Adjuvant Analgesics In Propofol Based Sedation For Digestive Endoscopy

BackgroundDigestive endoscopy is an important method for the diagnosis and treatment ofdigestive tract diseases.As an invasive operation,endoscopic surgery often makespatients feel anxiety,pain,cough and other discomfort,and some patients can't evencooperate with the procedure.In recent years,with the improvement of people's livingstandards and the popularization of comfortable medical treatment,more and morepatients choose to undergo endoscopic examination and treatment with sedation.Atthe same time,the application of sedation technology enables some complex digestiveendoscopic operations to be completed,which promotes the development ofendoscopic therapy.Propofol is a short-acting sedative and hypnotic drug,which is widely used ingastrointestinal endoscopy sedation due to its rapid-acting and short-half-lifepharmacological profile.However,high-dose propofol can inhibit respiratory andcirculatory system and cause adverse respiratory and cardiovascular events.In orderto reduce the occurrence of cardio-cerebrovascular and other adverse events,low-doseadjuvant analgesics can be used to reduce the dosage of propofol.So far,there aremany studies on adjuvant analgesics in propofol-based sedation regimens,but there isstill not a recognized best scheme.Endoscopic retrograde cholangiopancreatography(ERCP)is a technicallychallenging,time-consuming and invasive endoscopic procedure.The procedure is often painful and unbearable for the patients,and they cannot cooperate with theoperation in a consious state.The operator will be affected by the patient's physicalmovement.Hence,deep sedation for the patients is required in most endoscopycenters.In addition,most patients scheduled for ERCP are elderly and invalid,with American Society of Anesthesiologists(ASA)physical status III-IV,and higherASA class is a risk factor for respiratory events during ERGP procedures.Theoccurrence of severe cardiorespiratory complication derived from propofol sedationduring ERCP is significantly higher than during other endoscopy examinations.Lidocaine is mainly used to treat arrhythmias clinically.A large number of trials have proved that intravenous lidocaine could relieve visceral pain,reduce the dose of opioids and propofol,and accelerate the recovery of intestinal function after abdominal operation.Intravenous lidocaine has visceral analgesia and does not inhibitrespiratory and cardiac function at the recommended dose,so we speculate thatlidocaine can reduce the dosage of propofol in ERCP sedation and improve the safetyof sedation.However,there is no relevant research data on the application ofintravenous lidocaine in ERCP sedation.Patient satisfaction is not only an important index to evaluate the sedation scheme of digestive endoscopy,but also an important factor affects the willingness of patients to undergo digestive endoscopy again.Propofol is often used alone or in combination with opioids/benzodiazepines in gastroscopy sedation.When propofol was usedalone,the patient satisfaction was higher,but the dosage was higher.The combinationof propofol and opioids can reduce the dosage of propofol.The side effects offentanyl as a commonly used opioid can not be ignored,such as nausea,vomiting,constipation,migraine and so on,most of which occur after operation.Whether theaddition of low-dose fentanyl to propofol-based sedation will reduce patientsatisfaction has not been specifically studied in previous literatures.Research objective1.To evaluate the efficacy and safety of intravenous lidocaine in propofol-based ERCP sedation regimen2.To evaluate the effect of propofol-based sedation regimen with or without fentanyl on patient satisfaction and efficacy in gastroscopy sedation.Part I:Efficacy and safety of intravenous lidocaine in propofol-based sedationfor ERCP proceduresMethodPatients who were eligible for ERCP in the endoscopic unit of Qilu Hospital fromJuly to November 2019 were randomly divided into lidocaine group and control group.Only the investigator and the nurse who prepared the drugs knew the patients'assignments.The patients,endoscopist,anesthetist,and data-collection observerswere all blinded to the group allocation.The sedation of all patients was performed by an anesthesiologist who did not know about the location of the patients.All patients were given 0.02 mg/kg midazolam and 0.1?g/kg sufentanil intravenously as premedication.The patients inthe lidocaine group received a bolus of 1.5 mg/kg lidocaine intravenously followed bycontinuous infusion of 2 mg/kg/h while the control group received the same volumes of saline.An initial bolus