4 Oliceridine respiratory effects Results A total of 341 individuals responded to an online mailing for participation in our study. Twenty-two were assessed for eligibility of which four were excluded because they did not show up on the first study day (n = 1), they met exclusion criteria (n = 2), or they declined to participate (n = 1). Eighteen subjects (9 men and 9 women) were enrolled in the study and randomly assigned; seventeen subjects successfully completed the trial. One male subject withdrew consent after the second visit because of a (transient) painful hematoma that developed at the location of the vascular access line after the subject returned home; his data are included in the analyses. All other subjects completed the study without any serious or unexpected adverse effects. The mean age of the participants was 71 yr (range 56 to 87 yr), height 170 cm (155 to 189 cm), and body mass index 26 kg/m2 (20 to 34 kg/m2). Five subjects, with age range 69 to 75 yr, had a body mass index greater than 30 kg/m2 (mean value 33 kg/m2, with range 32 to 34 kg/m2); the other subjects (age range 56 to 87 yr) had a mean body mass index of 24 kg/m2 (20 to 29 kg/m2). Primary Endpoint: Opioid Effect on ˙V E55 The effect of oliceridine and morphine on mean isohypercapnic ventilation, ˙V E55, are given in Figure 4.1 on page 74. The dynamic patterns observed after the opioid infusions were different for the two opioids. High-dose oliceridine and high- and low-dose morphine showed a rapid drop in ˙VE55, an indication of rapid onset of respiratory depression, i.e., within 30 min of administration. High-dose oliceridine and low-dose morphine returned toward baseline within 3 h, and high-dose morphine lagged behind, and a slow return toward baseline (more than 6 h) was observed. Low-dose oliceridine did not produce any significant respiratory depression. In contrast to ˙VE55 after highdose morphine, ˙VE55 after low- and high-dose oliceridine infusion had mean values greater than predrug baseline values fromt = 4 h on. 73
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