Effects of Different Doses of Esketamine on Pain Sensitivity of Patients Undergoing Thyroidectomy: A Randomized Controlled Trial

Introduction: Several factors may lead to increased postoperative pain sensitivity, of which remifentanil-induced hyperalgesia (RIH) is one of the main factors. High-dose remifentanil exposure during anesthesia may induce RIH. Esketamine may prevent RIH by antagonizing N-methyl-D-as-partate (NMDA) receptors, thereby reducing the postoperative pain sensitivity. This study examined the effects of different esketamine doses on pain sensitivity in patients undergoing thyroidectomy and determined the optimal dose.Methods: This study included 117 patients who received elective thyroidectomy. They were randomized into four groups: saline group (group C), esketamine 0.2 mg center dot kg(-1) group (group RK1), esketamine 0.4 mg center dot kg(-1) group (group RK2), and esketamine 0.6 mg center dot kg(-1) group (group RK3). Five minutes before anesthesia induction, the same volume of study drugs were injected respectively in groups C, RK1, RK2, and RK3. Remifentanil was pumped at the same rate of 0.3 lg center dot kg(-1)center dot min(-1) during surgery to ensure uniformity. This study's primary outcomes were the mechanical pain thresholds measured before surgery, as well as at 30 min, 6 h, 24 h, and 48 h after surgery. Hyperalgesia, rescue analgesia, numerical rating scale (NRS) score, and adverse reactions were recorded.Results: Compared with baseline, the mechanical pain threshold was significantly decreased in group C [(94.67 +/- 22.85) versus (112.00 +/- 36.62) versus (161.33 +/- 53.28) g, P < 0.001 at 30 min, P < 0.001 at 6 h] and group RK1 [(102.86 +/- 24.17) versus (114.29 +/- 41.05) versus (160.00 +/- 54.98) g, P < 0.001 at 30 min, P < 0.001 at 6 h] around the surgical incision, and in group C [(112.00 +/- 31.78) versus (170.67 +/- 56.26) g, P < 0.001 at 30 min, (118.67 +/- 34.42) versus (170.67 +/- 56.26) g, P = 0.001 at 6 h] and group RK1 [(114.29 +/- 45.17) versus (175.71 +/- 54.80) g, P = 0.001 at 30 min, (121.43 +/- 38.46) versus (175.71 +/- 54.80) g, P = 0.002 at 6 h] on the forearm at 30 min and 6 h after surgery; compared with group C, the mechanical pain threshold was higher in group RK2 [(142.76 +/- 50.06) versus (94.67 +/- 22.85) g, P < 0.001 at 30 min, (145.52 +/- 49.83) versus (112.00 +/- 36.62) g, P < 0.001 at 6 h] and group RK3 [(140.00 +/- 40.68) versus (94.67 +/- 22.85) g, P < 0.001 at 30 min, (150.67 +/- 56.50) versus (112.00 +/- 36.62) g, P = 0.010 at 6 h] around the surgical incision, and in group RK2 [(149.66 +/- 39.50) versus (112.00 +/- 31.78) g, P = 0.006 at 30 min, (156.55 +/- 47.23) versus (118.67 +/- 34.42) g, P = 0.005 at 6 h] and group RK3 [(145.33 +/- 51.18) versus (112.00 +/- 31.78) g, P = 0.018 at 30 min, (154.67 +/- 47.54) versus (118.67 +/- 34.42) g, P = 0.008 at 6 h] on the forearm at 30 min and 6 h after surgery. Group RK3had more glandular secretions than the other three groups (P = 0.042).Conclusions: Intravenous injection of esketamine 0.4 mg center dot kg(-1) before anesthesia induction is a suitable dose to reduce pain sensitivity in patients undergoing thyroidectomy without increasing adverse reactions. However, future research needs to be extended to other populations. Trial Registration: Registered at the Chinese Clinical Trials Registry http://www.chictr.org. cn/ (09/06/2022, ChiCTR-2200060741).

Automated summary

This study investigated the effects of different doses of esketamine on pain sensitivity in patients undergoing thyroidectomy. It was found that the dose of 0.4 mg/kg of esketamine reduced pain sensitivity without increasing adverse reactions. Preoperative administration of esketamine can effectively alleviate postoperative pain sensitivity.