围术期静脉注射S-氯胺酮治疗成人急性术后疼痛的系统回顾和meta分析

研究目的：评价S-氯胺酮用于外科手术患者镇痛的有效性和安全性。

设计：随机对照试验(RCT)的系统回顾和meta分析。

设置：围手术期。

患者：共有905名成人患者使用全身麻醉进行手术：S-氯胺酮组504名患者，安慰剂组401名患者。

干预措施：静脉注射S-氯胺酮作为全身麻醉的辅助药物，并与安慰剂进行比较。

测量指标：主要结果为术后4、12、24和48h内的静息和运动疼痛评分(VAS/NRS 0~10)和吗啡用量。次要结果包括术后并发症，如恶心、呕吐和拟精神病不良事件。我们使用推荐、评估、开发和评估(GRADE)系统的指导方针来评估主要结果的确定性水平。

主要结果：共纳入12项研究。手术类型包括腹部手术、开胸手术、妇科手术、关节镜下前交叉韧带修补术、心脏手术、腹腔镜胆囊切除术、腰椎融合术、前列腺癌根治术和痔疮切除术。与安慰剂组比较，S-氯胺酮治疗后4、12和24h的静息疼痛评分均有显著改善[4h：标准化平均差值-1.11；95%CI −1.53，−0.68，p<0.00001；GRADE=中度；12h：标准化平均差值−为0.88；95%CI：−1.42，−0.34，p=0.001；GRADE=中度；24 h：标准化平均差值为-0.39；95%CI：−为0.73，−为0.0 6，p=0.0 2；GRADE为中度]。两组48h疼痛评分发生率差异无统计学意义(−-0.2 7；95%CI：SMD1.12，0.5 8，p=0.5 3，GRADE为中度)。两组在各时间点的运动疼痛评分差异无显著性(4h：SMD−0.34；95%CI：−0.73，0.0 5，p=0.0 9，GRADE=中度；12h：SMD−0.42；95%CI：−1.4 6，0.6 3，p=0.44，GRADE为低；24h：SMD−0.5 8；95%CI：−1.2 5，0.0 9，p=0.0 9，GRADE=中度；48h：SMD−0.4 9，4 8h：SMD−0.5 8；95%CI：−1.2 5，0.0 9，p=0.0 9，GRADE=中度；48h：SMD−0.49；95%CI：−为1.11，0.14，p=0.13，GRADE为低度)。术后4、12h，S-氯胺酮组吗啡用量明显减少(4h：SMD−0.98；95%CI：−1.37，−0.06，p<0.00001，GRADE为中度；12h：SMD−1.36；95%CI：−2.26，−0.46，p=0.003，GRADE为低)。2 4h和48h吗啡用量两组间差异无显著性(2 4h：SMD−0.70；95%CI：−1.42，0.02，p=0.06，GRADE=低度；48h：SMD−0.79；95%CI：−2.2 6，1.0 3，p=0.39，GRADE=低度)。氯胺酮组出现恶心[相对危险度(RR)=1.04；95%CI：0.83，1.30，p=0.73]、呕吐(RR=1.07；95%CI：0.84，1.38，p=0.57)和拟精神病不良事件(RR=1.57；95%CI：0.82，2.99，p=0.17)的风险没有明显增加。

结论：静脉注射S-氯胺酮作为全麻的辅助镇痛有效，可在术后较短时间内降低疼痛强度和阿片类药物用量，但可能会增加拟精神病药不良事件的发生率。总体而言，确定性水平是中等至较低的。

原始文献来源：Xuemei Wang, Cheng Lin, Lifang Lan, Jingchen Liu.Perioperative intravenous S-ketamine for acute postoperative pain in adults: A systematic review and meta-analysis.J Clin Anesth. 2020 Sep 29;68:110071.

Perioperative intravenous S-ketamine for acute postoperative pain in adults: A systematic review and meta-analysis

Study objective: To evaluate the effectiveness and safety of S-ketamine for pain relief and analgesic consumption in surgical patients.

Design: Systematic review and meta-analysis of randomized controlled trials (RCTs).

Setting: Perioperative setting.

Patients: A total of 905 adult patients undergoing surgery using general anesthesia: 504 patients in the S-ketamine group and 401 patients in the placebo group.

Intervention: Intravenous S-ketamine as an adjuvant to general anesthesia compared with placebo.

Measurements: The primary outcomes were resting and movement pain scores (VAS/NRS 0–10) and morphine consumption within 4, 12, 24 and 48 h after surgery. The secondary outcomes included postoperative complications such as nausea, vomiting, and psychotomimetic adverse events. We used the guidelines of the Recommendation Assessment, Development, and Evaluation (GRADE) system to evaluate the level of certainty for the main results.

Main results: A total of 12 studies were included. The types of surgery included abdominal surgery, thoracotomy, gynecologic surgery, arthroscopic anterior cruciate ligament repair, cardiac surgery, laparoscopic cholecystectomy, lumbar spinal fusion surgery, radical prostatectomy, and hemorrhoidectomy. There were significant improvements in resting pain scores at 4, 12 and 24 h with S-ketamine versus placebo [4 h: standardized mean difference (SMD) -1.11; 95% confidence interval (CI): −1.53, −0.68, p < 0.00001; GRADE = moderate; 12 h: SMD −0.88; 95%CI: −1.42, −0.34, p = 0.001; GRADE = moderate; 24 h: SMD -0.39; 95%CI: −0.73, −0.06, p = 0.02; GRADE = moderate]. The incidence of pain scores at 48 h showed no statistical difference between the two groups (SMD -0.27; 95%CI: −1.12, 0.58, p = 0.53, GRADE = moderate). The movement pain scores were not significantly different between the two groups at each time point (4 h: SMD −0.34; 95%CI: −0.73, 0.05, p = 0.09, GRADE = moderate; 12 h: SMD −0.42; 95%CI: −1.46, 0.63, p = 0.44, GRADE = low; 24 h: SMD −0.58; 95%CI: −1.25, 0.09, p = 0.09, GRADE = moderate; 48 h: SMD −0.49; 95%CI: −1.11, 0.14, p = 0.13, GRADE = low). At 4 and 12 h after surgery, the consumption of morphine was significantly reduced in the S-ketamine group (4 h: SMD −0.98; 95%CI: −1.37, −0.06, p < 0.00001, GRADE = moderate; 12 h: SMD −1.36; 95%CI: −2.26, −0.46, p = 0.003, GRADE = low). There were no significant differences in morphine use at 24 and 48 h between the two groups (24 h: SMD −0.70; 95%CI: −1.42, 0.02, p = 0.06, GRADE = low; 48 h: SMD −0.79; 95%CI: −2.26, 1.03, p = 0.39, GRADE = low). The risk for nausea [relative risk (RR) = 1.04; 95%CI: 0.83, 1.30, p = 0.73], vomiting (RR = 1.07; 95%CI: 0.84, 1.38, p = 0.57), and psychotomimetic adverse events (RR = 1.57; 95%CI: 0.82, 2.99, p = 0.17) showed no significant increase in the Sketamine group.

Conclusions: Intravenous S-ketamine as an adjunct to general anesthesia is effective for assisting analgesia and decreases the intensity of pain and opioid requirements in a short period of time after surgery, but it may increase the psychotomimetic adverse event rate. Overall, the level of certainty is moderate to low.