Intraoperative Ketamine For Prevention Of Postpartum Depression After Cesarean Delivery: A Double-blind,Randomized Clinical Trail

Background:Postpartum depression(PPD)is a common mental disease happens in perinatal period.Ketamine as an anesthesia and analgesia drug has been used for a long time.In recent years,ketamine is proved to have an anti-depression effect with a single administration.We hypothesized that intraoperative ketamine can reduce postpartum depressive symptoms after cesarean delivery Methods:In a randomized,double-blind,placebo-controlled study trail,healthy women scheduled for cesarean delivery were randomly assigned to receive intravenous ketamine(0.25 mg/kg diluted to 5m L with 0.9% saline)or placebo(5m L of 0.9% saline)within 5 min following clamping of the neonatal umbilical cord.The primary outcome was the degree of postpartum depressive symptoms,which was evaluated by Edinburgh Postnatal Depression Scale(EPDS,a threshold of 9/10 was used)at 1 week,2 weeks and 1 month after delivery.The secondary outcome was the numerical rating scale(NRS)score of pain at 2 days postpartum.This trail is registered in the Chinese Clinical Trial Registry,number Chi CTR1900022464.Results:Between Jan.01,2018,and Nov 30,2018,464 subjects were screened and 330 were randomly allocated: 165(50%)to the ketamine group and 165(50%)to the placebo group.There were significant differences in the degree of postpartum depressive symptoms between subjects in the ketamine group and the placebo group at 1 week postpartum(13.1% vs 22.6%,respectively;p=0.029).However,no difference was found between subjects in the two groups at 2 weeks(11.8% vs 16.8%,respectively;p=0.209)and 1 month postpartum(10.5% vs 14.2%,respectively;p=0.319).The NRS score of wound pain(3.0 ± 0.9 vs 4.0 ± 1.0,respectively;p<0.001)and uterine contraction pain(3.0 ± 0.9 vs 4.1 ± 0.9,respectively;p<0.001)was lower in the ketamine group at 2 days postpartum compared with placebo group.The prevalence of headache,hallucination and dizziness were higher in the ketamine group than the placebo group during the operation.Conclusions: Operative intravenous ketamine(0.25 mg/kg)can reduce the postpartum depressive symptoms for 1 week.The long-time effect is remained to be seen.