Tourniquet-induced ischemia creates increased risk of organ dysfunction and mortality following delayed limb amputation

Cassie J Rowe; Sarah A Walsh; Andrea H Dragon; Alisha M Rhodes; Olivia L Pak; Elsa Ronzier; Benjamin Levi; Benjamin K Potter; Philip J Spreadborough; Thomas A Davis

doi:10.1016/j.injury.2023.02.047

Tourniquet-induced ischemia creates increased risk of organ dysfunction and mortality following delayed limb amputation

Injury. 2023 Mar 4:S0020-1383(23)00179-1. doi: 10.1016/j.injury.2023.02.047. Online ahead of print.

Authors

Affiliations

¹ Department of Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, United States; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, United States.
² Department of Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, United States.
³ Center for Organogenesis Research and Trauma, University of Texas Southwestern, Dallas, TX, United States.
⁴ Department of Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, United States; Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine, Birmingham, United Kingdom.
⁵ Department of Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, United States. Electronic address: thomas.davis@usuhs.edu.

PMID: 36906480
DOI: 10.1016/j.injury.2023.02.047

Abstract

Tourniquets are critical for the control of traumatic extremity hemorrhage. In this study, we sought to determine, in a rodent blast-related extremity amputation model, the impact of prolonged tourniquet application and delayed limb amputation on survival, systemic inflammation, and remote end organ injury. Adult male Sprague Dawley rats were subjected to blast overpressure (120±7 kPa) and orthopedic extremity injury consisting femur fracture, one-minute soft tissue crush injury (20 psi), ± 180 min of tourniquet-induced hindlimb ischemia followed by delayed (60 min of reperfusion) hindlimb amputation (dHLA). All animals in the non-tourniquet group survived whereas 7/21 (33%) of the animals in the tourniquet group died within the first 72 h with no deaths observed between 72 and 168 h post-injury. Tourniquet induced ischemia-reperfusion injury (tIRI) likewise resulted in a more robust systemic inflammation (cytokines and chemokines) and concomitant remote pulmonary, renal, and hepatic dysfunction (BUN, CR, ALT. AST, IRI/inflammation-mediated genes). These results indicate prolonged tourniquet application and dHLA increases risk of complications from tIRI, leading to greater risk of local and systemic complications including organ dysfunction or death. We thus need enhanced strategies to mitigate the systemic effects of tIRI, particularly in the military prolonged field care (PFC) setting. Furthermore, future work is needed to extend the window within which tourniquet deflation to assess limb viability remains feasible, as well as new, limb-specific or systemic point of care tests to better assess the risks of tourniquet deflation with limb preservation in order to optimize patient care and save both limb and life.

Keywords: Blast; Extremity trauma; Inflammation; Ischemia reperfusion injury; Multi-organ dysfunction; Rat; Rattus norvegicus; Tourniquet.