Impact of Anesthesia Maintenance Methods on Incidence of Postoperative Delirium

NCT ID: NCT02662257

Last Updated: 2022-03-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

1228 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-04-01

Study Completion Date

2017-11-26

Brief Summary

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Surgery is one of the major treatment methods for patients with malignant tumor. And, alone with ageing process, more and more elderly patients undergo surgery for malignant tumor. Evidence emerges that choice of anesthetics, i.e., either inhalational or intravenous anesthetics, may influence the outcome of elderly patients undergoing cancer surgery. Delirium is a commonly occurred early postoperative cognitive complication in the elderly, and its occurrence is associated with the worsening outcomes. Choice anesthetics may influence the occurrence of postoperative delirium. However, evidence in this aspect is conflicting.

Detailed Description

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It is estimated that 234.2 million major surgical procedures are undertaken every year worldwide. Surgery is one of the major treatment methods for patients with malignant tumor. And, alone with ageing process, more and more elderly patients undergo surgery for malignant tumor. Evidence emerges that choice of anesthetics, i.e., either inhalational or intravenous anesthetics, may influence the outcome of elderly patients undergoing cancer surgery.

Delirium is a commonly occurred cognitive complication in elderly patients after surgery. The occurrence of delirium is associated with the worsening outcomes, including increased morbidity and mortality, prolonged hospital stay, elevated medical care cost, and declined cognitive function. High age, major surgery, and critical illness are major risk factors of postoperative delirium (POD). However, the relationship between use of general anesthetics and occurrence of delirium cannot be excluded.

There are studies that compared the effects of two kinds of anesthetics on the cognitive outcomes after surgery. In the study of Nishikawa et al., 50 elderly (≥ 65 years) patients undergoing long-duration laparoscope-assisted surgery randomly received sevoflurane or propofol anesthesia. The results showed that, although the incidence of POD was not significantly different between the two groups, the delirium rating scale (DRS) score was significantly lower in the sevoflurane group than in the propofol group at postoperative days 2-3 (P = 0.007 and 0.002, respectively). In the study of Schoen et al., 128 patients undergoing on-pump cardiac surgery were randomized into two groups. The results showed that early postoperative cognitive function was significantly better in sevoflurane group than in the propofol group, especially in those who experienced cerebral desaturation during surgery.

On the other hand, some studies reported contrary results. In a large sample size study of 2000 patients undergoing general anesthesia, patients carrying ApoE4 epsilon 4 allele were more likely to develop early postoperative cognitive decline after inhalational anesthesia (odd ratio 3.31, 95% confidence interval 1.25-6.39, P \< 0.05), but not after intravenous anesthesia (odd ratio 0.93, 95% confidence interval 0.37-2.39, P \> 0.05). In a randomized control trail of 44 patients undergoing carotid endarterectomy, the mini-mental state examination (MMSE) score was significantly higher, whereas blood S100B concentration was significantly lower in the propofol group than in the sevoflurane group at 24 hours after surgery. In the study of Tang et al., 200 elderly (≥ 60 years) patients with mild cognitive impairment who planned to undergo radical rectal resection randomly received either sevoflurane or propofol anesthesia. The results showed that, although there was no difference in the incidence of cognitive dysfunction at 7 days after surgery, the negative cognitive effects was more severe after sevoflurane anesthesia than after propofol anesthesia (P = 0.01).

It seems that more evidence suggests the harmful cognitive effects of inhalational anesthetics. However, care must be taken when explaining these results: (1) target patients population were different; (2) sample size were small in the majority of studies; (3) the diagnostic criteria of cognitive complications were different, make it hard to do meta-analysis; (4) the clinical significance the of early postoperative cognitive complication remains to be elucidated.

Conditions

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Delirium Postoperative Complications Postoperative Cognitive Dysfunction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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Sevoflurane group

Sevoflurane will be administered by inhalation for anesthesia maintenance. The concentration of inhaled sevoflurane will be adjusted to maintain the bispectral index (BIS) value between 40 and 60. Analgesia will be supplemented with remifentanil (administered by continuous infusion), sufentanil (administered by intermittent injection/continuous infusion), or fentanyl (administered by intermittent injection).

