Endoscopic management of biliary disorders during pregnancy

Vui Heng Chong and Anand Jalihal

Bandar Seri Begawan, Brunei Darussalam

Endoscopic management of biliary disorders during pregnancy

Vui Heng Chong and Anand Jalihal

Bandar Seri Begawan, Brunei Darussalam

BACKGROUND:Biliary interventions during pregnancy are associated with risks to both the pregnancy and developing fetus. In this report we summarize our experience with endoscopic interventions including endoscopic ultrasound (EUS) in the management of biliary disorders during pregnancy.

METHODS:Endoscopic retrograde cholangiopancreatographies (ERCPs) performed between May 2003 through January 2010 (n=607) were identified from our database, and cases of interventions during pregnancy were reviewed. All procedures were done using conscious sedation and lead shielding.

RESULTS:Nine ERCPs (1.5%) were performed in 8 pregnant patients. Their median gestational period was 22 weeks (range, <2-36 weeks). Two, 5 and 2 patients were in their first, second and third trimester, respectively. Indications for ERCP included obstructive jaundice (6 patients) cholangitis (2), and acute pancreatitis/obstructive jaundice (1). Two patients underwent EUS before ERCP. Fluoroscopy was used in 5 ERCPs (median 12 seconds; range 2-20 seconds), and the overall time for a ERCP ranged from 5 to 25 minutes. During ERCP endoscopic sphincterotomy was performed in 5 patients, stenting in 6, and balloon clearance in 3. One procedure caused complication in induction of labor. During pregnancy, there were 4 non-procedure related complications including acute cholecystitis (1), HELLP syndrome resulting in spontaneous abortion (1) and stent migrations (2). Five pregnancies had uncomplicated term deliveries, whereas 2 required urgent caesarian sections (one for fetal distress and 1 for cholangitis secondary to stent migration). One patient was well in her second trimester during follow-up. Seven babies were well at birth with median APGAR scores of 9, and 10 at 5 and 10 minutes, respectively. One baby died of sudden death syndrome at age of 40 days.CONCLUSIONS:ERCP is a safe procedure for pregnant women. It can be conducted for biliary stenting and subsequent clearance after deliveries. EUS has a complementary role. Different strategies can be applied according to the conditions or expertise of endoscopists.

(Hepatobiliary Pancreat Dis Int 2010; 9: 180-185)

choledocholithiasis; cholangitis; obstructive jaundice; pregnancy; endoscopy; endoscopic ultrasound

Introduction

Gallstone disease is common during pregnancy. The incidence of sludge and gallstones is known to be as high as 31% and between 3% to 12% respectively when pregnancy progresses.[1,2]Acute cholecystitis is the second most common nonobstetric emergency in pregnant women. Fortunately a large proportion of patients with gallstone disease are asymptomatic and do not require any treatment. However, symptomatic gallstone disease can be associated with significant complications. The treatment of gallstone-related problem during pregnancy is similar to that in the non-pregnancy state.[3,4]However, any interventions during pregnancy are associated with risk to both the pregnancy and the developing fetus. The main concerns are radiation exposure and interventions which are potentially harm to the pregnancy and the developing fetus[5,6]Non-radiation endoscopic biliary interventions have been reported to be effective without increasing the risk.[7-10]In this report, we summarized our experience with endoscopic interventions including endoscopic ultrasound (EUS) in the management of biliary disorders during pregnancy.

Methods

SettingThe Endoscopy Unit, Department of Medicine, RIPAS Hospital (a 550-bed tertiary hospital) is the main referral center for biliary interventions with a population catchments of approximately 388 000. In the earlier period, the interventional procedures were performed for in-patients, but in the later period, day-case procedures became common.

Patients

Endoscopic biliary interventions were performed for patients who were pregnant from May 2003 to January 2010. These patients were identified from the endoscopic register of the hospital.

Procedures

Endoscopic retrograde cholangiopancreatography (ERCP) or other endoscopic procedures were performed for patients lying in the left lateral position to avoid compromise of venous return especially in those patients at the later stage of pregnancy. Midazolam supplied with fentayl or pethidine was given to the patients according to the level of sedation while monitoring saturation and pulse. Supplemental oxygen was routinely used in all patients. ERCPs were performed using the Olympus video-endoscope system (JF260V, Olympus®, Japan) by experienced endoscopists. Fluoroscopic imaging was carried out with the use of a C-arm (Siremobil Compact L, Siemen® AG, Munich, Germany). Pre- and periprocedural preparations and monitoring were made as each our usual Endoscopy Unit protocol. Lead apron shielding of the lower abdomen was done for all patients and precautionary measures were taken to minimize radiation exposure and the duration of interventions.

