Effect of Titrated Administration of Ciprofol on Perioperative Hypotension in Elderly Patients Undergoing Laparoscopic Abdominal Surgery: A Randomized Controlled Trial

Official title

Effect of Titrated Administration of Ciprofol Combined With Remifentanil on Perioperative Hypotension in Elderly Patients Undergoing Laparoscopic Abdominal Surgery: A Randomized Controlled Trial

Overview

Elderly patients are frequently burdened with age-associated comorbidities and frailty, accompanied by physiological changes such as vascular stiffening, cardiac dysfunction, and impaired autonomic regulation. These factors not only increase the risk of adverse perioperative outcomes but also heighten sensitivity to anesthetic agents, making elderly patients particularly susceptible to anesthesia-related complications, especially hypotension. Consequently, optimizing anesthesia strategies for this high-risk population has become a critical goal in perioperative management. Titrated anesthesia, which individualizes anesthetic drug delivery based on patient response to achieve predefined endpoints, offers a potential approach to mitigating anesthetic risks. Ciprofol, a novel intravenous anesthetic, has been associated with less hemodynamic suppression compared with traditional agents; however, higher single doses may still predispose patients to hypotension. Remifentanil, an ultra-short-acting opioid, exerts significant cardiovascular depressive effects, further contributing to perioperative hypotension. It is hypothesized that titrated administration of anesthetic agents during both the induction and maintenance phases, compared with conventional fixed-dose protocols, may reduce the incidence of perioperative hypotension in elderly patients.

Detailed description

This study aims to investigate whether titrated anesthesia can provide more stable hemodynamic conditions during surgery and whether this approach is associated with improved postoperative recovery in elderly patients.

Interventions

• Drug titrated anesthesia
  Anesthesia induction and maintenance will be performed with ciprofol and remifentanil. During the entire procedure, infusion rates will be adjusted according to a target BIS value of approximately 50, with anesthetic dosing continuously modified in response to BIS monitoring. The attending anesthesiologist will titrate anesthetic delivery based on BIS guidance rather than routine clinical judgment alone.

Primary outcome measures

• Incidence of intraoperative hypotension. [Time frame: From induction of general anesthesia to the end of surgery, assessed intraoperatively for up to 6 hours.]

Secondary outcome measures (12)

• the time-weighted area under the curve (TWA) for MAP <65 mmHg during the anesthesia period [Time frame: From induction of general anesthesia to the end of surgery, assessed intraoperatively for up to 6 hours.]
• cumulative dose of norepinephrine and the proportion of patients requiring vasoactive support; [Time frame: From induction of general anesthesia to the end of surgery, assessed intraoperatively for up to 6 hours.]
• the time-weighted area under the curve (TWA) for MAP <0.8 baseline during the anesthesia period [Time frame: From induction of general anesthesia to the end of surgery, assessed intraoperatively for up to 6 hours.]
• Time to first hypotension [Time frame: From induction of general anesthesia to the end of surgery, assessed intraoperatively for up to 6 hours.]
• CI trend during anesthesia [Time frame: From induction of general anesthesia to the beginning of surgery, assessed intraoperatively for up to 2 hours.]
• The time periods with a higher incidence of hypotension between the two groups [Time frame: From induction of general anesthesia to the end of surgery, assessed intraoperatively for up to 6 hours.]
• Total dose of ciprofol and remifentanil during surgery [Time frame: From induction of general anesthesia to the end of surgery, assessed intraoperatively for up to 6 hours.]
• Whether blood pressure variability (CV) and the average rate of blood pressure variation (ARV) are different. [Time frame: From induction of general anesthesia to the end of surgery, assessed intraoperatively for up to 6 hours.]
• The incidence of severe intraoperative hypotension [Time frame: From induction of general anesthesia to the end of surgery, assessed intraoperatively for up to 6 hours.]
• Time from discontinuation of anesthetic drugs to awakening. [Time frame: From discontinuation of anesthetic drugs to awakening, assessed up to 2 hours postoperatively.]
• the rate of postoperative delirium [Time frame: Postoperatively (4-6 hours), Day 1, Day 2, Day 3]
• Postoperative complications [Time frame: 30 days after the operation]

Eligibility criteria

Inclusion criteria

• Age ≥65 years, scheduled for elective laparoscopic abdominal surgery
• American Society of Anesthesiologists (ASA) physical status I-III
• Requirement for invasive arterial blood pressure monitoring

