The effect of early sedation with dexmedetomidine compared with placebo on 90-day mortality in older critically ill patients

The proportion of elderly patients presenting to intensive care units following complex surgery or life threatening medical illness requiring mechanical ventilation, cardiovascular and other organ support is rising. More than 180,000 patients are admitted to intensive care units in Australia every year. More than 50% are over the age of 65. The SPICE III study, evaluated the use of early dexmedetomidine (DEX) as primary sedative agent in ventilated critically ill patients compared with usual care. In a pre-specified subgroup analysis, SPICE III found a significant interaction between age and DEX treatment on 90-day mortality with a significant reduction of mortality in mechanically ventilated adults older than the cohort median age of 63.7 yrs. These compelling findings, need to be urgently confirmed because their confirmation will change the practice of sedation in older adults worldwide. Accordingly, we will conduct a complementary multicentre randomised controlled trial in ventilated patients, who are older than 65 years, and expected to remain ventilated for longer than 24 hours. Patients will be randomised to receive DEX infusion started at 1 µg/kg/h or Usual-Care and titrated to target Richmond Agitation Sedation Score of -1 to +1. The primary outcome will be 90-day mortality. A sample size of 3500 will be recruited to detect a 5% reduction in mortality (baseline 37%). Such a cohort will then be merged into a harmonised individual patient based meta-analysis with the 1834 patients of > 63 years of age randomized in the recently completed SPICE III study to provide the most efficient and robust (90% power to detect 4.4% difference) assessment of the effect of dexmedetomidine on mortality in older ventilated adults to date, transform sedation practice, and save thousands of lives in Australia and worldwide.