Therapeutic Efficacy of Endoscopic Retrograde Cholangiopancreatography Among Pregnant Women with Severe Acute Biliary Pancreatitis

Abstract

Objective:

To explore the feasibility of endoscopic retrograde cholangiopancreatography (ERCP) in pregnant women with severe acute biliary pancreatitis.

Subjects and Methods:

In total, 24 pregnant patients with severe acute biliary pancreatitis were enrolled in our study between January 2003 and January 2008. Emergency ERCP and endoscopic nasobiliary drainage (ENBD) without fluoroscopy were performed successfully in all 24 patients within 12–72 hours of admission. Once stabilized, 15 patients in late pregnancy underwent a second ERCP with fluoroscopy to remove common bile duct (CBD) stones after pregnancy termination. Nine patients in early or mid-pregnancy continued gestating and underwent endoscopic retrograde biliary drainage (ERBD) with a second ERCP without fluoroscopy, and their stents and CBD stones were removed during a third ERCP with fluoroscopy 1 week after parturition.

Results:

Among the mothers, all 24 patients were cured, and none of them died. The CBD stones in all 24 patients were completely removed with a two-step ERCP, and no serious post-ERCP complications occurred, although 2 patients had mild hemorrhage in the final ERCP to remove CBD stones. No recurrent pancreatitis or cholangitis occurred in patients who underwent ERBD. Among the infants, all survived without developmental problems or abnormality. Twenty infants were born at term; four infants were born prematurely at 35–37 weeks of gestation without developmental problems or complications.

Conclusions:

Emergency ERCP and ENBD without fluoroscopy in pregnant women with severe acute biliary pancreatitis are feasible and safe for both mothers and infants. It is also appropriate to remove CBD stones with two-step ERCP in pregnant women according to the stage of pregnancy.

Introduction

The prevalence of acute pancreatitis (AP) during pregnancy is rare, approximately 3 cases per 10,000 women. The estimated maternal and perinatal mortalities associated with AP, however, are relatively high at 0%–37% and 11%–37%, respectively, and may be even higher in severe AP (SAP) because of accompanying multiple organ failures or other serious complications.^1–5 Therefore, AP remains a challenge for all physicians.⁶

The major causes of AP in pregnancy have been found to be of biliary origin.⁷ Today, endoscopic retrograde cholangiopancreatography (ERCP) has become the first choice of treatment for acute biliary pancreatitis, but whether ERCP should be performed for AP during pregnancy remains controversial. In order to protect the fetus, fluoroscopic examination is recommended to be used in a limited fashion or simply prohibited during pregnancy,⁸ especially in the first trimester, because high radiation exposure at that time may result in fetal wastage.⁹ However, some researchers have reported that it may be safe to perform ERCP when the patient's exposure to X-rays is minimized by limiting fluoroscopy time, shielding the pelvis with lead, and avoiding direct X-ray exposure unless absolutely necessary.^10,11 Nevertheless, Samara et al.¹² showed that radiation risks to the fetus associated with fluoroscopically guided ERCP performed on a pregnant patient cannot be ignored.

Accordingly, ERCP without fluoroscopy has been proposed as an alternative for pregnant women in an effort to decrease potential risks to the fetus. There have been several case reports on minimization of radiation exposure by direct cannulation with a sphincterotome.^8,13–15 Freistuhler et al.¹⁶ reported a case of using ultrasound-controlled endoscopic papillotomy for the treatment of a pregnant woman with severe biliary pancreatitis. However, because these were only case reports it remains unclear whether ERCP can be effectively performed without fluoroscopy in patients with acute biliary pancreatitis during pregnancy, and it is difficult to identify whether the common bile duct (CBD) stones were removed completely without cholangiogram.

To address this question, from January 2003 to January 2008 we performed emergency ERCP and endoscopic nasobiliary drainage (ENBD) without fluoroscopy in 24 pregnant women with severe acute biliary pancreatitis and removed CBD stones using a two-step ERCP according to the stage of pregnancy.

