Case Control Study Open Access
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2024; 30(15): 2118-2127
Published online Apr 21, 2024. doi: 10.3748/wjg.v30.i15.2118
Urgent one-stage endoscopic treatment for choledocholithiasis related moderate to severe acute cholangitis: A propensity score-matched analysis
Yang Zhou, Shuai-Jing Huang, Yan Liang, Xiao Liang, Masoom Wali, Ya-Dong Feng, Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
Yin-Qiu Zhang, Department of Gastroenterology, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing 210019, Jiangsu Province, China
ORCID number: Yang Zhou (0009-0009-2701-6882); Yin-Qiu Zhang (0000-0002-8730-575X); Ya-Dong Feng (0000-0001-9259-3840).
Co-first authors: Yang Zhou and Ying-Qiu Zhang.
Author contributions: Zhou Y wrote the manuscript; Feng YD was responsible for the case design; Zhang YQ and Huang SJ collected the data and analyzed the data; Liang Y and Wali M revised the manuscript; and all the authors have read and agreed to the published version of the manuscript.
Institutional review board statement: The study was conducted at Zhongda Hospital Affiliated with Southeast University. The study was approved by the Ethics Committee (2019ZDSYLL094-P01).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All the data are available upon request to the corresponding author (email: drfengyd@126.com).
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ya-Dong Feng, MD, PhD, Chief Doctor, Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing 210009, Jiangsu Province, China. drfengyd@126.com
Received: January 18, 2024
Peer-review started: January 18, 2024
First decision: February 9, 2024
Revised: February 19, 2024
Accepted: March 27, 2024
Article in press: March 27, 2024
Published online: April 21, 2024

Abstract
BACKGROUND

During emergency endoscopic retrograde cholangiopancreatography (ERCP), the safety and feasibility of performing one-stage endoscopic treatment for patients with acute cholangitis (AC) due to choledocholithiasis are unclear.

AIM

To investigate the safety and feasibility of one-stage endoscopic treatment for moderate to severe AC.

METHODS

We enrolled all patients diagnosed with moderate to severe cholangitis due to common bile duct stones from January 2019 to July 2023. The outcomes were compared in this study between patients who underwent ERCP within 24 h and those who underwent ERCP 24 h later, employing a propensity score (PS) framework. Our primary outcomes were intensive care unit (ICU) admission rates, ICU length of stay, and duration of antibiotic use.

RESULTS

In total, we included 254 patients and categorized them into two groups based on the time elapsed between admission and intervention: The urgent group (≤ 24 h, n = 102) and the elective group (> 24 h, n = 152). Ninety-three pairs of patients with similar characteristics were selected by PS matching. The urgent ERCP group had more ICU admissions (34.4% vs 21.5%, P = 0.05), shorter ICU stays (3 d vs 9 d, P < 0.001), fewer antibiotic use (6 d vs 9 d, P < 0.001), and shorter hospital stays (9 d vs 18.5 d, P < 0.001). There were no significant differences observed in adverse events, in-hospital mortality, recurrent cholangitis occurrence, 30-d readmission rate or 30-d mortality.

CONCLUSION

Urgent one-stage ERCP provides the advantages of a shorter ICU stay, a shorter duration of antibiotic use, and a shorter hospital stay.

Key Words: Acute cholangitis, Endoscopic retrograde cholangiopancreatography, One-stage treatment, Optimal time

Core Tip: We investigated the safety and feasibility of one-stage endoscopic treatment for moderate to severe acute cholangitis. Our study found that patients who underwent endoscopic retrograde cholangiopancreatography within 24 h had a shorter intensive care unit stay, a shorter duration of antibiotic use, and a shorter hospital stay.



INTRODUCTION

Acute cholangitis (AC) is a severe and life-threatening infection that affects the biliary tract. It is a significant digestive disorder characterized by rapid onset and is common. Approximately 10%-29% of people with AC develop sepsis[1,2], and approximately 5% of patients progress to septic shock[3]. In severe cases, AC can be fatal. Currently, the Tokyo Guideline 2018 (TG18) criteria are used to diagnose and categorize ACs as mild, moderate, or severe cholangitis[4]. The primary cause of AC is biliary obstruction, which is often caused by cholelithiasis. Approximately 53% of patients with severe AC (SAC) require admission to the intensive care unit (ICU)[5].

While treating SAC, fluid resuscitation and antibiotics need to be administered as initial therapy. In addition, emergent biliary decompression is necessary to improve clinical outcomes[4]. The primary treatment choice for AC is endoscopic retrograde cholangiopancreatography (ERCP), which benefits approximately 90% of patients[6-10]. It is essential to adhere to the principle of “the sooner, the better” when performing ERCP treatment for AC. However, emergency ERCP biliary drainage in patients with severe cholangitis is associated with a significantly high risk of morbidity and mortality. In cases of early ERCP for AC associated with choledocholithiasis, patients with severe cholangitis are frequently subjected to brief procedures such as endoscopic nasobiliary drainage (ENBD) or stenting[9,11,12]. Nevertheless, this additional ERCP procedure not only prolongs the duration of hospital stay but also increases associated risks[12-16]. It is unclear whether single-stage stone removal is feasible for individuals with AC. The optimal timing for ERCP is yet a matter of debate. Therefore, we retrospectively examined and evaluated patients who underwent ERCP for moderate to SAC with choledocholithiasis. The aim was to assess the feasibility and safety of urgent single-stage stone removal for moderate to SAC.

MATERIALS AND METHODS

The study was conducted at Zhongda Hospital Affiliated with Southeast University. The study was approved by the Ethics Committee (2019ZDSYLL094-P01). All methodologies employed in this study strictly adhered to the pertinent guidelines and regulations.

