Sedation and analgesia in patients with sepsis and hemodynamic instability may be challenging in the ICU. Opioids and propofol can further exacerbate tissue infusion in septic shock by reducing cardiac contractility, increasing vasodilation, and reducing respiratory drive. Ketamine is an NMDA receptor antagonist, which has no effect on respiratory drive and has diastolic airway smooth muscle and anti-inflammatory properties. Esketamine is a dextrorotatory cleavage twice as potent and reduces the incidence of dose-dependent side effects of ketamine. Although it has been successfully used in burn patients undergoing multiple operations and anesthesia-related maintenance analgesia, it has not been reported in ICU septic shock patients undergoing mechanical ventilation. The purpose of this study was to explore the use of esketamine in mechanically ventilated ICU septic shock patients in a single-center randomized controlled trial.

In order to further clarify whether Esketamine can be used as a conventional continuous intravenous infusion drug in the ICU, further RCT is required. Therefore, this project assumes that low-dose Esketamine has a clear analgesic and sedative effect, and has advantages such as less adverse reactions in hemodynamics, respiratory inhibition, and gastrointestinal peristalsis. It is proposed to complete the following work: on the standard analgesia and sedation scheme (remifentanil+propofol), evaluate the feasibility, effectiveness and safety of the auxiliary analgesia scheme added with esketamine for septic shock patients with mechanical ventilation by whether to load small dose of esketamine for infusion, so as to provide basis for follow-up individualized diagnosis and treatment.

Inclusion Criteria:

• Age ≥ 18;
• A patient diagnosed with septic shock;
• It needs to be treated with analgesics, sedatives, and vasopressors for a period of not less than 48 hours;
• Mechanical ventilation by the ventilator is needed;
• Obtain the informed consent of the human subjects or their legal representatives;

Exclusion Criteria:

• Currently pregnant or breastfeeding;
• Confirmed acute severe intracranial or spinal neurologic diseases caused by vascular, intracranial expansion, or injury;
• History of uncontrolled or malignant hypertension (sustained (>3 hours) heart rate >150 beats/min or systolic blood pressure >180 mmHg); recent history of ketamine use；
• Hearing or vision loss, or any other conditions likely to severely interfere with the collection of research data;
• Long-term use of benzodiazepines or opioids;
• Known allergy to any investigational drug;
• Subject receiving sedative therapy not for tolerance to mechanical ventilation (e.g., seizures);
• Unlikely to require ongoing sedation during mechanical ventilation (e.g., Guillain-Barré syndrome);
• Patients deemed unlikely by the attending physician to be weaned from mechanical ventilation, such as those with diseases/injuries primarily affecting respiratory neuromuscular function and conditions requiring prolonged ventilatory support, which are clearly irreversible (e.g., high spinal cord injury);
• Open eye injury or other ophthalmic diseases;
• Concurrent participation in any other interventional study (any study assigning subjects to different treatment groups and/or conducting unconventional diagnostic or monitoring procedures).