health and disease. Signal Transduction and Targeted Therapy, 7(1), 305. https://doi.org/10.1038/s41392-022-01151-3
Marcarelli, M., Trovato, L., Novarese, E., Riccio, M., & Graziano, A. (2017). Rigenera protocol in the treatment of surgical wound dehiscence. International Wound Journal, 14(1), 277–281. https://doi.org/10.1111/iwj.12601
Moxey, P. W., Gogalniceanu, P., Hinchliffe, R. J., Loftus, I. M., Jones, K. J., Thompson, M. M., & Holt, P. J. (2011). Lower extremity amputations - a review of global variability in incidence. Diabetic Medicine, 28(10), 1144–1153. https://doi.org/10.1111/j.1464-5491.2011.03279.x
Muller-Sloof, E., de Laat, E., Zwanenburg, P., Wijlens, A., Vermeulen, H., Hummelink, S., & Ulrich, D. (2024). Exploring the definition of surgical wound dehiscence in literature: a Scoping Review. Journal of Tissue Viability, 33(4), 923–929. https://doi.org/10.1016/j.jtv.2024.09.006
Nair, P., Arunagiri, K., Tan, W., Suresh, R., & Lee, C. (2020). Preoperative lactate levels and risk of postoperative complications in peripheral arterial disease. Annals of Vascular Surgery, 66, 326–333.
Sandy‐Hodgetts, K., Carville, K., & Leslie, G. D. (2015). Determining risk factors for surgical wound dehiscence: a literature review. International Wound Journal, 12(3), 265–275. https://doi.org/10.1111/iwj.12088
Septiani, A. E., Rahardjo, S. S., & Prasetya, H. (2021). Meta-Analysis of Risk Factors for Lower Extremity Amputation in Diabetes Mellitus Patients with Foot Ulcers. Indonesian Journal of Medicine, 5(4), 343–355. https://doi.org/10.26911/theijmed.2020.5.4.355
ter Avest, E., Griggs, J., Wijesuriya, J., Russell, M. Q., & Lyon, R. M. (2020). Determinants of prehospital lactate in trauma patients: a retrospective cohort study. BMC Emergency Medicine, 20(1), 18. https://doi.org/10.1186/s12873-020-00314-1
Thorud, J. C., Plemmons, B., Buckley, C. J., Shibuya, N., & Jupiter, D. C. (2016). Mortality After Nontraumatic Major Amputation Among Patients With Diabetes and Peripheral Vascular Disease: A Systematic Review. The Journal of Foot and Ankle Surgery, 55(3), 591–599. https://doi.org/10.1053/j.jfas.2016.01.012
Yunir, E., Hidayah, C. D., Harimurti, K., & Kshanti, I. A. M. (2022). Three Years Survival and Factor Predicting Amputation or Mortality in Patients with High Risk for Diabetic Foot Ulcer in Fatmawati General Hospital, Jakarta. Journal of Primary Care & Community Health, 13, 21501319211063708. https://doi.org/10.1177/21501319211063707
Zhang, Y., Jordan, A., Schaffer, J. V., Brown, K., & Karim, R. (2021). Risk factors for wound complications after lower extremity amputations: A systematic review. Wound Repair and Regeneration, 29(2), 159–169.
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