Inclusion criteria

We collected data from the endoscopic reporting system for all patients who underwent ERCP procedures following admission to the emergency department between January 2019 and July 2023. The inclusion criteria were as follows: (1) Diagnosed with AC in accordance with the TG13 or TG18[17,18]; (2) Aged > 18 years; and (3) Willing to undergo ERCP.

Exclusion criteria

The exclusion criteria were as follows: (1) Had mild AC; (2) Did not undergo endoscopic retrograde lithotomy; and (3) Had non-common bile duct (CBD) stones detected via cholangiopancreatography.

Data records

We retrieved data for all emergency ERCP procedures performed from January 2019 to July 2023 from the endoscopy reporting system, all patients were diagnosed with moderate to severe cholangitis due to CBD stones. The flowchart of this study is listed as Figure 1. The patients in the study were categorized into two groups based on the time between admission and intervention. These patients were classified into urgent (≤ 24 h, n = 102) and elective (> 24 h, n = 152) ERCP groups. The time span from admission to intervention was considered the time between registration in the emergency room and ERCP. We then sorted and reviewed patient demographic data, presenting symptoms, and ERCP outcomes. These data included the date, time between symptom onset and ERCP, admission and ERCP procedures, as well as laboratory data upon admission, such as the white blood cell (WBC) count, platelets (PLT), total bilirubin (TB), international normalized ratio (INR), creatinine (Cr), serum albumin, C-reactive protein (CRP), and neutrophil/lymphocyte ratio. The time span for biliary drainage was calculated as the duration between admission and the ERCP procedure. Furthermore, postoperative follow-up data were acquired through outpatient examinations or postoperative telephone follow-ups conducted after discharge. Disease severity was graded using the TG18 severity scale[18].

Figure 1
Figure 1 Flow diagram of patients’ selection. ERCP: Endoscopic retrograde cholangiopancreatography; PTBD: Percutaneous transhepatic biliary drainage; PTGBD: Percutaneous transhepatic gallbladder drainage; CBD: Common bile duct.
Procedure

Prior to ERCP, we monitored the patients’ vital signs, established intravenous access, and administered empiric antibiotic therapy with third-generation cephalosporins. In instances where patients exhibited postshock symptoms, the execution of ERCP was postponed until their condition improved. Urgent ERCP was considered the primary treatment for patients who did not respond to drug therapy or who had moderate to severe disease. Prior to commencing the procedure, all participants provided informed consent. ERCP procedures were performed under general anesthesia and supervised by an anesthesiologist. During ERCP, the maternal endoscope used in this procedure was a therapeutic duodenoscope (Olympus TJF-260, Tokyo, Japan).

In the initial step, we established biliary access. Conventional biliary cannulation was attempted by using a sphincterotome (Microtech, Nanjing, China) and a 0.035-inch guidewire (Microtech, Nanjing, China). Successful biliary access was confirmed by observing visible bile aspiration, and bile samples were extracted for bacterial cultivation upon the manifestation of turbid bile flow. Subsequently, a 3-mm endoscopic sphincterotomy (EST) combined with endoscopic papillary balloon dilation was performed to establish a proper biliary orifice. The balloon was gradually inflated with 0.9% saline solution to the proposed pressure or until the biliary wall could be seen. For the extraction of stones, we employed either a basket or a balloon; for larger stones, mechanical lithotripsy was employed at the discretion of the endoscopist. In cases of cannulation failure, percutaneous transhepatic biliary drainage was explored as an alternative therapeutic option. Subsequently, a nasal biliary drainage tube was placed, and bile acid samples were collected for bacterial culture on postoperative days 1 and 2. The decision to drain the nasal biliary tube was contingent upon the patient’s clinical condition. Adverse reactions after drainage were classified according to the ASGE dictionary[19] and included post-ERCP pancreatitis (PEP), bleeding, and infection, among others.

Statistical analysis

The quantitative parameters are reported as either the mean (with range) or median (with interquartile range), depending on the distribution. Categorical variables are presented as the frequency and percentage. The propensity score (PS) framework was used to compare the clinical endpoints of ERCP within 24 h of onset and 24 h after onset. The PS method was used to create a new dataset in which the probability of ERCP occurring within 24 h of or after its occurrence was equal (as in a purely randomized trial) to balance the baseline characteristics of patients. First, multivariate logistic regression was used to predict the probability of ERCP within 24 h (i.e., estimated PS), controlling for the following prespecified covariates: Sex, age, Charlson Comorbidity Index (CCI) score, previous discharge ERCP, history of gallbladder surgery, TB, albumin, Cr, the INR, the PLT, the WBC, and the Tokyo score. The 1:1 nearest neighbor matching algorithm was used to match the two groups (urgent group and elective group) without substitution, and the caliper was 0.2[20] of the PS standard deviation of the logit score. The clinical endpoints were subsequently compared between the two groups in the matched datasets. Statistical analysis, including the χ2 test, one-way analysis of variance (ANOVA) and multivariate linear regression, was performed using the Statistical Package for Social Sciences (SPSS, Inc., version 27.0 for Windows, Chicago, IL, United States). A P value of < 0.05 was considered to indicate statistical significance.

