Efficacy and safety of oral tizanidine premedication as pre-emptive analgesia in adult patients undergoing elective surgeries- A systematic review

Abstract

Tizanidine is a centrally acting α2 agonist which has been used as a premedication due to its opioid-sparing and sympatholytic properties. This systematic review assessed the safety and feasibility of oral tizanidine. After registering the protocol with PROSPERO (CRD42022368546), randomized controlled trials and non-randomized observational studies were searched in various databases. The primary outcome was intraoperative opioid use; the secondary outcomes were 24-hr opioid consumption, pain scores, time to rescue analgesia, and adverse events. The risk of bias scale was used to assess the quality of evidence. Out of 202 studies identified, five studies fulfilled the inclusion criteria. Intraoperative opioid consumption was significantly less in the tizanidine group (MD: -2.40; 95% CI: -4.22, -0.59; P = 0.010; I² = 0 %). The 24-hr opioid consumption was comparable between both groups (MD: -42.53, 95% CI: -91.45, 6.39; P = 0.09; I² = 99%). Time to rescue analgesia was comparable between both groups (MD: 308.22; 95% CI: -263.67, 880.11, P = 0.29, I² = 100%). Pain scores at 6 and 12 hours were comparable (MD: -1.37; 95% CI: -3.68, 0.94; P = 0.24; I² = 97%) and (MD: -1.76; 95% CI: -4.06, 0.53; P = 0.13; I² = 95%); however, at 24 hours the scores were better in the tizanidine group (MD: -1.10; 95% CI: -1.50, -0.69; P < 0.0001 I² = 0%). Although dry mouth was significantly more in the tizanidine group (MD: 5.35; 95% CI: 1.72, 16.62; P = 0.004; I² = 0%), postoperative nausea/vomiting and dizziness were comparable. Tizanidine reduces intraoperative opioid consumption without significant adverse events. However, it does not provide effective opioid-sparing analgesia or reduced opioid requirement in the first 24 hours after surgery.

Keywords: Acute pain; meta-analysis; postoperative pain; systematic review; tizanidine.

Figure 1

PRISMA flowchart

Figure 2

(a) Traffic light plot. (b) Summary plot

Figure 3

(a) Forest plot showing comparison of intraoperative opioid consumption. (b) Forest plot showing comparison of 24-hour opioid consumption. (c) Forest plot showing comparison of time to rescue analgesia

Figure 4

(a) Forest plot showing comparison of pain scores at 6 hours. (b) Forest plot showing comparison of pain scores at 12 hours. (c) Pain scores at 24 hours

Figure 5

(a) Forest plot showing comparison of postoperative nausea/vomiting. (b) Forest plot showing comparison of dizziness. (c) Forest plot showing comparison of dry mouth