Towards the end of surgery, sevoflurane inhalational concentration will be decreased and fentanyl/sufentanil will be administered when necessary. Sevoflurane inhalation will be stopped at the end of surgery.

Group Type ACTIVE_COMPARATOR

Sevoflurane

Intervention Type DRUG

Sevoflurane will be administered by inhalation for anesthesia maintenance. The concentration of inhaled sevoflurane will be adjusted to maintain the bispectral index (BIS) value between 40 and 60. Analgesia will be supplemented with remifentanil (administered by continuous infusion), sufentanil (administered by intermittent injection/continuous infusion), or fentanyl (administered by intermittent injection).

Towards the end of surgery, sevoflurane inhalational concentration will be decreased and fentanyl/sufentanil will be administered when necessary. Sevoflurane inhalation will be stopped at the end of surgery.

Propofol group

Propofol will be administered by intravenous infusion for anesthesia maintenance. The infusion rate of propofol will be adjusted to maintain the BIS value between 40 and 60. Analgesia will be supplemented with remifentanil (administered by continuous infusion), sufentanil (administered by intermittent injection/continuous infusion), or fentanyl (administered by intermittent injection).

Towards the end of surgery, propofol infusion rate will be decreased and fentanyl/sufentanil will be administered when necessary. Propofol infusion will be stopped at the end of surgery.

Group Type EXPERIMENTAL

Propofol

Intervention Type DRUG

Propofol will be administered by intravenous infusion for anesthesia maintenance. The infusion rate of propofol will be adjusted to maintain the BIS value between 40 and 60. Analgesia will be supplemented with remifentanil (administered by continuous infusion), sufentanil (administered by intermittent injection/continuous infusion), or fentanyl (administered by intermittent injection).

Towards the end of surgery, propofol infusion rate will be decreased and fentanyl/sufentanil will be administered when necessary. Propofol infusion will be stopped at the end of surgery.

Interventions

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Sevoflurane

Sevoflurane will be administered by inhalation for anesthesia maintenance. The concentration of inhaled sevoflurane will be adjusted to maintain the bispectral index (BIS) value between 40 and 60. Analgesia will be supplemented with remifentanil (administered by continuous infusion), sufentanil (administered by intermittent injection/continuous infusion), or fentanyl (administered by intermittent injection).

Towards the end of surgery, sevoflurane inhalational concentration will be decreased and fentanyl/sufentanil will be administered when necessary. Sevoflurane inhalation will be stopped at the end of surgery.

Intervention Type DRUG

Propofol

Propofol will be administered by intravenous infusion for anesthesia maintenance. The infusion rate of propofol will be adjusted to maintain the BIS value between 40 and 60. Analgesia will be supplemented with remifentanil (administered by continuous infusion), sufentanil (administered by intermittent injection/continuous infusion), or fentanyl (administered by intermittent injection).

Towards the end of surgery, propofol infusion rate will be decreased and fentanyl/sufentanil will be administered when necessary. Propofol infusion will be stopped at the end of surgery.

Intervention Type DRUG

Other Intervention Names

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Sevoflurane for inhalation Propofol for injection

Eligibility Criteria

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Inclusion Criteria

Participants will be included if they meet all the following criteria:

1. Age ≥ 65 years and \< 90 years;
2. Primary malignant tumor;
3. Do not receive radiation therapy or chemotherapy before surgery;
4. Scheduled to undergo surgery for the treatment of tumors, with an expected duration of 2 hours or more, under general anesthesia;
5. Agree to participate, and give signed written informed consent.

