| Part I The Effect and Safety of Chloroprocaine for Activating Epidural Analgesia During LaborBackground Pain is a fundamental feature of childbirth and labor pain is one of the most unforgettable and painful events in women’s life.Continuous epidural labor analgesia is the gold standard of labor analgesia with its accurate effect and is the most widely used method for labor analgesia on clinic with the small amounts of drugs passing through the placenta,rare adverse effects on mother and baby.However,the main drawback of continuous epidural labor analgesia is its slow onset,which takes about 15-30 minutes.Chloroprocaine hydrochloride,an amino ester local anesthetic,has fast onset and strong diffusion ability through epidural space,with the unique advantages of minimal placenta tranfer and rapid hydrolysis by plasma cholinesterase,so it has a high maternal and infant safety.Clinically,chloroprocaine is mainly used in emergency cesarean section under epidural block,intrapartum cesarean section during labor analgesia.It has the advantages of fast onset,superior epidural blockage and low toxicity,but its application in labor analgesia is still rare.Therefore,this study hypothesized that chloroprocaine can provide faster and better labor analgesia effect without increasing the incidence of adverse reactions on mothers or fetuses.Methods The parturients who delivered vaginally in our hospital from July to October 2021 and required epidural analgesia were enrolled with singleton,term and primipara,ASA grade I-Ⅱ,age 20-40 years,body mass index（BMI）20-35 kg/cm2,cervical dilatation 2-3cm,and signed written informed consent.The parturients were randomly divided into LD,CP1.5 and CP1.2 group.LD group:patients received routine initial dose of 1%lidocaine 6ml;CP1.5:patients received 1.5%chloroprocaine 6ml（9mg）;CP1.2:patients received 1.2%chloroprocaine 7.5ml（9mg）.All participants were performed epidural puncture in the left lying position at L2-3 space and a soft-tip catheter was inserted 4-4.5 cm into the epidural space.After aspiration of the catheter to exclude intravascular and intrathecal placement,the patients were administered an initial bolus（1st bolus）according to the grouping scheme described above via the syringe.If no abnormal response was reported（eg,dizziness,tinnitus,metallic taste,lower limb atony or unconsciousness）after 5 minutes,a second dose of 8 mL of 0.083%ropivacaine combined with 0.4 μg/mL sufentanil（2nd bolus）was injected via the PCEA pump in programmed intermittent epidural bolus（PIEB）mode.The same solution was used for the maintenance of labor analgesia.The time when VAS scores decreased to 3,VAS scores,uterine contraction interval and duration at the timepoints of baseline,2nd,4th,6th,6th,8th,10th and 12th contractions before labor analgesia and during the first 12 contractions after epidural loading dose were recorded.Results A total of 96 eligible pregnant women were recruited,of which 6 participants were excluded due to delivery within one hour,unilateral block or accidental rupture of dura mater.The data of 90 pregnant women were collected for statistical analysis.There was no significant difference in maternal demographic data and baseline characteristics,（P>0.05）.Parturients in the CP1.5 and CP1.2 groups achieved a VAS pain score≤3 significantly faster than those in the LD group（hazard ratio（HR）=6.540;95%CI,3.503-12.210;P<0.001 and HR=3.460;95%CI,1.905-6.282;P<0.001,respectively）.The median time（95%CI）to adequate analgesia was 12.0（10.9-13.1）min in the LD group,7.0（6.2-7.8）min in the CP1.5 group and 8.0（7.5-8.5）min in the CP1.2 group.The lowest VAS scores（median（IQR））achieved during the first 12 contractions were significantly higher in the LD group than in the CP1.5 and CP1.2 groups（P<0.001,P=0.005）,while the difference between the CP 1.5 and CP1.2 groups was not significant（P=0.056）.The interval between two consecutive uterine contractions and the duration of uterine contractions were significantly different over every beat of active contractions（P<0.001,P<0.001）.No significant differences were observed among the groups（P=0.204,P=0.093）.The number of total PCEA doses administered during the course of labor and the consumption of analgesic solution in the CP1.5 groups were significantly lower than those in the LD group（P<0.01）.The time from epidural initiation to the first PCEA demand was significantly later and maternal satisfaction with the onset of analgesia was significantly higher in the CP1.5 and CP 1.2 groups than those in the LD group（P<0.05）.The degree of sensory and motor blockade,maternal satisfaction with overall analgesia and incidence of adverse effects,the first or second labor stage duration,delivery mode,Apgar score at 1 or 5 min after birth,or umbilical artery pH or lactate level were comparable among the three groups（P>0.05）.Conclusion To compared with lidocaine,chloroprocaine achieved more rapid onset time of analgesia as the first dosage to activate labor analgesia,followed by lower consumption of analgesic drugs,higher maternal satisfaction,and without increasing maternal and fetal adverse reactions and affecting the outcome of delivery.The concentration and volume compatibility scheme of 1.5%chloroprocaine 6 ml may be superior than that of 1.2%chloroprocaine 7.5ml,suggesting that a relatively high concentration is still needed to