In our unit, we had no specific protocol with regard to fluoroscopy use in pregnant patients. However, we attempted non-fluoroscopy cannulation using bile aspiration or flow of bile around the cannula as indicator of a successful bile duct cannulation. Imaging was used if required but only for a short duration. In the later period, endoscopic ultrasound (EUS) video-endoscope system (GF UM2000, Olympus®, Japan) was also selectively used for the patients in whom the presence of biliary stones was uncertain. We also used EUS to delineate the distal anatomy and pathology such as size and location of stones. Endoscopic sphincterotomy (ES) was carried out when required using bipolar current.

After the procedures, patients were monitored for immediate complications and were followed up daily until discharge. After discharge from the hospital, the patients were asked to monitor complications such as obstructions or stent migrations. They were subjected to repeat ERCP for stent extraction, but stone clearances were attempted usually after delivery. After that, they received cholecystectomy according to the protocol. For patients with failed stone clearances by ERCP, surgical clearance was considered.

Data collection

Case notes were retrieved and relevant data were collected using a predefined proforma. Collected data included demographics of patients, gestations, clinical presentations, results of laboratory investigations, ultrasound findings, procedural data such as sedations, duration of procedures (the time from insertion to the withdrawal of an endoscope), monitoring, duration of fluoroscopy, interventions and outcomes, post-operative complications, progress of pregnancy, dates and mode of delivery, health of patients and babies at the time of delivery, follow-up , and subsequent interventions.

Results

A total of 607 ERCPs and 9 interventions (1.5%) were performed during the pregnancy of 8 patients. One patient underwent an intervention during two pregnancies. The median age of the patients was 29 years (range 20-35). Two patients were in the first trimester, 5 in the second, and 2 in the third respectively. Two patients were not aware of their pregnancy before admission or 20-week gestation, and 2 weeks (<2 wks) after ERCP, respectively.

Clinical presentations of the patients included obstructive jaundice in 6 patients (77.8%), cholangitis in 2 (22.2%), and acute gallstones pancreatitis in 1 (11.1%). One patient presented with acute pancreatitis and obstructive jaundice. Seven patients had previous admissions or consultations (median one, range 0-4) for symptoms induced by gallstone disease. All patients underwent ERCP at a median of 2 days after admission (0-9) and were given sedato-analgesia medications such as midazolam (a median dose of 3.75 mg, range 2.5-6) and fentanyl (a median dose of 50 mcg, range 0-100). Two patients were given pethidine.

The patient who underwent two ERCPs presented with biliary colic and was referred to the Gastroenterology Service. However, she was lost to follow-up and revisited the service a few months later for cholangitis. ERCP was performed with stent insertion (7Fr 10 cm, Cotton-Leung biliary stent®; Wilson-Cook Medical, Winston-Salem, NC, USA) without using fluoroscopy. She was lost to the follow-up and revisited the hospital four months later with stent migration-relatedEscherichia colicholangitis, requiring lower section caesarian section (LSCS).ERCP after LSCS showed large common bile duct (CBD) stones (1.5-2.0 cm). She was treated with stent replacement (10Fr 9 cm) (Fig. A). She again defaulted follow-up and had her second stent migration 11 months after insertion. ERCP biliary stenting was done without use of a fluoroscope. The progress of pregnancy was then uncomplicated. ERCP stone clearance five months after delivery was unsuccessful, and surgical exploration, clearance and cholecystectomy were required.

Fig. A: Migrated stent in the ascending colon with a newly replaced larger stent in the biliary tree (case 1);B:EUS showing thickened wall of the gallbladder with sludge (indicated by asterix) that was not detected during trans-cutaneous USS (case 4);C:ERCP cholangiography after delivery showing a dilated duct and two CBD stones (case 4).

Table. Patients undergoing biliary interventions

Fluoroscopy was used in 5 procedures with a median exposure time of 12 seconds (range 2-20 seconds). ES was performed in 5 patients, stenting in 6 and balloon clearance in 3. The overall time for the procedures was between 5 to 25 minutes.

