Clinical trial NCT02662257: Impact of Anesthesia Maintenance Methods on Incidence of Postoperative Delirium
Official title: Impact of Inhalational Versus Intravenous Anesthesia Maintenance Methods on Incidence of Postoperative Delirium in Elderly Patients After Cancer Surgery: An Open-label, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Delirium
Postoperative Complications
Postoperative Cognitive Dysfunction
Keywords: Sevoflurane
Propofol
Aged
Neoplasm
Surgical Procedure, Operative
Delirium
Postoperative Complications
Postoperative Cognitive Dysfunction
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
Collaborators: name: Hebei Medical University Fourth Hospital
name: The People's Hospital of Ningxia
name: Beijing Shijitan Hospital, Capital Medical University
name: Guizhou Provincial People's Hospital
name: Affiliated Hospital of Qinghai University
name: The Third Xiangya Hospital of Central South University
name: Cancer Hospital of Guangxi Medical University
name: Shanxi Provincial People's Hospital
name: Zhongda Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: Tang-Du Hospital
name: Tianjin Nankai Hospital
name: Shenzhen Second People's Hospital
First posted: 2016-01-25
Enrollment: 1228
Sex: ALL
Minimum age (years): 65
Maximum age (years): 90
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Incidence of delirium within 7 days after surgery.
timeFrame: Up to 7 days after surgery
Secondary outcomes:
measure: Percentage of intensive care unit (ICU) admission after surgery.
timeFrame: Within 24 hours after surgery.
measure: Percentage of ICU admission with endotracheal intubation after surgery.
timeFrame: Within 24 hours after surgery.
measure: Length of stay in ICU after surgery.
timeFrame: Up to 30 days after surgery.
measure: Length of stay in hospital after surgery.
timeFrame: Up to 30 days after surgery.
measure: Incidence of non-delirium complications within 30 days.
timeFrame: Up to 30 days after surgery.
measure: Cognitive function at 30 days after surgery.
timeFrame: On the 30th day after surgery.
Other outcomes:
measure: Intensity of pain within 3 days after surgery.
timeFrame: Up to 3 days after surgery.
measure: Subjective sleep quality within 7 days after surgery.
timeFrame: Up to 7 days after surgery.
measure: Cognitive dysfunction assessment
timeFrame: The day before surgery and on the 7th day after surgery
measure: Serum vitamine D concentration
timeFrame: The day before surgery
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Shijitan Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University School and Hospital of Stomatology
state: Beijing
city: Nanning
country: China
facility: Cancer Hospital of Guangxi Medical University
state: Guangxi
city: Shenzhen
country: China
facility: Shenzhen Second People's Hospital
state: Guangzhou
city: Guiyang
country: China
facility: Guizhou Provincial People's Hospital
state: Guizhou
city: Shijiazhuang
country: China
facility: Hebei Medical University Forth Hospital
state: Hebei
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Zhongda Hospital
state: Jiangsu
city: Yinchuan
country: China
facility: Ningxia People's Hospital
state: Ningxia
city: Xining
country: China
facility: Affiliated Hospital of Qinghai University
state: Qinghai
city: Xi'an
country: China
facility: Tang-Du Hospital
state: Shaanxi
city: Taiyuan
country: China
facility: Shaanxi Provincial People's Hospital
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Province Cancer Hospital
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Nankai Hospital
Study officials:
affiliation: Peking University First Hospital
name: Dong-Xin Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: 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.
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citation: 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.
citation: 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.
citation: 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.
citation: 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.