RESULTS
Population characteristics

From January 2019 to July 2023, a total of 456 patients with acute cholangitis were screened. Among these, 74, 16, 19 and 16 patients were excluded due to mild acute cholangitis, refusal of endoscopic treatment, upper gastrointestinal anatomy changes, and preference of PTBD or PTGBD, respectively. Additionally, 19, 20, 12 and 26 patients were excluded due to intrahepatic stone, acute acalculous cholecystitis, dysfunction of previous biliary stents and malignant obstructions, respectively. Consequently, 254 patients were included, 102 (40.2%) of whom underwent ERCP within 24 h of presentation and 152 (59.8%) after 24 h. The mean age was 69.47 (± 15.81) years, 47.6% were male, and 100% had choledocholithiasis-related cholangitis. The mean CCI score was 1 (0-7), and ERCP was performed for a mean time span of 48 (1-312) h. Cholangitis severity was categorized per Tokyo guidelines: Score 1 = 0%, score 2 = 72%, and score 3 = 28%. Table 1 shows the baseline patient characteristics before and after PS matching. After PS matching, 93 pairs of patients with similar traits were selected (Algorithm 1, Table 1). The proportion of patients who underwent one-step stone extraction after matching was consistent (100% vs 100%, P = 1) (Table 1).

Table 1 Characteristics of the study population and endoscopic retrograde cholangiopancreatography procedures.
Before matching
After matching
Total, n = 254
ERCP ≤ 24 h, n = 102
ERCP > 24 h, n = 152
P value
Total, n = 186
ERCP ≤ 24 h, n = 93
ERCP > 24 h, n = 93
P value
Age, yr69.47 ± 15.8170.73 ± 15.2468.63 ± 16.180.36270.32 ± 15.3971.05 ± 15.2669.58 ± 15.560.515
Male sex, n (%)121 (47.6)58 (56.9)63 (41.4)0.01694 (50.5)54 (58.1)40 (43)0.04
CCI1 (0-7)1 (0-5)1 (0-7)0.1081 (0-7)1 (0-3)1 (0-7)0.187
Past medical history
ERCP, n (%)30 (11.8)13 (12.7)17 (11.2)0.70622 (11.8)13 (14)9 (9.7)0.364
Cholecystectomy, n (%)67 (26.4)27 (26.5)40 (26.3)0.97844 (23.7)22 (23.7)22 (23.7)1
Lab values
WBC count as/μL10.32 ± 6.7112.57 ± 6.618.81 ± 6.37< 0.00110.58 ± 7.0312.11 ± 6.449.06 ± 7.30.003
Platelet count as/μL173.96 ± 71.08164.21 ± 73.35180.5 ± 68.990.594168.11 ± 71.33164.85 ± 74.65171.38 ± 68.090.534
CRP in mg/L75.17 ± 76.0394.9 ± 79.3261.75 ± 70.95< 0.00178.53 ± 76.689.66 ± 76.3776.37 ± 75.750.079
NLR (%)7.94 (0.81-106.31)15.67 (1.36-106.31)6.9 (0.805-64.13)< 0.00118.545 (2.55-64.13)19.87 (11.2)16.42 (2.55-64.13)< 0.001
INR1.2 ± 0.221.23 ± 0.971.14 ± 0.92< 0.0011.21 ± 0.231.25 ± 0.271.17 ± 0.170.012
D2 polymers657 (0.21-26652)1567 (76-26652)504 (0.38-15502)< 0.0011193.5 (479-15502)1455 (479-4811)832 (504-15502)0.005
Creatinine in mg/dL0.826 (0.34-8.32)1.01 (0.34-5.86)0.76 (0.44-8.32)< 0.0011.10 (0.77-5.86)1.15 (0.77-5.86)1.02 (0.79-3.1)0.013
TB in mg/dL2.61 (0.28-22.52)3.7 (0.29-15.02)2.14 (0.28-22.52)0.0213.58 ± 2.983.78 ± 2.83.38 ± 3.140.363
AST in U/L108.5 (13-4051)128.5 (13-744)104 (15-4051)0.168118 (40-539)131 (40-497)116 (46-539)0.53
ALT in U/L201.68 ± 206.61196.67 ± 173.10205.03 ± 226.840.652222 (68-512)259 (68-512)209 (88-479)0.55
γ-GT in U/L406.66 ± 354.98425.8 ± 376.89393.82 ± 340.160.463383.61 ± 332.61405.97 ± 347.74361.25 ± 361.250.361
Albumin in g/dL35.8 (15.9-46.6)35.9 (15.9-48.7)37.8 (25.1-49.1)0.03333.7 (24.3-36.1)32.6 (24.3-35.7)33.8 (25.4-36.1)0.163
Tokyo Score
348 (28)39 (38.2)32 (21.1)0.00358 (31.2)35 (37.6)23 (24.7)0.058
2206 (72)63 (61.8)120 (78.9)128 (68.8)58 (62.4)70 (75.3)
ERCP procedure
Door to ERCP time in h48 (1-312)8.5 (1-24)120 (27-312)< 0.00125.5 (1-312)9 (1-24)120 (27-312)< 0.001
ERCP procedure time (min)60 (25-780)60 (30-200)60 (30-335)0.71460 (26-780)60 (30-200)60 (30-335)0.52
One-stage ERCP, n (%)254 (100)102 (100)152 (100)1186 (100)93 (100)93 (100)1
CBD, n (%)254 (100)102 (100)152 (100)1186 (100)93 (100)93 (100)1
Stones size (mm)8 (2-25)9 (2-25)8 (2-25)0.2228 (2-25)9 (2-25)8 (2-25)0.368
Multiple stones, n (%)109 (42.9)35 (34.3)74 (48.7)0.02379 (42.5)32 (34.4)47 (50.5)0.026
Common bile duct width (mm)13 (4-33)14 (4-33)14 (5-33)0.01613 (4-33)13 (4-33)12.1 (5-25)0.038
EST, n (%)177 (69.7)75 (73.5)102 (67.1)0.275128 (68.8)69 (74.2)59 (63.4)0.113
EPBD, n (%)204 (80.3)90 (88.2)114 (75)0.009149 (80.1)83 (89.2)66 (71)0.002
Pancreatic stent placement, n (%)21 (8.3)5 (4.9)16 (10.5)0.11115 (8.1)5 (5.4)10 (10.8)0.178
Nasal Biliary Drainage Catheter placement, n (%)251 (98.8)100 (98)151 (99.3)0.346183 (98.4)91 (97.8)92 (98.9)0.561
HLL, n (%)21 (8.3)11 (10.8)10 (6.6)0.23316 (8.6)11 (11.8)5 (5.4)0.117
Primary clinical outcomes

