Optimal Dosing Regimen Of Indocyanine Green For Extrahepatic Cholangiography

Background and Aim In recent years,indocyanine green(ICG)fluorescence imaging technology has been widely used at home and abroad,due to the rapid development of new fluorescence imaging systems,especially fluorescence laparoscopy.However,this technique is still in the stage of exploration in the field of hepatobiliary surgery,and many issues are still controversial,especially in the aspect of ICG preoperative administration,there is no consensus at home and abroad for now.The purpose of this study was to explore the preoperative dose time window and the corresponding dose time of ICG when the results of extrahepatic biliary tract fluorescence imaging were optimal,so as to provide reference for clinical application.MethodsFirstly,literature about the application of ICG fluorescence cholangiography in laparoscopic biliary tract surgery in recent years was systematically searched on Pubmed to determine the preoperative administration of ICG in this study.Subsequently,data of patients undergoing indocyanine green fluorescence-assisted laparoscopic cholecystectomy in the Department of General Surgery of the First Affiliated Hospital of Anhui Medical University from January 2021 to July 2022 were collected.The patients were grouped according to the dose of ICG injected before surgery and the time interval between the injection of ICG at each dose and the first intraoperative fluorescence imaging.Intraoperative video recording and pictures were taken to record the development of liver,gallbladder,gallbladder duct,hepatic duct,common bile duct,and gallbladder duct-common bile duct junction before and after dissection of the gallbladder triangle.Then the fluorescence intensity of gallbladder duct,common bile duct and liver was measured by software,and the ratio of gallbladder duct-liver fluorescence intensity and the ratio of common bile duct to liver fluorescence intensity were calculated for statistical analysis.Finally,the effect of extrahepatic biliary tract development was evaluated and graded by experts to further compare the effect of development in each group.(The fluorescence effect is graded as A,B and C from excellent to inferior)ResultsThrough systematic literature search and analysis,preoperative intravenous injection of2.5mg ICG or ICG dose adjusted according to 0.05mg/kg body weight are the most commonly used biliary tract imaging route and dose at present,and the time is mostly concentrated in half an hour before surgery.Combined with years of practical experience of our center,the ICG injection scheme was set as 1.25 mg and 2.5mg ICG by peripheral intravenous injection preoperatively in this study.Then,according to the interval from preoperative ICG injection to intraoperative development,the 1.25 mg group was divided into 7 subgroups: 0-0.5 h,0.5-2 h,2-4 h,4-6 h,6-8 h,8-10 h and10-12 h.The 2.5mg group was divided into 9 subgroups,including 0-0.5 h,0.5-2 h,2-4h,4-6 h,6-8 h,8-10 h,10-12 h,12-14 h and 14-16 h.No ICG allergic reaction occurred in 81 patients in 1.25 mg group and 118 patients in 2.5mg group.The visualization rate of the cystic duct,common bile duct,common hepatic duct and cystic duct-common bile duct junction after dissection of the gallbladder triangle in 1.25 mg and 2.5mg groups was significantly improved compared with that before dissection,with statistical significance(P < 0.05).The fluorescence intensity of the liver decreased gradually as the interval between the injection and surgery increased.Taking the 0-0.5h group,which was used the most internationally at present,as the control group.For 1.25 mg group,the cystic duct-liver fluorescence intensity ratios at 0-0.5 h,4-6 h,and 6-8 h intervals and the cystic duct-liver fluorescence intensity ratios at 0-0.5 h,2-4 h,4-6 h,6-8 h intervals were significantly different(p < 0.05).The highest fluorescence intensities were observed with the 4-6 h interval.The proportion of patients with grade A visualization increased with increase in interval up to 4-6 h and decreased thereafter.For 2.5 mg group,the cystic duct-liver fluorescence intensity ratios at 0-0.5 h,6-8 h,8-10 h,and 10-12 h and the common bile duct-liver fluorescence intensity ratios at0-0.5 h,6-8 h,8-10 h,and 10-12 h were significantly different(p < 0.05).The highest fluorescence intensity ratios were observed with the 8-10 h interval.The proportion of patients with grade A visualization increased with increase in interval up to 8-10 h and decreased thereafter.Conclusion:Most of the published literature only studies the feasibility of ICG fluorescence imaging technology,and few studies discuss the relationship between preoperative administration schedule and intraoperative cholangiography effect.The current study have confirmed that prolonging the preoperative time interval of ICG administration or reducing the dose of ICG can effectively reduce the fluorescence intensity of liver background,thereby increasing the ratio of gallbladder duct to liver fluorescence intensity and the ratio of common bile duct to liver fluorescence intensity,thus improving the development effect.This study found that intravenous injection of1.25 mg ICG 4-6h before surgery or 2.5mg ICG 8-10 h before surgery had the best effect on intraoperative extrahepatic biliary tract imaging.In clinical application,ICG dosage and time could be flexibly selected according to the patient’s surgical schedule.