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

Abstract

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-aspartate (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. This study included 117 patients who received elective thyroidectomy. They were randomized into four groups: saline group (group C), esketamine 0.2mg·kg-1 group (group RK1), esketamine 0.4mg·kg-1 group (group RK2), and esketamine 0.6mg·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 0.3µg·kg-1·min-1 during surgery to ensure uniformity. This study's primary outcomes were the mechanical pain thresholds measured before surgery, as well as at 30min, 6h, 24h, and 48h after surgery. Hyperalgesia, rescue analgesia, numerical rating scale (NRS) score, and adverse reactions were recorded. 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 30min, P < 0.001 at 6h] and group RK1 [(102.86 ± 24.17) versus (114.29 ± 41.05) versus (160.00 ± 54.98) g, P < 0.001 at 30min, P < 0.001 at 6h] around the surgical incision, and in group C [(112.00 ± 31.78) versus (170.67 ± 56.26) g, P < 0.001 at 30min, (118.67 ± 34.42) versus (170.67 ± 56.26) g, P = 0.001 at 6h] and group RK1 [(114.29 ± 45.17) versus (175.71 ± 54.80) g, P = 0.001 at 30min, (121.43 ± 38.46) versus (175.71 ± 54.80) g, P = 0.002 at 6h] on the forearm at 30min and 6h 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 30min, (145.52 ± 49.83) versus (112.00 ± 36.62) g, P < 0.001 at 6h] and group RK3 [(140.00 ± 40.68) versus (94.67 ± 22.85) g, P < 0.001 at 30min, (150.67 ± 56.50) versus (112.00 ± 36.62) g, P = 0.010 at 6h] around the surgical incision, and in group RK2 [(149.66 ± 39.50) versus (112.00 ± 31.78) g, P = 0.006 at 30min, (156.55 ± 47.23) versus (118.67 ± 34.42) g, P = 0.005 at 6h] and group RK3 [(145.33 ± 51.18) versus (112.00 ± 31.78) g, P = 0.018 at 30min, (154.67 ± 47.54) versus (118.67 ± 34.42) g, P = 0.008 at 6h] on the forearm at 30min and 6h after surgery. Group RK3 had more glandular secretions than the other three groups (P = 0.042). Intravenous injection of esketamine 0.4mg·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. Registered at the Chinese Clinical Trials Registry http://www.chictr.org.cn/ (09/06/2022, ChiCTR-2200060741).