Anesthesia-analgesia Methods and Postoperative Delirium

This study is currently recruiting participants.
Verified August 2012 by Peking University First Hospital
Sponsor:
Collaborators:
Peking University People's Hospital
Peking University Third Hospital
Beijing Hospital
China-Japan Friendship Hospital
Beijing Shijitan Hospital
Peking University
Information provided by (Responsible Party):
Dongxin Wang, Peking University First Hospital
ClinicalTrials.gov Identifier:
NCT01661907
First received: August 2, 2012
Last updated: August 7, 2012
Last verified: August 2012
  Purpose

Postoperative delirium is a common complication in critically ill patients after surgery. Its occurrence is associated with poorer prognosis of the patients. The pathophysiology of delirium remains poorly understood. A universal phenomenon is that delirium was frequently identified in elderly patients after major complicated surgery, but was rarely noted after minor ambulatory surgery (such as cataract surgery). This indicated that stress response produced by surgery might have an important role in the pathogenesis of delirium. It has been reported that, when compared with general anesthesia and postoperative intravenous analgesia, neuraxial anesthesia and analgesia reduced the occurrence of postoperative complications and mortality in high risk patients. Combined epidural-general anesthesia is frequently used in clinical practice. This anesthesia method provides advantages of both epidural and general anesthesia, i.e. it blocks the afferent pathway of nociceptive stimulus by neuraxial blockade during and after surgery, and allows patients to endure lengthy complicated operations without any awareness. The investigators hypothesize that combined epidural-general anesthesia and postoperative epidural analgesia can decrease the incidence of postoperative delirium and, thus, improve the prognosis of critically ill elderly patients undergoing major surgery. The purpose of this study is to compare the effects of combined epidural-general anesthesia/postoperative epidural analgesia and general anesthesia/postoperative intravenous analgesia on the incidence of postoperative delirium in elderly patients undergoing major surgery.


Condition Intervention
Delirium
Postoperative Complications
Other: Combined Epi-GA/PCEA

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Effects of Two Different Anesthesia-analgesia Methods on the Incidence of Postoperative Delirium: a Multicenter, Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by Peking University First Hospital:

Primary Outcome Measures:
  • Incidence of postoperative delirium [ Time Frame: during the first 7 postoperative days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of postoperative complications [ Time Frame: within 30 days after surgery ] [ Designated as safety issue: Yes ]
  • 30-day mortality [ Time Frame: within 30 days after surgery ] [ Designated as safety issue: Yes ]
  • VAS pain score [ Time Frame: during the first 3 postoperative days ] [ Designated as safety issue: No ]
  • Duration of hospital stay after surgery [ Time Frame: from date of surgery until hospital discharge, an expected average of 1 to 2 weeks ] [ Designated as safety issue: Yes ]
  • Daily prevalence of postoperative delirium [ Time Frame: during the first 7 postoperative days ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Serum cortisol concentration [ Time Frame: before anesthesia, the 1st and 3rd day after surgery ] [ Designated as safety issue: No ]
  • Serum IL-6 concentration [ Time Frame: before anesthesia, the 1st and 3rd day after surgery ] [ Designated as safety issue: No ]
  • Serum IL-8 concentration [ Time Frame: before anesthesia, the 1st and 3rd day after surgery ] [ Designated as safety issue: No ]

Estimated Enrollment: 1800
Study Start Date: November 2011
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combined Epi-GA/PCEA

Patients assigned to this group (experimental group) will receive combined epidural-general anesthesia (combined Epi-GA) and patient controlled epidural analgesia (PCEA).

An epidural catheter will be placed prior to anesthesia induction. General anesthesia will be induced and maintained in the same manner as in the control group, with the addition of continuous infusion or intermittent boluses of 0.5%-0.75% ropivacaine given through the epidural catheter for analgesia maintenance. If necessary, other types of opioids and muscle relaxants will also be allowed. Patient controlled epidural analgesia will be used for postoperative analgesia (1% ropivacaine 30ml and sufentanil 125ug diluted with normal saline to 250ml, continuous infusion 4 ml/hr, bolus 2ml and lockout interval 20 minutes).

