Sedative and Immunosuppressive Effects of Dexmedetomidine in Transplantation

Abstract

Dexmedetomidine, an α2-adrenergic receptor agonist, is used as an anti-anxiety medication. It exerts a cholinergic effect, thereby reducing the release of tumor necrosis factor alpha (TNF-α). We hypothesized that the use of dexmedetomidine as a sedative agent in transplantation would also protect allografts. We examined our patients who underwent living donor liver transplantation. Subsequently, we generated a series of mouse models to investigate the effect of dexmedetomidine on sedation-based tolerance post transplantation. A total of 49 liver recipients were enrolled in this study, of which 23 (47%) were administered dexmedetomidine through 24 h infusion on postoperative day 1. A trend toward the improvement of hepatocyte injury along with better liver function was observed in the dexmedetomidine-treated group during the first postoperative week. In animal models, dexmedetomidine inhibited the proliferation of CD4+ and CD8+ T cells and TNF-α production in a dose-dependent manner. We used dexmedetomidine to treat skin-transplanted mice and observed a significantly prolonged graft survival in mice that were administered a higher dose of dexmedetomidine. Our results revealed that dexmedetomidine exerts a dual effect of sedation and immunosuppression. This light-sedation approach will not only make patients calmer in the intensive care unit but also protect allografts from injury.

Effect of dexmedetomidine on liver transplantation: a meta-analysis

“…No new clinical trial was found after searching the clinical trial registration platform ClinicalTrial.gov and WHO ICTRP. Finally, nine studies were included in the meta-analysis, with a total of 648 participants ( Choi et al, 2016 ; Fayed et al, 2016 ; Sayed and Yassen, 2016 ; Xu et al, 2016 ; Lee et al, 2020 ; Lee et al, 2021 ; Ustun et al, 2021 ; Zhang et al, 2021 ; Zhang et al, 2022 ). See Figure 1 for the combined search results.…”

Reno-protective effects of perioperative dexmedetomidine in kidney transplantation: a systematic review and meta-analysis of randomized controlled trials

“…Some studies reported a decrease in the incidence of acute kidney injury [ 20 , 45 , 46 ], while others reported no renal benefits of its use [ 55 , 61 , 62 ]. Perioperative DEX in liver transplantation decreased the IRI and improved graft outcomes through its sedative and immunosuppressive effects [ 63 ].…”

Dexmedetomidine ameliorates liver injury and maintains liver function in patients with hepatocellular carcinoma after hepatectomy: a retrospective cohort study with propensity score matching

“…DEX, a widely used sedative during surgery, was approved for sedation and analgesia by the United States Drug and Food Administration in 1999 (7). Owing to its excellent advantages of sedation, analgesia, antianxiety, inhibition of sympathetic nervous excitation, cardiovascular stabilization, and prevention of postoperative delirium, DEX has been widely used in clinical anesthesia and the ICU (8,10,27,28). The contraindications of DEX mainly include 1) patients allergic to DEX, 2) pregnant, lactating women, and patients with severe heart block.…”

“…Another meta-analysis reported that perioperative DEX infusion inhibited the release of epinephrine, norepinephrine, and cortisol and decreased the levels of blood glucose, interleukin (IL)-6, tumor necrosis factor-a (TNF-a), and CRP (5). In addition, the immune function was improved (5,28,32). Li et al ( 27) also systematically reviewed the anti-inflammatory effects of perioperative DEX administration as an adjunct to general anesthesia in 15 clinical trials and reported significant decreases in the serum levels of IL-6, IL-8, and TNF-a after DEX use.…”