Impact of Anesthesia Maintenance Methods on Incidence of Postoperative Delirium

Delirium Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02662257
• Other study ID #: 2015[869]-1
• Secondary ID: ChiCTR-IPR-15006
• Status: Completed
• Phase: N/A
• Start date: April 1, 2015
• Est. completion date: November 26, 2017

Study information

• Verified date: March 2022
• Source: Peking University First Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1228
• Est. completion date: November 26, 2017
• Est. primary completion date: September 29, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 90 Years

Eligibility

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).

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Delirium
• Postoperative Cognitive Complications
• Postoperative Cognitive Dysfunction
• Postoperative Complications

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Beijing Shijitan Hospital	Beijing	Beijing
China	Peking University Cancer Hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	Peking University School and Hospital of Stomatology	Beijing	Beijing
China	The Third Xiangya Hospital of Central South University	Changsha	Hunan
China	Guizhou Provincial People's Hospital	Guiyang	Guizhou
China	Zhongda Hospital	Nanjing	Jiangsu
China	Cancer Hospital of Guangxi Medical University	Nanning	Guangxi
China	Shenzhen Second People's Hospital	Shenzhen	Guangzhou
China	Hebei Medical University Forth Hospital	Shijiazhuang	Hebei
China	Shaanxi Provincial People's Hospital	Taiyuan	Shanxi
China	Shanxi Province Cancer Hospital	Taiyuan	Shanxi
China	Tianjin Nankai Hospital	Tianjin
China	Tang-Du Hospital	Xi'an	Shaanxi
China	Affiliated Hospital of Qinghai University	Xining	Qinghai
China	Ningxia People's Hospital	Yinchuan	Ningxia
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (14)

Lead Sponsor

Collaborator

Peking University First Hospital

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

Country where clinical trial is conducted

China, 

References & Publications (6)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Intensity of pain within 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).	Up to 3 days after surgery.
Other	Subjective sleep quality within 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).	Up to 7 days after surgery.
Other	Cognitive dysfunction assessment	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.	The day before surgery and on the 7th day after surgery
Other	Serum vitamine D concentration	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.	The day before surgery
Primary	Incidence of delirium within 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.	Up to 7 days after surgery
Secondary	Percentage of intensive care unit (ICU) admission after surgery.	Percentage of intensive care unit (ICU) admission after surgery.	Within 24 hours after surgery.
Secondary	Percentage of ICU admission with endotracheal intubation after surgery.	Percentage of ICU admission with endotracheal intubation after surgery.	Within 24 hours after surgery.
Secondary	Length of stay in ICU after surgery.	Length of stay in ICU after surgery (in patients admitted to the ICU after surgery).	Up to 30 days after surgery.
Secondary	Length of stay in hospital after surgery.	Length of stay in hospital after surgery.	Up to 30 days after surgery.
Secondary	Incidence of non-delirium complications within 30 days.	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.	Up to 30 days after surgery.
Secondary	Cognitive function at 30 days after surgery.	Cognitive function assessed with Telephone Interview for Cognitive Status-Modified (TICS-m).	On the 30th day after surgery.