Comparison of endoscopic retrograde cholangiopancreatography drainage vs percutaneous transhepatic biliary drainage in severe cholangitis: A study from low-middle income country

Abstract

BACKGROUND

Severe acute cholangitis is a potentially life-threatening disease in low-middle income countries (LMIC). Due to limited endoscopic services, these patients mostly undergo percutaneous transhepatic biliary drainage (PTBD). Studies from developed countries reported more complications with PTBD as compared with endoscopic retrograde cholangiopancreatography (ERCP).

AIM

To compare safety, therapeutic success, and survival among the PTBD and ERCP procedure in severe cholangitis in LMIC.

METHODS

A retrospective study was conducted in the Aga Khan University Hospital from January 2017 to December 2023. All patients who had severe acute cholangitis and underwent ERCP or PTBD were included. Patients were followed for complications, procedure success, and mortality. Data was gathered through an electronic medical record system and analyzed using χ² and two sample t-tests.

RESULTS

A total of 33 patients were recruited, consisting of 12 females and 21 males with a mean age of 61 years. Among these participants, 12 patients underwent ERCP, and the remaining 21 patients underwent PTBD. Therapeutic success was seen more in the ERCP group [11/12 (97.1%)] than in the PTBD group [12/21 patients (57.1%)]. Post-procedure complications were seen in both groups; however, more were observed in the PTBD cohort with a significant P value of 0.02. There were no mortalities among the patients who underwent ERCP while 5 (23.8%) mortalities were seen in the PTBD group.

CONCLUSION

Fewer post-procedure complications and deaths were observed after ERCP than after PTBD, laying the foundation for large prospective studies and shifting the local paradigm of acute cholangitis treatment in LMICs.

Key Words: Endoscopy; Gallstones; Biliary drainage; Percutaneous transhepatic biliary drainage; Endoscopic retrograde cholangiopancreatography; Therapeutic biliary drainage; Biliary obstruction

Core Tip: Severe acute cholangitis is life-threatening, especially in low-middle income countries where percutaneous transhepatic biliary drainage (PTBD) is common due to limited endoscopic services. A retrospective study at Aga Khan University Hospital (2017-2023) found endoscopic retrograde cholangiopancreatography (ERCP) had higher therapeutic success (97.1%) compared with PTBD (57.1%) with PTBD having more complications (P = 0.02) and higher mortality (23.8%) compared with ERCP (0%). The study concluded that ERCP showed better outcomes, suggesting a shift towards ERCP in LMICs for severe cholangitis treatment.

INTRODUCTION

Acute cholangitis is a potentially life-threatening systemic disease resulting from a combination of infection and obstruction of the biliary tree, secondary to different underlying etiologies[1]. The most common etiologies are choledocholithiasis and benign or malignant strictures secondary to cancers such as pancreatic or cholangiocarcinoma. Acute cholangitis can be graded based on severity (Tokyo guidelines), consisting of mild, moderate, and severe acute cholangitis. This is decisive in determining the necessity and timing of early intervention for biliary drainage as well as the indication for intensive care measures[2].

Management is based on antimicrobial therapy and appropriate biliary drainage for a better prognostic outcome. Because of high biliary intraductal pressure, biliary secretion of antibiotics is impaired[3]. Therefore, biliary drainage is crucial. The type of intervention is usually based on the etiology of the obstruction, the patient’s physical health, and the severity of the disease. The overall mortality of acute cholangitis is less than 10% after biliary drainage[4].

Endoscopic retrograde cholangiopancreatography (ERCP) is considered one of the methods for biliary drainage. Although it was used for diagnosis in the early years, its role in treatment increased with the application of endoscopic sphincterotomy in 1974[5]. In a study conducted on the Diagnostic and Therapeutic value of ERCP in Acute Cholangitis, the success rate of ERCP was reported to be 94%[6]. However, it is associated with some common complications, such as pancreatitis, bleeding, and perforation. Pancreatitis is the most common adverse event after ERCP, and its incidence varies between 1%-7%[7].

