The Effects Of Bolus Low-dose Ketamine For The Prevention Of Postpartum Depression During Caesarean Section

Background Postpartum depression is a common complication of childbirth,and it has become an important public health problem.Conventional antidepressants act on monoamine oxidase and are slow-acting,with low efficacy.And in the last decade,a growing body of clinical evidence has shown that subdissociative-dose ketamine(0.5 mg/kg)had rapid antidepressant effects.ketamine may mediate synaptic plasticity to cause long-term behavioural changes.In addition,clinical studies indicates that pain is a risk factor of postpartum depression,and there is a meta analysis demonstrates that administration of a low dose of ketamine can attenuate postoperative pain intensity and prevent chronic pain,the mechanisms may be associated with reduction of central sensitization and hyperalgesia via inhibition of NMDA receptors.Therefore,based on the above two mechanisms of ketamine,we investigated the effect of low-dose ketamine(0.25 mg/kg)administered during caesarean section for preventing postpartum depression in a prospective,randomized,double-blind clinical trial.Methods The study was a randomized,double-blind,placebo-controlled,prospective clinical trial.The subjects were randomly assigned into the ketamine group or the saline group.The anaesthesiologist slowly injected(?)10 mL of 0.25 mg/kg ketamine or an equal volume of saline within 5 minutes after clamping the newborn's umbilical cord.Baseline data about the subjects included age,BMI,history of present pregnancy.The anaesthesiologist collected intra-operative data,including the amount of phenylephrine administered,intra-operative blood loss,duration of operative time,and neonatal information.After the investigational drug was administered,the anaesthesiologist asked the subject whether they experienced vomiting headache,hallucination,dizziness,drowsiness,and diplopia at 5 and 15 minutes after dosing and immediately prior to the subject being released from the operating room.Moreover,the anaesthesiologist rated the sedation effect(Ramsay Scale).The primary outcome indicator was the Edinburgh postnatal depression scale(EPDS)score,which was measured at 3 days and 6 weeks postpartum.The secondary outcome indicator was the pain intensity,which was assessed by numeric rating scale at 3 days and 6 weeks postpartum.Results 330 patients were enrolled into this study.No significant differences between the two groups were observed in the subjects' basic information or in the intra-operative maternal and neonatal information.At 5 minutes after dosing,the incidence of headache,hallucinations,dizziness,drowsiness,and diplopia,as well as Ramsay sedation scores>3,were higher in the ketamine group than in the control group.At 15 minutes after dosing,the incidence of vomiting,hallucinations,dizziness,drowsiness,and diplopia were higher in the ketamine group than in the control group,whereas no significant difference was observed in Ramsay sedation scores>3 between the two groups.When the subjects were released from the operating room,no significant differences were observed in ketamine-related side effects between the two groups.There is no significant differences were observed in the prevalence of postpartum depression between the two groups at 3 days and 6 weeks postpartum.Numeric rating scale pain scores did not differ between groups at 3 days postpartum,whereas lower pain scores for the ketamine group compared to controlled group were demonstrated at 6 weeks postpartum.Conclusion This study showed that intra-operative intravenous infusion of 0.25 mg/kg ketamine did not reduce the prevalence of postpartum depression at 3 days and 6 weeks postpartum but did significantly reduce the NRS scores by 6 weeks postpartum.Some subjects developed obvious ketamine-related side effects,but the symptoms were relieved quickly and had resolved by the time the subjects were released from the operating room.