Non-Operative Management of Cholecystitis in Pregnant Patients Remains Common

Abstract

Background:

Cholecystectomy is the recommended treatment for acute cholecystitis in pregnancy, leading to fewer pregnancy-related complications than non-operative management. However, past research demonstrated high rates of non-operative management despite these recommendations. Rates of cholecystostomy tube usage and outcomes in pregnancy are not well described. We hypothesized that rates of interventions for cholecystitis have increased over time.

Patients and Methods:

The National Readmissions Database was queried for all visits in the first three quarters of each year 2016 to 2019, which included a patient with an International Classification of Diseases-10 code for cholecystitis and pregnancy. These entries were then further investigated for demographics, gestation, rates of interventions at the index admission (cholecystectomy or cholecystostomy tube), 90-day readmissions, interventions at readmission, and pregnancy-related complications.

Results:

Annual rates of interventions for cholecystitis remained low over the study period (27.0%–34.9%). Of patients treated with non-operative management, 6.0% had cholecystectomy on readmission. Compared with the first trimester, interventions were more likely in the second trimester (p < 0.001) and less likely in the third trimester (p < 0.001). Length of stay was highest for cholecystostomy tube placement and lowest for patients who received non-operative management.

Conclusions:

Cholecystectomy rates in pregnancy remain low despite evidence that cholecystectomy is safe. Cholecystostomy appears to be a safe alternative but associated with a longer length of stay. Further study is needed to determine what barriers exist to adequate treatment of cholecystitis in pregnant patients.

Acute cholecystitis is the second most common non-obstetric surgical emergency in pregnant patients after appendicitis.^1,2 The traditional treatment for acute cholecystitis in most patients is cholecystectomy, but pregnant patients present a challenge owing to the increased difficulty of the case because of the enlarged uterus, as well as concern for the physiologic effects of the surgical procedure on the fetus. This can include acidosis from the carbon dioxide used for pneumoperitoneum, as well as concern for hypotension and reduced uterine and placental blood flow.^3,4

Despite these concerns, it has been repeatedly shown that cholecystectomy is safe in pregnancy.^3,5,6 A recent study of more than 5,500 pregnant patients demonstrated that cholecystectomy is associated with reduced fetal complications across all trimesters when compared with non-operative treatment.⁵ Current guidelines from the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) state that “laparoscopic cholecystectomy is the treatment of choice in the pregnant patient with symptomatic gallbladder disease, regardless of trimester.”⁷ The American College of Obstetrics and Gynecology adds that “a pregnant woman should never be denied medically necessary surgery or have that surgery delayed regardless of trimester because this can adversely affect the pregnant woman and her fetus.”⁸ Unlike many other emergency general surgical procedures, cholecystitis can be treated with a cholecystostomy tube instead of operation in some patients. However, the published evidence on outcomes for pregnant patients with acute cholecystitis treated with a cholecystostomy tube is limited to a few case reports and case series.^9,10

In 2020, Rios-Diaz and colleagues published a study that reviewed data from 2010 to 2015 using the National Readmissions Database (NRD) for pregnant patients diagnosed with acute cholecystitis.⁶ They found that operative rates for cholecystectomy were 43.9% in the first trimester, 59.1% in the second trimester, and 34.2% in the third trimester. They also found that patients managed non-operatively had greater rates of complications. The purpose of this study was to evaluate whether operative management of cholecystitis in pregnant patients has improved over time, as well as to determine if cholecystostomy is a viable alternative treatment by comparing current rates of maternal and fetal complications in the different treatment groups.

Patients and Methods

Data source

The NRD was reviewed using data from Q1 to Q3 during the years 2016–2019. We omitted Q4 because of the risk of readmission being the following calendar year and not being labeled a readmission. This database is part of a family of databases developed for the Healthcare Cost and Utilization Project and is maintained by the Agency for Healthcare Research and Quality. The database includes more than 100 clinical and non-clinical parameters for each hospital stay while maintaining safeguards to protect the privacy of individual patients, physicians, and hospitals.¹¹ Diagnoses are identified using International Classification of Diseases (ICD) 9 and 10 codes. This study was exempt from institutional review board approval.

