Pharmacokinetics and pharmacodynamics of ciprofol after continuous infusion in elderly patients

Abstract

Background

Ciprofol, a novel intravenous anesthetic, which has primarily been used for the induction and maintenance of general anesthesia in adults, is characterized by rapid onset, short duration of action, and quick and smooth recovery. However, the pharmacokinetic characteristics of continuous infusions and the correlation between the plasma concentration and the bispectral index (BIS) in elderly patients are still unknown.

Method

In this randomized, controlled study, thirty elderly patients (62–78 years old) undergoing elective gastrointestinal tumor resection were treated with propofol (N = 15) or ciprofol (N = 15) as sedatives during anesthesia. After induction, ciprofol/propofol was continuously infused intravenously until the end of the operation. Perioperative vital signs, injection pain, adverse events (AEs), BIS values, eyelid reflex disappearance times, and recovery times were recorded. The plasma concentrations of ciprofol and propofol were measured by liquid chromatography tandem mass spectrometry (LC‒MS/MS) and the pharmacokinetics were determined by noncompartmental analysis.

Results

Both drugs caused a decrease in blood pressure and heart rate after induction. Eight cases (53. 3%) of hypotension and 3 cases (20%) of bradycardia occurred in the propofol group, while 8 cases (53. 3%) of hypotension and 5 cases (33. 3%) of bradycardia occurred in the ciprofol group. At intubation, the ciprofol group experienced fewer fluctuations in blood pressure than the propofol group. Ciprofol resulted in only one case (6.7%) of mild injection pain, less than that produced by propofol (10/15, 66.7%) (P < 0.05). Anesthesia induction was successfully completed with both drugs, and there were no significant differences in eyelash reflex disappearance or recovery time between the two groups. The plasma concentrations during maintenance were relatively stable in both groups (propofol 1.78 ± 0.67 μg/mL, ciprofol 0.71 ± 0.23 μg/mL), and a suitable depth of sedation was achieved with a BIS of 40–60. The pharmacokinetic (PK) parameters for ciprofol are listed as follows: Maximum Plasma Concentration (Cmax) 6.02 ± 2.13 μg/ml; Time to Maximum Concentration (Tmax) 0.18 ± 0.62 min; Apparent Volume of Distribution (Vz) 3.96 ± 0.84 L/kg; Total Clearance (CL) 0.83 ± 0.14 L/h/kg; Half-life (t½) 3.47 ± 1.85 h; Area Under the Curve (AUC) 5000 ± 900 L/h/kg; Terminal Elimination Rate Constant (λz) 0.23 ± 0.07 1/h. Similar to propofol, the plasma concentration of ciprofol was linearly correlated with the BIS.

Conclusion

Ciprofol, a novel intravenous anesthetic, can be safely and effectively used in elderly patient continuous infusion with minimal injection pain. Plasma concentrations of ciprofol correlate well with BIS values, helping control sedation depth. For elderly patients undergoing gastrointestinal tumor surgery, an optimal maintenance dose of 0.8 mg/kg/h is recommended.

Trial registration

This clinical trial (registration No: ChiCTR2100047580, https://www.chictr.org.cn. The pre-registration date was June 20, 2021, and the review approval and official case solicitation began in December 2021; Retrospectively registered) was conducted in accordance with the World Medical Congress Declaration of Helsinki and Good Clinical Practice guidelines. All study subjects provided written informed consent.

Highlights

• Ciprofol can be safely and effectively used in elderly patients for continuous infusion.

• The plasma concentration of ciprofol has a good correlation with the BIS value.

• Sedation level during ciprofol anesthesia can be controlled according to the BIS value.

Key findings and recommendations

• Safety and Efficacy: Ciprofol can be administered safely and effectively via continuous infusion in elderly patients.

• Injection Pain: Administration of ciprofol results in minimal to no injection pain, which is a significant advantage over other anesthetics.

• Sedation Control: The plasma concentration of ciprofol is closely related to BIS values, facilitating precise control over the patient’s level of sedation.

• Recommended Maintenance Dose: For elderly patients undergoing gastrointestinal tumor surgery, the optimal maintenance dose of ciprofol is recommended to be 0.8 mg/kg/h.