There were no procedure-related complications except one post-procedure related complication, induction of labor, in a patient (case 6). Transient asymptomatic hyperamylasemia happened in one patient (case 2). During pregnancy, complications occurred in 5 patients: stent migrations resulting in cholangitis (case 1, two episodes), acute cholecystitis (case 2), HELLP syndrome (case 4) and fetal distress (case 5).

Altogether 7 pregnancies resulted in delivery of healthy babies with median APGAR scores of 9 and 10 at 5 and 10 minutes respectively: 3 by LSCS and 4 by normal vaginal delivery (NVD), all at term (>36 weeks). At the time of writing, one patient was well in her second trimester and under close follow-up for complications.

Follow-up for a median of 14 months (range 2-38 months) demonstrated that bile duct clearance was successful in 2 patients (Fig. C) and 4 underwent cholecystectomy, including additional bile duct exploration in one patient. One patient had an appointment for cholecystectomy, one still had a stentin situ. One child died of sudden infant death syndrome (SIDS) at age of 40 days. The clinical outcomes of the patients are shown in Table.

Discussion

Symptomatic gallstone diseases such as acute pancreatitis and cholangitis can be associated with significant complications, and ERCP is currently the standard management of the diseases. However, in pregnancy, both manifestations and interventions pose a significant risk to the pregnancy and developing fetus.[3,11]In the gestational stages, complications may occur such as spontaneous abortion, fetal abnormalities, premature labor and even death. The risk to the pregnancy is the highest in the first trimester. The lower rate of term pregnancy (73.3%), the higher rate of preterm delivery (20.0%) and low-birthweight (21.4%) are more common when interventions are required for complications during the first trimester.[12]Generally, the second trimester is related to the lowest risk for interventions.

The reported rates of complications due to endoscopic biliary interventions range from 7% to 16%. The complications consist mainly of post-ERCP pancreatitis, preterm labor and post-sphincterotomy bleeding.[12-16]Despite these concerns ERCP is considered to be safe.[11-15,17-19]But radiation exposure to the developing fetus and the impact of intervention on the pregnancy outcome are critically important.

Non-radiation techniques are thought to be as effective as the standard techniques.[7-10]They involve guide wire assisted cannulation, and successful cannulation is confirmed by the presence of bile flow along the side of the wire or cannula or by bile aspiration. The subsequent management depends on the situation or the endoscopist. Some physicians may proceed with ES and balloon clearance without the use of fluoroscopy and others may prefer to the placement of stent. Cholangioscopy has been used to confirm biliary clearance,[7]in addition to clinical profiles and transcutaneous ultrasound monitoring.[8]Despite radiation exposure, imaging guided procedures do not cause any significant adverse effects.[12-14]Although the cumulative dose of radiation exposure is less hazardous than the reported, it is still recommended to minimize radiation exposure when possible.[5]In patients in whom radiation exposure is required, lead apron shielding is suitable. In a study, however, lead shielding was ineffective in reducing radiation exposure.[16]

Reducing the overall time for a procedure can minimize the risk to the patients. In our series the time of the procedures ranged from 5 to 25 minutes which are comparable to the reports of other researchers. Complete stone clearance will prolong the time of a procedure especially in patients with multiple stones. This is also associated with the longer time of radiation exposure. The two-step technique or stenting followed by clearance after delivery is used to reduce the time of a procedure.[9]This can also be done without fluoroscopy. In our study, 6 interventions were performed with this technique and all except one had a short time. However, the disadvantages of this technique include the requirement of repeat interventions and the risk of stent blockage and migration. Two of our patients were lost to follow-up and one had stent migration and cholangitis.

EUS has been shown to reduce unnecessary interventions in patients with low or moderate probabilities for choledocholithiasis.[20-22]However, there are no studies on EUS for pregnant patients. Two of our patients underwent EUS before ERCP, which was performed in one patient because of the low probability of CBD stones. EUS was used to detect the gallbladder sludge which was undetected with US. In this patient,ERCP was performed and balloon dredging extracted some sludge. No fluoroscopy was used in this patient. In another patient, EUS provided information regarding the feasibility of stone clearance and the stent length. One may argue that EUS will prolong the overall time for a procedure. However, when EUS is normal,ERCP interventions can be avoided. In addition, EUS may provide other useful information. In experienced hands, the added time for EUS is only a few minutes. Further studies are required to assess the role of EUS in the management of pregnant patients. However, it is likely that EUS will complement ERCP.

