Sedation Practice in Intensive Care Evaluation in Older ventilated Critically Ill patients; Early Sedation with Dexmedetomidine in Older Ventilated Critically Ill Patients. A Randomised Double Blind Placebo Controlled Trial - SPICE IV

The mortality in patients ≥65 yrs old and ventilated in ICU for > 24 hrs, is double that seen in younger adults of < 65 yrs old. We recently completed an NHMRC funded, 4000 patients (in 74 ICUs, 8 countries, the SPICE III trial) comparing the use of dexmedetomidine (DEX), a sedative agent with unique properties, as a primary sedative agent with usual care. A subgroup analysis of SPICE III, revealed a significant improvement in survival 90-days following inclusion in the study in patients > 65 yrs old with DEX treatment. It also showed an increase in days free of come-delirium and alive-ventilator free. These analysis, however, are exploratory and could be a chance finding. Therefore, we plan to conduct a complementary trial, SPICE IV, to validate these results. SPICE IV is planned to be a randomised double blind multinational large scale clinical trial recruiting 3500 patients. It will compare the use early dexmedetomidine, an alpha-2 agonist, as a primary sedative agent with placebo in ventilated critically ill patients who are ≥ 65 yrs old and are expected to remain ventilated > 24 hrs. The prior knowledge from SPICE III, enable us to design and deliver an efficient economic trial. We also believe that, in mechanically ventilated older ICU patients, the early use of DEX will result in safe and arousable sedation, higher delirium free days, less time on mechanical ventilation, shorter ICU and in hospital stay, and increased survival. The primary outcome will be 90 day all-cause mortality. We will also explore the possible mechanistic explanation for the age effect seen in SPICE III. This will be second largest sedation trial after SPICE III. If the survival benefit is confirmed, this would be the first trial to prove that the choice of sedative agents is critical to the outcome of ventilated older ICU patients. Once completed, this landmark trial will provide definitive evidence to transform sedation practice in Australia and worldwide.