According to a recent national survey, sedatives are used for gastrointestinal endoscopy at a rate of about 50% in China [3]. However, there is no recommended optimal sedation regimen for painless colonoscopic procedures. Propofol is widely used worldwide for sedation/anesthesia [12]. However, propofol can cause dose-dependent respiratory depression and hemodynamic instability. In addition, the incidence of injection pain caused by propofol sedation is 25–74% [13].

Ciprofol is a new 2,6-dissubstituted phenol derivative and a close analog of propofol [14]. Ciprofol is considered superior to propofol because of the following advantages: (1) higher affinity for γ-aminobutyric acid-A receptor-4–5 times that of propofol; (2) favorable respiratory profile and maintenance of stable cardiac function; and (3) reduced injection pain [8, 9, 15]. Therefore, we compared intravenous induction by 0.4 mg/kg ciprofol with, in terms of hemodynamic stability, induction by 2 mg/kg propofol for sedation in patients undergoing painless colonoscopy.

HRV is a noninvasive indicator that reflects the dynamic balance of nervous system regulation of the heart and blood vessels and indirectly reflects hemodynamic stabilization. Intravenous anesthesia drugs affect the balance of autonomic nerves by acting on the central and autonomic nervous systems of patients, resulting in changes in HRV [16].

Propofol reduces systemic vascular resistance and is associated with perioperative hypotension. Additionally, HRV dynamics changed through propofol sedation and propofol induction was followed by an overall reduction of HRV [17]. HRV decreased further with the further reduction of blood pressure by propofol sedation [18]. Time of RMSSD was used to analyze the depth of anesthesia as well as the reduction of blood pressure.

Up to 46% of patients experienced at least one episode of hypotension during the painless colonoscopy by propofol sedation in an analysis of 380 patients [1]. In our study, almost 51% of patients experienced at least one episode of hypotension after induction by propofol which was similar with previous studies. Although both ciprofol and propofol groups exhibited a decrease in blood pressure, significantly fewer subjects experienced reduced blood pressure in the ciprofol group. In addition, rates of severe hypotension in patients induced with ciprofol were significantly lower than in patients induced with propofol, despite norepinephrine being given at different time points when systolic BP decreased by 20% more than the baseline.

During induction, 6 or 8 mg/kg/h of ciprofol was superior in hemodynamic stability to 40 mg/kg/h of propofol [19]. Similar to our study, intravenous induction with 0.4 mg/kg ciprofol was superior, in terms of hemodynamic stability, to induction with 2 mg/kg propofol for sedation in patients undergoing painless colonoscopy. In addition, time of RMSSD was correspondingly higher in patients induced by ciprofol as the less reduction of blood pressure after induction. However, in Li’s study [10], hypotension just occured in 7.7% and 13.2% of the patients in the colonoscopy in the propofol and ciprofol groups, respectively, as patients received 300–500 ml of sterile 0.9% sodium chloride solution before sedation, and were given 1.5 mg/kg propofol which offered more equilibrium liquid to increase preload and less dose of propofol to inhibit the decrease of peripheral vascular resistance in order to raise blood pressure than patients in our study.

In Zeng’s study, induction and maintenance anesthesia in elective surgical patients by ciprofol produced less drug-related hypotension, indicating that ciprofol was superior in terms of hemodynamic stability than propofol; the results of our study are consistent with these findings [20]. In our study, both ciprofol and propofol groups experienced a significant drop in mean blood pressure after induction anesthesia. However, compared with the ciprofol group, more patients in the propofol group received norepinephrine and experienced longer episodes of low blood pressure, which reduced further to severe low mean blood pressure in a higher proportion of cases after induction sedation. These results indicated that the incidence of out-of-range low blood pressure was significantly attributed to long-term preoperative fasting and fluid deficiency; 200–300 ml of equilibrium fluid was insufficient to improve preoperative fluid loss before sedation. Our research showed that a larger proportion of patients in the propofol group (18.18–64.71%) but no more than 50% patients (25.00–50.00%) in the ciprofol group suffered hypotension during the painless colonoscopy procedure. This was attributed to insufficient liquid capacity, because most patients experienced a long duration of fasting (more than 12 h) and withheld fluids (2 h). Painless colonoscopy was less likely to irritate to the oropharynx and cause reflux aspiration or hypoxemia. Gratifyingly, quite a few patients in both groups needed airway intervention to ensure oxygenation.

Propofol is commonly associated with pain at the injection site, which occurs in as high as 50–70% of cases [10, 21]. Aqueous propofol solutions directly stimulate nerve endings in blood vessel walls or produce substances that lead to injection pain [22]. According to our study, more propofol-induced patients experienced severe pain; ciprofol and propofol both caused injection pain, at a rate of 1.82% and 33.04%, respectively. This difference may be related to emulsion modification, in that ciprofol has a lower free drug concentration in the aqueous phase under the same conditions than propofol.

All patients maintained MOAA/S scores of ≤ 1 during the procedure. Ciprofol exhibited a rapid onset of action and maintenance-similar to that of propofol. The present trial showed a comparable induction time (58.63 ± 5.59 s vs. 57.43 ± 5.57 s, P = 0.109) and time to full alertness (7.16 ± 1.61 min vs. 7.38 ± 1.87 min, P = 0.347) for ciprofol and propofol sedation. These findings are consistent with those of a phase II clinical trial evaluating the efficacy and safety of ciprofol for the induction and maintenance of general anesthesia in patients undergoing elective surgery [20]. However, time to full alertness in the phase III clinical trial for patients undergoing colonoscopy was longer for ciprofol-induced patients [23]. A possible reason for this is that the average time during painless colonoscopy sedation in our study was shorter than their average time for sedation. In regard to the most common drug-related adverse reactions, such as bradycardia, dizziness, nausea, and vomiting, a reduction in the total amount of sedative required as well as in adverse events was observed when 0.05 μg/kg of sufentanil was combined with either ciprofol or propofol sedation, which was similar to the findings of previous studies [3, 24].

When evaluating anesthetics for painless colonoscopies, it is essential to provide a comfortable experience for patients to ensure their compliance and to reduce adverse effects. In previous trials, propofol sedation was associated with high patient satisfaction because of its rapid onset and short duration. To evaluate patient satisfaction and comfort levels after painless colonoscopy with ciprofol, patients were asked to rate their pain perception, comfort, and drug-related adverse reactions using a satisfaction scale from 1 to 10, with higher scores indicating higher satisfaction. A similar satisfaction scale was devised for the endoscopists fluent in the procedure in order to evaluate the effectiveness of the sedatives. In the completed study, the endoscopist perceived no significant difference in satisfaction for both groups as the vast majority of the patients successfully completed the painless colonoscopy procedure without experiencing body movement, which was the most annoying problem. Nevertheless, patients in the ciprofol group reported higher satisfaction scores, mainly resulting from less pain during injection. Modified Aldrete scores were used to assess whether patients could be discharged after the procedure when they were alert; there was no significant difference in modified Aldrete scores and recovery time between the two groups, as both propofol and ciprofol have rapid onset and short duration of action.