Our primary outcome was ICU admission rate, ICU length of stay, and duration of antibiotic use (Table 2). The results derived from our analysis of a PS-matched population indicated a significant difference in ICU admission rates between the urgent ERCP group and the elective ERCP group (34.4% vs 21.5%, P = 0.05). Importantly, there was a significant difference in ICU stay length between the urgent ERCP and elective ERCP groups, with the urgent group having a shorter stay (3 d vs 9 d, P < 0.001). Additionally, compared with those in the elective group, the patients in the urgent ERCP group had a shorter duration of antibiotic use (6 d vs 9 d, P < 0.001). Univariate linear regression analysis of ICU stay length revealed independent correlations with variables, including WBC [95% confidence interval (CI): 0.18-0.82, P = 0.003], CRP (95%CI: 0.01-0.08, P = 0.015), Cr (95%CI: 4.22-8.28, P < 0.001), age (95%CI: -0.66 to -0.07, P = 0.016), and the time span of ERCP (hours) (95%CI: 0.04-0.06, P < 0.001). Additionally, ICU stay length was not significantly correlated with one-stage endoscopic treatment, EST, ENBD, adverse events, 30-d readmission, or recurrent cholangitis (Table 3). Multivariate linear regression analysis of the matched data revealed significant correlations between ERCP delay time (95%CI: 0.03-0.06, P < 0.001), Cr level (95%CI: 0.07-3.56, P = 0.041), and ICU stay length.

Table 2 Outcomes of endoscopic retrograde cholangiopancreatography.
Before matching
After matching
Total, n = 254
ERCP ≤ 24 h, n = 102
ERCP > 24 h, n = 152
P value
Total, n = 186
ERCP ≤ 24 h, n = 93
ERCP > 24 h, n = 93
P value
ERCP intervention type, n (%)
Complete stone removal250 (98.4)101 (99)149 (98)0.533184 (98.9)92 (98.9)92 (98.9)1
Biliary stent insertion4 (1.6)1 (1)3 (2)0.5332 (1.1)1 (1.1)1 (1.1)1
Technical success rate, n (%)250 (98.4)101(99)149 (98)0.533183 (98.4)92 (98.9)91 (98)0.561
ERCP failure, n (%)4 (1.6)1 (1)3 (2)0.5333 (1.6)1 (1.1)2 (2.2)1
Duration of antibiotic use (d)7 (1-28)6 (2-15)8 (2-26)< 0.0017 (2-28)6 (2-18)9 (2-28)< 0.001
In-hospital mortality, n (%)3 (1.2)03 (2)0.1532 (1.1)02 (2.2)0.155
30-d mortality, n (%)7 (2.8)2 (2)5 (3.3)0.5265 (2.7)2 (2.2)3 (3.2)0.65
Recurrent cholangitis, n (%)7 (2.8)3 (2.9)4 (2.6)0.8836 (3.2)3 (3.2)3 (3.2)1
LOHS, (d)10 (3-71)9 (3-39)18 (5-71)< 0.0019 (3-71)9 (3-39)18.5 (7-71)< 0.001
Required ICU stay, n (%)61 (24)33 (32.4)28 (18.4)0.01152 (28)32 (34.4)20 (21.5)0.05
ICU stay length, (d)9 (1-71)3 (1-15)8 (1-71)0.0034.5 (1-71)3 (1-15)9 (1-71)< 0.001
30 d readmission, n (%)33 (13)15 (14.7)18 (11.8)0.50629 (15.6)14 (15.1)15 (16.1)0.84
ERCP-related complications, n (%)42 (16.5)18 (17.7)24 (15.8)0.69629 (15.6)16 (17.2)13 (14)0.544
PEP23 (9.1)9 (8.8)14 (9.2)0.91617 (9.1)9 (9.7)8 (8.6)0.799
Cholangitis9 (3.5)6 (5.9)3 (2)0.0997 (3.8)5 (5.4)2 (2.2)0.248
Bleeding6 (2.4)4 (3.9)2 (1.3)0.184 (2.2)3 (3.2)1 (1.1)0.312
Others2 (0.8)2 (2)00.0832 (1.1)2 (2.2)00.155
Table 3 Linear regression analyses to assess intensive care unit length of stay.
Univariate analysis
Multivariate analysis
OR (95%CI)
P value
OR (95%CI)
P value
WBC count0.503 (0.185 to 0.821)0.003-0.092 (-0.305 to 0.12)0.387
Platelet count-0.031 (-0.069 to 0.007)0.105
CRP0.046 (0.009 to 0.082)0.0150.002 (0.021 to 0.024)0.877
NLR-0.006 (-0.181 to 0.169)0.945
INR-4.986 (-15.932 to 5.961)0.365
TB-0.101 (-1.26 to 1.058)0.862
Cr6.248 (4.216 to 8.281)< 0.0011.818 (0.073 to 3.564)0.042
Albumin0.569 (0.043 to 1.095)0.0350.02 (-0.308 to 0.347)0.905
ALT-0.005 (-0.017 to 0.007)0.375
AST-0.001 (-0.007 to 0.005)0.789
Multiple stones-3.31 (-9.87 to 3.249)0.316
CCI1.466 (-0.713 to 3.644)0.183
Age-0.367 (-0.663 to -0.072)0.016-0.086 (-0.256 to 0.083)0.312
Severity of AC3.188 (-3.434 to 9.809)0.338
Time to ERCP0.051 (0.340 to 0.059)< 0.0010.044 (0.033 to 0.056)< 0.001
Common bile duct width-0.002 (-0.34 to 0.335)0.988
Secondary clinical outcomes