Exclusion criteria

• Participation in other clinical trials that may interfere with the intervention or outcomes of this study
• Severe hepatic or renal disease (GFR ≤30 mL/min/1.73 m², requirement for renal replacement therapy, or Child-Pugh class C liver function)
• Uncontrolled severe hypertension (preoperative SBP ≥180 mmHg or DBP ≥110 mmHg)
• Patients with severe mental disorders (such as schizophrenia), epilepsy, or Parkinson's disease, severe cognitive or intellectual impairment, severe visual or hearing impairments affecting assessment, or long-term alcohol abuse or use of sedative/analgesic medications;
• Known allergy to drugs used in this study
• Requirement for continuous vasopressor infusion before surgery, or intraoperative need for prolonged hemodynamic manipulation due to surgical factors
• Anticipated blood loss >15% of estimated blood volume
• Expected surgical duration <1 hours or >6 hours
• Expected postoperative hospital stay <72 hours

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 2 centers

• Sixth Affiliated Hospital, Sun Yat-sen University — Guangzhou
• Sixth Affiliated Hospital, Sun Yat-sen University — Guangzhou

Publications

• Cannon JW. Hemorrhagic Shock. N Engl J Med. 2018 Jan 25;378(4):370-379. doi: 10.1056/NEJMra1705649. No abstract available. PMID 29365303
• Dell-Kuster S, Gomes NV, Gawria L, Aghlmandi S, Aduse-Poku M, Bissett I, Blanc C, Brandt C, Ten Broek RB, Bruppacher HR, Clancy C, Delrio P, Espin E, Galanos-Demiris K, Gecim IE, Ghaffari S, Gie O, Goebel B, Hahnloser D, Herbst F, Ioannidis O, Joller S, Kang S, Martin R, Mayr J, Meier S, Murugesan J, Nally D, Ozcelik M, Pace U, Passeri M, Rabanser S, Ranter B, Rega D, Ridgway PF, Rosman C, Schmid PMID 32843333
• Lu Z, Zheng H, Chen Z, Xu S, Chen S, Mi W, Wang T, Chai X, Guo Q, Zhou H, Yu Y, Zheng X, Zhang J, Ai Y, Yu B, Bao H, Zheng H, Huang W, Wu A, Deng X, Ma H, Ma W, Tao L, Yang X, Zhang J, Liu T, Ma HP, Liang W, Wang X, Zhang Y, Du W, Ma T, Xie Y, Xie Y, Li N, Yang Y, Zheng T, Zhang C, Zhao Y, Dong R, Zhang C, Zhang G, Liu K, Wu Y, Fan X, Tan W, Li N, Dong H, Xiong L. Effect of Etomidate vs Propofol f PMID 35947398
• Futier E, Lefrant JY, Guinot PG, Godet T, Lorne E, Cuvillon P, Bertran S, Leone M, Pastene B, Piriou V, Molliex S, Albanese J, Julia JM, Tavernier B, Imhoff E, Bazin JE, Constantin JM, Pereira B, Jaber S; INPRESS Study Group. Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized C PMID 28973220
• Wildes TS, Mickle AM, Ben Abdallah A, Maybrier HR, Oberhaus J, Budelier TP, Kronzer A, McKinnon SL, Park D, Torres BA, Graetz TJ, Emmert DA, Palanca BJ, Goswami S, Jordan K, Lin N, Fritz BA, Stevens TW, Jacobsohn E, Schmitt EM, Inouye SK, Stark S, Lenze EJ, Avidan MS; ENGAGES Research Group. Effect of Electroencephalography-Guided Anesthetic Administration on Postoperative Delirium Among Older Adu PMID 30721296
• Salmasi V, Maheshwari K, Yang D, Mascha EJ, Singh A, Sessler DI, Kurz A. Relationship between Intraoperative Hypotension, Defined by Either Reduction from Baseline or Absolute Thresholds, and Acute Kidney and Myocardial Injury after Noncardiac Surgery: A Retrospective Cohort Analysis. Anesthesiology. 2017 Jan;126(1):47-65. doi: 10.1097/ALN.0000000000001432. PMID 27792044
• Maheshwari K, Turan A, Mao G, Yang D, Niazi AK, Agarwal D, Sessler DI, Kurz A. The association of hypotension during non-cardiac surgery, before and after skin incision, with postoperative acute kidney injury: a retrospective cohort analysis. Anaesthesia. 2018 Oct;73(10):1223-1228. doi: 10.1111/anae.14416. Epub 2018 Aug 24. PMID 30144029
• D'Souza AW, Hissen SL, Manabe K, Takeda R, Washio T, Coombs GB, Sanchez B, Fu Q, Shoemaker JK. Age- and sex-related differences in sympathetic vascular transduction and neurohemodynamic balance in humans. Am J Physiol Heart Circ Physiol. 2023 Oct 1;325(4):H917-H932. doi: 10.1152/ajpheart.00301.2023. Epub 2023 Aug 18. PMID 37594483

Identifiers

NCT: NCT07328958 · 2025ZSLYEC-415

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