Physician anesthesiologist at Stanford at Associated Anesthesiologists Medical Group
Richard Novak, MD is a Stanford physician board certified in anesthesiology and internal medicine.Dr. Novak is an Adjunct Clinical Professor in the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford University, the Medical Director at Waverley Surgery Center in Palo Alto, California, and a member of the Associated Anesthesiologists Medical Group in Palo Alto, California.
Latest posts by THE ANESTHESIA CONSULTANT (see all)


Ciprofol is a new intravenous (IV) anesthetic agent which is undergoing early clinical trials in China, and may become a significant tool in our anesthesia armamentarium if and when the drug is approved by the Food and Drug Administration (FDA) in the United States. Ciprofol has a chemical structure similar to propofol. Because of its rapid onset and rapid offset profile, propofol is currently the most used IV anesthetic drug in the world. Propofol is used for surgical anesthesia, procedural sedation, and intensive care unit (ICU) sedation. Propofol was FDA-approved in the United States in 1986 and is now off patent. Generic propofol is inexpensive, averaging about $2.27 for a 20 ml vial. Limitations of propofol include (a) respiratory depression, such that it can only be used by physicians who are expert in airway management (e.g. anesthesiologists, CRNAs, and emergency room doctors); (b) hemodynamic depression in some elderly or sick patients; (c) pain on injection; and (d) the propofol infusion syndrome (PIS) which can lead to hyperkalemia and cardiac arrest in ICU patients after prolonged exposure to propofol infusions.

The chemical formula of ciprofol is similar to propofol, but with single R-configured diastereoisomers.

Ciprofol is about 5 times more potent than propofol. Like propofol, ciprofol is formulated in a lipid emulsion with a drug concentration of 10 mg/mL. Let’s review the published literature on ciprofol to date. All of the following studies were done in China:

Phase 1 trials (small groups of subjects are given a single dose of the drug, and are observed and tested for a period of time to confirm safety):

Teng et al. (2021) conducted a phase I trial which demonstrated that a ciprofol dosing regimen of 0.4-0.9 mg/kg was well-tolerated and exhibited rapid onset and recovery properties. Peak plasma concentration occurred 2 minutes after injection, and all subjects recovered fully after ciprofol administration, with the shortest time being 9.2 minutes in the 0.4 mg/kg group.

Hu et al. (2021) also conducted a phase I trial in which subjects received continuous ciprofol or propofol infusions for up to 12 hours. The safety and tolerability of both drugs were comparable.

Phase II trials (performed on larger groups, e.g. 50–300 patients, to evaluate whether the drug has any biological activity or effect):

Teng et al. (2021) conducted a study on 1000 patients, which showed that ciprofol 0.4-0.5 mg/kg induced equivalent sedation/anesthesia to propofol 2.0 mg/kg during colonoscopy, and had a similar safety profile without producing serious adverse effects. No apnea was observed in any patients in the ciprofol group, but 5 patients in the propofol 2.0 mg/kg group experienced apnea. The incidence of injection pain was higher in the propofol group than in the ciprofol group (55% vs 6.8%). There were no significant dose-dependent changes in blood pressure in either the ciprofol or propofol groups.

Liu et al. (2021) conducted a phase II trial which involved 36 ICU patients who were on mechanical ventilation.  A remifentanil infusion of 0.02–0.15 μg·kg−1·min−1  plus either ciprofol or propofol were used for analgesia and sedation. The ciprofol loading dose was 0.1–0.2 mg/kg with a maintenance infusion rate of 0.3 mg/kg/h. The propofol loading was at 0.5–1.0 mg/kg, with a maintenance infusion rate of 1.5 mg/kg/h. The tolerability, sedation characteristics, and adverse events such as hypotension were comparable between both groups. The authors concluded that “ciprofol is comparable to propofol with good tolerance and efficacy for sedation of Chinese intensive care unit patients undergoing mechanical ventilation in the present study setting.”

The propofol infusion syndrome (PIS) is a potentially lethal syndrome that occurs due to prolonged infusion described in adults and pediatric ICU patients who are on mechanical ventilation. To date, published studies have not administered multi-day infusions of ciprofol to mechanically ventilated ICU patients to determine whether there is anything similar to PIS with ciprofol.