activate labor analgesia,although low concentration local anesthetics are recommended for labor analgesia.Part II The Effect and Safety of Intranasal Low-Dose Dexmedetomidine Pretreatment On Shortening The Onset Time of Epidural Labor AnalgesiaBackground Dexmedetomidine（DEX）is a new drug α2-adrenaline highly selective receptor agonist,which has the effects of hypnosis,sedation,analgesia,inhibition of sympathetic activity,anti-anxiety and "conscious sedation".The placental transfer rate of dexmedetomidine was 0.76,which did not inhibit uterine contraction.Intravenous dexmedetomidine before general anesthesia significantly reduced heart rate and blood pressure variability during intubation and extubation for cesarean section patients,and reduced the dosage of propofol and opioids.As an adjuvant of local anesthetics,it can be used for labor analgesia through epidural or subarachnoid pathway,which can significantly improve the analgesic effect and reduce the dosage of analgesic drugs,without increasing of adverse effect on neonatal Apgar scores and blood gas analysis.Dexmedetomidine combined with opioids for labor analgesia was also reported speeding up the onset time of labor analgesia.Dexmedetomidine has light taste without pungent smell.The peak drug concentration in plasma increased gentlly and well tolerated by patients intranasally.It is reported commonly used for sedation and anti-anxiety before anesthesia induction and procedure for children.However,it is unknown whether nasal dexmedetomidine pretreatment can be safely used for labor analgesia and shorten the onset time of labor analgesia.We hypothesized that intranasal dexmedetomidine pretreatment before analgesic operation,as an assistant of programmed interval labor analgesia,can shorten the onset time of labor analgesia without increasing the risk of mother and baby.Methods The parturients who delivered vaginally in our hospital from June to October 2020 and were randomly divided into CON and IND group with each 30 cases.In IND group,0.5 μg/kg dexmedetomidine was dropped intranasally with 1ml syringe at 15 minutes before epidural puncture,and the control group was dropped with the same amount of normal saline intranasally.Then they were brought into the labor analgesia room and performed epidural puncture in the left lying position and L2-3 space.After successful puncture,4-4.5cm soft tip catheter was inserted into epidural space,6ml of of 1%lidocaine was given as a test and 0.083%ropivacaine and 8ml of 0.4 μg/ml sufentanil was injected using the programmed intermittent epidural bolus（PIEB）as the loading dosage if there is no abnormal reaction for 3 minutes.The same solution is also used to maintain labor analgesia.VAS pain score and Ramsay Sedation score（RSS）within 60 minutes after epidural block were recorded（baseline,5 minutes,10 minutes,15 minutes,30 minutes and 60 minutes after analgesia）.The dosage of analgesics,PCEA dose,mode of delivery,labor duration,neonatal Apgar scores,maternal satisfaction and adverse reactions were evaluated within two hours after delivery.The rate of failure to achieve the onset time of analgesia is defined as the failure to achieve sufficient analgesia 15 minutes after the initial dose.Results Sixty-seven parturients were recruited,of which 7 participants were excluded due to delivery within 1 hour.The data of 60 pregnant women were collected for statistical analysis.There was no significant difference between the two groups in demographic data and baseline characteristics（P>0.05）.The time for achieving adequate analgesia in the IND group was significantly shorter than that in the CON group（Hazard ratio（HR）=2.069;95%CI,2.187-3.606;P=0.010）。The median time（95%Cl）for adequate analgesia was 10.0（8.5-11.5）min in the CON group and 6.0（4.9-7.1）min in the IND group,P=0.003.Within 30 minutes after analgesia,the VAS score of IND group was significantly lower than that of CON group（P=0.618,P<0.001,P<0.001,P=0.012,P=0.258）.Within 60 minutes after analgesia,the RSSs in the IND group was significantly higher than that in the CON group（P>0.999,P<0.001,P<0.001,P<0.001,P<0.001,P=0.001）.The consumption of analgesics and the number of maternal PCEA in the IND group were significantly lower and the maternal satisfaction score was significantly higher than that in the CON group（P=0.036,P=0.011,P=0.001）.Six parturients in the CON group（20.0%）and two parturients in the IND group（6.7%）did not reach VAS≤3 within 15 minutes after analgesia,but there was no significant difference between the two groups（P=0.255）.There was also no significant difference between the two groups on the mode of delivery,the time of the first and second stages of labor,the amount of bleeding,adverse reactions,Apgar score at 1 min and 5 min after birth,umbilical artery pH,PaO2 and lactate level（P>0.05）.Conclusion To compare with the traditional PIEB labor analgesia mode,pretreatment with nasal low-dose dexmedetomidine as an adjuvant for PIEB provided faster onset time of labor analgesia,improved the quality of labor analgesia,increased maternal satisfaction and reduced the consumption of analgesic drugs,without increasing adverse reactions and adverse effects on mothers and infants.However,whether dexmedetomidine will have an adverse effect on the intensity and frequency of uterine contraction needs further observation and research. |