Introduction

Propofol, a gamma-aminobutyric acid (GABA) receptor agonist, is a classic intravenous anesthetic that is characterized by a quick onset, rapid systemic clearance and small individual variations in the required dose [1]. It is widely used for induction and maintenance of general anesthesia, and for sedation in ICU or gastrointestinal endoscopy [2, 3]. However, it is encumbered with disadvantages such as respiratory depression, hemodynamic disorders, cardiac inhibition and injection pain [4].

A new intravenous anesthetic, ciprofol (HSK3486; Haisco Pharmaceutical Group Co. Ltd, Chengdu, China) [5, 6], was developed to avoid the adverse effects of propofol. Ciprofol is similar to propofol in chemical structure (Fig. 1) but with single R-configured diastereoisomers [5]. Ciprofol exhibits stronger binding to the GABA_A receptor, elicits a greater enhancement of GABA_A receptor-mediated neuronal currents in vitro and reduces the pain of injection compared to propofol [5, 7]. Additionally, ciprofol is also characterized by rapid induction and elimination [8] and has been shown to be safe for anesthesia induction, maintenance, and sedation among ICU patients [7, 9,10,11].

Fig. 1

Structures of ciprofol and propofol

An increasing number of older patients require anesthesia and surgery in China. Older patients are frail and have decreased tolerance to anesthesia and surgery, and increased risks for postoperative morbidity and mortality. Therefore, ensuring the quality and safety of anesthesia in elderly patients is particularly important, ideally via the development of individualized anesthesia plans with an emphasis on ensuring hemodynamic stability and selecting an appropriate general anesthesia protocol. To date, clinical research on ciprofol in elderly patients has focused on the efficacy, safety and dose of anesthesia induction [12]. However, there are few studies on continuous drug infusion, especially regarding the pharmacokinetics of continuous ciprofol infusions in elderly patients [13].

Therefore, in this single-center, randomized controlled study, elderly patients (over 60 years old) who underwent elective surgery for gastrointestinal tumors were recruited to assess the pharmacokinetics after continuous infusions of ciprofol in elderly patients in China. We evaluated the safety of ciprofol during the induction and maintenance period. The secondary objective was to study the blood concentration of ciprofol and its correlation with the bispectral index (BIS) in elderly patients. This study could provide a basis for the application of ciprofol in elderly patients.

Materials and methods

Human ethics and consent to participate declarations

This clinical trial was approved by the Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medicine University. This clinical trial (registration No: ChiCTR2100047580, https://www.chictr.org.cn. The pre-registration date was June 20, 2021, and the review approval and official case solicitation began in December 2021; Retrospectively registered) was conducted in accordance with the World Medical Congress Declaration of Helsinki and Good Clinical Practice guidelines. All study subjects provided written informed consent.

Subjects

From December 2021 to December 2022, 30 elderly patients who underwent elective gastrointestinal tumor surgery were enrolled and randomly assigned to the propofol group or the ciprofol group. The inclusion criteria were as follows: age greater than or equal to 60 years; American Society of Anesthesiologists (ASA) grades I-II; elective surgery for gastrointestinal tumor; and BMI between 18 and 30 kg/m². The duration of the operation was 3–4 h. The exclusion criteria were as follows: a history of previous anesthesia accidents; known or suspected allergies or contraindications to propofol or ciprofol injection excipients, benzodiazepines, opioids, muscle relaxants, etc.; significant cardiovascular, respiratory or renal disease; a family history of malignant hyperthermia; previous general anesthesia within 3 months; and a history of drug abuse.

