Comparison of Intravenous Anesthetics to Volatile Anesthetics on Postoperative Cognitive Dysfunction

Comparison of Total Intravenous Anesthesia With Sevoflurane-based Balanced Anesthesia on Postoperative Cognitive Dysfunction in Elderly Patients for Major Elective Intra-abdominal Surgery

Post-operative cognitive dysfunction (POCD) is a fairly well-documented clinical phenomenon. Most patients will receive general anesthesia during surgery. Two groups of general anesthetics are used for this purpose. We hypothesize that the incidence of POCD is not different in patients received intravenous anesthetics only or sevoflurane (a volatile anesthetic-based general anesthesia) for their major intra-abdominal surgery.

Study Overview

• Status: Completed
• Conditions: Intra-abdominal and Intrapelvic Surgery
• Intervention / Treatment: Drug: Sevoflurane; Drug: propofol; Drug: remifentanil

Detailed Description

Patients who are 60 years old or older for laparoscopic abdominal surgery will be randomly assigned into two groups: 1) sevoflurane-based general anesthesia group, and 2) propofol-based general anesthesia group. Each group will need 221 patients to detect 1/3 of decrease or increase in the rate of POCD of one group compared with another group at about one week after surgery, assuming the overall rate of POCD at this time is about 40% at this time. Considering about 10% loss to follow-up, we will have 250 patients in each group. In addition, investigators will need 184 subjects in the control group. The data of these control subjects will be used to normalize the data of the two studied groups to diagnose POCD. The subjects in control groups will also be elderly but without the exposure to anesthesia and surgery.

• Study Type: Interventional
• Enrollment (Estimated): 684
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-sen Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. major elective gastrointestinal, gynecological, prostate or bladder surgery patients who are ≥ 60 years old.
2. the surgery is laparoscopic surgery and is expected to last for ≥ 2 hours under general anesthesia and the patient will stay in hospital for at least 7 days after surgery.
3. lack of serious hearing and vision impairment and be able to read so that neurobehavioral tests can be performed.

Exclusion Criteria:

1. Patients are not expected to be alive for longer than 3 months.
2. Mini-mental State Examination (MMSE) [18] score ≤ 23.
3. history of dementia, psychiatric illness or any diseases of central nervous system.
4. current use of sedatives or antidepressant.
5. alcoholism and drug dependence.
6. patients previously included in this study (for patients who have second intra-abdominal surgery during the study period).
7. difficult to follow up or patients with poor compliance.
8. uncontrolled hypertension (> 180/100 mmHg)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sevoflurane & remifentanil; sevoflurane at 0.5 to 1.5 minimum alveolar concentrations plus remifentanil (0.1 - 0.5 µg/kg/min) during the surgery.	Drug: Sevoflurane; Drug: remifentanil
Active Comparator: propofol & remifentanil; propofol (50 - 150 µg/kg/min) and remifentanil (0.1 - 0.5 µg/kg/min)	Drug: propofol; Drug: remifentanil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with postoperative cognitive dysfunction (POCD) (POCD is a composite outcome measure)	Incidence of POCD in patients will be determined by a set of cognitive tests.	At 7 days after the surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with postoperative cognitive dysfunction (POCD) (POCD is a composite outcome measure)	Incidence of POCD in patients will be determined by a set of cognitive tests.	At 3 months after the surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time for bowel function return after surgery	when bowel movement is returned.	up to 2 weeks after the surgery
Degree of increase of stress hormones	blood concentrations of stress hormones.	Up to 1 day after the surgery
Length of hospital stay	duration of staying in the hospital	Up to 3 months after the surgery
colorectal cancer progress	Migration, invasion and metastasis of the cancer	Up to one year after the surgery
degree of systemic inflammation	inflammatory cytokines in the blood	Up to 7 days after surgery
aging biochemical markers	such as length of the telomere	Up to 7 days after surgery

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: First Affiliated Hospital, Sun Yat-Sen University; Nanfang Hospital of Southern Medical University; Third Affiliated Hospital, Sun Yat-Sen University; First People's Hospital of Foshan; Huaqiao Hospital in Guangzhou, China; Guangdong Provincial People's Hospital, China; Baxter (China) Investment Co. Ltd.

Publications and helpful links

General Publications

• Monk TG, Weldon BC, Garvan CW, Dede DE, van der Aa MT, Heilman KM, Gravenstein JS. Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology. 2008 Jan;108(1):18-30. doi: 10.1097/01.anes.0000296071.19434.1e.
• Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, Mark DB, Reves JG, Blumenthal JA; Neurological Outcome Research Group and the Cardiothoracic Anesthesiology Research Endeavors Investigators. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med. 2001 Feb 8;344(6):395-402. doi: 10.1056/NEJM200102083440601. Erratum In: N Engl J Med 2001 Jun 14;344(24):1876.
• Steinmetz J, Christensen KB, Lund T, Lohse N, Rasmussen LS; ISPOCD Group. Long-term consequences of postoperative cognitive dysfunction. Anesthesiology. 2009 Mar;110(3):548-55. doi: 10.1097/ALN.0b013e318195b569.
• Williams-Russo P, Sharrock NE, Mattis S, Szatrowski TP, Charlson ME. Cognitive effects after epidural vs general anesthesia in older adults. A randomized trial. JAMA. 1995 Jul 5;274(1):44-50.
• Rasmussen LS, Johnson T, Kuipers HM, Kristensen D, Siersma VD, Vila P, Jolles J, Papaioannou A, Abildstrom H, Silverstein JH, Bonal JA, Raeder J, Nielsen IK, Korttila K, Munoz L, Dodds C, Hanning CD, Moller JT; ISPOCD2(International Study of Postoperative Cognitive Dysfunction) Investigators. Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients. Acta Anaesthesiol Scand. 2003 Mar;47(3):260-6. doi: 10.1034/j.1399-6576.2003.00057.x.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): April 1, 2019
• Study Completion (Actual): April 1, 2019

Study Registration Dates

• First Submitted: March 6, 2013
• First Submitted That Met QC Criteria: March 8, 2013
• First Posted (Estimated): March 12, 2013

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 19, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Postoperative Complications; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Postoperative Cognitive Complications; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Platelet Aggregation Inhibitors; Analgesics, Opioid; Narcotics; Hypnotics and Sedatives; Anesthetics, Inhalation; Remifentanil; Propofol; Sevoflurane
• Other Study ID Numbers: ZZuo-POCD-1