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

Tizanidine is a centrally acting a2 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; I-2 = 97%) and (MD: -1.76; 95% CI: -4.06, 0.53; P = 0.13; I-2 = 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 I-2 = 0%). Although dry mouth was significantly more in the tizanidine group (MD: 5.35; 95% CI: 1.72, 16.62; P = 0.004; I-2 = 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.