Real-time Evaluation of the Independent Analgesic Efficacy of Dexmedetomidine

XiaoHua Wang; SiYuan Zhang; Chunxiu Wang; Yi Huang; Hao Wu; Guoguang Zhao; TianLong Wang


BMC Anesthesiol. 2023;23(68) 

In This Article

Abstract and Introduction


Background: Dexmedetomidine has analgesic properties, but the intraoperative analgesic effect of dexmedetomidine is often masked by the effects of other general anaesthetics. Therefore, the degree to which it reduces intraoperative pain intensity remains unclear. The objective of this double-blind, randomised controlled trial was to evaluate the independent intraoperative analgesic efficacy of dexmedetomidine in real-time.

Methods: This single-centre study enrolled 181 patients who were hospitalised for below-knee orthopaedic surgeries between 19 January 2021 to 3 August 2021 were eligible for this is single-centre study. Peripheral neural block was performed on patients scheduled for below-knee orthopaedic surgeries. Patients were randomly assigned to the dexmedetomidine or midazolam group and were intravenously administered with 1.5 μg kg−1 h−1 dexmedetomidine or 50 μg kg−1 h−1 midazolam, respectively. The analgesic efficacy was evaluated using the real-time non-invasive nociception monitoring. The primary endpoint was the attainment rate of the nociception index target. The secondary endpoints included the occurrence of intraoperative hypoxemia, haemodynamic parameters, the consciousness index, electromyography and patient outcomes.

Results: On Kaplan–Meier survival analysis, the defined nociception index target was attained in 95.45% and 40.91% of patients receiving dexmedetomidine and midazolam, respectively. Log-rank analysis revealed that the dexmedetomidine group attained the nociception index target significantly faster and the median attainment time of the nociception index target in the dexmedetomidine group was 15 min. Dexmedetomidine group was associated with a significantly lower incidence of hypoxemia. There was no significant difference in blood pressure between the dexmedetomidine and midazolam groups. Further, the dexmedetomidine group had a lower maximum visual analogue scale score and lower analgesic consumption postoperatively.

Conclusions: Dexmedetomidine has independent analgesia and systemically administered as an adjuvant agent has better analgesic efficacy than midazolam without severe side effects.

Trial Registration: Registry Identifier: NCT-04675372. Registered on 19/12/2020.


Dexmedetomidine (DEX), a highly selective a2-adrenoreceptor agonist, is a relatively new adjuvant drug with sympatholytic, anxiolytic and analgesic properties.[1] As a key adjuvant of multimodal analgesia, DEX can significantly enhance the analgesic effect of general anaesthetics even at a low dose and can effectively inhibit opioid pain hypersensitivity and analgesic tolerance.[2] Furthermore, DEX has the beneficial property of an analgesia-sparing effect.[3] Moreover, it provides good intraoperative analgesia, reduces postoperative pain and opioid requirements, helps attain stable haemodynamic conditions and has minimal side effects.[4] It is widely used in clinical practice for its analgesic effect.[5] However, the intraoperative analgesic effect of DEX is often masked by the effects of other general anaesthetics. Therefore, the degree to which DEX reduces intraoperative pain intensity remains unclear, and its adverse effects during the maintenance period have not been fully elucidated.

Patients hospitalised for fractures have a high risk of pain and anxiety.[6] Pain can accentuate the body's stress response and adversely affect endocrine and immune functions.[7,8] Peripheral neural block (PNB) is the preferred technique and standard of anaesthesia care for below-knee orthopaedic surgeries. The systemically administered DEX as an adjuvant analgesic during PNB can prevent disturbances from other general anaesthetics, act on distinct pharmacologic sites and exhibit its independent anti-nociceptive effect.

Another challenge in analgesia is objectively monitoring the analgesia level in real-time to evaluate pain in an unconscious patient. Most trials have been limited by the use of visual analogue scales to evaluate the level of analgesia; however, this is subjective and cannot be used in deeply sedated patients. Our recent studies have shown that the nociception index (IOC2, namely qNOX), a new real-time monitoring index, responds to external noxious stimuli and thus allows us to objectively evaluate analgesic effects and pain intensity in patients under general anaesthesia.[9–12]

This study aimed to quantitatively evaluate the analgesic effects of DEX using IOC2 by determining the rate and time required to attain the target IOC2 (i.e. mean optimal analgesia) in patients who underwent below-knee orthopaedic surgery. Further, the safety and postoperative efficacy of DEX were assessed.