Iatrogenic Bile Duct Injury and Its Management with Intensive Care Unit Process: A Single-Center Experience

Background: The delayed recognition of bile duct injury (BDI) and the challenges in its diagnosis lead to clinical variability. The management of BDI is complicated and ranges from ERCP to liver transplantation. But infections related to BDI and sepsis control, prior to the bile flow reestablishment, are the mainstay of the treatment. In this study, we aimed to report the clinical outcomes of iatrogenic BDI and intensive care unit (ICU) process in a tertiary state hospital. Materials and methods: In this single-center, retrospective, cohort study, 17 patients admitted to our hospital with BDI after LC or ERCP were enrolled from January 2016 to July 2018. The outcomes of BDI were assessed only in short term period-as long as the length of hospital stay-and the statistical analysis was performed using SPSS version 20.0 for Windows (SPSS Inc., Chicago, IL, USA). Statistical significance was determined by a p value less than 0.05. Results: Throughout the study period, the patients with BDI were referred mostly after LC (n = 14, 82.4%). The mean age was 52.5 years and 14 of these patients were referred us from another hospital. 94.1% of the patients admitted to ICU in the first week after injury and the main symptom in the admission was right quadrant pain. Surgery was required only in seven cases (41.2%) and the in-hospital mortality rate was 17.6% (n = 3). It was clearly shown that mortality and sepsis relation was significant statistically (p < 0.001) whereas delayed admission was not related to morbidity or mortality statistically. Discussion: The rate of BDI after LC or ERCP varies and the challenge in the diagnosis of BDI is that they are not recognized at the time of LC or ERCP in the majority of cases. The identification of sepsis in the early phase leads to proper management of BDI while the morbidity and mortality rates are increasing in cases of major BDI, delayed referral and sepsis involvement. In our study, the in-hospital mortality rate was higher than the mortality rate related to BDI (17.2% vs. 7.2%) in the literature. There are many studies comparing surgical techniques and the timing of the definitive treatment while endoscopic methods have become more preferable than surgery in the early phase of BDI. Conclusion: In conclusion, early recognition of BDI after LC or ERCP is essential and the management of this feared complication requires a multidisciplinary approach with the contribution of a surgeon, gastroenterologist, and intensivist.


Results
Throughout the study period, 17 patients with BDI were managed in our institution and they were referred mostly after LC (n = 14, 82.4%). Nine of the patients were males and eight of them were females. The mean age was 52.5 years (minimum 23 and maximum 87 years). 14 of these 70% of the transection of the common bile duct (CBD) and true partial injury may be recognized and repaired during the surgery or ERCP [2]. Delayed recognition and the challenges in the diagnosis of BDI lead to clinical variability from mild tenderness and asymptomatic abdominal pain to the life-threatening complications like septic shock at presentation [3].
The management of BDI is also complicated and ranges from nonsurgical interventions like ERCP to liver transplantation. But infections related to BDI and sepsis control, prior to the bile flow reestablishment, is the mainstay of the treatment [1]. More recently ERCP becomes one of the definitive treatment modality among with surgery and percutaneous transhepatic cholangiography (PTC). Especially in cases of bile leak without transection ERCP was found adequate for definitive treatment [4]. The ERCP intervention includes ERCP, sphincterotomy, and stenting while the surgical options for BDI are simple repair, End-to-end bile duct anastomosis, Roux-en-Y biliary enteric anastomosis and partial hepatectomy [3]. Although the advancements in surgery, gastroenterology and intensive care ameliorate the outcomes of BDI, the mortality and morbidity rates are still high [5]. In this study, we aimed to report the clinical outcomes of iatrogenic BDI and intensive care unit (ICU) process in a tertiary state hospital.

