Intra-articular administration of dexmedetomidine (DEX) improved pain outcomes in the early postoperative period after knee arthroscopy

Arthroscopic knee surgery is a surgical procedure that can diagnose and treat problems in the knee joint. Patients with knee pain are managed on a day-case basis; therefore, appropriate postoperative pain relief is critical to facilitate patient discharge and early recovery. A simple method to treat knee joint pain providing prolonged duration of action, and minimal adverse effects is in demand.

It was well reported in the previous studies that systemic administration of DEX produces sedative, analgesic, sympatholytic, and anesthetic-sparing effects. It was also suggested that DEX alone or in combination with already marketed anesthetics drugs significantly reduce the postoperative pain without any adverse events. A study conducted on the combination of DEX and local anesthetic agent demonstrate this an ideal combination for relief of pain after knee arthroscopy.

A critical literature search found no published meta-analysis investigating the effects of intra-articular administration of DEX on postoperative pain after arthroscopic knee procedures. Therefore, the present study was conducted to determine the benefits and adverse effects of intra-articular administration of DEX in arthroscopic knee surgery.

Rationale behind the research:

To the author’s knowledge, there are no published meta-analyses investigating the effects of DEX on postoperative pain after arthroscopic knee procedures.

Therefore, the author designed this research to determine the effect of DEX on the postoperative pain after knee surgery.

Objective:

To evaluate the analgesic effects of intra-articular (DEX in arthroscopic knee surgery. 

Study outcome measures:

• Primary endpoints: Postoperative pain and cumulative opioid consumption.
• Secondary endpoints: Time to first request for postoperative analgesia and incidence of PONV, hypotension, bradycardia, or somnolence.

Quality assessment: The methodological quality was assessed with the Cochrane risk of bias tool. The quality of evidence for each outcome measure was evaluated with Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.

Time period:  At rest, 1, 2, 4, 6, 8, 12, and 24 h

Study Outcomes:

• There were significant reduction in postoperative pain intensity at rest (1 h, 2-24h postoperatively: WMD, −1.57 [95% CI −1.94 to −1.20]; P = 0.0001) in patients treated with intra-articular DEX monotherapy or a combination of DEX and local anesthetic when compared to saline or local anesthetic alone. The findings were robust with publication bias demonstrated by sensitivity analysis and funnel plot respectively.
• There was a significant reduction observed in opioid consumption at postoperative 0–24 h, opioid consumption with a WMD of −8.54 mg morphine-equivalents in patients treated with intra-articular DEX monotherapy or a combination of DEX and local anesthetic when compared to saline or local anesthetic alone. The findings were robust with no evidence of publication bias when demonstrated by sensitivity analysis and funnel plot respectively.
• The time for postoperative analgesia increased in patients treated with intra-articular DEX or a combination of DEX and local anesthetic compared to saline or local anesthetic alone (WMD=257.57min). The findings were robust with publication bias when demonstrated by sensitivity analysis and funnel plot respectively.

This meta-analysis revealed that intra-articular DEX significantly decreases postoperative pain and opioid consumption. The findings of this study also established the prolonged analgesic effect of DEX. Concerning the secondary outcomes, no difference was found in the incidence of PONV, hypotension, or bradycardia between the DEX and control groups.

The previous study conducted by Al-Metwalli et al. had shown that patients treated with intra-articular and intra venous saline reported pain intensity of 5 points on a VAS up to 12 h postoperatively. That resulted in delayed patient discharge and postoperative rehabilitation. Due to the adverse effects associated with systemic opioid use, administration of intra-articular analgesia is simple and may provide a better alternative.

In this meta-analysis, DEX treatment decreased VAS pain scores by 1.57 points at rest and 1.71 points on movement at postoperative 1 h. At 24 h the postoperative pain was more dropped to 0.34 points, but the difference remained significant.

The mechanism underlying the effects of intra-articular DEX is unknown. A recent study has demonstrated that combination of clonidine and DEX prolonged sensory and motor blockade by local anesthetics. Similar to clonidine, it was reported that DEX acts on presynaptic receptors and inhibits the release of norepinephrine at peripheral afferent nociceptors. Some of the studies also suggest that DEX acts by direct inhibition of tetrodotoxin-resistant sodium (Na+) channels may contribute to the antinociceptive effects of clonidine and DEX when used in addition to local anesthesia. Another study indicated that DEX inhibited neuronal delayed-rectifier potassium currents and sodium currents to produce local anesthetic effects.

In this meta-analysis, intra-articular DEX did not increase the incidence of hypotension or bradycardia compared to that in the control group. The low incidence of adverse effects may be related to the lack of vessels in the articular surface, and the relatively small dose of DEX administered.

In conclusion, intra-articular administration of DEX improved pain outcomes in the early postoperative period after knee arthroscopy.