In our practice, we try to minimize radiation exposure by avoiding continuous fluoroscopy screening and also minimize the time of a procedure whenever possible. Six patients used the two-step technique: fluoroscopy not used in 3 patients and limited fluoroscopy screening used to confirm wire or stent positions in another 3. In the latter patients EUS was proven useful. All of these procedures were relatively easy and cannulations were easily achieved. This contributed to the low radiation exposure time.

In our study no immediate procedure related complications were observed but one patient went into labor within 24 hours of ERCP. This resulted in normal delivery of a healthy baby. Fortunately, the patient was already near the term. We did not consider biochemical hyperamlysemia as a complication in a patient as she was asymptomatic. Four non-intervention related complications occurred as pregnancies progressed and 2 patients had stent migration, acute cholecystitis and HELLP syndrome resulting in spontaneous abortion. The procedure was uncomplicated and no fluoroscopy was used. Yet we could not exclude the possibility that the intervention might have contributed to the complication. SIDS occurred in an infant who was well at birth. One patient was only found to be pregnant several weeks after ERCP stone clearance without any extra precautions. Fortunately the procedure was uncomplicated and the fluoroscopy time was short. Her pregnancy was complicated by acute cholecystitis which was treated with conservative treatment and subsequently the patient had a normal delivery of a healthy baby.

The limitation of our study is the small sample size. But the results were reflections of the situation in our country which has a small population. Our results were consistent with those from other studies on biliary interventions during pregnancy. Despite only 2 patients undergoing EUS, EUS is shown to be effective in the management of biliary disorders in pregnancy. Yet further studies with larger samples are required to confirm our findings in the present study.

In conclusion, ERCP intervention is safe for women during pregnancy. However, it is necessary to minimize radiation exposure and the time of the procedure. Different techniques can be applied according to the conditions of the patient as well as the technical expertise and preference of the endoscopist. When EUS is negative,

ERCP interventions can be avoided. Further studies with larger sample sizes are required to assess the role of EUS in pregnancy related biliary disorders. However, it is very likely that EUS may have a complementary role.

Funding:None.

Ethical approval:Not needed.

Contributors:CVH conceived the idea for the study, collected the data and wrote the first draft. JA contributed to the idea for the study. Both authors approved the final manuscript. CVH is the guarantor.

Competing interest:No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

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Received December 1, 2009

Accepted after revision March 20, 2010

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— O. Henry

nts

EUS before ERCP. The first one (case 4) came to the surgical service because of abdominal pain. Abdominal ultrasonography (US) showed acute acalculous cholecystitis and normal CBD. Because her symptoms persisted and liver profiles became deranged, biliary stones/sludge was suspected. EUS revealed ascites, normal CBD and thickened gallbladder containing sludge that was not detected with US (Fig. B). ERCP cannulation was uncomplicated and ES was performed. Balloon dredging extracted some sludge. These procedures were performed without using fluoroscopy. The condition of the patient was improved, and she was discharged home. Unfortunately, her pregnancy was complicated later by hemolysis elevated liver enzyme and low platelet (HELLP) syndrome, spontaneous abortion and pulmonary embolism. The second patient (case 5) presented with acute pancreatitis and obstructive jaundice. US showed dilated CBD and gallstones. EUS showed a bit of ascites, dilated CBD with a large stone (1.5 cm) located in the proximal CBD. ERCP and stenting (11.5Fr 9 cm) were carried out through a supra-papilla fistula using limited fluoroscopy to confirm stent location.

Author Affiliations: Gastroenterology Unit, Department of Medicine, Raja Isteri Pengiran Anak Saleha (RIPAS) Hospital, Bandar Seri Begawan BA 1710, Brunei Darussalam (Chong VH and Jalihal A)

Vui Heng Chong, FRCP, Gastroenterology Unit, Department of Medicine, Raja Isteri Pengiran Anak Saleha (RIPAS) Hospital, Bandar Seri Begawan BA 1710, Brunei Darussalam (Tel: +673 8778218; Fax: +673 2242690; Email: chongvuih@yahoo.co.uk)

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