Abstract
Introduction: Ischaemia-reperfusion-injury (IRI) is one of the most common metabolic insults in orthopaedic practice. It is often a mild insult after brief tourniquet use with minimal clinical implications; but much more severe insults may result from excessive tourniquet-times, vascular trauma or release of compartment-syndrome. It is mediated largely by oxidatively-induced endothe-lial disruption and leukocyte infiltration. Antioxidants attenuate or prevent this effect in animal models.
Hypothesis: That IRI can be attenuated using established antioxidant medications (ascorbate and n-acetyl-cysteine) in the controlled setting of elective knee arthroscopy.
Methods: A EudraCT registered, prospective, randomized-controlled trial was performed. Patients (n=24) undergoing elective knee arthroscopy were randomized to one of 3 groups (IV NAC/oral ascorbate/placebo). Full blood counts, a broad array of cytokines and adhesion molecules, physiological response, pain scores and analgesia were recorded pre-operatively and at 3 postoperative time-points (10mins, 2hours, 4hours).
Results: Physiological response, analgesia and VAS did not differ. Systemic leukocytes and neutrophils were increased (p=0.001) indicating a measurable reperfusion injury. Ascorbate tended to inhibit ICAM-1 (p=0.10) and IFN-gamma (p=0.080). NAC inhibited VCAM-1 (p=0.003) and tended to inhibit ICAM-1 (p=0.094). Selectins responded in a similar pattern but not significantly. NAC tended to increase circulating leukocytes (0.093), neutrophils (0.12) and monocytes (0.04) and also induced a transient early increase in IFN-gamma (p=0.022).
Conclusions: Elevated circulating leukocytes indicate reduced leukocyte trapping and infiltration due to reduced adhesion molecule expression. NAC attenuates IRI resulting from tourniquet use in knee arthroscopy. The study was underpowered to confirm the efficacy of ascorbate in this setting. Further studies are necessary on the effects of these substances in more extreme ischaemic insults in which they may confer significant local and systemic benefits for the patient. Ascorbate and NAC act at different points in the inflammatory cascade and their potential synergistic effects warrant investigation.
The abstracts were prepared by Mr Matt Costa and Mr Ben Ollivere. Correspondence should be addressed to Mr Costa at Clinical Sciences Research Institute, University of Warwick, Clifford Bridge Road, Coventry CV2 2DX, UK.