In patients who are elderly and fragile or who have multiple comorbidities, ERCP may be a difficult choice due to the risk of procedure-related complications, anesthesia-related challenges, and availability of expertise. Also, in some cases the chances of ERCP failure are high. Hence, percutaneous transhepatic biliary drainage (PTBD) is considered an alternative option. PTBD has been reported to be successful even in patients at higher risk for complications[8,9]. In a study conducted in India regarding the therapeutic success of PTBD in patients with severe cholangitis, it was clinically successful in 64.2% of the patients[10]. Disadvantages generally include an increased risk of hospital-acquired infections, intraperitoneal hemorrhage, and biliary peritonitis leading to a longer hospital stay. It is uncomfortable for the patient, and the risk of pulling it out is always there in patients who are suffering from dementia or other cognitive disorders[11]. It is, however, contraindicated in patients with ascites, coagulopathies[3], and anatomical variations that make it difficult to access the biliary tree.

Both procedures, ERCP and PTBD, have their therapeutic benefits and some limitations in patients with different clinical status and disease severity. ERCP is usually preferred in mild to moderate acute cholangitis, but in severe acute cholangitis safety of procedures and tolerance of anesthesia always remain under debate. Both procedures are not without risk of adverse events and labeling one procedure better than the other is difficult. However, in low-income and middle-income countries due to limited established endoscopy centers and a lack of ERCP training and expertise, physicians and surgeons are mostly inclined toward PTBD in treating patients with acute severe cholangitis.

Therefore, we aimed to study the safety and therapeutic and clinical success between both biliary drainage methods (ERCP and PTBD) in patients with severe acute cholangitis in our low-middle income country.

MATERIALS AND METHODS

This comparative study was conducted in the Department of Gastroenterology at the Aga Khan University Hospital, Karachi from January 2017 to December 2023. Data were collected from patients who underwent ERCP and PTBD due to severe acute cholangitis and arranged into two groups.

All patients underwent relevant laboratory and radiological investigations before the intervention. According to the Tokyo guidelines, severe acute cholangitis is cholangitis with dysfunction of one of the following organs, shock requiring the need for vasopressor support, inability to maintain oxygen saturation on room air, altered mental status, acute kidney injury (creatinine more than 2.0 mg/dL), raised international normalized ratio and low platelets levels (< 100000/μL)[12]. All patients were assessed on these parameters, and those who met the criteria of severe acute cholangitis were selected. Patients under 18 years of age, those who had already undergone the procedure at another hospital before presenting in the emergency, and those with incomplete medical records were excluded from this study.

The two groups of patients were compared with respect to age, comorbidities, vitals at the time of presentation, procedure performed, complications post-procedure, and the outcome. The laboratory values obtained were taken at the time of initial presentation. The following laboratory values were analyzed: Hemoglobin; total leukocyte count; platelets; prothrombin time; creatinine; and liver function tests. Appropriate radiological modalities were used like transabdominal ultrasonography, CT, or magnetic resonance cholangiopancreatography to confirm the diagnosis. An algorithm, the Charlson Comorbidity Index, was used to calculate the estimated 10-year mortality in these patients based on the comorbidities[13].

Outcomes were divided into primary and secondary outcomes. The primary outcome was therapeutic success, defined as the clinical and biochemical resolution of cholangitis and clinical follow-up in stable condition after the procedure (ERCP or PTBD). Secondary outcomes were technical success, post-procedure complications, hospital readmission, and mortality within 1 month of the procedure. Technical success is defined as the successful completion of the procedure (ERCP or PTBD).

The patients and the public were not involved in the design, conduct, reporting, or dissemination plans of our research.

