Ciprofol

The intravenous pharmacotherapy in patients with critically ill and perioperative intravenous anesthesia is extremely challenging due to the large number of drugs administered. In-line incompatibility remains a significant safety concern. We therefore evaluated the physico- chemical compatibility of combinations of ciprofol injection with cardiovascular drugs during simulated Y-site administration frequently used in intensive care unit setting or intravenous anesthesia. Ciprofol injection was mixed with clinical concentrations of dopamine, sodium nitroprusside, dobutamine, phentolamine, papaverine, nitroglycerin, metaraminol and methoxamine solution at a 1:1 vol ratio under ambient conditions (25 ± 1 °C). Physicochemical compatibility changes in appearance, pH values, Zeta potential, particle size/polydispersity index (PDI), osmotic pressure, and relative percentage content are observed at predetermined time points (0, 2, 4, 6, and 8 h). During the 8-hour study period, the pH values change of all drug mixture remained within ±0.4. The relative drug concentration was maintained between 95 % and 105 %. The mean particle size was in the range of 200 to 220 nm, with a PDI below 0.2. Osmotic pressure changes were consistently <6 %. Notably, the Zeta potential of the metaraminol-ciprofol mixture exhibited a variation exceeding ±10 mV. Microscopic imaging analysis showed that the droplet sizes of dopamine-ciprofol, metaraminol-ciprofol, and papaverine-ciprofol mixtures, increased significantly. Based on this studies, ciprofol injection demonstrated compatibility and stability when administered via Y-site infusion with sodium nitroprusside, dobutamine, methoxamine, phentolamine, and nitroglycerin for up to 8 h at room temperature. However, the combination of ciprofol with dopamine, metaraminol, or papaverine was incompatibility during infusion. pH is a significant factor that could potentially influence the stability and compatibility of the combinations. Clinical strategies such as the use of inline filters and post-infusion irrigation tubes can prevent these risks.

Sepsis-Induced Cardiomyopathy (SIC) is a life-threatening complication with limited therapies, significantly contributing to septic mortality. This study investigated the cardioprotective effects of ciprofol, a novel anesthetic, in SIC and elucidated the role of the α7 nicotinic acetylcholine receptor (α7nAChR) pathway. Using a cecal ligation and puncture (CLP)-induced murine sepsis model, we assessed ciprofol pretreatment's impact on myocardial injury, cardiac function, survival, and inflammation. The α7nAChR antagonist methyllycaconitine (MLA) was used to investigate pathway involvement. Our findings demonstrated that ciprofol pretreatment significantly mitigated sepsis-induced myocardial injury, evidenced by reduced serum creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH). Ciprofol also improved cardiac function, indicated by increased left ventricular ejection fraction (LVEF) and fractional shortening (FS), and markedly enhanced 14-day survival. These benefits were accompanied by attenuated cardiac inflammation, characterized by reduced myocardial infiltration of CD68⁺ macrophages (including pro-inflammatory CD86⁺ M1 phenotype) and myeloperoxidase (MPO) + neutrophils, alongside decreased systemic IL-6 and TNF-α. Crucially, MLA co-administration largely abrogated ciprofol's cardioprotective and anti-inflammatory effects. Mechanistically, ciprofol modulated α7nAChR signaling, inhibiting cardiac NF-κB p65 and STAT3 phosphorylation; MLA reversed these modulatory effects. In conclusion, ciprofol exerts significant cardioprotection against SIC, primarily via an α7nAChR-dependent pathway. This pathway suppresses myocardial inflammation by reducing inflammatory cell infiltration, cytokine production, and beneficially modulating NF-κB/STAT3 signaling. These insights suggest ciprofol's potential as an anesthetic with valuable organ-protective properties for critically ill septic patients.