Feb 11, 2025 | Clinical Edition

Ciprofol Chronicles: The New Star in Procedural Sedation

 

 

Check out the timestamps below to help you navigate through the many topics we discussed.

On This Episode:

This week, we’re shining a spotlight on Ciprofol, a cutting-edge intravenous anesthetic that has been making headlines in both clinical research and operating rooms worldwide.

With its innovative formulation and promising safety profile, Ciprofol is poised to transform the landscape of anesthetic practice. Join us as we explore how this new drug compares to established agents like propofol and what it could mean for the future of procedural sedation and anesthesia.

Ciprofol’s development is a testament to the progress in anesthetic pharmacology, addressing long-standing challenges such as pain on injection, adverse cardiovascular effects, and variability in patient response. Recent studies have highlighted its potential to offer smoother induction, better hemodynamic stability, and fewer complications, making it an attractive option for both routine and high-risk procedures. In this episode, we’ll dissect the science behind Ciprofol, examining its pharmacokinetics, clinical applications, and the data from key trials that support its use.

Here’s some of what we discuss in this episode:

  • What is Ciprofol, and why are nurse anesthetists buzzing about it?
  • The reduction in dosage isn’t just about using less drug—it has ripple effects.
  • What about its pharmacokinetics? Does it have the same quick onset and recovery profile that we’ve come to rely on with Propofol?
  • How does Ciprofol stack up when it comes to adverse events?
  • We dissect the study—a randomized, double-blind trial conducted in China.
  • Is Ciprofol the future?

Important Links: 

 


"Embrace innovations, but do so with a critical eye and a commitment to evidence-based practice."

- Garry & Terry


Reference

Aminnejad, R., Hormati, A., Shafiee, H., Alemi, F., Hormati, M., Saeidi, M., et al. (2022). Comparing the efficacy and safety of Dexmedetomidine/ketamine with Propofol/fentanyl for sedation in colonoscopy patients: A double-blinded randomized clinical trial. CNS Neurol Disord Drug Targets, 21, 724–731. https://doi.org/10.2174/1871527320666211006141406

Baker, M. T., Naguib, M., & Warltier, D. C. (2005). Propofol. Anesthesiology, 103(4), 860–876.

Bian, Y. C., Zhang, H., Ma, S., et al. (2021). Mass balance, pharmacokinetics, and pharmacodynamics of intravenous HSK3486, a novel anesthetic, administered to healthy subjects. British Journal of Clinical Pharmacology, 87(1), 93–105.

Chen, B. Z., Yin, X. Y., Jiang, L. H., Liu, J. H., Shi, Y. Y., & Yuan, B. Y. (2022). The efficacy and safety of ciprofol use for the induction of general anesthesia in patients undergoing gynecological surgery: A prospective randomized controlled study. BMC Anesthesiology, 22(1), 245.

Chen, X., Guo, P., Yang, L., Liu, Z., & Yu, D. (2022). Comparison and clinical value of ciprofol and propofol in intraoperative adverse reactions, operation, resuscitation, and satisfaction of patients under painless gastroenteroscopy anesthesia. Contrast Media & Molecular Imaging, 2022, article 9541060.

Child, K. J., Currie, J. P., Dis, B., Dodds, M. G., Pearce, D. R., & Twissell, D. J. (1971). The pharmacological properties in animals of CT1341–a new steroid anesthetic agent. British Journal of Anaesthesia, 43(1), 2–13.

Devaud, J. C., Berger, M. M., Pannatier, A., et al. (2012). Hypertriglyceridemia: A potential side effect of propofol sedation in critical illness. Intensive Care Medicine, 38(12), 1990–1998.

Desousa, K. A. (2016). Pain on propofol injection: Causes and remedies. Indian J Pharm, 48, 617–623. https://doi.org/10.4103/0253-7613.194845

Doi, M., Morita, K., Takeda, J., Sakamoto, A., Yamakage, M., & Suzuki, T. (2020). Efficacy and safety of remimazolam versus propofol for general anesthesia: A multicenter, single-blind, randomized, parallel-group, phase IIb/III trial. J Anesth, 34, 543–553. https://doi.org/10.1007/s00540-020-02788-6

Eghbali, M., Gage, P. W., & Birnir, B. (2003). Effects of propofol on GABAA channel conductance in rat-cultured hippocampal neurons. European Journal of Pharmacology, 468(2), 75–82.

Goudra, B., Gouda, G., & Mohinder, P. (2020). Recent developments in drugs for GI endoscopy sedation. Dig Dis Sci, 65, 2781–2788. https://doi.org/10.1007/s10620-020-06044-5

Hatch, D. J. (1999). Propofol-infusion syndrome in children. Lancet, 353(9159), 1117-1118.