According to our analysis of the PS-matched population (Table 2), the length of hospital stay (LOHS) in the urgent group was significantly shorter than that in the elective group (9 d vs 18.5 d, P < 0.001). The two groups exhibited no significant differences in 30-d readmission (15.1% vs 16.1%, P = 0.84), recurrent cholangitis (2.9% vs 2.6%, P = 0.883), in-hospital mortality (0% vs 2.2%, P = 0.155), 30-d mortality (2.2% vs 3.2%, P = 0.65), adverse events after ERCP (17.65% vs 15.79%, P = 0.696), PEP (8.82% vs 9.21%, P = 0.916), bleeding (3.9% vs 1.3%, P = 0.180), biliary tract infection (5.9% vs 1.97%, P = 0.099), or other ERCP-related adverse events (1.96% vs 0, P = 0.083).

Subgroup analysis of patients with SAC

After PS matching (Table 4), 58 patients in the cohort presented with severe biliary tract infection according to a Tokyo score of 3. Among these patients, 60.3% underwent ERCP within 24 h of onset, while 39.7% underwent ERCP after 24 h. Subsequently, we compared outcomes between the urgent ERCP group and the elective ERCP group within the subset of patients who experienced severe cholangitis. No significant difference in ICU admission rates was observed between the two groups (60% vs 47.8%, P = 0.362). The urgent group had a significantly shorter ICU stay than did the elective group (4 d vs 11 d, P = 0.014), a significantly shorter duration of antibiotic use (17.1% vs 17.4%, P = 0.98), and a markedly shorter LOHS (9 d vs 20 d, P < 0.001). Additionally, within 30 d, there were no significant differences between the two subgroups in terms of readmission (17.1% vs 17.4%, P = 0.98), in-hospital mortality (0% vs 4.3%, P = 0.213), 30-d mortality (5.7% vs 8.7%, P = 0.661), occurrence of adverse events after ERCP (22.86% vs 13.04%, P = 0.351), PEP (8.57% vs 4.35%, P = 0.535), bleeding (2.86% vs 4.35%, P = 0.761), biliary tract infection (8.57% vs 0%, P = 0.149), or occurrence of other ERCP-related adverse events (2.86% vs 0, P = 0.414).

Table 4 Outcomes of endoscopic retrograde cholangiopancreatography in the propensity matched population (Tokyo score 3 subgroup).
Patients with Grade III AC
Total, n = 58
ERCP ≤ 24 h, n = 35
ERCP > 24 h, n = 23
P value
Duration of antibiotic use (d)8 (3-28)7 (3-15)11 (3-28)0.004
In-hospital mortality, n (%)1 (1.7)01 (4.3)0.213
30-d mortality, n (%)4 (6.9)2 (5.7)2 (8.7)0.661
Recurrent cholangitis, n (%)4 (6.9)2 (5.7)2 (8.7)0.661
LOHS, (d)13 (6-71)9 (6-17)20 (14-71)< 0.001
Required ICU stay, n (%)32 (55.2)21 (60)11 (47.8)0.362
ICU stay length, (d)6 (1-71)4 (1-15)11 (1-71)0.014
30 d readmission, n (%)10 (17.2)6 (17.1)4 (17.4)0.98
ERCP-related complications, n (%)11 (19)8 (22.9)3 (13)0.351
PEP4 (6.9)3 (8.6)1 (4.3)0.535
Cholangitis3 (5.2)3 (8.6)00.149
Bleeding2 (3.4)1 (2.9)1 (4.3)0.761
Others1 (1.7)1 (2.9)00.414
DISCUSSION

Numerous studies have been conducted to determine the best timing for biliary decompression in patients with AC. However, the advantages of urgent one-stage endoscopic procedures via ERCP for treating moderate to severe cholangitis associated with CBD stones still need further clarification[20-23]. We comprehensively analyzed the characteristics and diagnostic findings of 254 patients diagnosed with AC who were admitted to Zhongda Hospital of Southeast University over the past four years. Within our PS-matched population, multivariate regression analysis was used to identify independent predictors of ICU stay length, including preoperative Cr levels and delay in performing ERCP. Notably, elective ERCP was associated with a longer duration of ICU stay (3 d vs 8 d, P < 0.001) and a prolonged course of antibiotic treatment (6 d vs 9 d, P < 0.001). Additionally, elective ERCP resulted in an increased LOHS (9 d vs 18.5 d, P < 0.001). Similar findings were observed in the unadjusted cohort analysis: ICU stay length (3 d vs 8 d, P = 0.003), antibiotic duration (6 d vs 8 d, P < 0.001), and LOHS (9 d vs 18 d, P < 0.001).

Our investigation concentrated on patients who underwent single-stage endoscopic procedures for AC. In our PS-matched population, the mortality rate was 2.7%. This figure aligns with the findings reported by Park et al[12] and Zhang et al[14]. Notably, our observation rate was lower than the 5%-11% range documented in other studies[11,21]. One plausible rationale for this variance may stem from the fact that all subjects in our study exclusively underwent single-stage endoscopic procedures, potentially contributing to the observed lower mortality rate. Notably, single-stage endoscopic procedures exhibit both safety and efficacy in addressing biliary drainage and CBD stone clearance in individuals with AC. Previous studies have revealed that one-stage endoscopic treatment has a high cure rate and low complication rate in patients with mild to moderate cholangitis. In a multicenter retrospective study conducted by our team in 2019, the safety and efficacy of this approach were reaffirmed, particularly in patients with severe complications[14]. Eto et al[24] also reported a cure rate of 90% within 4 d of single-stage treatment for AC (45 out of 50 patients), as well as complete stone clearance achieved in all patients and a complication rate of only 10% (5 out of 50 individuals). This approach effectively reduces the risks associated with two-stage ERCP procedures. Our study included 254 patients who underwent urgent single-stage endoscopic procedures, all of which resulted in complete stone clearance and a low complication rate of 16.5%. These results suggested that single-stage treatment can be an effective and safe method for treating moderate to SAC associated with stone removal.

