Safety and Efficacy of Esketamine Combined With Dexmedetomidine for Sedation of Mechanically Ventilated Patients

Inclusion Criteria: * Mechanically ventilated with oral endotracheal intubation in the ICU; * Patients aged \>18 years and \<70 years; * Patients with expected mechanical ventilation time \>24 hours. Exclusion Criteria: * Known or suspected allergy to esketamine, dexmedetomidine, remifentanil, or propofol; * Pregnancy or lactation periods; * Obesity defined as Body Mass Index \>35kg/m2; * Extreme hemodynamic or respiratory instability due to severe burn or trauma (defined as Injury Severity Score ≥25); * Heavy drinking defined by WHO as drinking at least 60g of pure alcohol every day for men and at least 40g for women; * Terminally ill patients near death, such as patients with extensively metastatic tumor or refractory shock; * Long-term exposure to sedatives, opioid analgesics or antianxiety drugs; * Severe central nervous system disease such as cerebrovascular accidents, status epilepsy, or coma; * Acute or chronic severe liver disease (Child-Pugh class C or history of liver transplant); * Acute or chronic renal insufficiency needing dialysis; * Patients or authorized surrogates refuse to provide informed consents; * Mechanically ventilated for more than 24 hours prior to enrollment (not including the time on ventilators in the operation room).