of propofol adjusted to patient's condition(0.25mg/kg forage>75 or ASA III;0.75mg/kg for age<40;and 0.5mg/kg for the rest of patients)was administered.Repeated dose of 10 mg propofol was injected to achieve the target level of sedation.The targeted depth of sedation was to the modified observer's assessment of alertness/sedation scale(MOAA/S)1 or 2 in all patients.Then,2-4mg/kg/h(2mg/kg/h for age>75 or ASA?;3mg/kg/h for age<40;4mg/kg/h for therest of patients)propofol was continuously pumped to the patients.If the patientsexpressed any discomfort or hemodynamic changes,repeated dose of propofol(20-30mg)was given.At the same time,the infusion rate of propofol was increased.During the procedure,data on the patients'basic vital signs,patient movement andsedation related time were recorded by an independent observer.The dose of thepropofol was recorded by the anesthesiologist.The endoscopist assessed the satisfaction of the sedation and the cooperation of the patient by a 10-point visual analogue scale(VAS).When the patients retained full recovery,they were asked to rate the satisfaction of sedation,pain and fatigue by VAS.1 hour after operation,another observer,recorded the patient's score for fatigue and pain,and other sedation-related adverse reactions.Results1 Patient enrollment and characteristicsFrom July 1,2019 to November 31,2019,a total of 76 patients scheduled for diagnostic or therapeutic ERCP were included.The patients who did not meet theadmission criteria were excluded.Ultimately,24 patients were included in each groupin this study.There was no significant difference in age,sex,height,.weight,ASAstatus,smoking and drinking history between the two groups.Hypertension is themost common complication in patients.Choledocholithiasis is the most commonindication of ERCP in both groups.Additionally,interventional ERCP such as stoneretrieval or endoscopic nasobiliary drainage(ENBD)was performed in most cases.2 Propofol consumption and sedation related timeDuring ERCP sedation,intravenous lidocaine reduced propofol requirement by33.8%(P=0.023).The induction dose of propofol was similar between the two groups(P=0.088).Patients in the lidocaine group needed less time to reach the target sedation level(P=0.015).There was no significant difference in operation time between the two groups(P=0.618).The awake time in the lidocaine group wassignificantly shorter than that in the control group(P<0.001).Compared to thecontrol group,the recovery time of lidocaine group was faster(P<0.001).3 Adverse events and satisfactionInvoluntary movements in the lidocaine group were less than those in the control group(P=0.049).The incidence of hypoxemia,hypotension and bradycardia in thelidocaine group was lower than that in the control group,but with no significant difference.None of the patients in our study was observed adverse events associated with intravenous lidocaine,such as cardiovascular or neurological side effects.Inaddition,there were no other serious sedation-related adverse events such as cardiacarrest,arrhythmia or endotracheal intubation in both groups.The patients in the lidocaine group exhibited relatively better cooperation asevaluated by the endoscopist than the control group,with a dramatic difference(P=0.008)Similarly,the satisfaction of endoscopic physicians in the lidocaine groupwas significantly higher than that in the control group(P=0.003).Most of the patientswere satisfied with the sedation in both groups(P=0.633).4 Change in vital parametersThe mean lowest systolic blood pressure was similar between the two groups(P=0.257);compared with the values before sedation,there were significant decreasesin both groups(P<0.001).The mean lowest heart rate during the procedure was66.5±9.5 beats/min in the lidocaine group and 64.3±12.1 be.ats/min in the control group,with no significant difference between the two groups.5 Postprocedure evaluation.The patients in the lidocaine group experienced less pain than those in the control group(P=0.005).The post-procedure fatigue scores were also significantly lower inthe lidocaine group(P<0.001).Similar results were observed 1 h after the procedure.No difference was found in the incidence of postprocedure recall,dizziness andnausea between the groups.ConclusionsIntravenous lidocaine can significantly decrease propofol requirements during ERCP,with higher sedation quality and endoscopist satisfaction.Part II:Patient satisfaction and efficacy with propofol-based sedation with or without fentanyl for gastroscopyMethodFrom January 2019 to January 2020,480 patients who were eligible forgastroscopy in Qilu Hospital were randomly divided into fentanyl group and control group.Only the investigator and the nurse who prepared the drugs knew the patients'assignments.The patients,the endoscopist,the anesthesiologist,the observers were allblinded to the group allocation.An anesthesiologist who did not know the patients' allocation performed all the sedation.Before the procedure,patients in the control group received 0.02 mg/kg midazolam,while patients in the fentanyl group received midazolam 0.02 mg/kg and 1?