Subjects and Methods

Study population

Twenty-four consecutive pregnant women with severe acute biliary pancreatitis, according to the Chinese guidelines of diagnosis and therapy of acute pancreatitis,¹⁷ were hospitalized between January 2003 and January 2008, with a mean age of 28.5 years. Nine patients were in early or mid-pregnancy (<28 weeks of gestation); 15 patients were in late pregnancy (≥28 weeks of gestation).

The clinical manifestation during treatment and procedure-related complications were recorded. The study was approved by the hospital institutional review board. All patients signed the consent form prior to the procedure. Patients who aborted the fetus or in whom the fetus had already died before ERCP were excluded.

The average blood leukocyte counts in 24 patients were 15–29×10⁹/L, and serum amylase levels were 500–2000 U/L. Serum bilirubin was elevated in 20 patients: total bilirubin was 52–342 mol/L, whereas direct bilirubin was 32–252 mol/L. The Ranson scores were 3–9. All patients were diagnosed with common duct stones by transabdominal ultrasonic inspection or magnetic resonance cholangiopancreatography.

Treatment methods

All 24 patients received supportive treatment, including fasting, fluid replacement, and maintenance of water-electrolyte and pH balance. Changes in vital signs, blood and urinary amylase, blood leukocyte, and biochemistry were monitored carefully.

All patients underwent emergency ERCP (within 12–72 hours of admission) successfully without using fluoroscopic examination. While ENBD was finished, fetal heart rate and frequency of fetal movements were monitored. The patients' conditions stabilized in 3 days to 2 weeks. Fifteen patients in late pregnancy had their pregnancy terminated (7 patients underwent induced deliveries, 6 patients underwent cesarean section, and 2 had full-term normal deliveries) before they underwent a second ERCP with fluoroscopy to remove CBD stones.

The remaining 9 patients in early or mid-pregnancy continued gestating and underwent endoscopic retrograde biliary drainage (ERBD) with a second ERCP without fluoroscopy to avoid recurrent AP. The average plastic stent retention time was 3.8 months, with the longest at 5.5 months. These patients experienced full-term normal deliveries and had their stents and stones removed during a third ERCP with fluoroscopy 1 week after parturition.

Emergency ERCP without fluoroscopy

All procedures were performed with a duodenoscope (model JF-260; Olympus Medical Systems Co., Tokyo, Japan) by two gastroenterologists and three assistants. Patients in early pregnancy were placed in the prone position, and patients in middle to late pregnancy were in the left-lateral position. Isonipecaine (50 mg), diazepam (5 mg), and drotaverine (40 mg) were injected intravenously before ERCP, and the electrocardiogram was monitored during the procedure. After the duodenoscope was inserted into the duodenum, it was maneuvered so that the papilla was located at the 12 o'clock position. A catheter was advanced into the orifice of the papilla aiming to the left upper side of the ampulla, to access the CBD, approaching the papillary orifice from the right and below, aiming up and toward the 11 o'clock position. The average time of cannulation was 10 minutes with one to five attempts. When bile was aspirated into the catheter with a syringe, it was confirmed that the catheter had been successfully inserted into the CBD. Subsequently, a guide wire was inserted into the CBD through the catheter, and ENBD was performed. The total ERCP time was about 10–15 minutes.

Results

Maternal outcome

Abdominal pain and distention of the 24 patients who underwent emergency ERCP was relieved or disappeared, and serum amylase, total bilirubin, and direct bilirubin levels returned to normal values within 1 week (mean, 5.8 days). None of the patients died, nor did they require surgical intervention. The CBD stones in all 24 patients were completely removed with a two-step ERCP, and no serious post-ERCP complications occurred, although 2 patients had a mild hemorrhage in the second ERCP to remove CBD stones. No AP or cholangitis recurred in patients who underwent ERBD.

Fetal outcome

All the infants survived without developmental problems or abnormality. Twenty infants were born at term; four infants were born prematurely through uterine-incision delivery, without developmental problems or complications, because of severe intrauterine distress in late pregnancies.

Discussion

To date, the utility and safety of ERCP during pregnancy have been largely unknown. In this study, we reported our experience with ERCP in pregnant patients with severe acute biliary pancreatitis.