Material and Method
In this single-center, retrospective, cohort study, 17 patients admitted to our hospital with BDI after LC or ERCP were enrolled from January 1, 2016, to July 31, 2018. Patient characteristics, details of BDI, and hospital courses were derived from the hospital database and patients' medical records. The patients with BDI presented to our intensive care unit either as acute bile duct injury (before 48 h) or as delayed (after 48 h) injury, and BDI were classified according to Bismuth-Strasberg Classification [6]. The patients with BDI after PTC, trauma or surgical operations other than LC were excluded. The outcomes of BDI were assessed only in short term period-as long as the length of hospital stay-because the data about long-term outcomes could not be derived from the hospital database.
Statistical analysis was performed using SPSS version 20.0 for Windows (SPSS Inc., Chicago, IL, USA). Since the number of patients included in this study was small and the variables did not show a normal distribution in Kolmogorov-Smirnov test, the variables were evaluated by nonparametric tests. The correlation between variables was assessed with Spearman Rho Correlation Coefficient test, and the Mann-Whitney U test was used for categorical variables. Statistical significance was determined by a p value less than 0.05. An extra formal consent other than the patients had given prior to the admission to as a routine procedure, was not required for the current study because it was a case-control medical record review. This study adhered to the principles in accordance with the Helsinki Declaration of 1975, as revised in 2008. of BDI. The identification of the biliary peritonitis and sepsis in the early phase lead to proper management of BDI while the morbidity and mortality rates are increasing in cases of major BDI, delayed referral and sepsis involvement [11,12].
Schreuder, et al. [7] claimed that delayed referral after BDI was related to increased morbidity and in our study delayed admission group had longer LOS in ICU and in-hospital (27.4 days vs. 14.2 and 18.2 days vs. 10.1 days respectively). Although this difference in our study was not significant statistically (p > 0.05) it was in line with Martinez-Lopez, et al. study [13] in which the relation between longer LOS in hospital and delayed referral was shown.
In our study, the in-hospital mortality rate was higher than the mortality rate related to BDI (17.2% vs. 7.2%) in the literature [1]. This is probably due to the deteriorating effect of sepsis and septic shock which was detected in 66% of mortal cases in our study. Also, the majority of cases (n = 9, 52.8%) in our study was presented with Strasberg type E injuries unlike the literature and this factor might affect the mortality rate.
There are many studies comparing surgical techniques for BDI as a definitive management modality [1,11,12]. The timing of the definitive treatment (either in the early phase or after controlling the sepsis and bile leak) is another disputable issue although endoscopic methods have become more preferable than surgery in the early phase of BDI [4,10]. Sendino, et al. [14] claimed that endoscopic methods like ERCP and stenting could be utilized for BDI even after liver transplantation.

Conclusion
In conclusion, early recognition of BDI after LC or ERCP is essential and the management of this feared complication re-patients were referred us from another hospital and only 17.6% of cases sustained BDI in our institution. The demographic variables and data related to hospital admission were summarized in Table 1 and 94.1% of the patients admitted to ICU in the first week after injury. 70.6% of patients were classified as acute (n = 12) and 29.4% of them were classified as delayed admission. The main symptom in the admission was right quadrant pain.
Surgery was required only in seven cases (41.2%) and the in-hospital mortality rate was 17.6% (n = 3). The length of stay (LOS) in hospital and in ICU was 18.12 and 12.47 days respectively as mentioned in results Table 2. Table 2 summarizes the outcomes and their relations with sepsis and delayed admission. It is clearly shown that mortality and sepsis relation was significant statistically (p < 0.001) whereas delayed admission was not related to morbidity or mortality statistically.

Discussion
The rate of BDI after LC or ERCP varies between 0.3% and 2.6% in the literature [1] while major BDI was reported as low as 0.08% [7,8]. In a recent review, it was reported that the majority of the BDI cases after LC were Strasberg type A injury (about 83%) and managed with ERCP successfully [1]. In this review, the definitive treatment of Strasberg type D injuries was reported as ERCP and stenting in 75% of cases. Even in extreme cases of CBD complete transection without tissue defect ERCP and PTC combination was used due to high operative risks and the outcomes were defined as good [9].
The challenge in the diagnosis of BDI is that they are not recognized at the time of LC or ERCP in a majority of cases (as high as 80%) and the presentation after interventions can be covert by nonspecific symptoms [10]. This mandates the clinicians and the intensivists to be suspicious about the risk The variables were presented either as mean ± SD or frequency and percentage. * The relations between variables and outcomes were calculated for "septic shock" factor. +* The relations between variables and outcomes were calculated for "delayed admission" factor.