/kg fentanyl intravenously as premedication.All patients received a loading doseof propofol adjusted to body weight(0.5 mg/kg for age>70 or ASA III;1 mg/kg forage?70)before the endoscopy procedure,and approximately 20-30 mg ofpropofol was given repeatedly to maintain moderate sedation as needed in bothgroups.Vital signs were monitored every 3 min.Data about the patients' basic vital signs,propofol consumption,patient responseand sedation-related time were recorded by the anesthetist in a record list.At the end of the procedure,the endoscopist and the anesthetists rated the satisfaction of thesedation on a 5-point Likert scale.Then the patients were transferred into thepostanesthesia care unit(PACU).When the patients attained full recovery,thepatient's satisfaction with sedation,other adverse reactions and discharge time were recorded by independent observers.Patients were contacted by a telephone call madeby an investigator 24 hours after the procedure to collect the postdischarge data.Results1 Patient enrollment and characteristicsA total of 500 patients scheduled to undergo diagnostic gastroscopy from Januaiy14,2019,to January 31,2020,were enrolled initially.Excluding 20 patients,240patients for each group participated in the study.There was no significant differencein age,sex,height,weight,BMI,smoking and drinking history,education level,ASA status and Mallampati score between the two groups.Hypertension was the mostcommon complication between the two groups,and there was no significant difference between the two groups.Abdominal discomfort is the most commonindication of gastroscopy in both groups.In addition,gastric screening was the second most common reason.In tenns of baseline HR,blood pressure,and SpO2?the twogroups were comparable.2 Patient satisfaction with sedationThe overall patient satisfaction was 95.4%in the fentanyl group and 96.3%in thecontrol group,with a rate difference of-0.9%.As the upper bound of the 1-sided 97.5%Cl lay below 5%(noninferiority margin),the null hypothesis that the fentanyl groupwould be inferior to the control group was rejected.The overall patient satisfaction ofthe fentanyl group was not inferior to that of the control group.In contrast,theendoscopist and anesthetist was more satisfied with the fentanyl group than with thecontrol group,with a dramatic difference(P<0.0019 P<0.001).There was nosignificant difference in the incidence of dizziness,nausea and vomiting between the two groups.3 Incidence of negative and adverse events.The incidence of hypoxemia,hypotension,bradycardia and tachycardia in thefentanyl group was slightly lower than that in the control group,but with no statistical difference.There were no serious cardiovascular events including heart failure andcardiac arrest in both groups.Bucking occurred in 15.8% of patients in tjie fentanylgroup,while it occurred in 32.5% of patients in the control group,with a pronounced significant difference(P<0.001).Similarly,involuntary movement of patients was lesscommon in the fentanyl groups(P<0.001).The incidence rate of hiccups in thefentanyl group was similar to that in the control group(P=0.308).4Propofol consumption and sedation-related timeFentanyl significantly reduced the propofol requirements during the gastroscopy procedure(P<0.001).In addition,the induced dose of propofol in the fentanyl groupwas significantly lower than that in the control group(P<0.001).There was nosignificant difference in operation time between the two groups.The induction time offentanyl group was significantly shorter than that of control group(P<0.001).Theawake time of fentanyl group was shorter than that of control group(P<0.001).Similarly,the patients in the fentanyl group had a faster fbll recovery than those in the control group(P<0.001).Conclusions1.Combination with fentanyl does not reduce patient satisfaction in propofol-basedsedation during gastroscopy.2.Combination with fentanyl can improve the satisfaction of endoscopist and anesthesiologist and reduce the occurrence of cough and other negative events during operation.3.Combination with fentanyl can reduce the dosage of propofol,reduce recovery time and improve the efficiency of clinical turnover.