Wu et al. (2022) published a single-center trial on 92 patients titled “Efficacy and safety of ciprofol-remifentanil versus propofol-remifentanil during fiberoptic bronchoscopy.” Fentanyl (50 μg) was given to all patient 2 minutes before the intravenous administration of either 0.3 mg/kg of ciprofol or 1.2 mg/kg of propofol, followed by a remifentanil infusion in both groups. Top-up doses of one-third to one-fourth of the initial dose of ciprofol or propofol were repeated at 2-minute intervals as needed. The two drugs were comparable. The authors concluded that “ciprofol-remifentanil was non-inferior to propofol-remifentanil with regard to successful sedation for flexible bronchoscopy.” Systolic, diastolic, and mean blood pressures declined significantly less in the ciprofol-remifentanil group (p < 0.05). There was no difference in respiratory depression between the two groups, and the only statistical difference in adverse effects was a decrease in pain on injection for ciprofol over propofol (p=.001).

Chen et al. (2022) compared ciprofol and propofol in 120 women for the induction of anesthesia in gynecologic surgery. Intravenous midazolam (0.03 mg/kg) and sufentanil (0.3 μg/kg) were administered initially, followed by ciprofol (0.4 mg/kg) or propofol (2 mg/kg). After the loss of consciousness, rocuronium (0.6 mg/kg) was administered and endotracheal intubation was performed. Within the initial 10 minutes following study drug administration, blood pressure declined significantly less in the ciprofol group than in the propofol group. The authors concluded that “ciprofol was associated with slightly less pronounced effects on the cardiovascular system.” The incidence of injection pain was higher in the propofol group than in the ciprofol group (58% vs 16%, p < 0.001).

Chen et al. (2022) studied adverse reactions of ciprofol and propofol in 96 patients for gastroenteroscopy. Neither ciprofol nor propofol caused statistically significant differences in vital signs. The authors concluded that “in painless gastroenteroscopy, compared with propofol, ciprofol is equally safe and effective for patients.”

Lan et al. (2022) randomized 150 patients to ciprofol or propofol for hysteroscopy. All patients received intravenous sufentanil 0.1 μg/kg IV initially. Ciprofol patients then received an induction dose of 0.4 mg/kg and a maintenance dosage of 1.0 mg/kg/h. Propofol patients received an induction dose of  2.0 mg/kg and a maintenance dosage of 5.0 mg/kg/h. After the sedative administration, the systolic, diastolic, and mean pressures all  dropped significantly lower in the propofol group than in the ciprofol group. During the procedure, 2/75 ciprofol patients vs 17/75 propofol patients required an airway intervention such as a chin-lift or jaw-thrust maneuver (p< 0.05). The authors concluded that “the lower level of respiratory depression seen with ciprofol makes this drug more suitable and safer than propofol for hysteroscopic procedures.”

Phase III trials (randomized controlled multicenter trials on larger patient groups, aimed at determining how effective the drug is in comparison with the current “gold standard” treatment, i.e. propofol):

Li et al. (2022) conducted a phase III study at ten teaching hospitals, comparing ciprofol and propofol for deep sedation for colonoscopy or gastroscopy. A total of 289 patients were studied. Each patient received 50 μg fentanyl 1 minute before the intravenous infusion of either ciprofol (0.4 mg/kg) or propofol (1.5 mg/kg). Up to five top-up doses of 1/2 the initial dose were given upon signs of inadequate sedation, and repeated at 2-minute intervals as required. The mean time for a patient to become fully alert after the procedure was 3.3 minutes in the ciprofol group vs. 2.0 minutes for the propofol group (P < 0.001). The time to discharge was 7.4 minutes for the ciprofol group vs. 6.0 minutes for the propofol group (P < 0.001). Nine patients (6.3%) in the ciprofol group and 15 patients (10.3%) in the propofol group had respiratory events (respiratory depression, apnea, or hypoxemia), all of which were mild or moderate in severity. The authors concluded that “at a dose of 0.4 mg/kg for deep sedation, ciprofol was non-inferior to 1.5 mg/kg propofol in the success rate of gastroscopy and colonoscopy and exhibited a good safety profile.”

Wang et al. (2022) published a multi-center, double-blind phase III trial in which 186 surgery patients were randomly assigned to either ciprofol 0.4 mg/kg or propofol 2.0 mg/kg for the induction of general anesthesia. Ciprofol was “non-inferior” to propofol. Once again, the incidence of injection pain was significantly lower in the ciprofol patients compared to the propofol patients (6.8% vs. 20.5%, p < 0.05).


It depends.