In 2023, Hedjoudje et al[22] conducted an analytical study based on a substantial database that included 85 patients with severe cholangitis. These patients underwent drainage within 24 h, while the remaining 51 patients underwent drainage 24 h later. The study revealed that the elective ERCP procedure was linked to higher mortality rates (13.0% vs 45.5%, P < 0.001), prolonged length of ICU stays (4.61 d vs 7.41 d, P = 0.004), and increased LOHS. In a retrospective study conducted by Muangkaew et al[25], a cohort of patients diagnosed with acute biliary pancreatitis associated with cholangitis was analyzed. Of these, 67 out of 95 patients underwent drainage within 72 h. The study revealed no statistically significant differences in mortality, ERCP-related complications, or disease-related complications between the early and elective ERCP groups. However, the early ERCP (< 72 h) group had a shorter LOHS (6.3 ± 4.4 d) than did the elective ERCP group (9.8 ± 6.1 d; P = 0.002). The difference in mortality outcomes between the two studies may be attributed to the study of Hedjoudje et al[22], patients specifically with severe cholangitis were enrolled, which potentially resulted in significantly greater mortality rates than those in the study of Muangkaew et al[25]. This discrepancy may partially explain the differences in mortality outcomes between the two studies.

Given the relatively low mortality rate observed among cholangitis patients in our study, our primary outcome measures included the ICU admission rate, ICU length of stay, and duration of antibiotic use. After analyzing multiple factors within our matched cohort, we found that for every hour of delay in ERCP, patients’ ICU stay increased by 0.033 d. Such a prolonged ICU stay not only contributes to increased hospital expenses but also amplifies the risks of hospital-acquired infections and associated adverse events. Our research underscores the imperative for urgent ERCP in patients experiencing moderate to SAC. The delay in receiving ERCP correlates with extended hospital and ICU stays, aligning with findings from prior investigations[11,21,22,25,26]. Nevertheless, we observed a heightened ICU admission rate in the urgent ERCP group, potentially attributed to the greater prevalence of severe cases in that cohort (34.4% vs 21.5%, P = 0.05). After surgery, medical practitioners typically move patients with severe biliary tract inflammation to the ICU for stabilization. Contrary to this norm, our study demonstrated that patients receiving urgent ERCP exhibited a shorter ICU stay (3 d vs 8 d, P < 0.001), with no discernible differences in post-ERCP prognostic indicators between the two groups. Despite a higher percentage of severe patients in the urgent group, patients in this subset recovered faster post surgery. Additionally, we assessed the duration of antibiotic usage among patients who underwent ERCP. Patients in the urgent group had a significantly shorter duration of antibiotic usage than did those in the nonurgent group (7 d vs 16 d, P < 0.001). Simultaneously, our results indicate a reduction in overall hospitalization within the urgent group. These findings collectively affirm the quicker postoperative recovery observed in the urgent group. Furthermore, our multifactorial linear analysis of ICU stay length revealed that Cr levels had a significant impact on ICU stay.

There are several limitations to our research. First, there may be inherent selection bias present, and the results of our research may only reflect the clinical situation within our facility because this was a retrospective single-center study. Second, we implemented strict inclusion and exclusion criteria, which led to a relatively small sample size. To address these issues, further large-scale clinical studies are necessary to confirm our findings.

CONCLUSION

To summarize, urgent one-stage endoscopic treatment is feasible and safe for patients with moderate to SAC. Our research also showed that if ERCP is performed more than 24 h after admission for moderate to SAC, it may lead to longer stays in the ICU and hospital.

ACKNOWLEDGEMENTS

Thanks to Ya-Dong Feng for the case design; Ying-Qiu Zhang and Shuai-Jing Huang on the collection and analysis of data; revisions to article by Yan Liang and Masoom Wali. Thanks for all participants for their contributions.

Footnotes

Provenance and peer review: Unsolicited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Gastroenterology and hepatology

Country/Territory of origin: China

Peer-review report’s scientific quality classification

Grade A (Excellent): A

Grade B (Very good): 0

Grade C (Good): 0

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Covantsev S, Russia S-Editor: Wang JJ L-Editor: A P-Editor: Cai YX

