Dexmedetomidine and Long-term Outcome in Elderly Patients After Surgery

Impact of Dexmedetomidine on Long-term Outcome in Elderly Patients After Noncardiac Surgery: 3-year Follow-up of a Randomized Controlled Trial

Delirium is a frequent postoperative complication. Its occurrence is associated with worse long-term outcomes. In a previous randomized controlled trial, prophylactic low-dose dexmedetomidine infusion during the early postoperative period decreased the incidence of delirium in elderly patients after surgery. The purpose of this 3-year follow-up study is to evaluate whether prophylactic low-dose dexmedetomidine infusion can improve the 3-year outcome in elderly patients recruited in the previous randomized controlled trial.

Delirium is a frequent postoperative complication; a systematic review revealed that postoperative delirium occurs in 36.8% of surgical patients, and its prevalence increases with age. The occurrence of delirium is associated with worse long-term outcomes including worse functional recovery, decline in cognitive function, and increased mortality rate. Surgical stress, pain, and sleep disturbances are important factors leading to postoperative delirium in the elderly. Dexmedetomidine is a highly selective alpha-2 adrenoreceptor agonist that provides anti-anxiety, sedation, and modest analgesia with minimal respiratory depression. For mechanically ventilated intensive care unit (ICU) patients, dexmedetomidine sedation improves the quality of sleep, decreases the incidence of delirium, and shortens the duration of ICU stay. For patients undergoing surgery, perioperative dexmedetomidine relieves the severity of stress response, decreases the requirement of anesthetics, and improves postoperative analgesia. In the previous stage of the current study, 700 elderly patients who were admitted to the ICU after noncardiac surgery were recruited and randomized into two groups (dexmedetomidine group and placebo [normal saline] group). The results showed that prophylactic low-dose dexmedetomidine infusion during the early postoperative period ameliorated the subjective sleep quality and decreased the incidence of delirium (22.6% [79/350] with placebo vs. 9.1% [32/350] with dexmedetomidine; Odds Ratio 0.35, 95% Confidence Interval 0.22 to 0.54; p < 0.0001). The investigators hypothesize that low-dose dexmedetomidine infusion may also improve long-term outcome in this patient population. The purpose of this 3-year follow-up study is to evaluate whether prophylactic low-dose dexmedetomidine infusion during the early postoperative period can improve the 3-year outcome in elderly patients recruited in the previous randomized controlled trial.

For patients who were not intubated, dexmedetomidine was infused at a rate of 0.1 microgram/kg per hour from study recruitment on the day of surgery until 8:00 am on the first day after surgery. For patients who were intubated and mechanically ventilated, dexmedetomidine infusion was started after the Richmond Agitation Sedation Scale was -2 or higher after intensive care unit admission until 8:00 am on the first day after surgery.

Health related quality of life is assessed with World Health Organization Quality of Life-BREF (WHOQOL-BREF).

Survival rates at different timepoints in the subgroup of patients after cancer or non-cancer surgery

Health related quality of life in the subgroup of 3-year survivors after cancer or non-cancer surgery

Health related quality of life is assessed with World Health Organization Quality of Life-BREF (WHOQOL-BREF).

Inclusion Criteria: Patients were included if they met all of the following criteria: Age of 65 years or older; Underwent elective noncardiac surgery under general anesthesia; Admitted to ICU after surgery. Exclusion Criteria: Patients were excluded if they met any of the following criteria: Preoperative history of schizophrenia, epilepsy, Parkinsonism or myasthenia gravis; Inability to communicate in the preoperative period (because of coma, profound dementia or language barrier); Brain injury or neurosurgery; Preoperative left ventricular ejection fraction < 30%, sick sinus syndrome, severe sinus bradycardia (< 50 beats per minute), or second-degree or greater atrioventricular block without pacemaker; Serious hepatic dysfunction (Child-Pugh class C); Serious renal dysfunction (undergoing dialysis before surgery); or Unlikely to survive for more than 24 hours.

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