Study protocol

A certified anesthesiologist was present during the whole surgery until the subject recovered consciousness and demonstrated normal cardiovascular and respiratory function. The monitoring of vital signs started 10 min before induction and included blood pressure (BP), electrocardiography (ECG), SpO₂ and BIS (obtained with a BIS VISTA™ monitor, Aspect Medical Systems, Norwood, MA, United States). Before anesthesia induction, 500 ml of sodium lactate Ringer’s balanced salt solution was infused. Intravenous induction was used for all patients. The induction scheme was as follows: sufentanil 0.4 µg/kg; ciprofol/propofol 0.4/2 mg/kg; atracurium 0.2 mg/kg. The loading doses in both groups were given over 1 min. Endotracheal intubation was performed 1 min after the administration of the muscle relaxant. The maintenance medication was started 2 min after induction. According to the latest study [14], the initial maintenance dose of ciprofol was 1.0 mg/kg/h and that of propofol was 5 mg/kg/h. Remifentanil was administered at 0.1–0.4 μg/kg/min. The maintenance doses were adjusted to maintain the BIS in a suitable and safe range of 40–60. Ciprofol was initially administered at 1.0 mg /kg/h and the infusion rate was adjusted by 0.1–0.4 mg/kg/h, with minimum and maximum allowed infusion rates of 0.4 mg/kg/h and 1.5 mg/kg/h, respectively. Propofol was administered initially at 5.0 mg/kg/h and the rate was adjusted as appropriate by 1–2 mg/kg/h, with minimum and maximum allowed infusion rates of 2.0 mg/kg/h and 7.5 mg/kg/h, respectively. Intravenous drug infusion was stopped at the end of surgery, and the antagonist was given if the train-of-four (TOF) ratio was still < 0.9. The tracheal tube was removed when consciousness and spontaneous breathing were restored. The patient’s BIS value was monitored during the whole process until the patient was awake and the tracheal tube was removed. The flowchart of the study could be seen in Fig. 2.

Fig. 2

Flowchart of the study

Safety

Perioperative adverse events (AEs), including hypoxia, bradycardia, hypotension, and perioperative vital signs, were recorded. Hypoxia was defined as SpO₂ < 90% for > 30 s; bradycardia was defined as heart rate < 50 beats/minute and > 0.2 min duration; and hypotension was defined as systolic blood pressure (SBP) < 90 mmHg or a relative 30% decrease from baseline. Perioperative vital signs, including heart rate, respiratory rate, SpO₂, SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP), and temperature, were also recorded.

Injection pain

Injection pain was assessed before consciousness disappeared. Injection pain was defined as a complaint of pain from the patient or movement of the fingers of the injected hand. Pain was measured by the Faces Pain Scale-Revised (FPS-R).

Efficacy

The outcomes included successful induction of anesthesia, stabilization of the BIS value during maintenance, eyelash reflex disappearance time, and time to recovery of consciousness after discontinuation.

Measurements

Plasma concentrations of ciprofol and propofol

Radial artery blood samples (2 ml) were collected in K₂EDTA vacuum-anticoagulant tubes at the time of loss of eyelash reflex (LOR), 2 min after induction, and during maintenance at 5 min, 10 min, 15 min, 25 min and every 30 min thereafter. After drug discontinuation, further blood samples were collected at 5 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, and 6 h.

Ciprofol and propofol concentrations were determined by validated liquid chromatography methods with tandem mass spectrometric detection (LC‒MS/MS) [15]. The HSK23287 internal standard was used for both ciprofol and propofol. The LLOQ (Lower Limit of Quantitation) was 10 ng/mL for ciprofol and 200 ng/mL for propofol, respectively.

The average plasma concentration during maintenance was determined in each patient as the mean of the measured plasma concentrations within this period.

Pharmacokinetics

The pharmacokinetics of ciprofol and propofol were assessed by standard noncompartmental analysis using DAS 3.0 (Chinese Pharmacological Association, Anhui, China) [16]. The maximum plasma concentration (Cmax) and time to maximum plasma concentration (Tmax) were calculated from the individual concentration–time data. The area under the plasma concentration–time curve from 0 to the last quantifiable concentration (AUC0–t) was computed using the linear trapezoidal rule. The AUC from time zero extrapolated to infinity AUC (0-∞) was calculated as the sum of AUC0-t and a residual part extrapolated to infinite time. The terminal elimination half-life (t1/2), total clearance (CL), distribution volume (Vz), and mean residence time (MRT) were also calculated.

Statistical analysis

The data were processed by SPSS 20.0 statistical software. Continuous variables are given as mean ± standard deviation (SD), and categorical variables are given as numbers and percentages. Continuous data were tested for differences between propofol and ciprofol using the t-test, intragroup comparisons were performed using the paired t-test. The Mann–Whitney and the Wilcoxon test were used if the data were not normally distributed. Categorical variables were compared using the χ2 test. The relationship between the plasma concentrations of propofol or ciprofol and BIS was assessed by linear regression analysis. A P value less than 0.05 was considered statistically significant.