Exclusion Criteria

Patients will be excluded if they meet any of the following criteria:

1. Preoperative history of schizophrenia, epilepsy, parkinsonism or myasthenia gravis;
2. Inability to communicate in the preoperative period (coma, profound dementia, language barrier, or end-stage disease);
3. Critical illness (preoperative American Society of Anesthesiologists physical status classification ≥ IV), severe hepatic dysfunction (Child-Pugh class C), or severe renal dysfunction (undergoing dialysis before surgery);
4. Neurosurgery;
5. Other reasons that are considered unsuitable for participation by the responsible surgeons or investigators (reasons must be recorded in the case report form).
Minimum Eligible Age

65 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hebei Medical University Fourth Hospital

OTHER

Sponsor Role collaborator

The People's Hospital of Ningxia

OTHER

Sponsor Role collaborator

Beijing Shijitan Hospital, Capital Medical University

OTHER

Sponsor Role collaborator

Guizhou Provincial People's Hospital

OTHER

Sponsor Role collaborator

Affiliated Hospital of Qinghai University

OTHER

Sponsor Role collaborator

The Third Xiangya Hospital of Central South University

OTHER

Sponsor Role collaborator

Cancer Hospital of Guangxi Medical University

OTHER

Sponsor Role collaborator

Shanxi Provincial People's Hospital

OTHER_GOV

Sponsor Role collaborator

Zhongda Hospital

OTHER

Sponsor Role collaborator

The First Affiliated Hospital of Zhengzhou University

OTHER

Sponsor Role collaborator

Tang-Du Hospital

OTHER

Sponsor Role collaborator

Tianjin Nankai Hospital

OTHER

Sponsor Role collaborator

Shenzhen Second People's Hospital

OTHER

Sponsor Role collaborator

Peking University First Hospital

OTHER

Sponsor Role lead

Responsible Party

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Dong-Xin Wang

Professor and Chairman, Department of Anesthesiology and Critical Care Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Dong-Xin Wang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Peking University First Hospital

Locations

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Peking University First Hospital

Beijing, Beijing Municipality, China

Site Status

Beijing Shijitan Hospital

Beijing, Beijing Municipality, China

Site Status

Peking University Cancer Hospital

Beijing, Beijing Municipality, China

Site Status

Peking University School and Hospital of Stomatology

Beijing, Beijing Municipality, China

Site Status

Cancer Hospital of Guangxi Medical University

Nanning, Guangxi, China

Site Status

Shenzhen Second People's Hospital

Shenzhen, Guangzhou, China

Site Status

Guizhou Provincial People's Hospital

Guiyang, Guizhou, China

Site Status

Hebei Medical University Forth Hospital

Shijiazhuang, Hebei, China

Site Status

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Site Status

The Third Xiangya Hospital of Central South University

Changsha, Hunan, China

Site Status

Zhongda Hospital

Nanjing, Jiangsu, China

Site Status

Ningxia People's Hospital

Yinchuan, Ningxia, China

Site Status

Affiliated Hospital of Qinghai University

Xining, Qinghai, China

Site Status

Tang-Du Hospital

Xi'an, Shaanxi, China

Site Status

Shaanxi Provincial People's Hospital

Taiyuan, Shanxi, China

Site Status

Shanxi Province Cancer Hospital

Taiyuan, Shanxi, China

Site Status

Tianjin Nankai Hospital

Tianjin, , China

Site Status

Countries

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China

References

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Weiser TG, Regenbogen SE, Thompson KD, Haynes AB, Lipsitz SR, Berry WR, Gawande AA. An estimation of the global volume of surgery: a modelling strategy based on available data. Lancet. 2008 Jul 12;372(9633):139-144. doi: 10.1016/S0140-6736(08)60878-8. Epub 2008 Jun 24.

Reference Type BACKGROUND
PMID: 18582931 (View on PubMed)

Nishikawa K, Nakayama M, Omote K, Namiki A. Recovery characteristics and post-operative delirium after long-duration laparoscope-assisted surgery in elderly patients: propofol-based vs. sevoflurane-based anesthesia. Acta Anaesthesiol Scand. 2004 Feb;48(2):162-8. doi: 10.1111/j.0001-5172.2004.00264.x.

