TY - JOUR
T1 - Intraoperative ketamine for prevention of depressive symptoms after major surgery in older adults
T2 - an international, multicentre, double-blind, randomised clinical trial
AU - PODCAST Research Group
AU - Mashour, G. A.
AU - Ben Abdallah, A.
AU - Pryor, K. O.
AU - El-Gabalawy, R.
AU - Vlisides, P. E.
AU - Jacobsohn, E.
AU - Lenze, E.
AU - Maybrier, H. R.
AU - Veselis, R. A.
AU - Avidan, M. S.
N1 - Publisher Copyright:
© 2018 British Journal of Anaesthesia
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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.
KW - anti-depressant
KW - depression
KW - ketamine
KW - surgery
UR - http://www.scopus.com/inward/record.url?scp=85047228668&partnerID=8YFLogxK
U2 - 10.1016/j.bja.2018.03.030
DO - 10.1016/j.bja.2018.03.030
M3 - Article
C2 - 30336852
AN - SCOPUS:85047228668
SN - 0007-0912
VL - 121
SP - 1075
EP - 1083
JO - British journal of anaesthesia
JF - British journal of anaesthesia
IS - 5
ER -