Results

Demographic and clinical data

From December 2021 to December 2022, 32 eligible patients participated in this study. Ultimately, 30 patients (15 in the propofol group and 15 in the ciprofol group) were analyzed. In the propofol group, 2 patients were excluded from the analysis because their blood samples were taken at the wrong time. The types of surgery included radical gastrectomy and colorectal tumorectomy. There were no significant differences in the patient data between the two groups (Table 1).

Table 1 Demographic and clinical data

The anesthesia duration; total doses of propofol/Ciprofol (mg), and remifentanil (μg/kg); maintenance infusion rates of propofol and Ciprofol (mg/kg/h) were shown in Table 2.

Table 2 Summary of anesthesia time and drug dosage

Efficacy

Ciprofol was noninferior to propofol in terms of effectiveness. All patients in both groups lost consciousness after the loading dose, manifested by loss of eyelash reflexes and decreased BIS values. Both groups successfully completed the anesthesia induction.

There was no significant difference in the BIS value at LOR or eyelash reflex disappearance time between the two groups after induction. However, patients injected with ciprofol had a slightly longer recovery time than those injected with propofol, but the difference was not significant (Table 3).

Table 3 Efficacy analysis of both groups

Safety

We monitored and documented AEs during anesthesia including hypoxia, injection pain, delayed postoperative recovery, bradycardia, hypotension, and intraoperative awareness. Few adverse events occurred in either group. Phenylephrine and atropine were used to treat hypotension and bradycardia, respectively, and none of the patients experienced serious sequelae, and patients in the ciprofol group clearly experienced less injection pain (Table 4).

Table 4 Adverse events

Injection pain

We observed that fewer patients experienced injection pain with ciprofol compared to those who received propofol (Table 4). Additionally, the injection pain associated with propofol was mostly moderate, whereas the pain from ciprofol was generally mild (Table 5).

Table 5 Injection pain in both groups

Circulatory system changes during the induction phase

We observed that both ciprofol and propofol caused a decrease in blood pressure and heart rate after induction. The maximum decrease in mean arterial pressure (MAP) and heart rate (HR) occurred between induction and tracheal intubation (T2), with MAP decreasing by 29.3% ± 4.55 for ciprofol and 29.3% ± 4.25 for propofol, and HR decreasing by 17.8% ± 4.15 for ciprofol and 18.9% ± 4.14 for propofol, respectively. Following intubation, both MAP and HR began to increase and gradually recovered within 1 min (Fig. 3 A, B). There were no significant differences in the fluctuations of MAP and HR after induction (Fig. 3 A, B, D). However, at T3 (1 min after tracheal intubation), the difference in MAP fluctuations between the two groups was statistically significant (Fig. 3 C), with the ciprofol group exhibiting lower-amplitude fluctuations compared to the propofol group.

Fig. 3

Effects of propofol or ciprofol induction on mean arterial pressure and heart rate. A Average change in mean arterial pressure during induction. B Average change in heart rate during induction. C Percentage change in mean arterial pressure during induction relative to preoperative pressure. D Percentage change in heart rate during induction relative to preoperative heart rate. T0 before induction, T1 1 min after induction, T2 before tracheal intubation, T3 1 min after tracheal intubation, T4 3 min after tracheal intubation, T5 5 min after tracheal intubation. * Indicates a statistically significant difference between the two groups (P = 0.027)

Pharmacokinetics

Plasma concentrations

The plasma concentrations of the two drugs are shown in Fig. 4. Peak concentrations of both ciprofol and propofol appeared shortly after induction. The plasma concentrations of propofol and ciprofol during maintenance were relatively stable with average concentrations of 1.78 ± 0.66 μg/mL for propofol and 0.71 ± 0.23 μg/mL for ciprofol, respectively. The plasma concentration of both drugs decreased gradually over time after the infusion ended.

Fig. 4

Plasma concentration–time curves of ciprofol and propofol. Data are reported as the mean ± standard deviation

Pharmacokinetic parameters

The pharmacokinetic parameters of the patients are shown in Table 6. The This table provided a comprehensive comparison of the pharmacokinetic parameters between ciprofol and propofol, highlighting significant differences in Cmax, AUC, λz, and CL, while Tmax, t1/2, MRT, and Vz show less pronounced or non-significant differences.

