Oliceridine for Analgesia After Cardiac Surgery

Cardiac surgery has the characteristics of long duration and large amount of intraoperative bleeding, easy to involve multiple organs and severe tissue injury, which is one of the most serious surgical procedures with postoperative pain and the incidence of postoperative pain after open-heart surgery is as high as 50%, with the incidence of moderate-to-severe pain ranging from 3% to 18% . Currently, opioids are commonly used in clinical practice for postoperative cardiac analgesia, but due to the abnormal cardiac structure of cardiac surgery patients, surgery and extracorporeal circulation effects, hemodynamic fluctuations and respiratory depression, nausea and vomiting, dizziness, constipation, and other adverse reactions occur during analgesia [3]. Therefore, it is especially necessary to find an analgesic drug with good analgesic effect and able to reduce such adverse effects.

Oliceridine is a G-protein biased μ-opioid receptor agonist, which selectively activates the G-protein signaling pathway and significantly reduces the activation of the β-inhibitory protein pathway, preserving the analgesic effect while reducing the opioid-related adverse effects, and is currently used for intraoperative analgesia and analgesic treatment of acute moderate-to-severe pain occurring after surgery such as abdominal surgery and bunion bursitis, and is mostly administered by a single injection into the vein .A series of national and international clinical studies have been conducted on OliceridineA phase 1 clinical trial study conducted by Soergel et al. demonstrated that in healthy subjects, 3 and 4.5 mg ofOliceridine demonstrated higher peak analgesia (75 sec latency) compared to morphine. In addition, all doses were associated with lower respiratory drive reductions compared to morphine (- 7.3, - 7.6, and - 9.4 h*L/min vs - 15.9 h*L/min). Respiratory depression persisted with Oliceridine but was very transient, and subjects on the 1.5 mg and 3 mg doses experienced less nausea compared to subjects on the 4.5 mg dose and morphine. Overall, the 3 mg dose provided significant efficacy while still maintaining the reduction in PONV demonstrated by the low dose of choline.

To further investigate the effects of Oliceridine on the respiratory system, Simons et al. conducted a crossover study of 18 healthy elderly volunteers. The study found that while low doses of Oliceridine did not result in any significant respiratory effects, high doses of Oliceridine and two doses of morphine resulted in respiratory depression that peaked 0.5 to 1 hour after administration. However, similar to the earlier findings of Soergel et al, the respiratory depression induced by Oliceridine was more transient, characterized by a more rapid return to baseline, with an equilibrium half-life at the blood effector site of 44.3 ± 6.1 minutes compared with 214 ± 27 minutes for morphine.A subsequent phase III study was also conducted on the use of Oliceridine in the management of moderate to severe acute postoperative pain after abdominoplasty. The results showed that Oliceridine is a safe and effective intravenous analgesic for the relief of moderate to severe acute postoperative pain in patients undergoing abdominoplasty. Since the low-dose regimen of 0.1 mg of oseltamivirine was superior to placebo but not as effective as the morphine regimen, safety comparisons with morphine were only relevant to the 2 isoanalgesic dose groups of 0.35 and 0.5 mg, and oseltamivirine showed a favorable safety profile in terms of respiratory and gastrointestinal adverse effects tolerability compared with morphine. This suggests that Oliceridine may offer a new therapeutic option for patients with moderate to severe acute pain requiring intravenous opioids.Based on the relatively long duration of analgesia in postoperative cardiac surgery patients, there is a need to explore drugs with the advantages of better analgesic effect, less hemodynamic impact, sustained analgesia with fewer adverse effects, and rapid metabolism after discontinuation of the drug. Combining the existing research base of this project and the above domestic and international findings, we propose the conjecture that Oliceridine may provide better analgesia with fewer adverse effects in the postoperative period of cardiac surgery relative to other opioid analgesic drugs. In this study, we propose to study the analgesic effect of different doses of Oliceridine for pumping in postoperative cardiac surgery patients, its effect on hemodynamics and safety assessment, and we intend to expect to determine the optimal dosing regimen for postoperative cardiac analgesia.