Statistical analysis

Statistical analysis was performed using STATA version 14.2. Categorical data were analyzed using the χ² test. At the same time descriptive data were shown as mean and standard error. Two sample t-tests were used to compare the mean among the patients who underwent ERCP and PTBD. Overall, a P value < 0.05 was considered statistically significant.

RESULTS

A total of 718 patients were evaluated, out of which 33 were selected who met the criteria of severe acute cholangitis. The mean age of the patients was 61 years, ranging from 38 to 84 years. Among them there were more male patients, 21 (63.6%), than female patients, 12 (36.4%). PTBD was performed in 21 patients (63.6%), and ERCP was performed in 12 of the patients (36.4%). Baseline characteristics are given in Table 1.

Table 1 Comparative analysis of baseline features.

Characteristic	ERCP (n = 12)	PTBD (n = 21)	P value
Severe cholangitis (n = 33)	12 (36.4)	21 (63.6)
Mean age (years)	60.4	62.7	0.63
Female	4 (33.3)	8 (38.1)	0.78
Male	8 (66.7)	13 (61.9)
Charlson Comorbidity Index score	3.3 ± 2.4	5.0 ± 2.7	0.09
Comorbidities
Hypertension	7 (58.3)	12 (57.1)	0.94
Diabetes	4 (33.3)	8 (38.1)	0.78
Ischemic heart disease	1 (8.3)	6 (28.6)	0.17
Chronic kidney disease	0 (0.0)	2 (9.5)	0.27
Chronic liver disease	1 (8.3)	1 (4.8)	0.67
Nonalcoholic fatty liver disease	1 (8.3)	0 (0.0)	0.17
Clinical features
Abdominal pain	8 (66.7)	18 (85.7)	0.19
Fever	7 (58.3)	13 (61.9)	0.80
Jaundice	5 (41.7)	15 (71.4)	0.09
Nausea and vomiting	5 (41.7)	5 (23.8)	0.28
Weight loss	1 (8.3)	7 (33.3)	0.10
Altered consciousness	1 (8.3)	5 (23.8)	0.26
Lethargy	0 (0.0)	3 (14.3)	0.17
Vitals
Temperature	37.0 ± 0.4	37.3 ± 0.4	0.11
Heart rate	96.2 ± 14.8	102.3 ± 19.5	0.35
Mean arterial pressure	64.9 ± 7.4	60.7 ± 4.6	0.05
Respiratory rate	20.7 ± 6.1	20.6 ± 2.1	0.97
SpO2	95.1 ± 2.6	94.9 ± 1.3	0.79
Laboratory investigations
Hemoglobin	11.2 ± 2.8	10.3 ± 1.8	0.29
Total leukocyte count	18.2 ± 7.8	18.2 ± 8.7	0.98
Platelets	216.7 ± 126.3	223 ± 130.4	0.88
Prothrombin time	15.6 ± 7.3	16.2 ± 8.4	0.83
Organ severity
Cardiac dysfunction	6 (50.0)	17 (80.9)	0.06
Hepatic dysfunction	4 (33.3)	10 (47.6)	0.42
Renal dysfunction	3 (25.0)	8 (38.1)	0.44
Hematological dysfunction	3 (25.0)	4 (19.1)	0.68
Neurological dysfunction	0 (0.0)	3 (14.3)	0.17
Pulmonary dysfunction	0 (0.0)	2 (9.6)	0.27

Data are presented as n (%) or mean ± SD. ERCP: Endoscopic retrograde cholangiopancreatography; PTBD: Percutaneous transhepatic biliary drainage; SpO₂: Peripheral capillary oxygen saturation.

Hypertension and diabetes mellitus were the most common comorbidities in both groups of patients. Other comorbidities such as ischemic heart disease, chronic kidney disease, chronic liver disease, and nonalcoholic fatty liver disease were comparable in both groups without statistical difference.