Data

The NRD was queried for patients who were identified as female with ICD-10 codes for pregnancy (Z33.1, Z33.3, Z3A.0-Z34.49) and cholecystitis (K81, K81.0-K81.9). These entries were evaluated for demographic data including age, race, gestational age, and insurance status. They were also reviewed for procedures including cholecystostomy tube placement (0F943*) and cholecystectomy at the current or subsequent visit (0FB4*, 0F54*, 0FT4*, 0FC90ZZ, 0FJB0ZZ, 0FJB4ZZ, 0F99*). Entries were further reviewed for readmission within 30, 60, 90, 120, and 180 days from initial admission as well as time to readmission, as well as rates of mortality at initial presentation or readmission.

Fetal and pregnancy-associated complications were assessed including complication after induced abortion (O04.5, O04.6, O04.7, O04.8; O04.8*), complication after spontaneous abortion (O03.1, O03.2, O03.3, O03.3*), threatened abortion (O20.0), missed abortion (O02.1), ectopic pregnancy (O00.9, O00.91), hemorrhage during pregnancy/placenta previa/abruptio placenta (O20.0, O20.8, O20.9, O44.3, O44.30-3, O44.1, O44.10-3, O45, O45.0, O45.00, O45.001-3, O45.01-3), hypertension complication of pregnancy (O10, O10.0, O10.01, O10.011-3, O10.019, O10.02), preterm labor (O60, O60.0, O60.02, O60.03, O60.1, O60.10), prolonged pregnancy (O48.1), gestational diabetes (O24.4, O24.41, O24.410, O24.414, O24.415, O24.419, O24.42, O24.420, O24.424, O24.425, O24.429, O24.43, O24.430, O24.434, O24.435, O24.439), fetal malposition (O64, O64.0, O64.0***), fetopelvic disproportion (O65.4), fetal distress complication delivery (O77, O77.0, O77.8, O77.9), polyhydramnios (O40, O40.1, O40.1***, O40.2, O40.2***, O40.3, O40.3***), infection of amniotic cavity (O41.1, O41.101, O41.101X, O41.102, O41.102*), umbilical cord complication (O69, O69.0, O69.0***, O69.1***), intrapartum hemorrhage (O67, O67.0, O67.8, O67.9), postpartum hemorrhage (O72, O72.0, O72.1, O72.2, O72.3), obstetric-related trauma (O71, O71.0, O71.00, O71.02, O71.03, O71.1-9, O71.81, O71.82, O71.89), forceps delivery (O66.5), abnormal fetal heart rate (O76), and other complications of pregnancy (O99.891-3).

Maternal complications were assessed using cervical incompetence (N88.3, O34.3, O34.3*), vulvovaginitis (A56.02, A54.02, A60.04, N77.1), sepsis (R78.81), peritonitis (K65.*), venous thromboembolism (O87.9, O88.2, O88.21, O88.21*, O88.22, O88.23), neurologic complications (I97.811, I97.821, I63.**, O29.2), cardiac complications (O29.1**, O89.1, I50, I46), respiratory complications (O99.5, O99.51, O99.51*, O99.52, O99.53, J95.89), acute renal failure (O90.4, N17.*), and urinary tract infection (N39.0, O86.2, O23.4, O03.88).

Statistical analysis

Proportions were compared with using chi-square tests. Means of continuous variables were compared using a student’s t-test or analysis of variance. Continuous variables with non-normal distributions were compared using the Mann-Whitney U or Kruskal-Wallis test. Statistical significance was set at p < 0.05. All statistical analyses were performed using STATA (StataCorp LLC, College Station, TX) or SPSS v28 (IBM, Armonk, NY).

Results

A total of 1,373 patients met inclusion criteria; 390 (28.4%) received cholecystectomy at the index admission, 25 (1.8%) received cholecystostomy tube placement, and the rest (69.8%) received non-operative treatment with antibiotic agents alone. Of those receiving non-operative management, 58 (6.0%) received cholecystectomy on readmission, while 20% of those treated with cholecystostomy received a cholecystectomy at readmission. A total of 28 (2.9%) of patients treated with non-operative management were readmitted with a diagnosis of cholecystitis, compared with 20% of cholecystostomy patients. Of the 453 total patients who received an inpatient cholecystectomy, 63 (13.9%) were after delivery.

Demographic data are shown in Table 1. Patients receiving non-operative management had the shortest length of stay and greater gestational age, while those receiving cholecystostomy had the longest length of stay.