Reference Type BACKGROUND
PMID: 14995937 (View on PubMed)

Schoen J, Husemann L, Tiemeyer C, Lueloh A, Sedemund-Adib B, Berger KU, Hueppe M, Heringlake M. Cognitive function after sevoflurane- vs propofol-based anaesthesia for on-pump cardiac surgery: a randomized controlled trial. Br J Anaesth. 2011 Jun;106(6):840-50. doi: 10.1093/bja/aer091. Epub 2011 Apr 25.

Reference Type BACKGROUND
PMID: 21518736 (View on PubMed)

Cai Y, Hu H, Liu P, Feng G, Dong W, Yu B, Zhu Y, Song J, Zhao M. Association between the apolipoprotein E4 and postoperative cognitive dysfunction in elderly patients undergoing intravenous anesthesia and inhalation anesthesia. Anesthesiology. 2012 Jan;116(1):84-93. doi: 10.1097/ALN.0b013e31823da7a2.

Reference Type BACKGROUND
PMID: 22108393 (View on PubMed)

Kalimeris K, Kouni S, Kostopanagiotou G, Nomikos T, Fragopoulou E, Kakisis J, Vasdekis S, Matsota P, Pandazi A. Cognitive function and oxidative stress after carotid endarterectomy: comparison of propofol to sevoflurane anesthesia. J Cardiothorac Vasc Anesth. 2013 Dec;27(6):1246-52. doi: 10.1053/j.jvca.2012.12.009. Epub 2013 May 30.

Reference Type BACKGROUND
PMID: 23725684 (View on PubMed)

Tang N, Ou C, Liu Y, Zuo Y, Bai Y. Effect of inhalational anaesthetic on postoperative cognitive dysfunction following radical rectal resection in elderly patients with mild cognitive impairment. J Int Med Res. 2014 Dec;42(6):1252-61. doi: 10.1177/0300060514549781. Epub 2014 Oct 22.

Reference Type BACKGROUND
PMID: 25339455 (View on PubMed)

Cao SJ, Zhang Y, Zhang YX, Zhao W, Pan LH, Sun XD, Jia Z, Ouyang W, Ye QS, Zhang FX, Guo YQ, Ai YQ, Zhao BJ, Yu JB, Liu ZH, Yin N, Li XY, Ma JH, Li HJ, Wang MR, Sessler DI, Ma D, Wang DX; First Study of Perioperative Organ Protection (SPOP1) investigators. Delirium in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: a multicentre randomised trial. Br J Anaesth. 2023 Aug;131(2):253-265. doi: 10.1016/j.bja.2023.04.024. Epub 2023 Jun 4.

Reference Type DERIVED
PMID: 37474241 (View on PubMed)

Zhang Y, Shan GJ, Zhang YX, Cao SJ, Zhu SN, Li HJ, Ma D, Wang DX; First Study of Perioperative Organ Protection (SPOP1) Investigators. Preoperative vitamin D deficiency increases the risk of postoperative cognitive dysfunction: a predefined exploratory sub-analysis. Acta Anaesthesiol Scand. 2018 Aug;62(7):924-935. doi: 10.1111/aas.13116. Epub 2018 Mar 26.

Reference Type DERIVED
PMID: 29578249 (View on PubMed)

Zhang Y, Li HJ, Wang DX, Jia HQ, Sun XD, Pan LH, Ye QS, Ouyang W, Jia Z, Zhang FX, Guo YQ, Ai YQ, Zhao BJ, Yang XD, Zhang QG, Yin N, Tan HY, Liu ZH, Yu JB, Ma D. Impact of inhalational versus intravenous anaesthesia on early delirium and long-term survival in elderly patients after cancer surgery: study protocol of a multicentre, open-label, and randomised controlled trial. BMJ Open. 2017 Nov 28;7(11):e018607. doi: 10.1136/bmjopen-2017-018607.

Reference Type DERIVED
PMID: 29187413 (View on PubMed)

Other Identifiers

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ChiCTR-IPR-15006209

Identifier Type: REGISTRY

Identifier Source: secondary_id

2015[869]-1

Identifier Type: -

Identifier Source: org_study_id

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