Page 22 - CASA Bulletin of Anesthesiology 2022; 9(5)

CASA Bulletin of Anesthesiology

midazolam were included. It demonstrated that perioperative DEX was associated with
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decreased release of epinephrine, norepinephrine, cortisol, and glucose; decreased concentrations
of IL-6, TNF-a, CRP, and increased concentration of IL-10. Recently published RCTs further
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supported the notion that DEX has a predominantly anti-inflammatory effect. 11,12 One RCT
among patients undergoing posterior lumbar interbody fusion compared the post-operative
effects of fentanyl versus fentanyl and DEX on T cell function. It found higher levels of T helper
1 (Th1) cells, which suggested intact cell-mediated immunity, and higher levels of regulatory T
(Treg) cells which are known to secrete anti-inflammatory cytokines. Another study comparing
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intraoperative and postoperative DEX versus placebo on natural killer cell function among
uterine cancer patients found increased IFN-γ in the DEX group. These results were surprising
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as DEX was previously associated with decreased IFN-γ, and authors postulate these unexpected
findings may be due to the tumor environment created by invasive cervical carcinoma. Another
study among healthy patients undergoing laparoscopic cholecystectomy found a dose-dependent
inverse relationship between DEX and CRP, suggesting that its anti-inflammatory effect may be
titratable.
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Immune Cells

Wang et al. meta-analysis demonstrated that DEX was associated with higher NK cell
expression or count. Another RCT study among patients with lung cancer comparing
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flurbiprofen versus flurbiprofen and DEX found similar results with higher NK cell count in the
flurbiprofen and DEX group. Among patients with uterine cancer, no significant difference in
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NK cell activity was detected. In terms of monocyte function, an RCT study among patients in
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ASA category 1 or 2 undergoing multilevel spinal fusion found decreased levels of secreted
cytokines associated with inflammation and increased levels of secreted cytokines associated
with intact immune function in the DEX group, but less is known about DEX’s effects on
monocyte phagocytosis and antigen presentation. In Wang et al. meta-analysis and other RCTs
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among patients in ASA category 1 or 2, patients with oral cancer, and patients with colon cancer,
use of perioperative DEX was also associated with increased Th1:Th2 ratio and increased
CD4+:CD8+ ratio, consistent with intact host ability to launch cell-mediated immune
defenses. 10,11,14,16,17 In Lee et al. study among healthy patients undergoing laparoscopic
cholecystectomy, investigators found that higher doses of intraoperative DEX were associated
with higher IFN-γ/IL-4 ratio (surrogate for Th1:Th2 ratio), and higher IL-17/IL-10 ratio
(surrogate for Th17:Treg ratio, which can be interpreted as a marker of immune balance similar
to Th1:Th2), suggesting that the immunomodulatory effects may be titratable. DEX may have
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beneficial immunomodulatory role in offsetting the effect of surgical trauma, which has been
associated with a decrease the Th1:Th2 ratio, and that undesired immunomodulatory effects of
DEX may be able to be titrated in a dose-dependent manner. 18,19 However, the mechanism behind
alpha-2 agonists’ effects on immunomodulation of the Th1:Th2 ratio and the Th17:Treg ratio is
still unclear.

Wang et al. meta-analysis found that DEX was associated with increased expression of B
cells. However, a more recent study found no difference in B lymphocyte count in the DEX
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group vs control, suggesting that while cellular adaptive immunity is more preserved, there is a
smaller or no observed difference in humoral immunity. Further investigation is needed to
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understand the effect of DEX on adaptive humoral immunity.

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