Anesthesia-analgesia Methods and Postoperative Delirium
Condition: Elderly; Epidural Anesthesia; General Anesthesia; Major Surgery; Postoperative Delirium
MeSH terms: Delirium; Emergence Delirium
Study type: Interventional

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.
    

Intervention name(s): Combined Epi-GA/PCEA; GA/PCIA
Intervention type(s): Procedure; Procedure
Intervention description(s): 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.; 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.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention
Keywords: Elderly; Epidural anesthesia; General anesthesia; Major surgery; Postoperative delirium