CBD stone was a major cause of AP in pregnancy, and it is vital to remove the stone(s) as quickly as possible because the duration of ampullary blockage is positively correlated with degree of severity of AP. ERCP has become the first choice of treatment for acute biliary pancreatitis, especially in SAP. It is recommend that urgent ERCP be performed for patients with SAP within 72 hours of admission.^17–20

In this study, ENBD was performed first in emergent ERCP without fluoroscopic examination to resolve the blockage of biliary and pancreatic fluid flow. The clinical manifestations and jaundice in all 24 patients in this study were reduced or disappeared within 1 week, and no ERCP-related complications occurred. Therefore, we consider it is safe and feasible to perform emergency ERCP without fluoroscopy in patients with severe acute biliary pancreatitis during pregnancy. However, there are important points to be noted about performing the ERCP procedure during pregnancy. First, ERCP should only be performed by endoscopists who have excellent endoscopic techniques. Second, the ERCP procedure should be performed as expeditiously as possible.

Some studies have reported that pregnant women with acute biliary pancreatitis had a high recurrence rate if treated conservatively.^21–23 However, it was difficult to determine whether the common duct stones were completely removed without a cholangiogram. Shelton et al.¹⁵ reported successful bile-duct cannulation with sphincterotomy and the removal of biliary stones or sludge without fluoroscopy in 21 pregnant women with the confirmation of ductal clearance by choledochoscopy. However, this involved a prolonged procedure time to which SAP patients may not tolerate. In addition, few hospitals have choledochoscopy available.

We removed CBD stones with two-step ERCP for pregnant women according to the stage of pregnancy. If the patients were in late pregnancy, the stones were removed through a second ERCP with fluoroscopy after the pregnancy was terminated. If the patients were in early or mid-pregnancy, they underwent ERBD and continued gestation. Their stents and stones were removed through a third ERCP with fluoroscopy 1 week after parturition. In this study, the 9 patients who underwent ERBD did not suffer recurrent AP. This suggests that ERBD may be a worthy therapeutic method to prevent AP recurrence in pregnant patients, although this should be further confirmed with larger multicenter prospective studies.

The rates of preterm delivery and perinatal fetal death remain high for pregnant women with AP. Hernandez et al.²⁴ reported a perinatal death rate of 4.8%. Eddy et al.² reported one fetal death (7.1%) at 22 weeks and one preterm delivery (7.1%) at 36 weeks out of 14 women received antepartum cholecystectomy or ERCP. Recently, Tang et al.²⁵ reported patients who had ERCP in their first trimester had the lowest percentage of term delivery (73.3%) and the highest risk of preterm delivery (20.0%) or low-birth-weight newborns (21.4%). In our study, the 9 patients in early or mid-pregnancy all had term deliveries. All fetuses in this study survived as well. However, four infants were born prematurely becauseof severe intrauterine distress in late pregnancy. For a group of high-risk patients with severe pancreatitis the rate of prematurity (16.7% [4/24]) was considerable. There are a few measures that can be taken to reduce the rates of prematurity and mortality. We considered it vital to perform emergency ERCP and ENBD to relieve compression of the biliary duct, which could have helped to improve the patient's pathologic condition. In addition, if the fetal intrauterine distress is severe, the patient should undergo cesarean section to terminate pregnancy as soon as possible.

In summary, it is feasible, safe, and effective to treat pregnant patients who have acute biliary pancreatitis with emergency ERCP and ENBD. It is also appropriate to remove CBD stones with two-step ERCP according to their stage of pregnancy. Larger multicenter prospective studies are needed to confirm these results.

Footnotes

Acknowledgments

We thank Ning Dai, MD, for polishing the grammar and language of the article.

Disclosure Statement

No competing financial interests exist.

References

Nanda

, Gupta

, Dora

et al. Acute pancreatitis: A rare cause of acute abdomen in pregnancy. Arch Gynecol Obstet, 2008; 279:577–578.

Eddy

, Gideonsen

, Song

et al. Pancreatitis in pregnancy. Obstet Gynecol, 2008; 112:1075–1081.

Daluiso

, Daluiso

. Acute pancreatitis in pregnancy treated with somatostatin. A case report. Minerva Chir, 1994; 49:733–736.

Maev

, Burkov

, Kucheriavyi

IuA

et al.

