Hellinga Marieke, Algera Marijke Hyke, van der Schrier Rutger, Sarton Elise, van Velzen Monique, Dahan Albert, Olofsen Erik, Niesters Marieke
Department of Anesthesiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
PainLess Foundation, 2333 ZA Leiden, the Netherlands.
iScience. 2023 Mar 30;26(4):106520. doi: 10.1016/j.isci.2023.106520. eCollection 2023 Apr 21.
Opioids are commonly used painkillers and drugs of abuse and have serious toxic effects including potentially lethal respiratory depression. It remains unknown which respiratory parameter is the most sensitive biomarker of opioid-induced respiratory depression (OIRD). To evaluate this issue, we studied 24 volunteers and measured resting ventilation, resting end-tidal PCO (PCO) and the hypercapnic ventilatory response (HCVR) before and at 1-h intervals following intake of the opioid tapentadol. Pharmacokinetic/pharmacodynamic analyses that included CO kinetics were applied to model the responses with focus on resting variables obtained without added CO, HCVR slope and ventilation at an extrapolated PCO of 55 mmHg ( 55). The HCVR, particularly 55 followed by slope, was most sensitive in terms of potency; resting variables were least sensitive and responded slower to the opioid. Using 55 as biomarker in quantitative studies on OIRD allows standardized comparison among opioids in the assessment of their safety.
阿片类药物是常用的止痛药和滥用药物，具有严重的毒性作用，包括潜在致命的呼吸抑制。目前尚不清楚哪种呼吸参数是阿片类药物引起的呼吸抑制（OIRD）最敏感的生物标志物。为了评估这个问题，我们研究了24名志愿者，并在摄入阿片类药物曲马多之前以及之后每隔1小时测量静息通气、静息呼气末PCO（PCO）和高碳酸通气反应（HCVR）。应用包括CO动力学的药代动力学/药效学分析来模拟反应，重点关注在不添加CO的情况下获得的静息变量、HCVR斜率以及在推算的PCO为55 mmHg（55）时的通气情况。就效力而言，HCVR，尤其是55，其次是斜率，最为敏感；静息变量最不敏感，对阿片类药物的反应也较慢。在关于OIRD的定量研究中使用55作为生物标志物，可以在评估阿片类药物安全性时对它们进行标准化比较。
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