Hemphill, S., McMenamin, L., Bellamy, M. C., & Hopkins, P. M. (2019). Propofol infusion syndrome: A structured literature review and analysis of published case reports. British Journal of Anaesthesia, 122(4), 448–459.

Hu, C., Ou, X. F., Teng, Y., et al. (2021). Sedation effects produced by a ciprofol initial infusion or bolus dose followed by continuous maintenance infusion in healthy subjects: A phase 1 trial. Advances in Therapy, 38(11), 5484–5500.

Jalota, L., Kalira, V., George, E., et al. (2011). Prevention of pain on injection of propofol: Systematic review and meta-analysis. BMJ, 342, article d1110.

Hu, C., Ou, X., Teng, Y., Shu, S., Wang, Y., Zhu, X., et al. (2021). Sedation effects produced by a Ciprofol initial infusion or bolus dose followed by continuous maintenance infusion in healthy subjects: A phase 1 trial. Adv Ther, 38, 5484–5500. https://doi.org/10.1007/s12325-021-01914-4

Kam, P. C., & Cardone, D. (2007). Propofol infusion syndrome. Anaesthesia, 62(7), 690–701.

Kazama, T., Ikeda, K., Morita, K., Kikura, M., Ikeda, T., Kurita, T., et al. (2000). Investigation of effective anesthesia induction doses using a wide range of infusion rates with undiluted and diluted propofol. Anesthesiology, 92, 1017–1028. https://doi.org/10.1097/00000542-200004000-00019

Kreuzer, M., Butovas, S., García, P. S., et al. (2020). Propofol affects cortico-hippocampal interactions via β3 subunit-containing GABAA receptors. International Journal of Molecular Sciences, 21(16), 5844.

Li, J., Wang, X., Liu, J., et al. (2022). Comparison of ciprofol (HSK3486) versus propofol for the induction of deep sedation during gastroscopy and colonoscopy procedures: A multi-centre, noninferiority, randomized, controlled phase 3 clinical trial. Basic & Clinical Pharmacology & Toxicology, 131(2), 138–148.

Liao, J., Li, M. T., Huang, C. L., et al. (2022). Pharmacodynamics and pharmacokinetics of HSK3486, a novel 2, 6-disubstituted phenol derivative as a general anesthetic. Frontiers in Pharmacology, 13, article 830791.

Liu, Q., Kong, A. L., Chen, R., et al. (2011). Propofol and arrhythmias: Two sides of the coin. Acta Pharmacologica Sinica, 32(6), 817–823.

Liu, Y. J., Chen, C. X., Liu, N., et al. (2021). Efficacy and safety of ciprofol sedation in ICU patients with mechanical ventilation: A clinical trial study protocol. Advances in Therapy, 38(10), 5412–5423.

Long, Y. Q., Feng, C. D., Ding, Y. Y., et al. (2022). Esketamine as an adjuvant to ciprofol or propofol sedation for same-day bidirectional endoscopy: Protocol for a randomized, double-blind, controlled trial with factorial design. Frontiers in Pharmacology, 13, article 821691.

Luo, Z., Tu, H., Zhang, X., Wang, X., Ouyang, W., Wei, X., et al. (2022). Efficacy and safety of HSK3486 for anesthesia/sedation in patients undergoing Fiberoptic bronchoscopy: A multicenter, double-blind, Propofol-controlled, randomized, phase 3 study. CNS Drugs, 36, 301–313. https://doi.org/10.1007/s40263-021-00890-1

Makito, K., Matsui, H., Fushimi, K., & Yasunaga, H. (2020). Volatile versus total intravenous anesthesia for cancer prognosis in patients having digestive cancer surgery. Anesthesiology, 133(4), 764–773.

Marik, P. E. (2004). Propofol: Therapeutic indications and side effects. Current Pharmaceutical Design, 10(29), 3639–3649.

Mashour, G. A., Sanders, R. D., & Lee, U. (2022). Propofol anesthesia: A leap into the void? Anesthesiology, 136(3), 405–407.

Nørreslet, J., & Wahlgreen, C. (1990). Propofol infusion for sedation of children. Critical Care Medicine, 18(8), 890–891.

Nummela, A. J., Laaksonen, L. T., Laitio, T. T., Kallionpää, R. E., Långsjö, J. W., Scheinin, J. M., et al. (2022). Effects of dexmedetomidine, propofol, sevoflurane, and S-ketamine on the human metabolome: A randomised trial using nuclear magnetic resonance spectroscopy. Eur J Anaesthesiol, 39, 521–532. https://doi.org/10.1097/EJA.0000000000001591

Parke, T. J., Stevens, J. E., Rice, A. S., et al. (1992). Metabolic acidosis and fatal myocardial failure after propofol infusion in children: Five case reports. BMJ, 305(6854), 613–616.

