Effects of dexmedetomidine on inflammatory mediators after tourniquet-induced ischemia-reperfusion injury: a randomized, double-blinded, controlled study

Minerva Anestesiol. 2019 Mar;85(3):279-287. doi: 10.23736/S0375-9393.18.13015-X. Epub 2018 Sep 10.

Abstract

Background: Tourniquet use during total knee arthroplasty (TKA) produces ischemia-reperfusion injury (IRI), with systemic release of inflammatory cytokines and reactive oxygen species upon tourniquet release. We conducted a randomized, placebo-controlled, double-blind trial to examine whether dexmedetomidine (DEX) as an adjunct during general anesthesia in patients undergoing unilateral TKA could attenuate the rise in inflammatory cytokines and oxidative stress.

Methods: Sixty-eight patients were randomized to either the control or DEX group. DEX was administered at a loading dose of 0.5 μg/kg, followed by an infusion of 0.4 μg/kg/h. We measured serum levels of malondialdehyde (biomarker of oxidative stress) and proinflammatory cytokines (interleukin-6 [IL-6] and tumour necrosis factor-α [TNF-α]) preinduction (baseline), 60 and 90 min post-tourniquet release. We also assessed hemodynamics, intraoperative remifentanil consumption, and postoperative pain scores and analgesic consumption.

Results: Malondialdehyde was higher than baseline after tourniquet release in both groups (P≤0.001), but the levels were similar between groups at all times. TNF-α was significantly higher than baseline at 60 min post-tourniquet release only in the control group (P=0.009). Serum IL-6 increased significantly above baseline at 60 and 90 min post-tourniquet release in both groups (P<0.001). At 90 min, IL-6 was significantly lower in the dexmedetomidine group than in the control group (P=0.049). Remifentanil consumption, heart rate, and pain scores were significantly lower in the dexmedetomidine group.

Conclusions: Our results suggest that dexmedetomidine as an adjunct to general anesthesia attenuated the rise in proinflammatory cytokines, providing protective effects in tourniquet-induced IRI.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anesthesia, General*
  • Dexmedetomidine / pharmacology*
  • Dexmedetomidine / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects*
  • Postoperative Complications / etiology*
  • Postoperative Complications / prevention & control*
  • Reperfusion Injury / etiology*
  • Reperfusion Injury / prevention & control*
  • Tourniquets / adverse effects*
  • Tumor Necrosis Factor-alpha / blood*
  • Tumor Necrosis Factor-alpha / drug effects*

Substances

  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Dexmedetomidine