Anesthesia-analgesia Methods and Postoperative Delirium
- Conditions
- ElderlyPostoperative DeliriumEpidural AnesthesiaGeneral AnesthesiaMajor Surgery
- Interventions
- Procedure: Combined Epi-GA/PCEAProcedure: GA/PCIA
- Registration Number
- NCT01661907
- Lead Sponsor
- Peking University First Hospital
- Brief Summary
Postoperative delirium is a common complication in elderly patients after surgery. Its occurrence is associated with worse outcomes. The pathophysiology of delirium remains poorly understood. However, an universal phenomenon is that delirium frequently occurs in elderly patients after major complicated surgery, but is rarely seen after minor ambulatory surgery (such as cataract surgery). This indicates 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 anesthetic 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 long-duration surgery without any awareness. The investigators hypothesize that combined epidural-general anesthesia and postoperative epidural analgesia can decrease the incidence of delirium in elderly patients after major surgery when compared with general anesthesia alone and postoperative intravenous analgesia.
- Detailed Description
Delirium is an acutely occurred and transient mental syndrome 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 elderly 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 occurs in up to 80% of patients in the intensive care unit (ICU). Our recent studies found that delirium occurred in 51.0% of patients after cardiac surgery and in 44.5% of patients after non-cardiac surgery.
The occurrence of postoperative delirium is associated with worse outcomes. Studies showed that delirious patients have 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 cancer, etc, the occurrence of postoperative delirium still remained an independent predictor of long-term mortality.
The pathophysiology of delirium remains poorly understood. An universal phenomenon is that delirium frequently occurs in elderly patients after major complicated surgery, but is rarely seen after minor ambulatory surgery (such as cataract surgery). Studies also found that postoperative pain is an independent risk factor of delirium, whereas effective pain relief may help to reduce the incidence of delirium. Our recent studies showed that high serum cortisol level is an independent risk factor 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 attenuates the hypersecretion of cortisol, and decreases the intensity of inflammatory response more effectively after surgery. And epidural analgesia provides better postoperative pain relief than intravenous analgesia. It was also reported that, when compared with general anesthesia and intravenous analgesia, neuraxial anesthesia and analgesia reduces 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 anesthetic 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 long-duration complicated surgeries without any awareness. However, there is no evidence whether combined epidural-general anesthesia/postoperative epidural analgesia can decrease the incidence of postoperative delirium in elderly patients undergoing major surgery.
The objective of the 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 noncardiac surgery.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1800
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Combined Epi-GA/PCEA 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 before anesthesia induction. General anesthesia will be induced and maintained in the same manner as in the control group, with the addition of a continuous infusion or intermittent boluses of 0.375%-0.5% ropivacaine given through the epidural catheter for analgesia maintenance. Patient-controlled epidural analgesia will be provided for postoperative analgesia (established with 0.12% ropivacaine and 0.5 μg/mL sufentanil in 250 mL normal saline, programmed to deliver a 2-mL bolus with a lockout interval of 20 minutes and a background infusion of 4 mL/hr). GA/PCIA 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 will then be maintained by inhalation of sevoflurane with or without nitrous oxide, and/or continuous intravenous infusion of propofol. Sufentanil and rocuronium will be given when needed. Patient-controlled intravenous analgesia will be provided for postoperative analgesia (established with 50 mg morphine in 100 mL normal saline, programmed to deliver a 2-mL bolus with a 6-10 minutes lockout interval and a 1 mL/hr background infusion).
- Primary Outcome Measures
Name Time Method Incidence of postoperative delirium During the first 7 days after surgery. Patients will be visited twice daily during the first seven days after surgery (between 08:00 h and 10:00 h, and between 18:00 h and 20:00 h). Delirium will be assessed with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). The incidence is calculated as percentage of patients who develope any episode of delirium during that period.
- Secondary Outcome Measures
Name Time Method Intensive care unit (ICU) admission after surgery During the day of surgery. The proportion of patients admitted to the ICU after surgery
APACHE II score at ICU admission Within 24 hours after surgery. For patients admitted to the ICU after surgery, the worst Acute Physiology and Chronic Health Evaluation II (APACHE II) score within 24 h will be recorded.
The percentage of ICU admission with endotracheal intubation During the day of surgery. The percentage of ICU admission with endotracheal intubation.
The duration of Mechanical Ventilation in ICU Up to 30 days after surgery. For patients admitted to the ICU after surgery, the duration of mechanical ventilation (for those with endotracheal tubes) will be recorded.
The Length of ICU stay Up to 30 days after surgery. For patients admitted to the ICU after surgery, the length of ICU stay will be recorded.
Time to the first onset of delirium Up to 7 days after surgery. Patients will be visited twice daily during the first seven days after surgery (between 08:00 h and 10:00 h, and between 18:00 h and 20:00 h). Delirium will be assessed with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).
Time to fluid/food intake Up to 30 days after surgery. Patients will be followed-up until 30 days after surgery and time to fluid and food intake after surgery will be recorded.
Length of stay in hospital after surgery Up to 30 days after surgery. Patients will be followed-up until 30 days after surgery.
All-cause 30-day mortality Within the first 30 days after surgery. All-cause 30-day mortality
Non-delirium complications within 30 days after surgery surgery Within the first 30 days after surgery. Defined as newly occurred medical conditions other than delirium that are harmful to patients' postoperative recovery and required therapeutic intervention (i.e., grade II or higher on the Clavien-Dindo classification).
The intensity of postoperative pain During the first 3 postoperative days. The intensity of postoperative pain both at rest and with movement will be evaluated twice daily at the same time of delirium assessment (between 08:00 h and 10:00 h, and between 18:00 h and 20:00 h) with the numeric rating scale (NRS, an 11-point scale where 0=no pain and 10=the worst pain).
Trial Locations
- Locations (1)
Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital
🇨🇳Beijing, China