Table 1.

Demographic Data for Patients Treated Operatively Versus Non-Operatively over the Study Period (2016–2019)

	Non-operative management(n = 959)	Cholecystectomy(n = 390)	Cholecystostomy(n = 25)	p
Age (years)	28 ± 6	28 ± 6	28 ± 5	0.826
Gestational age (weeks)	30.5 ± 11.4	20.0 ± 10.8	22.2 ± 11.9	<0.001
Length of stay (days)	3 ± 3	4 ± 7	9 ± 12	<0.001
Insurance status				<0.001
Medicare	15	^a	^a
Medicaid	501	208	15
Private insurance	384	149	^a
Self-pay	25	13	0
No charge	^a	^a	^a
Other	26	14	0
Hospital type				0.221
Metropolitan non-teaching	221	78	^a
Metropolitan teaching	650	270	21
Non-metropolitan hospital	88	42	0

Too low to report.

Maternal complications are shown in Table 2. Rates of hemorrhage and respiratory complications were substantially greater in patients treated with non-operative management. Mortality and rates of cardiac, neurologic, and renal complications were equally low across all categories. Table 3 shows obstetric and fetal complications by treatment tactic. Rates of spontaneous abortion, threatened abortion, missed abortion, and ectopic pregnancy were equally low in all categories. However, rates of peri-partum hemorrhagic, polyhydramnios, fetal distress, abnormal fetal heart rate, and pre-term labor were all substantially greater in patients treated with non-operative management.

Table 2.

A Comparison of Maternal Complications by Type of Management over the Study Period (2016–2019)

	Non-operative management(n = 959)	Cholecystectomy(n = 390)	Cholecystostomy(n = 25)	p
Mortality	0	^a	0	0.283
Cardiac complication	0	^a	0	0.283
Respiratory complication	65 (6.8%)	26 (6.7%)	^a	0.036
Renal failure	^a	^a	0	0.187
Hemorrhage	40 (4.2%)	^a	^a	0.028
Neurologic complication	0	0	0
Venous Thromboembolism	0	0	0
Urinary Tract Infection (UTI)	44 (4.6%)	29 (7.4%)	^a	0.097
Sepsis	0	0	0

“a” indicates values which are too low to report.

Table 3.

A Comparison of Obstetric Complications by Type of Management over the Study Period (2016–2019)

	Non-operative management (n = 959)	Cholecystectomy (n = 390)	Cholecystostomy (n = 25)	p
Spontaneous abortion	^a	^a	^a	0.865
Pre-term labor	64 (6.7%)	^a	^a	0.003
Peri-partum hemorrhage	16 (1.7%)	^a	^a	0.014
Amniotic infection	16 (1.7%)	^a	0	0.202
Polyhydramnios	13 (1.4%)	0	^a	0.026
Fetal distress	37 (3.5%)	^a	0	0.03
Abnormal fetal heart rate	102 (10.6%)	17 (4.4%)	^a	<0.001

“a” indicates values which are too low to report.

Trends in management over time are shown in Table 4. Rates of non-operative management ranged from 65% to 73%, and there is no evidence of increased operative rate over time. When operative rates are examined based on trimester, patients were most likely to receive operative treatment when presenting during the second trimester (see Table 5). However, even in the second trimester, operative rates were only 60%. Operative rates were lowest in the third trimester, when only 13.8% of patients received cholecystectomy or cholecystostomy.

Table 4.

Rates of Operative Versus Non-Operative Management over Time

	2016 (n = 338)	2017 (n = 365)	2018 (n = 334)	2019 (n = 337)
Cholecystectomy or cholecystostomy (n, %)	118 (34.9%)	104 (28.5%)	102 (30.5%)	91 (27%)
Non-operative management (n, %)	220 (65.1%)	261 (71.5%)	232 (69.5%)	246 (73.0%)

Table 5.

