Dexmedetomidine Supplemented Analgesia and Incidence of Postoperative Delirium
Condition: Elderly; Surgery; Analgesia; Dexmedetomidine; Complication, Postoperative; Delirium
MeSH terms: Delirium; Postoperative Complications
Study type: Interventional

Summary: 
      Delirium is a frequently occurred cerebral complication in elderly patients after surgery,
      and its occurrence is associated with worse outcomes. Sleep disturbances is considered to be
      one of the most important risk factors of postoperative delirium. Previous studies showed
      that, for elderly patients admitted to the ICU after surgery, low-dose dexmedetomidine
      infusion improved the quality of sleep and decreased the incidence of delirium. The
      investigators hypothesize that, for elderly patients after cancer surgery, dexmedetomidine
      supplemented analgesia can also decrease the incidence of delirium, possibly by improving
      sleep quality. The purpose of this multicenter, randomized controlled trial is to investigate
      the impact of dexmedetomidine supplemented analgesia on the incidence of delirium in elderly
      patients after cancer surgery.
    

Detailed description: 
      Delirium is a state of acutely occurred and transient cerebral dysfunction. It is a common
      complication in elderly patients after surgery. A systematic review showed that an average of
      36.8% (range 0 to 73.5%) of surgical patients developed postoperative delirium, and its
      occurrence increased with age. According to our previous studies, postoperative delirium
      developed in 51.0% of patients after cardiac surgery and in 44.5% of patients after
      non-cardiac surgery. The occurrence of delirium is associated with worse short-term outcomes,
      including increased postoperative complications, prolonged hospital stay, and increased
      in-hospital mortality; it is also associated with worse long-term outcomes, including
      declined cognitive function, decreased quality of life, and increased post-hospital
      mortality. Delirium is the result of multiple factors. Studies showed that postoperative pain
      is an important risk factor of delirium, whereas good postoperative analgesia reduces the
      incidence of delirium. For postoperative patients, sleep disturbances occurs frequently and
      increases the risk of delirium, whereas improving sleep quality reduces the incidence of
      delirium. Furthermore, the studies found that surgery related inflammatory response also
      plays an important role in the development of delirium.

      Dexmedetomidine is a highly selective alpha-2 (α2) adrenoreceptor agonist that provides
      anxiolysis, sedation, hypnosis and analgesia. It exerts the sedative and hypnotic effects by
      activating the endogenous sleep pathways, and produces a condition similar to phase 2
      non-rapid eye movement sleep. For patients undergoing mechanical ventilation in the ICU,
      dexmedetomidine sedation helps to maintain a normal circadian rhythm of sleep and improves
      sleep architecture. Dexmedetomidine also provides analgesic effect by activating α2
      adrenergic receptors in the dorsal horn of spinal cord. When used as a supplemental drug it
      decreases intraoperative and postoperative requirement of opioids. Moreover, animal studies
      showed that dexmedetomidine significantly inhibits the degree of inflammatory response
      induced by endotoxin or during spinal cord injury. In clinical studies, dexmedetomidine
      attenuates the degree of inflammatory response following Coronary Artery Bypass Grafting
      surgery.

      These effects of dexmedetomidine make it suitable for prevention of postoperative delirium in
      high-risk patients. Studies have shown that, for ICU patients requiring mechanical
      ventilation, sedation with dexmedetomidine reduces the incidence of delirium when compared
      with other sedatives; for postoperative patients, dexmedetomidine administered in combined
      with opioids improves analgesia and reduces opioid requirements. A recent study showed that,
      for elderly patients admitted to the ICU after surgery, low-dose dexmedetomidine infusion (at
      a rate of 0.1 ug/kg/h, for an average of 15 hours) improves analgesia for up to 24 hours,
      ameliorates subjective sleep quality for up to 3 days, and reduces the incidence of delirium
      during the first 7 postoperative days. The investigators hypothesized that the use of
      dexmedetomidine as a supplement to patient-controlled intravenous analgesia may also reduce
      the incidence of postoperative delirium.
    

Intervention name(s): Dexmedetomidine supplemented morphine analgesia; Morphine analgesia
Intervention type(s): Drug; Drug
Intervention description(s): Patients in this group will receive patient-controlled intravenous analgesia for 3 days after surgery. The formula is a mixture of dexmedetomidine (1.25 ug/ml) and morphine (0.5 mg/ml), diluted with normal saline to 160 ml. 5-HT3 receptor antagonist is added when necessary. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml each time and a lockout time from 6 to 8 minutes according to patients' condition.; Patients in this group will receive patient-controlled intravenous analgesia for 3 days after surgery. The formula is morphine (0.5 mg/ml) diluted with normal saline to 160 ml. 5-HT3 receptor antagonist is added when necessary. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml each time and a lockout time from 6 to 8 minutes according to patients' condition.
Intervention MeSH terms: Dexmedetomidine; Morphine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: elderly; surgery; analgesia; dexmedetomidine; delirium