Page 21 - CASA Bulletin of Anesthesiology 2022; 9(5)

Vol. 9, No 5, 2022

The Role of Dexmedetomidine on Immunoregulation in Perioperative
Pain Management

Isabelle Yang MD, Jingping Wang MD, Ph.D.

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General
Hospital, Harvard Medical School.

Introduction

With growing concerns related to the opioid crisis, multimodal analgesia has been employed
increasingly in clinical settings over the last two decades. Multimodal analgesia is a strategy to
1, 2
use multiple drugs that act by different mechanisms along multiple sites of the nociceptive
pathway. Effective perioperative analgesia can be achieved via opioid-sparing or even opioid-
3, 4
free analgesia, though it may not always clinically necessary or appropriate.
5, 6
Common perioperative analgesic agents include opioids as well as non-opioid systemic
analgesics such as dexmedetomidine, ketamine, acetaminophen, non-steroidal anti-inflammatory
drugs, gabapentinoids, regional anesthesia, and local anesthetics administered intravenously or
by infiltration.

Among the potential perioperative analgesics, dexmedetomidine (DEX) has emerged as a
common alternative or adjunct to opioids. One unique advantage of DEX over opioids is its
beneficial effects on the immune system. Whereas the studied effects of opioids, primarily
morphine, have been shown to exhibit predominantly immunosuppressive effects, DEX has been
shown to have reduced immunosuppressive effects and even beneficial immunomodulatory
effects in pre-clinical studies. These observations raised the possibility that DEX is a superior
7
alternative to opioids in cases where intact immune response to surgical and other stressors is
beneficial such as cancer and sepsis.
8
Several pre-clinical studies have been performed on the effects of DEX on innate immune
function. DEX exerts effects on the immune system via several pathways, including directly via
alpha-2 adrenergic receptors which are found on many immune cells, indirectly through its
sympatholytic effects on the central and peripheral nervous system and the associated changes
with increased catecholamines, and indirectly through other cell signaling mechanisms. In
8
general, DEX is thought to preserve innate immunity through preserved natural killer cell
function, neutrophil function (chemotaxis, phagocytosis, and production of superoxide radicals),
and intact macrophage activation and function but decreased secretion of inflammatory
cytokines. However, more research is needed to test these observations in clinical studies.
9
Immune markers
A meta-analysis conducted by Wang et al in 2019 reviewed sixty-seven studies (including
fifty-nine randomized controlled trials (RCTs) and eight cohort studies) with 4842 patients
assessed, of which 2454 patients were in DEX groups and 2388 patients were in control (without
DEX) groups. Cardiac, abdominal, thoracic, spine, orthopedic, genitourinary, and other cancer
surgeries comparing DEX to placebo, propofol, morphine, hydromorphone, fentanyl, and
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