Yoshimura Akiko, Nozaki-Taguchi Natsuko, Suganuma Dai, Sakashita Yoshihiko, Fujisato Masami, Isono Shiroh
Division of Palliative Care, Chiba Cancer Center, Chiba, Japan.
Department of Anesthesiology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Palliat Med Rep. 2024 Sep 10;5(1):399-407. doi: 10.1089/pmr.2024.0021. eCollection 2024.
Despite the risk of respiratory depression, benzodiazepines are often prescribed to patients receiving palliative care owing to their efficacy in symptom control. Opioids, which also cause respiratory depression, are often administered to patients with advanced-stage cancer. However, the additive effect of the two drugs has not been systematically analyzed.
This prospective observational study aimed to determine the respiratory effects of coadministration of benzodiazepines and opioids in terminally ill patients with cancer.
The respiratory variables (primary endpoint) and activity index (ACI) (secondary endpoint) of 24 patients were assessed using a continuous noncontact, nonrestraining vital sign monitor placed under the legs of the bed.
The respiratory rate (RR) changed from 12.0 ± 3.9/min to 10.3 ± 3.3/min ( = 24, = 0.0005) following administration of the first dose of benzodiazepine in addition to regular opioid treatment, indicating no difference ( > 0.83) from the decrease in the RR observed on the previous day at the same time (12.1 ± 3.3/min to 10.3 ± 3.4/min). No increase in apnea-hypopnea frequency and respiratory irregularity or no decrease in respiratory size was observed. The ACI showed a significant decrease following the administration of benzodiazepine, suggesting remission of the symptoms. The effect of five repeated doses of benzodiazepines in nine patients showed no significant change in the respiratory variables compared with the first dose.
Addition of single or consecutive benzodiazepine-type drugs at clinically useful dose in patients receiving palliative care for cancer with opioid analgesics, readily exposed to respiratory depression, was observed with a decreased RR similar to the decrease observed during sleep with opioid alone.
尽管存在呼吸抑制风险，但由于苯二氮䓬类药物在症状控制方面的疗效，常被开给接受姑息治疗的患者。同样会导致呼吸抑制的阿片类药物，也常被用于晚期癌症患者。然而，这两种药物的相加作用尚未得到系统分析。
这项前瞻性观察性研究旨在确定苯二氮䓬类药物和阿片类药物联合使用对晚期癌症临终患者的呼吸影响。
使用置于床腿下方的连续非接触、无约束生命体征监测仪，评估24例患者的呼吸变量（主要终点）和活动指数（ACI）（次要终点）。
在常规阿片类药物治疗基础上，首次给予苯二氮䓬类药物后，呼吸频率（RR）从12.0±3.9次/分钟变为10.3±3.3次/分钟（n = 24，P = 0.0005），这与前一天同一时间观察到的RR下降（从12.1±3.3次/分钟降至10.3±3.4次/分钟）无差异（P>0.83）。未观察到呼吸暂停低通气频率和呼吸不规则性增加，或呼吸幅度减小。给予苯二氮䓬类药物后ACI显著下降，提示症状缓解。9例患者重复给予5次苯二氮䓬类药物后，与首次给药相比，呼吸变量无显著变化。
在接受癌症姑息治疗且易发生呼吸抑制的患者中，添加临床常用剂量的单次或连续苯二氮䓬类药物，观察到RR下降，类似于单独使用阿片类药物睡眠期间的下降情况。