References
1.  Baykara N, Akalın H, Arslantaş MK, Hancı V, Çağlayan Ç, Kahveci F, Demirağ K, Baydemir C, Ünal N; Sepsis Study Group. Epidemiology of sepsis in intensive care units in Turkey: a multicenter, point-prevalence study. Crit Care. 2018;22:93.  [PubMed]  [DOI]  [Cited in This Article: ]
2.  Annane D, Aegerter P, Jars-Guincestre MC, Guidet B; CUB-Réa Network. Current epidemiology of septic shock: the CUB-Réa Network. Am J Respir Crit Care Med. 2003;168:165-172.  [PubMed]  [DOI]  [Cited in This Article: ]
3.  Leligdowicz A, Dodek PM, Norena M, Wong H, Kumar A; Co-operative Antimicrobial Therapy of Septic Shock Database Research Group. Association between source of infection and hospital mortality in patients who have septic shock. Am J Respir Crit Care Med. 2014;189:1204-1213.  [PubMed]  [DOI]  [Cited in This Article: ]
4.  Kiriyama S, Kozaka K, Takada T, Strasberg SM, Pitt HA, Gabata T, Hata J, Liau KH, Miura F, Horiguchi A, Liu KH, Su CH, Wada K, Jagannath P, Itoi T, Gouma DJ, Mori Y, Mukai S, Giménez ME, Huang WS, Kim MH, Okamoto K, Belli G, Dervenis C, Chan ACW, Lau WY, Endo I, Gomi H, Yoshida M, Mayumi T, Baron TH, de Santibañes E, Teoh AYB, Hwang TL, Ker CG, Chen MF, Han HS, Yoon YS, Choi IS, Yoon DS, Higuchi R, Kitano S, Inomata M, Deziel DJ, Jonas E, Hirata K, Sumiyama Y, Inui K, Yamamoto M. Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos). J Hepatobiliary Pancreat Sci. 2018;25:17-30.  [PubMed]  [DOI]  [Cited in This Article: ]
5.  Lavillegrand JR, Mercier-Des-Rochettes E, Baron E, Pène F, Contou D, Favory R, Préau S, Galbois A, Molliere C, Miailhe AF, Reignier J, Monchi M, Pichereau C, Thietart S, Vieille T, Piton G, Preda G, Abdallah I, Camus M, Maury E, Guidet B, Dumas G, Ait-Oufella H. Acute cholangitis in intensive care units: clinical, biological, microbiological spectrum and risk factors for mortality: a multicenter study. Crit Care. 2021;25:49.  [PubMed]  [DOI]  [Cited in This Article: ]
6.  Nishino T, Hamano T, Mitsunaga Y, Shirato I, Shirato M, Tagata T, Shimada M, Yoshida S, Mitsunaga A. Clinical evaluation of the Tokyo Guidelines 2013 for severity assessment of acute cholangitis. J Hepatobiliary Pancreat Sci. 2014;21:841-849.  [PubMed]  [DOI]  [Cited in This Article: ]
7.  Buxbaum JL, Buitrago C, Lee A, Elmunzer BJ, Riaz A, Ceppa EP, Al-Haddad M, Amateau SK, Calderwood AH, Fishman DS, Fujii-Lau LL, Jamil LH, Jue TL, Kwon RS, Law JK, Lee JK, Naveed M, Pawa S, Sawhney MS, Schilperoort H, Storm AC, Thosani NC, Qumseya BJ, Wani S. ASGE guideline on the management of cholangitis. Gastrointest Endosc. 2021;94:207-221.e14.  [PubMed]  [DOI]  [Cited in This Article: ]
8.  An Z, Braseth AL, Sahar N. Acute Cholangitis: Causes, Diagnosis, and Management. Gastroenterol Clin North Am. 2021;50:403-414.  [PubMed]  [DOI]  [Cited in This Article: ]
9.  Yokoe M, Takada T, Strasberg SM, Solomkin JS, Mayumi T, Gomi H, Pitt HA, Garden OJ, Kiriyama S, Hata J, Gabata T, Yoshida M, Miura F, Okamoto K, Tsuyuguchi T, Itoi T, Yamashita Y, Dervenis C, Chan AC, Lau WY, Supe AN, Belli G, Hilvano SC, Liau KH, Kim MH, Kim SW, Ker CG; Tokyo Guidelines Revision Committee. TG13 diagnostic criteria and severity grading of acute cholecystitis (with videos). J Hepatobiliary Pancreat Sci. 2013;20:35-46.  [PubMed]  [DOI]  [Cited in This Article: ]
10.  Navuluri R, Hoyer M, Osman M, Fergus J. Emergent Treatment of Acute Cholangitis and Acute Cholecystitis. Semin Intervent Radiol. 2020;37:14-23.  [PubMed]  [DOI]  [Cited in This Article: ]
11.  Lee F, Ohanian E, Rheem J, Laine L, Che K, Kim JJ. Delayed endoscopic retrograde cholangiopancreatography is associated with persistent organ failure in hospitalised patients with acute cholangitis. Aliment Pharmacol Ther. 2015;42:212-220.  [PubMed]  [DOI]  [Cited in This Article: ]
12.  Park CS, Jeong HS, Kim KB, Han JH, Chae HB, Youn SJ, Park SM. Urgent ERCP for acute cholangitis reduces mortality and hospital stay in elderly and very elderly patients. Hepatobiliary Pancreat Dis Int. 2016;15:619-625.  [PubMed]  [DOI]  [Cited in This Article: ]
13.  Sato J, Nakahara K, Morita R, Morita N, Suetani K, Michikawa Y, Kobayashi S, Itoh F. Efficacy and Safety of Single-Session Endoscopic Stone Removal for Acute Cholangitis Associated with Choledocholithiasis. Can J Gastroenterol Hepatol. 2018;2018:3145107.  [PubMed]  [DOI]  [Cited in This Article: ]
14.  Zhang X, Li G, Pan L, Chen Y, Shi R, Xu W, Zhou K, Cheng Y, Feng Y, Zhou A, Zhao K. The efficacy and safety of one-stage endoscopic treatment for ascending acute cholangitis caused by choledocholithiasis with severe comorbidities. Surg Endosc. 2020;34:3963-3970.  [PubMed]  [DOI]  [Cited in This Article: ]