Table 6 Pharmacokinetics of ciprofol and propofol

Pharmacodynamics: BIS

We recorded the BIS (Bispectral Index) values of each volunteer at specific time points (Fig. 5A, B). There were no significant differences in BIS values between the two groups of patients at baseline, after induction, during the continuous drug infusion, and at the time of recovery.. There was a linear relationship between the drug concentration and BIS value in both the ciprofol group (r = 0.33, P < 0.01) and the propofol group (r = 0.26, P < 0.01) (Fig. 6).

Fig. 5

The BIS (Bispectral Index) values of the two drugs at various time points. A ciprofol; B propofol. (A1, Pre-induction BIS; A2, BIS before intubation; A3, BIS one minute after intubation; A4, BIS three minutes after intubation; A5, BIS five minutes after intubation. Descriptions of the remaining time points can be found in the Methods section.)

Fig. 6

Correlation between bispectral index (BIS) values and plasma concentrations of ciprofol and propofol

Discussion

Ciprofol has been widely used for induction of anesthesia. Several studies have confirmed that it can be safely used for anesthesia induction in patients [7] and for continuous sedation [13] in patients on mechanical ventilation in the ICU [17]. This study is the first to assess the safety, efficacy, and pharmacokinetic (PK) properties of ciprofol during continuous infusion in elderly patients undergoing elective gastrointestinal tumor resection according to the actual clinical use. Additionally, we investigated the correlation between plasma drug concentrations and BIS values.

Dosage requirements, individualized administration and AEs

The literature indicates that elderly patients are more sensitive to anesthetics due to reduced metabolic capacity and increased central nervous system responsiveness. A recommended induction dose of 0.3 mg/kg for ciprofol in this population aims to mitigate hemodynamic adverse effects [10]. Regarding the induction dose of ciprofol, we indeed referred to some literature recommending a dose of 0.3 mg/kg during the study design. However, previous studies only evaluated a single injection, without considering its effects on intubation. In our study, a 0.3 mg/kg induction dose was insufficient to effectively suppress the hemodynamic response to tracheal intubation, necessitating an increase to 0.4 mg/kg [10]. Based on previous findings, we further tested a dose of 0.4 mg/kg administered via a micro-infusion pump over 1 min. This approach demonstrated better sedation and more effective suppression of the intubation response in clinical practice. This adjustment may have contributed to the high incidence of hypotension (53.3%) and bradycardia (33.3%). Larger-scale studies are needed to further validate the safety and efficacy of this dosing regimen.

Propofol, a classic general anesthetic, is known for its drawbacks, including respiratory depression, hemodynamic instability, cardiac inhibition, and injection pain [4]. In contrast, most AEs associated with ciprofol were mild, and no severe AEs were observed. Although this study demonstrated that ciprofol exhibited smaller mean arterial pressure (MAP) fluctuations during induction (at the T3 time point) compared to propofol, there were no significant differences in hemodynamic trends between the two drugs at other observation time points. Therefore, we cannot conclusively infer that ciprofol provides more hemodynamic stability than propofol during the induction phase. Based on the current data, the hemodynamic effects of ciprofol during induction in elderly patients appear to be similar to those of propofol. We believe that the clinical relevance of this difference may be further validated in a study with a larger sample size.Therefore, we conclude that there are no clinically significant hemodynamic differences between the two drugs. Furthermore, ciprofol was non-inferior to propofol in terms of effectiveness, providing satisfactory sedation with induction doses of 0.4 mg/kg and maintenance doses of 0.8 mg/kg/h.

BIS values and continuous intravenous infusion

Excessive anesthesia depth can lead to complications such as delayed postoperative recovery and delirium, which affect patient recovery and increase medical costs [18]. Monitoring anesthesia depth is therefore crucial. Propofol’s advantage lies in its strong correlation between plasma drug concentration and BIS value, allowing anesthesiologists to adjust dosing intraoperatively to maintain appropriate anesthesia depth and reduce complications [19]. Our study demonstrated a good linear relationship between ciprofol’s plasma concentration and BIS values, likely related to its action on GABA receptors [10]. Clinically, BIS values can serve as a reference for monitoring ciprofol-induced anesthesia depth.

In our study, BIS values were maintained within a suitable range of 40–60. The average plasma concentration during the maintenance phase in the ciprofol group was 0.71 ± 0.23 μg/mL, with a corresponding continuous intravenous infusion rate of 0.82 ± 0.23 mg/kg/h, suitable for elderly patients. This provides a basis for the administration of ciprofol as target-controlled infusion (TCI) in this population.