Common presenting complaints were abdominal pain, jaundice, and fever associated with nausea and vomiting. Abdominal pain and fever were the most common in the PTBD group (fever: 13/21, 61.9%; abdominal pain: 18/21, 85.7%) as compared with the ERCP group (fever: 7/12, 58.3%; abdominal pain: 8/12, 66.7%). However, there were no significant differences. This is further demonstrated in Table 1.

Cardiac dysfunction was the most common among all the patients (23/33, 69.6%). Almost half of the patients presented with hepatic and renal involvement and required monitoring. The rest of the organ dysfunctions were relatively less common. Serum alkaline phosphatase levels of patients who underwent PTBD were higher compared with patients who underwent ERCP (mean value of 392.5 in ERCP and 690.3 in PTBD) with a significant value of P = 0.02 (Table 1).

The technical success of both procedures was 100%. Therapeutic success was favorable in patients who underwent ERCP as most patients were discharged in stable condition after resolution of cholangitis with early follow-up [11/12 (91.7%)] whereas therapeutic success was observed in 12/21 patients (57.1%) in the PTBD group (P = 0.03).

The PTBD group had more total complications (n = 12 patients, 57.1%) than the ERCP group (n = 2 patients, 16.7%) (P = 0.02). Complications mainly consisted of hospital- acquired infections such as hospital-acquired pneumonia, bloodstream infections, and catheter-associated urinary tract infections [PTBD 11/21 (52.4%) vs ERCP 2/12 (16.7%), P = 0.04].

Pulmonary complications such as pleural effusion and pulmonary edema were seen in 6/21 (28.6%) patients who underwent PTBD and 1/12 patients who underwent ERCP (8.3%). Among the patients who underwent PTBD, dislodgement of the drain was seen in only 3/21 (14.3%) of the patients. Another, less common complication was bleeding, which was seen in only 2 of the patients (4.8%) who had PTBD, and arrhythmias were seen in only 1 patient (4.7%) in PTBD group (Table 1).

Readmissions were seen more in the PTBD group [4 patients (19.1%)] compared with the ERCP group [1 patient (8.3%)] although this was not a significant difference. There were 5/21 (23.8%) mortalities in the PTBD group and zero deaths in the ERCP group (Table 1).

DISCUSSION

Acute severe cholangitis is a critical condition caused by bile duct obstruction. Without timely treatment and intervention to relieve the obstruction, it can progress to sepsis and ultimately lead to mortality. Only well-equipped tertiary care hospitals can facilitate such patients. Early medical therapy, including appropriate antibiotic coverage followed by a biliary drainage procedure is mandatory[1].

Our study evaluated the role of two methods of biliary drainage: ERCP and PTBD. Out of the 33 patients who had severe cholangitis and underwent the procedure, the majority were middle-aged males (68.6%). These patients had multiple comorbidities. The main comorbidities noticed were hypertension, diabetes, and ischemic heart disease, which all increased disease severity. Previous studies have shown that serious comorbid conditions accompanying geriatric age contribute to the increased and more severe courses of acute cholangitis[14].

Clinical features showed that the patients presented with the classic triad of fever, abdominal pain (right hypochondrial pain), and jaundice. However, abdominal pain was associated with nausea and vomiting. Altered consciousness was noted in some patients, adding to the severity of the disease. This corroborated the laboratory investigations and confirmed that the patients needed immediate intervention. Multiorgan involvement was observed, but cardiac dysfunction was the most prevalent among the two groups (6/12 50.0% in ERCP and 17/21 80.9% in PTBD) (P = 0.06). Thus, patients required constant monitoring and vasopressor support (Table 2).

Table 2 Technical success, complications and outcome of patients.

