A biomarker of opioid-induced respiratory toxicity in experimental studies
Marieke Hellinga,
Marijke Hyke Algera,
Rutger van der Schrier,
Elise Sarton,
Monique van Velzen,
Albert Dahan,
Erik Olofsen,
Marieke Niesters
Affiliations
Marieke Hellinga
Department of Anesthesiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
Marijke Hyke Algera
Department of Anesthesiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
Rutger van der Schrier
Department of Anesthesiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
Elise Sarton
Department of Anesthesiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
Monique van Velzen
Department of Anesthesiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
Albert Dahan
Department of Anesthesiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; PainLess Foundation, 2333 ZA Leiden, the Netherlands; Corresponding author
Erik Olofsen
Department of Anesthesiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
Marieke Niesters
Department of Anesthesiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Corresponding author
Summary: 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 PCO2 (PETCO2) and the hypercapnic ventilatory response (HCVR) before and at 1-h intervals following intake of the opioid tapentadol. Pharmacokinetic/pharmacodynamic analyses that included CO2 kinetics were applied to model the responses with focus on resting variables obtained without added CO2, HCVR slope and ventilation at an extrapolated PETCO2 of 55 mmHg (V˙E55). The HCVR, particularly V˙E55 followed by slope, was most sensitive in terms of potency; resting variables were least sensitive and responded slower to the opioid. Using V˙E55 as biomarker in quantitative studies on OIRD allows standardized comparison among opioids in the assessment of their safety.