Comparison of pharmacokinetic characteristics of ciprofol and propofol in elderly patients

In this study, we compared the pharmacokinetic characteristics of ciprofol and propofol in elderly patients. Through the analysis of various pharmacokinetic parameters, we have made several important findings. Despite showing certain similarities in metabolic properties among elderly patients, ciprofol and propofol exhibit significant differences in multiple pharmacokinetic parameters (Cmax, AUC, λz, and CL). We hope that this study can provide additional guidance for clinical applications.

Cmax represents the maximum plasma concentration reached by a drug, which is an important parameter for assessing drug absorption rate and initial exposure levels, reflecting the immediate effects of the drug. AUC reflects the overall systemic exposure to the drug, directly impacting treatment efficacy and side effect risk, making it a key parameter for evaluating drug efficacy and safety. Our study found that in elderly patients, ciprofol had significantly lower Cmax (6.02 ± 2.13 μg/mL vs. 15.0 ± 8.20 μg/mL, P < 0.001) and AUC (4750 ± 800 μg/L·h vs. 11,200 ± 3260 μg/L·h, P < 0.001) compared to propofol. Lower Cmax and AUC theoretically may help reduce rapid-onset side effects such as hypotension and respiratory depression, making ciprofol potentially advantageous in clinical settings requiring sustained, stable efficacy. Notably, at the T3 time point (1 min after tracheal intubation), the variability in mean arterial pressure (MAP) and heart rate was less for ciprofol than for propofol (P = 0.027). However, no differences were observed between the two drugs in circulatory effects during induction or recovery quality at other time points. Further validation with larger sample sizes is needed to confirm these theoretical assumptions.

CL (Clearance) is the rate at which a drug is removed from the body, directly affecting its duration of action. λz (Elimination Rate Constant) is a critical parameter for assessing the rate at which a drug is eliminated from the body. Our study found that ciprofol’s clearance (0.83 ± 0.14 L/h/kg vs. 1.52 ± 0.48 L/h/kg, P < 0.001) and elimination rate constant (0.23 ± 0.07 1/h vs. 0.47 ± 0.37 1/h, P = 0.02) were significantly lower than those of propofol. This suggests that ciprofol remains in the body for a longer period, and prolonged continuous infusion or delayed cessation could extend patient recovery time. This is particularly important for elderly patients. Additionally, the clearance rate of ciprofol in our study was lower than reported in non-elderly populations [20]. This discrepancy may be due to the fact that our participants were elderly cancer patients, whose pathophysiological conditions and prior treatments could influence the PK/PD characteristics of the drugs used. Considering the physiological differences in elderly patients, such as decreased liver and kidney function and increased fat content [21], the reduced clearance rate is understandable. This highlights the risk of slower drug clearance in elderly patients, which should be considered in clinical practice.

Injection pain

Injection pain, a common issue with propofol (incidence 60–70%), can be a significant source of discomfort [22]. Various methods, such as lidocaine, opioid, or ketamine pretreatment, or antecubital vein injection, have been considered but do not completely eliminate pain [22]. Ciprofol did not result in significant injection pain in this study, which might be related to its high hydrophilicity [5]. This would greatly enhance the comfort of the patient during the anesthesia process and increase usability.

Limitations

Elderly patients often have comorbidities, and interindividual metabolic differences are considerable. The 6-h post-infusion sampling, which may underestimate the terminal half-life. All patients regained consciousness 6 h post-surgery without any symptoms, suggesting that additional blood samples beyond this point may not be clinically meaningful. Future research should include extended sampling times, such as up to 12 h or longer, to better characterize terminal PK parameters. Moreover, this investigation only included surgeries lasting no more than four hours; further studies are needed to assess drug accumulation and delayed awakening times with longer infusions.

Conclusion

Ciprofol is a novel intravenous anesthetic. This study provides preliminary pharmacokinetic data on the continuous administration of ciprofol in elderly patients, offering initial insights into its clinical application in this population. The findings suggest that ciprofol can be safely and effectively used for continuous infusion in elderly patients with almost no noticeable injection pain. Plasma concentrations of ciprofol are closely correlated with Bispectral Index (BIS) values, aiding in the control of sedation depth. For elderly patients undergoing gastrointestinal tumor surgery, the optimal maintenance dose of ciprofol is recommended to be 0.8 mg/kg/h.