Perioperative depressive symptoms (PDS) are common in population undergoing surgery, and this would be sharpened especially for complicated, high-risk major surgery. However, None of treatments could resolve this clinical problem during limited perioperative period. The remarkable effects of ketamine on treatment resistant depression have been verified by several clinical trials and the enantiomer S-ketamine (esketamine) showed similar antidepressant efficacy with better safety in recent studies. The efficacy and safety of esketamine administrated intra-operatively for PDS will be verified in this study. Other secondary outcomes such as anxiety, postoperative pain and psychiatric symptoms will also be investigated.

Inclusion Criteria:

• Patient undergoing elective major surgery
• Ages between 18 and 65 years old
• Moderate to severe depressive symptoms ( the Patient Health Questionnaire-9 scores equal to or more than 10 and Montgomery-Åsberg Depression Rating Scale scores equal to or more than 22 )
• Signed informed consent

Exclusion Criteria:

• had aphasia or any conditions that prevented mental health assessments,
• had a history of psychotic or bipolar disorder,
• had a comorbidity that affected hormone levels,
• required prolonged postoperative mechanical ventilation,
• had received treatment with antidepressants within 2 weeks prior to the screening,
• had a body mass index greater than 30 kg/m2 and a Child-Pugh score greater than 6 points.
• had made repeated suicide attempts (as assessed by the 12-item Quick Inventory of Depressive Symptomatology scores less than 3),
• had experienced adverse reactions to ketamine or esketamine,
• had known drug use disorders,
• pregnant or breastfeeding

The datasets will be available from the primary investigator (Ruquan Han, Email: ruquan.han@ccmu.edu.cn) upon reasonable request after the publication of the study results.

After the publication of the study results.

Publication in peer reviewed journal