Other: Combined Epi-GA/PCEA
General anesthesia will be performed in both arms. In the arm of combined Epi-GA/PCEA, an epidural catheter will be placed and a test dose of lidocaine will be administered before the induction of general anesthesia. Besides conventional general anesthesia, epidural anesthesia will be added with the use of 0.5%-0.75% ropivacaine during surgery. Patient controlled epidural analgesia will be used after surgery. In the arm of GA/PCIA, only general anesthesia will be performed during surgery and patient controlled intravenous analgesia will be used after surgery.
GA/PCIA

Patients assigned to this group (control group) will receive general anesthesia (GA) and patient controlled intravenous analgesia (PCIA).

General anesthesia will be induced with midazolam, sufentanil, propofol and rocuronium. Anesthesia is then maintained by inhalation of oxygen-nitrous oxide mixture (1:2) and sevoflurane, or continuous intravenous infusing of propofol. Sufentanil and rocuronium will be given when needed. If necessary, other types of opioids and muscle relaxants are also allowed. Patient controlled intravenous analgesia will be used for postoperative analgesia (morphine 50mg diluted with normal saline to 100 ml, continuous infusion 1 ml/hr, bolus 2ml and lockout interval 6-10 minutes).

Other: Combined Epi-GA/PCEA
General anesthesia will be performed in both arms. In the arm of combined Epi-GA/PCEA, an epidural catheter will be placed and a test dose of lidocaine will be administered before the induction of general anesthesia. Besides conventional general anesthesia, epidural anesthesia will be added with the use of 0.5%-0.75% ropivacaine during surgery. Patient controlled epidural analgesia will be used after surgery. In the arm of GA/PCIA, only general anesthesia will be performed during surgery and patient controlled intravenous analgesia will be used after surgery.

Detailed Description:

Delirium is a transient mental syndrome of acute onset characterized by global impairment of cognitive functions, reduced level of consciousness, abnormalities of attention, increased or decreased psychomotor activity, and disordered sleep-wake cycle. Postoperative delirium is a common complication in critically ill patients after surgery. Dyer et al reviewed 80 primary studies and found that the mean incidence of postoperative delirium is about 36.8% (range 0%-73.5%) after surgery. It occurred in up to 80% of patients in the ICU. Our recent studies found that the incidence of postoperative delirium occurring in patients at the SICU was 51.0% after cardiac surgery and 44.5% after non-cardiac surgery.

The occurrence of postoperative delirium is associated with poorer prognosis of the patients. Studies showed that delirious patients had prolonged ICU stay, increased incidence of complications, prolonged hospitalization, high mortality rate, and increased health care costs. Delirium is also associated with increased risk of long-term cognitive decline and poor quality of life. A recent follow-up study (mean follow-up time 27.9 ± 3.1 months) by our research group found that, after adjusting factors such as age, occurrence of postoperative complications, and stage of malignant tumors, etc, the occurrence of postoperative delirium still remained an independent predictor of long-term mortality in patients.

The pathophysiology of delirium remains poorly understood. A universal phenomenon is that delirium was frequently identified in elderly patients after major complicated surgery, but was rarely noted after minor ambulatory surgery (such as cataract surgery). Studies also found that postoperative pain was an independent risk factor of delirium, and effective pain relief may help to reduce the incidence of delirium. Our recent studies of patients undergoing cardiac or non-cardiac surgeries both showed that high serum cortisol level was an independent predictor of postoperative delirium. In addition, inflammatory response may also contribute to the pathogenesis of delirium. Trauma, pain, cortisol secretion and inflammation are all important components of surgical stress response. The above results indicated that stress response produced by surgery might have an important role in the pathogenesis of delirium.