Pancreatitis in pregnant women [in Russian]

Klin Med (Mosk), 2008; 86:23–29.

Qin

, Zhu

, Zhou

. Analysis on maternal deaths from pregnancy complicated with acute abdominal diseases in Shanghai during 1989–1998 [in Chinese] Zhonghua Fu Chan Ke Za Zhi, 2000; 35:712–714.

Robertson

, Stewart

, Imrie

. Severe acute pancreatitis and pregnancy. Pancreatology, 2006; 6:309–315.

Terzhumanov

, Uchikov

, Uchikova

et al.

Acute pancreatitis and pregnancy—Analysis of a 10 year period of time [in Bulgarian]

Akush Ginekol (Sofiia), 2004; 43:9–12.

Simmons

, Tarnasky

, Rivera-Alsina

et al. Endoscopic retrograde cholangiopancreatography (ERCP) in pregnancy without the use of radiation. Am J Obstet Gynecol, 2004; 190:1467–1469.

Scheurer

. Acute pancreatitis—ERCP/endoscopic papillotomy (EPT) yes or no? Swiss Surg, 2000; 6:246–248.

10.

Kahaleh

, Hartwell

, Arseneau

et al. Safety and efficacy of ERCP in pregnancy. Gastrointest Endosc, 2004; 60:287–292.

11.

Tham

, Vandervoort

, Wong

et al. Safety of ERCP during pregnancy. Am J Gastroenterol, 2003; 98:308–311.

12.

Samara

, Stratakis

, Enele Melono

et al.

Therapeutic ERCP and pregnancy: Is the radiation risk for the conceptus trivial?

Gastrointest Endosc, 2009; 69:824–831.

13.

Uomo

, Manes

, Piccotto

, Rabitti

. Endoscopic treatment of acute biliary pancreatitis in pregnancy. J Clin Gastroenterol, 1994; 18:250–252.

14.

Zagoni

, Tulassay

. Endoscopic sphincterotomy without fluoroscopic control in pregnancy. Am J Gastroenterol, 1995; 90:1028.

15.

Shelton

, Linder

, Rivera-Alsina

et al.

Commitment, confirmation, and clearance: New techniques for nonradiation ERCP during pregnancy (with videos)

Gastrointest Endosc, 2008; 67:364–368.

16.

Freistuhler

, Braess

, Petrides

. Ultrasound-controlled endoscopic papillotomy in pregnancy in severe biliary pancreatitis. Z Gastroenterol, 1999; 37:27–30.

17.

Society of Gastroenterology of Chinese Medical Association. The guidelines for diagnosis and therapy of AP in China [in Chinese] Chin J Dig, 2004; 190–192.

18.

AGA Institute medical position statement on acute pancreatitis. Gastroenterology, 2007; 132:2019–2021.

19.

Kimura

, Takada

, Kawarada

et al. JPN Guidelines for the management of acute pancreatitis: Treatment of gallstone-induced acute pancreatitis. J Hepatobiliary Pancreat Surg, 2006; 13:56–60.

20.

Pezzilli

, Uomo

, Zerbi

et al. Diagnosis and treatment of acute pancreatitis: The position statement of the Italian Association for the Study of the Pancreas. Dig Liver Dis, 2008; 40:803–808.

21.

Gurusamy

, Farouk

, Tweedie

. UK guidelines for management of acute pancreatitis: Is it time to change? Gut, 2005; 54:1344–1345.

22.

Gawrychowski

, Drozdz

, Olejek

et al. Treatment of mild acute pancreatitis during pregnancy using retrograde cholangiography and endoscopic sphincterotomy. Int J Gynaecol Obstet, 2007; 99:147–149.

23.

Swisher

, Hunt

, Schmit

et al. Management of pancreatitis complicating pregnancy. Am Surg, 1994; 60:759–762.

24.

Hernandez

, Petrov

, Brooks

et al. Acute pancreatitis and pregnancy: A 10-year single center experience. J Gastrointest Surg, 2007; 11:1623–1637.

25.

Tang

, Mayo

, Rodriguez-Frias

et al. Safety and utility of ERCP during pregnancy. Gastrointest Endosc, 2009; 69:453–461.