Intraoperative ketamine for prevention of depressive symptoms after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial Academic Article uri icon


MeSH Major

  • Brain
  • Cognition
  • Hemodynamics
  • Magnetic Resonance Imaging
  • Neuropsychological Tests
  • Stress, Psychological
  • Supine Position


  • © 2018 British Journal of Anaesthesia Background: Ketamine is a general anaesthetic with anti-depressant effects at subanaesthetic doses. We hypothesised that intraoperative administration of ketamine would prevent or mitigate postoperative depressive symptoms in surgical patients. Methods: We conducted an international, randomised clinical trial testing the effects of intraoperative administration of ketamine [0.5 mg kg −1 (Lo-K) or 1.0 mg kg −1 (Hi-K)] vs control [saline placebo (P)] in patients ≥60 yr old undergoing major surgery with general anaesthesia. We administered the Patient Health Questionnaire-8 before the operation, on postoperative day (POD) 3 (primary outcome), and on POD30 to assess depressive symptoms, a secondary outcome of the original trial. Results: There was no significant difference on POD3 in the proportion of patients with symptoms suggestive of depression between the placebo [23/156 (14.7%)] and combined ketamine (Lo-K plus Hi-K) [61/349 (17.5%)] groups [difference = –2.7%; 95% confidence interval (CI), 5.0% to –9.4%; P=0.446]. Of the total cohort, 9.6% (64/670; 95% CI, 7.6–12.0%) had symptoms suggestive of depression before operation, which increased to 16.6% (84/505; 95% CI, 13.6–20.1%) on POD3, and decreased to 11.9% (47/395; 95% CI, 9.1–15.5%) on POD30. Of the patients with depressive symptoms on POD3 and POD30, 51% and 49%, respectively, had no prior history of depression or depressive symptoms. Conclusions: Major surgery is associated with new-onset symptoms suggestive of depression in patients ≥60 yr old. Intraoperative administration of subanaesthetic ketamine does not appear to prevent or improve depressive symptoms. Clinical trials registration: NCT01690988.

publication date

  • January 2018



  • Academic Article


Digital Object Identifier (DOI)

  • 10.1016/j.bja.2018.03.030

Additional Document Info