Previous studies demonstrated that, when compared with general anesthesia, neuraxial anesthesia attenuated the hypersecretion of cortisol, and decreased the intensity of inflammatory response more effectively after surgery. And epidural analgesia provided better postoperative pain relief than intravenous analgesia. It was also reported that, when compared with general anesthesia and intravenous analgesia, neuraxial anesthesia and analgesia reduced the occurrence of postoperative complications and mortality in high risk patients. Combined epidural-general anesthesia is frequently used in clinical practice, and is performed in about 1/4 of patients undergoing surgery in the applicant's hospital. Theoretically, this anesthesia method provides advantages of both epidural and general anesthesia, i.e. it blocks the afferent pathway of nociceptive stimulus by neuraxial blockade during and after surgery, and allow patients to endure lengthy complicated operations without any awareness. However, because of the limitations of study methods and sample size, there were no clear answers to date on the difference between the incidences of postoperative delirium after general versus regional anesthesia. And there is no evidence whether combined epidural-general anesthesia can decrease the incidence of postoperative delirium and, thus, improve the prognosis of critically ill elderly patients undergoing major abdominal surgery.

The objective of the study is to compare the effects of combined epidural-general anesthesia and general anesthesia on the incidence of postoperative delirium in elderly patients undergoing major surgery.

  Eligibility

Ages Eligible for Study:   60 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Elderly (60-90 years) patients undergoing elective major (>=2 hours) open abdominal or open thoracic (non-cardiovascular) surgery;
  • Consent to use patient-controlled anesthesia after surgery;
  • Informed consent to participate in the study.

Exclusion Criteria:

  • Refusal to participate in the study;
  • Diagnosed psychiatric disorders and neurological diseases such as epilepsy, Parkinson's Disease; Unable to complete preoperative questionnaire, for example, patients with dementia, language disorder, end-stage diseases, in coma etc;
  • History of acute myocardial infarction during the last 3 months;
  • Contraindications to epidural anesthesia;
  • Severe hepatic disfunction or renal disfunction, or preoperative ASA grade IV;
  • Physician in charge do not agree the participation;
  • Allergy to drugs involved in the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01661907

Contacts
Contact: Ya-Wei Li, MD +86 13810481891 liyaweibmu@hotmail.com
Contact: Yuan Zeng, MD +86 13520703600 yuan_zeng@sina.com

Locations
China
Department of Anesthesiology and Surgical Intensive Care Recruiting
Beijing, China, 100034
Contact: Ya-Wei Li, MD    +86 13810481891    liyaweibmu@hotmail.com   
Contact: Yuan Zeng, MD    +86 13520703600    yuan_zeng@sina.com   
Sub-Investigator: Huai-Jin Li, MD         
Sub-Investigator: Da Huang, MD         
Sub-Investigator: Hao Kong, MD         
Sponsors and Collaborators
Peking University First Hospital
Peking University People's Hospital
Peking University Third Hospital
Beijing Hospital
China-Japan Friendship Hospital
Beijing Shijitan Hospital
Peking University
Investigators
Principal Investigator: Dong-Xin Wang, MD, PhD Peking University First Hopital
  More Information

Publications:

Responsible Party: Dongxin Wang, Professor and Chairman, Department of Anesthesiology and Surgical Intensive Care, Peking University First Hospital
ClinicalTrials.gov Identifier: NCT01661907     History of Changes
Other Study ID Numbers: PUCRP201101
Study First Received: August 2, 2012
Last Updated: August 7, 2012
Health Authority: China: Ethics Committee

Keywords provided by Peking University First Hospital:
Elderly
Anesthesia and analgesia
Postoperative period
Delirium
Postoperative complications

Additional relevant MeSH terms:
Delirium
Delirium, Dementia, Amnestic, Cognitive Disorders
Postoperative Complications
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Mental Disorders
Pathologic Processes
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 23, 2014