15.  Liang CM, Chiu YC, Lu LS, Wu CK, Sou FM, Chiu SM, Lee YC, Huang PY, Chuah SK, Kuo CM. Early and Direct Endoscopic Stone Removal in the Moderate Grade of Acute Cholangitis with Choledocholithiasis Was Safe and Effective: A Prospective Study. Life (Basel). 2022;12.  [PubMed]  [DOI]  [Cited in This Article: ]
16.  Ito T, Sai JK, Okubo H, Saito H, Ishii S, Kanazawa R, Tomishima K, Watanabe S, Shiina S. Safety of immediate endoscopic sphincterotomy in acute suppurative cholangitis caused by choledocholithiasis. World J Gastrointest Endosc. 2016;8:180-185.  [PubMed]  [DOI]  [Cited in This Article: ]
17.  Yokoe M, Hata J, Takada T, Strasberg SM, Asbun HJ, Wakabayashi G, Kozaka K, Endo I, Deziel DJ, Miura F, Okamoto K, Hwang TL, Huang WS, Ker CG, Chen MF, Han HS, Yoon YS, Choi IS, Yoon DS, Noguchi Y, Shikata S, Ukai T, Higuchi R, Gabata T, Mori Y, Iwashita Y, Hibi T, Jagannath P, Jonas E, Liau KH, Dervenis C, Gouma DJ, Cherqui D, Belli G, Garden OJ, Giménez ME, de Santibañes E, Suzuki K, Umezawa A, Supe AN, Pitt HA, Singh H, Chan ACW, Lau WY, Teoh AYB, Honda G, Sugioka A, Asai K, Gomi H, Itoi T, Kiriyama S, Yoshida M, Mayumi T, Matsumura N, Tokumura H, Kitano S, Hirata K, Inui K, Sumiyama Y, Yamamoto M. Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholecystitis (with videos). J Hepatobiliary Pancreat Sci. 2018;25:41-54.  [PubMed]  [DOI]  [Cited in This Article: ]
18.  Miura F, Okamoto K, Takada T, Strasberg SM, Asbun HJ, Pitt HA, Gomi H, Solomkin JS, Schlossberg D, Han HS, Kim MH, Hwang TL, Chen MF, Huang WS, Kiriyama S, Itoi T, Garden OJ, Liau KH, Horiguchi A, Liu KH, Su CH, Gouma DJ, Belli G, Dervenis C, Jagannath P, Chan ACW, Lau WY, Endo I, Suzuki K, Yoon YS, de Santibañes E, Giménez ME, Jonas E, Singh H, Honda G, Asai K, Mori Y, Wada K, Higuchi R, Watanabe M, Rikiyama T, Sata N, Kano N, Umezawa A, Mukai S, Tokumura H, Hata J, Kozaka K, Iwashita Y, Hibi T, Yokoe M, Kimura T, Kitano S, Inomata M, Hirata K, Sumiyama Y, Inui K, Yamamoto M. Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis. J Hepatobiliary Pancreat Sci. 2018;25:31-40.  [PubMed]  [DOI]  [Cited in This Article: ]
19.  Cotton PB, Eisen GM, Aabakken L, Baron TH, Hutter MM, Jacobson BC, Mergener K, Nemcek A Jr, Petersen BT, Petrini JL, Pike IM, Rabeneck L, Romagnuolo J, Vargo JJ. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc. 2010;71:446-454.  [PubMed]  [DOI]  [Cited in This Article: ]
20.  Parikh MP, Wadhwa V, Thota PN, Lopez R, Sanaka MR. Outcomes Associated With Timing of ERCP in Acute Cholangitis Secondary to Choledocholithiasis. J Clin Gastroenterol. 2018;52:e97-e102.  [PubMed]  [DOI]  [Cited in This Article: ]
21.  Khashab MA, Tariq A, Tariq U, Kim K, Ponor L, Lennon AM, Canto MI, Gurakar A, Yu Q, Dunbar K, Hutfless S, Kalloo AN, Singh VK. Delayed and unsuccessful endoscopic retrograde cholangiopancreatography are associated with worse outcomes in patients with acute cholangitis. Clin Gastroenterol Hepatol. 2012;10:1157-1161.  [PubMed]  [DOI]  [Cited in This Article: ]
22.  Hedjoudje A, Cheurfa C, Et Talby M, Levy P, Prat F, Piton G. Outcomes and predictors of delayed endoscopic biliary drainage for severe acute cholangitis due to choledocholithiasis in an intensive care unit. Dig Liver Dis. 2023;55:763-770.  [PubMed]  [DOI]  [Cited in This Article: ]
23.  Tan M, Schaffalitzky de Muckadell OB, Laursen SB. Association between early ERCP and mortality in patients with acute cholangitis. Gastrointest Endosc. 2018;87:185-192.  [PubMed]  [DOI]  [Cited in This Article: ]
24.  Eto K, Kawakami H, Haba S, Yamato H, Okuda T, Yane K, Hayashi T, Ehira N, Onodera M, Matsumoto R, Matsubara Y, Takagi T, Sakamoto N; Hokkaido Interventional EUS/ERCP study (HONEST) group. Single-stage endoscopic treatment for mild to moderate acute cholangitis associated with choledocholithiasis: a multicenter, non-randomized, open-label and exploratory clinical trial. J Hepatobiliary Pancreat Sci. 2015;22:825-830.  [PubMed]  [DOI]  [Cited in This Article: ]
25.  Muangkaew P, Kamalaporn P, Mingphruedhi S, Rungsakulkij N, Suragul W, Vassanasiri W, Tangtawee P. Outcomes of delayed endoscopic retrograde cholangiopancreatography in patients with acute biliary pancreatitis with cholangitis. Asian J Surg. 2020;43:913-918.  [PubMed]  [DOI]  [Cited in This Article: ]
26.  Iqbal U, Khara HS, Hu Y, Khan MA, Ovalle A, Siddique O, Sun H, Shellenberger MJ. Emergent versus urgent ERCP in acute cholangitis: a systematic review and meta-analysis. Gastrointest Endosc. 2020;91:753-760.e4.  [PubMed]  [DOI]  [Cited in This Article: ]