  • If ciprofol and propofol were cost-equivalent, ciprofol would gain some market share, and might prove to be a superior drug to propofol. However, when and if it is FDA-approved in the United States, ciprofol will cost significantly more than propofol because ciprofol will be on patent. Hospitals and surgery centers will be reluctant to pay more for the drug unless there are proven advantages. Ciprofol appears to have significantly less pain on injection when compared to propofol, but pain on injection with propofol is not a major issue. Pain on injection does not lead to any long term adverse outcomes, and the pain can be blocked by injecting IV lidocaine immediately prior the initial dose of IV propofol. 
  • The data that ciprofol leads to less blood pressure decreases than propofol shows only a mild difference—too small an advantage to mandate replacing propofol with ciprofol for that reason alone.
  • So far there are no data to confirm or deny that there is any equivalent to propofol infusion syndrome with ciprofol. If there is no prolonged infusion syndrome, then ciprofol may find a market for ICU sedation of mechanically ventilated patients.
  • Overall, I believe ciprofol must promise a lack of respiratory depression if the new drug is to capture any of propofol’s market share for procedural sedation/surgical anesthesia. The most bothersome issue with propofol is the risk of respiratory depression, which requires an anesthesia professional or airway expert administer the drug. If a patient is oversedated with propofol, that patient may stop breathing or have upper airway obstructed breathing, which can lead to hypoxia, cardiac arrest, and anoxic brain damage. The FDA warnings for propofol include:

For general anesthesia or monitored anesthesia care (MAC) sedation, DIPRIVAN Injectable Emulsion should be administered only by persons trained in the administration of general anesthesia and not involved in the conduct of the surgical/diagnostic procedure. Sedated patients should be continuously monitored, and facilities for maintenance of a patent airway, providing artificial ventilation, administering supplemental oxygen, and instituting cardiovascular resuscitation must be immediately available. Patients should be continuously monitored for early signs of hypotension, apnea, airway obstruction, and/or oxygen desaturation. These cardiorespiratory effects are more likely to occur following rapid bolus administration, especially in the elderly, debilitated, or ASA-PS III or IV patients.

In the Li study above6.3% of the ciprofol patients had mild to moderate respiratory adverse events when sedated for GI endoscopy. While the 6.3% rate is lower than the 10.3% rate for the propofol patients, the non-zero incidence of respiratory events with ciprofol in this one study points to an anesthesia professional still needing to be present if ciprofol is administered for endoscopy.

In the Lan study above, during IV sedation only 2/75 ciprofol patients, compared with 17/75 propofol patients, required airway intervention such as with a chin-lift or a jaw-thrust maneuver during hysteroscopy (p< 0.05). This lower incidence of required airway intervention is encouraging, but the incidence is still not zero, and we’ll need more data to document the respiratory risks of ciprofol.

If ciprofol sedation is found to NOT produce any significant respiratory depression, apnea, or upper airway obstruction (therefore less risk of hypoxia and anoxic brain damage), this would be a profound advance over propofol. Then ciprofol could be administered for procedural sedation, e.g. for gastroenteroscopy, without an anesthesia airway expert attending to the patient. There is insufficient studies to date to know whether this will be true or not.

My guess? After all the data is in, ciprofol will cause a non-zero incidence of respiratory depression, and therefore a non-zero risk of hypoxia and anoxic brain damage, so an anesthesia airway expert will be necessary to administer the drug. The advantage of ciprofol’s lower but non-zero incidence of required airway intervention will not be a major advance in the hands of anesthesia professionals. The higher cost of ciprofol will preclude the decision of hospitals and surgery centers to switch to ciprofol until the new drug is off patent.

We’ll have to wait for more data on ciprofol, but don’t be surprised if propofol remains on top of the intravenous sedative/hypnotic anesthesia drug pedestal after the studies are concluded.




The most popular posts for laypeople on The Anesthesia Consultant include: How Long Will It Take To Wake Up From General Anesthesia? Why Did Take Me So Long To Wake From General Anesthesia? Will I Have a Breathing Tube During Anesthesia? What Are the Common Anesthesia Medications? How Safe is Anesthesia in the 21st Century? Will I Be Nauseated After General Anesthesia? What Are the Anesthesia Risks For Children?


The most popular posts for anesthesia professionals on The Anesthesia Consultant  include: 10 Trends for the Future of Anesthesia Should You Cancel Anesthesia for a Potassium Level of 3.6? 12 Important Things to Know as You Near the End of Your Anesthesia Training Should You Cancel Surgery For a Blood Pressure = 170/99? Advice For Passing the Anesthesia Oral Board Exams What Personal Characteristics are Necessary to Become a Successful Anesthesiologist?