Outcome	ERCP (n = 12)	PTBD (n = 21)	P value
Technical success	12 (100.0)	21 (100.0)
Therapeutic success	11 (91.7)	12 (57.1)	0.03
Complications
Total complications	2 (16.7)	12 (57.1)	0.02
Hospital acquired infections	2 (16.7)	11 (52.4)	0.04
Pulmonary complications	1 (8.3)	6 (28.6)	0.17
Dislodgement	0 (0.0)	3 (14.3)	0.17
Arrhythmias	0 (0.0)	1 (4.7)	0.44
Bleeding	0 (0.0)	2 (4.8)	0.44
Mortality	0 (0.0)	5 (23.8)	0.06
Readmission	1 (8.3)	4 (19.1)	0.40

Data are presented as n (%) or mean ± SD. ERCP: Endoscopic retrograde cholangiopancreatography; PTBD: Percutaneous transhepatic biliary drainage.

This study showed a high technical success rate in both procedures; however, significantly better therapeutic success was observed in patients who underwent ERCP (P = 0.03) (Table 2). This was also noticed in a study conducted at a university in Morocco, showing that ERCP had better therapeutic outcomes with lower mortality rates and fewer hospitalizations. It also confirmed ERCP as the gold-standard procedure for patients with severe cholangitis[15].

Almost half of the patients who underwent PTBD had one or more post-procedure complications. Our study is not the first one to report complications after PTBD. A Dutch study conducted in 2016 comparing efficacy and safety of preoperative drainage via ERCP vs percutaneous transhepatic cholangial drainage in patients with perihilar cholangiocarcinoma was stopped due to overall adverse outcomes and increased mortality in the PTBD group [3/27 (11%) vs 11/27 (41%), respectively][16].

Common complications included hospital-acquired infections with microbes. Infections were more common in the PTBD group than in the ERCP group. Despite the administration of prophylactic antibiotics, individuals still experienced infections. Patients in the PTBD group experienced relatively more infections compared with the ERCP group; 11 out of 21 had an infection after the procedure. This was significant with a P value of 0.04. In another study the sepsis rate after PTBD was reported to be 60%[17]. At the same time the infection rate in patients who underwent ERCP was 0.6%, according to a study conducted in India[7]. The rest of the complications included the pulmonary system such as pleural effusion and pulmonary edema, which were reported in only 6 patients who underwent the PTBD procedure.

Dislodgement of the drain after PTBD was a common complication seen in patients [3/21 (14.3%)] at our hospital. It was one of the most common complications seen after this procedure in a study conducted in Hungary in 2018 in which 63 drain dislocations were noted from a total of 599 patients who underwent this procedure[18]. Complications like bleeding and post-ERCP pancreatitis were largely avoided. Cardiac arrhythmia was observed in 1 patient only, making it a rare complication (Table 2).

A higher number of readmissions were seen in the PTBD group compared with the ERCP group. However, this held no statistical significance. In the ERCP group there were no deaths; however, 5 out of 21 people who underwent PTBD expired within the same admission (P = 0.06) (Table 2).

PTBD is an adequate drainage method; however, it leads to more adverse outcomes in patients with severe cholangitis. ERCP has a reduced mortality rate that was further confirmed by a study conducted in Germany (from 2002-2016) stating that ERCP was safe in patients who were critically ill in the ICU, did not increase the overall mortality rate, and had a relatively low rate of procedure-associated complications[19].

There are multiple studies on PTBD and ERCP separately, but this is the first study conducted in an LMIC comparing the two procedures, their therapeutic success rate, and survival of patients. Our study had some limitations as it was a retrospective with a small cohort size and focusing on a single center.

CONCLUSION

Severe acute cholangitis has adverse outcomes if not treated in due time. Proper management with ERCP is only possible in tertiary care hospitals. Due to a lack of expertise, many hospitals in LMICs choose PTBD as a therapeutic intervention.

Our study concluded that both biliary drainage procedures (ERCP and PTBD) are comparable in technical success rate, but ERCP has a better therapeutic success and safety profile than PTBD in patients with acute severe cholangitis. We recommend ERCP to be the standard practice in LMIC. Our study paved a path for a paradigm shift from conventional intervention to standard of care intervention in LMICs. However, large, multicenter prospective studies are needed to validate our results.