Skip to content

Anesthesia-analgesia Methods and Postoperative Delirium

Effects of Two Different Anesthesia-analgesia Methods on the Incidence of Postoperative Delirium: a Multicenter, Randomized Controlled Trial

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01661907
Enrollment
1800
Registered
2012-08-10
Start date
2011-11-21
Completion date
2015-06-24
Last updated
2020-07-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Elderly, Epidural Anesthesia, General Anesthesia, Major Surgery, Postoperative Delirium

Keywords

Elderly, Epidural anesthesia, General anesthesia, Major surgery, Postoperative delirium

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.

Interventions

PROCEDUREGA/PCIA

General anesthesia will be induced with midazolam, propofol, sufentanil and rocuronium. Anesthesia will be maintained with either intravenous (propofol), inhalational (sevoflurane with or without nitrous oxide), or combined intravenous-inhalational anesthetics. Additional opioids (remifentanil, sufentanil, fentanyl, or morphine) and muscle relaxant (rocuronium, atracurium, or cisatracurium) will be administered when deemed necessary by the attending anesthesiologists. Patient-controlled intravenous analgesia will be provided after surgery.

PROCEDURECombined Epi-GA/PCEA

An epidural catheter will be placed before the induction of general anesthesia. General anesthesia will be induced and maintained as in the control group, with the addition of epidural anesthesia which will be maintained with the use of 0.375%-0.5% ropivacaine during surgery. Patient-controlled epidural analgesia will be provided after surgery.

Sponsors

Peking University People's Hospital
CollaboratorOTHER
Peking University Third Hospital
CollaboratorOTHER
Beijing Hospital
CollaboratorOTHER_GOV
Beijing Shijitan Hospital, Capital Medical University
CollaboratorOTHER
Peking University First Hospital
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
60 Years to 90 Years
Healthy volunteers
No

Inclusion criteria

1. elderly patients (age range 60-90 years); 2. scheduled to undergo noncardiac thoracic or abdominal surgery with an expected duration of 2 hours or longer. For those who undergo thoracoscopic or laparoscopic surgery, the expected length of incision must be 5 centimeters or more; 3. agree to receive patient-controlled postoperative analgesia.

Exclusion criteria

(patients who meet any of the following criteria will be excluded): 1. previous history of schizophrenia, epilepsy or Parkinson disease, or unable to complete preoperative assessment due to severe dementia, language barrier or end-stage disease; 2. history of myocardial infarction within 3 months before surgery; 3. any contraindication to epidural anesthesia and analgesia, including abnormal vertebral anatomy, previous spinal trauma or surgery, severe chronic back pain, coagulation disorder (prothrombin time or activated partial prothrombin time longer than 1.5 times of the upper limit of normal, or platelet count of less than 80 × 10\^9/L), local infection near the site of puncture, and severe sepsis; 4. severe heart dysfunction (New York Heart Association functional classification 3 or above), hepatic insufficiency (Child-Pugh grades C), or renal insufficiency (serum creatinine of 442 μmol/L or above, with or without serum potassium of 6.5 mmol/L or above, or requirement of renal replacement therapy); or 5. any other conditions that were considered unsuitable for study participation.

Design outcomes

Primary

MeasureTime frameDescription
Incidence of postoperative deliriumDuring 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

MeasureTime frameDescription
The Length of ICU stayUp to 30 days after surgery.For patients admitted to the ICU after surgery, the length of ICU stay will be recorded.
All-cause 30-day mortalityWithin the first 30 days after surgery.All-cause 30-day mortality
Non-delirium complications within 30 days after surgery surgeryWithin 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 painDuring 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).
The percentage of ICU admission with endotracheal intubationDuring the day of surgery.The percentage of ICU admission with endotracheal intubation.
Intensive care unit (ICU) admission after surgeryDuring the day of surgery.The proportion of patients admitted to the ICU after surgery
APACHE II score at ICU admissionWithin 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 duration of Mechanical Ventilation in ICUUp 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.
Time to the first onset of deliriumUp 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 intakeUp 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 surgeryUp to 30 days after surgery.Patients will be followed-up until 30 days after surgery.

Other

MeasureTime frameDescription
Serum IL-8 concentration (substudy)Blood samples will be collected from selected patients before surgery, and in the morning of the 1st and 3rd day after surgery.Serum IL-8 concentration (substudy)
Serum cortisol concentration (substudy)Blood samples will be collected from selected patients before surgery, and in the morning of the 1st and 3rd day after surgery.Serum cortisol concentration (substudy)
Serum IL-6 concentration (substudy)Blood samples will be collected from selected patients before surgery, and in the morning of the 1st and 3rd day after surgery.Serum IL-6 concentration (substudy)

Countries

China

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 15, 2026