Qin, L., Ren, L., Wan, S., Liu, G., Luo, X., Liu, Z., et al. (2017). Design, synthesis, and evaluation of novel 2,6-Disubstituted phenol derivatives as general anesthetics. J Med Chem, 60, 3606–3617. https://doi.org/10.1021/acs.jmedchem.7b00254

Sebel, P. S., & Lowdon, J. D. (1989). Propofol. Anesthesiology, 71(2), 260–277.

Sneyd, J. R., Absalom, A. R., Barends, C. R. M., & Jones, J. B. (2022). Hypotension during propofol sedation for colonoscopy: A retrospective exploratory analysis and meta-analysis. Br J Anaesth, 128, 610–622. https://doi.org/10.1016/j.jclinane.2021.110374

Song, D., Hamza, M., White, P. F., Klein, K., Recart, A., & Khodaparast, O. (2004). The pharmacodynamic effects of a lower-lipid emulsion of propofol: A comparison with the standard propofol emulsion. Anesth Analg, 98, 687–691. https://doi.org/10.1213/01.ane.0000103184.36451.d7

Song, D., Hamza, M. A., White, P. F., Byerly, S. I., Jones, S. B., & Macaluso, A. D. (2004). Comparison of a lower-lipid propofol emulsion with the standard emulsion for sedation during monitored anesthesia care. Anesthesiology, 100, 1072–1075. https://doi.org/10.1097/00000542-200405000-00007

Tan, C. H., & Onsiong, M. K. (1998). Pain on injection of propofol. Anaesthesia, 53(5), 468–476.

Teng, Y., Ou, M., Wang, X., Zhang, W., Liu, X., Liang, Y., et al. (2021). Efficacy and safety of ciprofol for the sedation/anesthesia in patients undergoing colonoscopy: Phase IIa and IIb multi-center clinical trials. Eur J Pharm Sci, 164, 105904. https://doi.org/10.1016/j.ejps.2021.105904

Trapani, G., Altomare, C., Liso, G., Sanna, E., & Biggio, G. (2000). Propofol in anesthesia, mechanism of action, structure-activity relationships, and drug delivery. Current Medicinal Chemistry, 7(2), 249–271.

Tung, A., Szafran, M. J., Bluhm, B., & Mendelson, W. B. (2002). Sleep deprivation potentiates the onset and duration of loss of righting reflex induced by propofol and isoflurane. Anesthesiology, 97(4), 906–911.

Voss, L. J., Sleigh, J. W., Barnard, J. P., & Kirsch, H. E. (2008). The howling cortex: Seizures and general anesthetic drugs. Anesthesia and Analgesia, 107(5), 1689–1703.

Walsh, C. T. (2018). Propofol: Milk of amnesia. Cell, 175(1), 10–13.

Wang, X., Wang, X., Liu, J., et al. (2022). Effects of ciprofol for the induction of general anesthesia in patients scheduled for elective surgery compared to propofol: A phase 3, multicenter, randomized, double-blind, comparative study. European Review for Medical and Pharmacological Sciences, 26(5), 1607–1617.

Wallentine, C. B., Shimode, N., Egan, T. D., & Pace, N. L. (2011). Propofol in a modified cyclodextrin formulation: First human study of dose-response with emphasis on injection pain. Anesth Analg, 113, 738–741. https://doi.org/10.1213/ANE.0b013e31822b8648

Wei, Y., Qiu, G., Lei, B., Qin, L., Chu, H., Lu, Y., et al. (2017). Oral delivery of Propofol with Methoxymethylphosphonic acid as the delivery vehicle. J Med Chem, 60, 8580–8590. https://doi.org/10.1021/acs.jmedchem.7b01133

Zeng, Y., Cao, S., Chen, M., Fang, C., & Ouyang, W. (2022). GABRA1 and GABRB2 polymorphisms are associated with Propofol susceptibility. Pharmacogenomics Personalized Med, 15, 105–117. https://doi.org/10.2147/PGPM.S348170

Zeng, Y., Wang, D. X., Lin, Z. M., et al. (2022). Efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients: A multicenter, randomized, open-label, propofol-controlled phase 2 clinical trial. European Review for Medical and Pharmacological Sciences, 26(4), 1114–1124.

Zhang, C., Li, F. Q., Yu, Y., et al. (2017). Design, synthesis, and evaluation of a series of novel benzocyclobutene derivatives as general anesthetics. Journal of Medicinal Chemistry, 60(9), 3618–3625