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新辅助免疫化疗治疗非小细胞肺癌患者中阿片类药物消耗增加:一项多中心前瞻性队列研究。

Increased opioid consumption in neoadjuvant immunotherapy plus chemotherapy for patients with non-small-cell lung cancer: A multicenter, prospective cohort study.

机构信息

Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

Department of Anesthesiology, Tianjin University Chest Hospital, Tianjin, China.

出版信息

CNS Neurosci Ther. 2024 Aug;30(8):e14893. doi: 10.1111/cns.14893.

Abstract

AIMS

PD-1 block was reported to impair opioid-induced antinociception and affect cognitive function in rodents and non-human primates. This prospective multicenter cohort study aims to investigate the possible impact of neoadjuvant immunotherapy with PD-1 antibody on perioperative analgesic effect of opioids and postoperative delirium (POD) for non-small-cell lung cancer (NSCLC) patients.

METHODS

Eighty-four NSCLC patients from three medical centers with neoadjuvant chemoimmunotherapy (nCIT) or chemotherapy (nCT) were enrolled. The primary outcome is the total perioperative opioid consumption defined as the sum of intraoperative and postoperative opioid use within 3 days after surgery. Secondary outcomes compromise of incidence of POD, pain intensity, and number of analgesic pump press. Tumor prognostic parameters and perioperative change of inflammatory cytokines and soluble PD-L1 level were also recorded.

RESULTS

Eighty-one patients were included in the final analysis. The total opioid consumption (sufentanil equivalent) perioperatively in the nCIT group was significantly higher than that in the nCT group, with mean difference of 60.39 μg, 95% CI (25.58-95.19), p < 0.001. Multiple linear regression analysis showed that nCIT was correlated with increased total opioid consumption (β = 0.305; 95% CI, 0.152-0.459; p < 0.001). The incidence of moderate-to-severe pain and cumulative analgesic pump press within 72 h was significantly higher in subjects with nCIT. There is no statistical difference in incidence of POD between groups within 72 h after surgery. The pathologic complete response rate and perioperative serum IL-6 level were higher in the nCIT group than in the nCT group.

CONCLUSION

Patients with NSCLC receiving nCIT warrant increased opioid consumption perioperatively and suffered from more postoperative pain.

CLINICAL TRIAL REGISTRATION

NCT05273827.

摘要

目的

PD-1 阻断被报道会损害阿片类药物诱导的镇痛作用,并影响啮齿动物和非人类灵长类动物的认知功能。本前瞻性多中心队列研究旨在调查 PD-1 抗体新辅助免疫治疗对非小细胞肺癌(NSCLC)患者围手术期阿片类药物镇痛效果和术后谵妄(POD)的可能影响。

方法

来自三个医疗中心的 84 名接受新辅助化疗免疫治疗(nCIT)或化疗(nCT)的 NSCLC 患者入组。主要结局是总围手术期阿片类药物消耗量,定义为术后 3 天内术中及术后阿片类药物使用的总和。次要结局包括 POD 的发生率、疼痛强度和镇痛泵按压次数。还记录了肿瘤预后参数和围手术期炎症细胞因子和可溶性 PD-L1 水平的变化。

结果

81 例患者最终纳入分析。nCIT 组围手术期总阿片类药物消耗量(舒芬太尼等效物)明显高于 nCT 组,平均差值为 60.39μg,95%CI(25.58-95.19),p<0.001。多元线性回归分析显示,nCIT 与总阿片类药物消耗量增加相关(β=0.305;95%CI,0.152-0.459;p<0.001)。nCIT 组中,在 72 小时内出现中度至重度疼痛和累积镇痛泵按压的比例显著较高。两组术后 72 小时内 POD 的发生率无统计学差异。nCIT 组的病理完全缓解率和围手术期血清 IL-6 水平高于 nCT 组。

结论

接受 nCIT 的 NSCLC 患者围手术期需要增加阿片类药物的消耗,并伴有更多的术后疼痛。

临床试验注册

NCT05273827。

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