The Possible Pathophysiological Outcomes and Mechanisms of Tourniquet‐Induced Ischemia‐Reperfusion Injury during Total Knee Arthroplasty

Abstract

Ischemia and reperfusion (I/R) injury induced by tourniquet (TQ) application leads to the release of both oxygen free radicals and inflammatory cytokines. The skeletal muscle I/R may contribute to local skeletal muscle and remote organ damage affecting outcomes after total knee arthroplasty (TKA). The aim of the study is to summarize the current findings associated with I/R injury following TKA using a thigh TQ, which include cellular alterations and protective therapeutic interventions. The PubMed database was searched using the keywords “ischemia reperfusion injury,” “oxidative stress,” “tourniquet,” and “knee arthroplasty.” The search was limited to research articles published in the English language. Twenty-eight clinical studies were included in this qualitative review. Skeletal muscle I/R reduces protein synthesis, increases protein degradation, and upregulates genes in cell stress pathways. The I/R of the lower extremity elevates local and systemic oxidative stress as well as inflammatory reactions and impairs renal function. Propofol reduces oxidative injury in this I/R model. Ischemic preconditioning (IPC) and vitamin C may prevent oxygen free radical production. However, a high dose of N-acetylcysteine possibly induces kidney injury. In summary, TQ-related I/R during TKA leads to muscle protein metabolism alteration, endothelial dysfunction, oxidative stress, inflammatory response, and renal function disturbance. Propofol, IPC, and vitamin C show protective effects on oxidative and inflammatory markers. However, a relationship between biochemical parameters and postoperative clinical outcomes has not been validated.

The effect of tourniquet uses on total blood loss, early function, and pain after primary total knee arthroplasty

“…Tourniquet use may weaken quadriceps because of muscle damage resulting from tourniquet-induced ischaemia or direct compressive injury. 33 The higher postoperative pain with a tourniquet may also prevent greater use of quadriceps, keeping them weak. Our results are consistent with previous work linking tourniquet use in TKA to 20% lower quadriceps muscle volume at one month postoperatively, as well as lower quadriceps strength for up to three months postoperatively.…”

Tourniquet use in routine primary total knee arthroplasty is associated with a higher transfusion rate and longer postoperative length of stay: a real-world study

“…Previous studies [9,10] suggested that use of a tourniquet in TKA decreases the thigh and quadriceps muscle volumes and delays the postoperative recovery of knee function, which may be correlated with ischemia-reperfusion injury caused by a tourniquet. Several previous studies showed that ischemia-reperfusion injury in human skeletal muscle accompanied by the full release of oxygen free radicals and inflammatory cytokines could reduce protein synthesis and increase protein degradation by triggering cascades of cellular processes, which include inhibiting the protein synthesis pathway of cap-dependent translation initiation and elongation, and upregulating the ubiquitin proteasome system, one of the important pathways of skeletal muscle proteolysis [26][27][28]. Besides this, tourniquet use in TKA may be related to increased postoperative knee pain and swelling.…”

<p>Protective Effects of Rocuronium Bromide on Ischemia-Reperfusion Injury in Skeletal Muscle Induced by Tourniquet in Patients Undergoing Elective Unilateral Total Knee Arthroplasty: A Prospective, Double Blind, Randomized, Controlled Study</p>

“…Radical oxygen species (ROS) form polyunsaturated fatty acids or lipoproteins through lipid peroxidation, which destroys the normal structure of the cytomembrane, and results in ischemiareperfusion injury (IRI). 8 Malondialdehyde (MDA) is one of the end-products of lipid peroxidation, which can indirectly reflect the production of ROS, and is an objective index to reflect the degree of lipid peroxidation and ischemia-reperfusion injury in the organism. 9 It is difficult to directly measure enzyme-generated NO in vivo, and generally, the production of NO can be indirectly reflected by measuring NOS.…”