Impact of Anesthesia Maintenance Methods on Incidence of Postoperative Delirium

Sponsor

Peking University First Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02662257

Collaborator

Hebei Medical University Fourth Hospital (Other), The People's Hospital of Ningxia (Other), Beijing Shijitan Hospital, Capital Medical University (Other), Guizhou Provincial People's Hospital (Other), Affiliated Hospital of Qinghai University (Other), The Third Xiangya Hospital of Central South University (Other), Cancer Hospital of Guangxi Medical University (Other), Shanxi Provincial People's Hospital (Other), Zhongda Hospital (Other), The First Affiliated Hospital of Zhengzhou University (Other), Tang-Du Hospital (Other), Tianjin Nankai Hospital (Other), Shenzhen Second People's Hospital (Other)

1,228

Enrollment

Locations

Arms

31.9

Actual Duration (Months)

72.2

Patients Per Site

2.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Delirium Postoperative Complications Postoperative Cognitive Dysfunction	Drug: Sevoflurane Drug: Propofol	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

1228 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Primary Purpose:

Prevention

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

Actual Study Start Date :

Apr 1, 2015

Actual Primary Completion Date :

Sep 29, 2017

Actual Study Completion Date :

Nov 26, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: 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. Other Names: Sevoflurane for inhalation
Experimental: 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.	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. Other Names: Propofol for injection

Arm

Intervention/Treatment

Active Comparator: 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.

Drug: Sevoflurane

Other Names:

Sevoflurane for inhalation

Experimental: 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.

Drug: Propofol

Other Names:

Propofol for injection

Outcome Measures

Primary Outcome Measures

Incidence of delirium within 7 days after surgery. [Up to 7 days after surgery]
Delirium is assessed twice daily (8-10 AM and 6-8 PM) with the Confusion Assessment Method for patients without endotracheal intubation or the Confusion Assessment Method for the Intensive Care Unit for patients with endotracheal intubation.

Secondary Outcome Measures

Percentage of intensive care unit (ICU) admission after surgery. [Within 24 hours after surgery.]
Percentage of intensive care unit (ICU) admission after surgery.
Percentage of ICU admission with endotracheal intubation after surgery. [Within 24 hours after surgery.]
Percentage of ICU admission with endotracheal intubation after surgery.
Length of stay in ICU after surgery. [Up to 30 days after surgery.]
Length of stay in ICU after surgery (in patients admitted to the ICU after surgery).
Length of stay in hospital after surgery. [Up to 30 days after surgery.]
Length of stay in hospital after surgery.
Incidence of non-delirium complications within 30 days. [Up to 30 days after surgery.]
Non-delirium complications are defined as newly occurred events other than delirium that are harmful to patients' recovery and required therapeutic intervention, i.e., grade 2 or higher on the Clavien-Dindo classification.
Cognitive function at 30 days after surgery. [On the 30th day after surgery.]
Cognitive function assessed with Telephone Interview for Cognitive Status-Modified (TICS-m).

Other Outcome Measures

Intensity of pain within 3 days after surgery. [Up to 3 days after surgery.]
Intensity of pain is assessed twice daily (8-10 AM and 6-8 PM) with the Numeric Rating Scale (an 11-point rating scale where 0 = no pain and 10 = the worst pain).
Subjective sleep quality within 7 days after surgery. [Up to 7 days after surgery.]
Subjective sleep quality is assessed once daily (8-10 AM) with the Numeric Rating Scale (an 11-point rating scale where 0 = the worst sleep and 10 = the best sleep).
Cognitive dysfunction assessment [The day before surgery and on the 7th day after surgery]
Cognitive function assessed with a battery of neuropsychological tests before surgery and on the 7th day after surgery. Performed in part of enrolled patients and in control subjects.
Serum vitamine D concentration [The day before surgery]
Blood samples are taken the day before surgery. Serum 25-hydroxyvitamin D concentration is measured with liquid chromatography-mass spectrometry. Performed in part of enrolled patients.

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria

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

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

Exclusion criteria

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

Preoperative history of schizophrenia, epilepsy, parkinsonism or myasthenia gravis;
Inability to communicate in the preoperative period (coma, profound dementia, language barrier, or end-stage disease);
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);
Neurosurgery;
Other reasons that are considered unsuitable for participation by the responsible surgeons or investigators (reasons must be recorded in the case report form).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking University First Hospital	Beijing	Beijing	China	10034
2	Beijing Shijitan Hospital	Beijing	Beijing	China
3	Peking University Cancer Hospital	Beijing	Beijing	China
4	Peking University School and Hospital of Stomatology	Beijing	Beijing	China
5	Cancer Hospital of Guangxi Medical University	Nanning	Guangxi	China
6	Shenzhen Second People's Hospital	Shenzhen	Guangzhou	China
7	Guizhou Provincial People's Hospital	Guiyang	Guizhou	China
8	Hebei Medical University Forth Hospital	Shijiazhuang	Hebei	China
9	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan	China
10	The Third Xiangya Hospital of Central South University	Changsha	Hunan	China
11	Zhongda Hospital	Nanjing	Jiangsu	China
12	Ningxia People's Hospital	Yinchuan	Ningxia	China
13	Affiliated Hospital of Qinghai University	Xining	Qinghai	China
14	Tang-Du Hospital	Xi'an	Shaanxi	China
15	Shaanxi Provincial People's Hospital	Taiyuan	Shanxi	China
16	Shanxi Province Cancer Hospital	Taiyuan	Shanxi	China
17	Tianjin Nankai Hospital	Tianjin		China