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General Orthopaedics

N-ACETYL-CYSTEINE ATTENUATES ISCHAEMIA REPERFUSION INJURY: A PROSPECTIVE, RANDOMISED CONTROLLED TRIAL

Combined Irish Orthopaedic Association, Welsh Orthopaedic Association, Scottish Orthopaedic Association (IOA, WOA, SOA)



Abstract

Introduction

Ischaemia reperfusion injury (IRI) is a very common metabolic insult in orthopaedics. It is often a subtle clinical event such as after brief tourniquet use, however severe injury, even multi-organ failure or death may result from prolonged tourniquet-use, crush injuries, vascular trauma or the release of compartment-syndrome. IRI is mediated by leukocyte infiltration and oxidatively-induced endothelial disruption. Antioxidants clearly attenuate or prevent this effect in animal models.

Hypothesis

That the antioxidant medications ascorbate and n-acetyl-cysteine attenuate IRI in the setting of elective knee arthroscopy.

Methods & Materials

A EudraCT-registered, prospective, randomized-controlled trial was performed. Patients undergoing elective knee arthroscopy (n=24) were randomized to one of 3 groups (IV NAC/oral ascorbate/placebo). Full blood counts, cytokines, adhesion molecules, physiological response, pain scores and analgesia were recorded pre-operatively and at 3 post-operative time-points.

Results

Physiological response, analgesia and VAS did not differ. NAC inhibited VCAM-1 (p=0.003) and tended to inhibit ICAM-1 (p=0.094). NAC tended to increase circulating leukocytes (p=0.093), neutrophils (p=0.12) and monocytes (p=0.04) and also induced a transient early increase in IFN-gamma (p=0.022).

Conclusions

NAC attenuates the IRI resulting from tourniquet use in elective knee arthroscopy by apparently reducing adhesion molecule expression and leukocyte trapping in the post-ischaemic limb. The potential systemic benefits of NAC warrant further study in the setting of a more extensive ischaemic insult.