Management of Symptomatic Cholelithiasis in Pregnancy

Introduction

Cholecystitis with cholelithiasis is among the most common surgical problems in the Kingdom of Saudi Arabia.^1,2 Among pregnant women, symptomatic cholelithiasis is only second to acute appendicitis as the most common cause of surgical abdominal pain.^3,4 In some populations of patients, it is arguably the most common cause of surgical admissions in pregnancy. Whether pregnancy itself, with its associated metabolic changes, known increase in the concentration of bile, increased incidence of sand in the biliary tree, and increased biliary dyskinesia,^5–7 is associated with increased incidence of cholecystitis is unclear and remains controversial.^5,8 Nevertheless, the occurrence of intra-abdominal inflammation during pregnancy exposes both the patient and her fetus to danger and this must be addressed.

Diabetes mellitus has a high incidence in our population. The serious consequences of cholelithiasis in diabetics are well established.^9–11 Accordingly, a subgroup of patients, the pregnant diabetic patients who present with calcular biliary disease, demand additional concern. This study aims to evaluate the incidence and management of biliary disease during pregnancy in our patient population.

Materials and Methods

All pregnant women admitted between June 1989 and June 1998 to Prince Abdul Rahman Sudery Hospital in Sakaka, with a diagnosis of symptomatic cholelithiasis were admitted to this retrospective study. Cholelithiasis and pregnancy were established by abdominal ultrasound and, where necessary, urine test for confirmation of pregnancy. There were a total of 162 patients. Pregnant patients who had a combination of established diagnosis of diabetes mellitus and cholelithiasis were selected out. These comprised 58 of the 162 patients and were designated Group A. The remaining 104 pregnant patients without diabetes were designated Group B. Patients admitted with a diagnosis of acalculous cholecystitis were excluded because pregnancy precluded objective proof of cholecystitis by nuclear medicine.

All patients had routine investigations, including full blood count, liver function tests, and amylase. Data obtained for all patients included treatment (surgical or medical), number of hospitalizations, number of days of hospitalization, number of postoperative days and complications. All patients were followed from the initial admission for symptomatic cholelithiasis through their hospitalizations, parturition, and for three months postpartum. Patients who underwent surgical management prior to parturition were followed for thirty days after parturition. Statistical analysis was by Student’s t-test, and chi-squared test as appropriate. P<0.05 was considered significant.

Results

One hundred and sixty-two pregnant women who presented with cholelithiasis provided data for this study. The patients were grouped into diabetic patients (58) and nondiabetic patients (104). Table 1 shows details of patient characteristics. These 162 patients with a mean age of 39.2 years represented 11.6% of the patients who underwent management for symptomatic cholelithiasis during the review period. Diabetic patients comprised 35.8% of the patients in this study, a reflection of the rather high prevalence of diabetes mellitus in our patient population.

Tables 2 and 3 show that 148 out of 162 were managed conservatively, while 14 (6 diabetic and 8 nondiabetic), underwent surgical management. Table 2 does not show a significant difference in the mean number of hospitalizations per patient, 3.6 and 3.2, respectively, in the two groups. The real difference is in the mean number of days of hospitalization. Thus the mean total number of days of hospitalization was higher for those treated conservatively, 18.8 and 16.6 days, than for those treated surgically, 12.8 and 12.2 (P<0.05), respectively. As well, whether treated conservatively or surgically, the mean total number of days spent in hospital per patient was also higher for diabetic patients, 18.4 and 12.8 days, respectively, than for the nondiabetic, 16.8 and 12.8 days (P<0.05). Table 3 shows that 48 (29.6%) of our patients presented with acute cholecystitis and 28 of them were from among the diabetic patients. The most common reason for admission was biliary colic. Only two of our patients presented with biliary pancreatitis.

Table 4 shows that of the 148 patients (52 diabetic and 96 nondiabetic) who had been treated conservatively, 35 (15 group A and 20 group B) returned within 30 days of parturition with early recrudescence of biliary tract symptoms. Ultimately, 130 patients returned and underwent uneventful laparoscopic cholecystectomy with a mean hospital stay of 2.8 to 3 days. Eighteen patients failed to keep their appointment for surgery and were lost to follow-up within the first 3-month follow-up period. Overall then, the total number of days of hospitalization for the patients managed conservatively was eight days higher than for surgical cases (20.5 days versus 12.5 days), P<0.001.

Discussion

The course and management of 162 women, consisting of 58 diabetic and 104 nondiabetic women who presented with symptomatic cholelithiasis during pregnancy, has been presented. These 162 patients represented 11.6% of all female gallbladder patients managed in our hospital over the review period. The number of pregnant patients managed over the same review period was 58,866.

