Goulooze SC, Krekels EH, Saleh MA, et al. - For both patient comfort and successful recovery following cardiac surgery, optimal postoperative analgesic treatment is identified as crucial. Given the scarcity of models quantifying the pharmacodynamics of analgesics, which is necessitated to predict optimal drug dosing, researchers here modelled the need for rescue morphine to manage unacceptable pain in 118 patients after cardiac surgery in order to quantify the pharmacodynamics of morphine. They analyzed the rescue morphine event data with repeated time-to-event (RTTE) modeling using NONMEM. Continuous morphine infusions (median duration 20.5 hours) with paracetamol 4 times daily and rescue morphine in case of unacceptable pain (numerical rating scale ≥ 4) were included in postoperative pain titration protocol. Following were identified to have significant influence on the hazard for rescue morphine following cardiac surgery: time after surgery, a day/night cycle with a peak at 23:00 each day, and an effect of morphine concentration with 50% hazard reduction at 9.3 ng·mL ₋₁ . RTTE modeling led to successful quantification of the pharmacodynamics of morphine after cardiac surgery. In future studies, expansion of the model can be done to better ascertain morphine’s pharmacodynamics on the individual level and to incorporate the pharmacodynamics of other analgesics so that development of improved postoperative pain treatment protocols can be done.