A finding of only 162 pregnant women with cholelithiasis in this population of pregnant women is small and is consistent with the reported relative rarity of symptomatic gallstones in pregnancy.^3,12 Recorded incidence of gallstones in pregnancy ranges from 0.02% to 12%.^3,4 Reflecting their youthful childbearing status, the median age of our patients, 39.2 years, falls slightly outside the mean age, 41.2, of the general population of our gallstone patients.⁵ Cholelithiasis in Saudi Arabia is found in the age group 38.9 to 42 years.^1,2,5,12,13

Several studies implicate pregnancy itself as a risk factor in the development of gallstones.^6,14,15 Although controversial,^5,8,15–17 it does seem plausible that the pregnancy state contributes to gallstone formation, based on the known metabolic changes associated with pregnancy, such as supersaruration of bile with cholesterol.^3,17–19 Other suggested factors include estrogen-mediated decrease in the activity of the Na pump in the gallbladder mucosa; impairment of cholecystokinin-mediated smooth muscle contraction leading to decrease in the gallbladder contraction and increase in the residual volume of the gallbladder.^17–20 As well, repeated pregnancies and multiparity are accepted as risk factors for cholelithiasis.^21,22

A total of 35.8% of the patients in this study had established diabetes mellitus. This is greater than the finding in our general population of gallstone patients, among whom diabetes mellitus is only 11.1%.⁹ This may suggest that patients with diabetes have a greater tendency to symptomatic gallstones in pregnancy. A more plausible explanation is that our diabetic patients, educated to the tendency of diabetes mellitus to exacerbate the seriousness of many illnesses, and already accustomed to the hospital, sought medical attention more often than the nonpregnant patients. The reported prevalence of diabetes mellitus in the Saudi Arabian population varies from 4.1 to 7.2%.^23,24

The management of symptomatic cholelithiasis in non-pregnant women is a straightforward issue. The presence of a second entity, the fetus, complicates decisions in the management of pregnant women. In the presence of severe biliary pancreatitis, severe acute cholecystitis or impending cholangitis, obstructive jaundice, and biliary colic unresponsive to conservative treatment, surgical management is incontrovertible. It is the management of the noncomplicated cholecystitis and cholelithiasis that remains controversial.^3,25 Most (91.4%) of our patients were successfully managed nonoperatively. This is in consonance with findings elsewhere that 90% of cholecystitis in pregnancy will resolve with conservative management.³ Thus conservative, nonsurgical management failed in only 14 (8.6% of our patients) and these underwent surgical management. A particularly lethal problem is severe biliary pancreatitis in pregnancy. Its reported incidence is 1/10,000 pregnancies. It is associated with severe morbidity and carries a maternal mortality of 15% and fetal loss of up to 60%.^3,4,21 Only two of our patients presented with biliary pancreatitis of the mild type and these resolved with conservative treatment.

Recent reports suggest a more aggressive approach, with surgical intervention, in order to avoid repeated hospitalizations and patient discomfort.^26,27 But surgical intervention in pregnancy is not innocuous. It could result in spontaneous abortion, perinatal mortality, prematurity, maternal morbidity and mortality.^3,4 Conservative management, on the other hand, is associated with multiple hospitalizations. The mean number of hospitalizations for our patients was 3.6/3.2. It was lower for the operative cases, 2.7/2.4, but not significantly so. A more significant difference was found in the mean total number of days of hospitalization, 20.5 for nonoperative cases versus 12.5 for operative cases (P<0.001). This amounted to a difference of 8 days.

Conventional wisdom holds that it is not the surgical intervention per se but the severity of the surgical disease which is more important in determining the occurrence of prematurity, spontaneous abortion and perinatal mortality. But the timing of surgical intervention during pregnancy is an important variable and a determinant of some of the unwanted consequences of surgical intervention. Thus spontaneous abortion (up to 60%) is most common in the first trimester, while prematurity (up to 40%) occurs mostly in the third trimester.²⁸ The second trimester thus provides the best window of opportunity for most successful surgical interventions in the management of biliary surgery in pregnancy. Slightly over 50% of our patients presented in the first trimester, while 18.5% and 30% presented in the second and third trimesters, respectively. Of our 14 operative cases, all of which had an uneventful course, 10 were in the second trimester of pregnancy, while four were in the third trimester.

With the advent of laparoscopic cholecystectomy as the new gold standard in the management of cholelithiasis, trochar placement and the possible interference of the uterine size during surgery have become added concerns. But the second trimester is considered to provide an ideal condition for an easier and safer laparoscopic cholecystectomy in pregnancy. Only one of our patients underwent laparoscopic cholecystectomy, and this was in the third trimester. Our experience does bear out the finding that nonoperative management is associated with multiple hospitalizations. Our study showed a significant difference in the mean total number of days of hospitalization between operative and nonoperative cases, especially when the nonoperative cases were also diabetic (P<0.001). We do however believe that the multiple and lengthy hospitalizations in our hospital reflect a rather low threshold for admissions for any discomfort in pregnant women, and diabetic patients in particular.

On the surface, our figures do seem to argue for a more aggressive management, namely surgical treatment. But this presupposes that the results of fetal loss and premature labor would remain at 0%. Evidence elsewhere suggests that surgical management carries a penalty of fetal loss (up to 60%) and premature labor (up to 40%). Admittedly, improvements in anesthesia, neonatology, and the availability of tocophylactic drugs belie these earlier reports and make surgery now much safer in pregnancy. Thus recent reports of laparoscopic surgery in cholelithiasis in the second trimester of pregnancy paint a very rosy picture, showing neither prematurity nor fetal loss.^4,25–30 Clearly our policy of operative management for only those patients who cannot be managed conservatively seems justified and in consonance with reports elsewhere. It must be admitted, however, that although our zero level of complications is currently attractive and optimal, it has been achieved for each patient at a price of four hospitalizations, with a mean total of eight extra days of hospitalization. Along with all the other improvements in the surgical management of the pregnant patient, the new era of laparoscopic cholecystectomy has brought with it a much better outlook in the management of cholecystectomy in pregnancy. In keeping with these trends, therefore, cost efficiency suggests that a more aggressive policy may be needed in our hospital.