Rates of Operative Versus Non-Operative Management in Each Trimester

	1–12 wks(n = 214)	13–27 wks(n = 326)	28+ wks(n = 807)	p
Cholecystectomy or cholecystostomy (n, %)	96 (44.9%)	196 (60.1%)	111 (13.8%)	<0.001
Non-operative management (n, %)	118 (55.1%)	130 (39.9%)	696 (86.2%)

Discussion

Our data demonstrate that 30.2% of pregnant patients receive operative management as treatment for acute cholecystitis, and there is no evidence of any improvement in the rates of cholecystectomy over the time period in this study. This is similar to the findings of Hantoui et al., who found that 34.5% of patients in their study received cholecystectomy,⁵ Rios-Diaz et al., who found that 38.2% of patients in their study receive operative management,⁶ and Cheng et al., who found a 36.3% cholecystectomy rate.¹ While this lack of improvement in operative rates is frustrating, it is not unique, as previous studies on research translation and implementation have demonstrated that it takes an average of 17 years for research evidence to be adopted as common clinical practice.¹² However, research has suggested that laparoscopy is safe in pregnancy for more than 25 years,³ and SAGES’ first set of guidelines recommending laparoscopic cholecystectomy as the treatment for acute cholecystitis was published in 2008.¹³ Additional efforts may be needed to draw attention to this disparity in the care of pregnant patients.

Our data suggest that cholecystectomy is safe in pregnancy, as operative management is associated with equal or lower rates of maternal and fetal complications when compared with non-operative management. This is consistent with prior research, which also demonstrates the safety of cholecystectomy in all trimesters of pregnancy.^1,3,5,6,14 While we cannot determine the specific barriers to offering or performing a cholecystectomy from this dataset, there are a number of reasons that likely contribute to the reduced operative rates in pregnant patients. First, the fact that operative rates were lowest in the late stages of pregnancy suggests that there may be concerns of the logistical aspects of performing the operation safely, working around the gravid uterus. The current SAGES guidelines describe methods for safe entry into the abdomen and establishing pneumoperitoneum in pregnancy, and these guidelines need to be widely distributed and emphasized.⁷ Second, there may be concerns over legal action if there are any maternal or fetal complications from surgical intervention. Obstetrics and gynecology physicians face the some of the highest rates of malpractice lawsuits of any specialty,¹⁵ and general surgeons may be reluctant to take on that same liability. However, while there may be more perceived harm when a complication occurs after a procedure, this does not mean that harm cannot occur when inaction is associated with worse outcomes. Finally, one reason that is frequently cited for the lack of consistency in the treatment of acute cholecystitis in pregnancy is the lack of clear clinical trial data on the best practices.^1,5 Pregnant women are often excluded from clinical research because they are viewed as a protected population. Ironically, what was meant to be a protection for a vulnerable population has left a void in high-quality research on how to best serve this population of patients whose physiology makes them unique.¹⁶ Efforts are being made to include pregnant women in clinical trials, but these efforts will take time.¹⁷ The best evidence currently available suggests that cholecystectomy in pregnancy is safe and the current preferred treatment for cholecystitis.

The role of cholecystostomy tube placement in the treatment of acute cholecystitis in pregnancy remains difficult to determine. It could be a temporizing measure that bridges patients from the first trimester, when risk of spontaneous abortion is highest, to the second trimester. It could also bridge patients from late in pregnancy until after delivery. While our data suggest that use of cholecystostomy is safe and associated with fewer complications than use of antibiotic agents alone, our data did find that patients who had a cholecystostomy placed had a greater length of stay as well as high rates of cholecystectomy at readmission. A review of the literature shows case reports give mixed results when using cholecystostomy tube placement to treat acute cholecystitis.⁹ A study published by Zhang et al. that included 29 patients treated with cholecystostomy late in pregnancy suggests that it can be a safe treatment alternative to operation, though it was associated with a prolonged length of stay, 3.5% preterm delivery rate, and 24% readmission rate, which are similar to our findings.¹⁸ Given the low rate of cholecystostomy tube placement in published data, a larger study would be necessary to offer recommendations on use of cholecystostomy in pregnancy.

Our study has multiple limitations. First, this is a review of a national database and does not include individual patient chart review that could add additional relevant context to a specific patient’s situation. Second, this database is based on ICD-9 and ICD-10 codes and may have inconsistencies or errors due to variation in how diagnoses and complications are coded. Third, the database itself includes data from approximately 30 states and thus may be limited in including some regional variations in outcomes.

Conclusions

In conclusion, rates of non-operative management of acute cholecystitis in pregnant patients remain high, despite continued evidence that cholecystectomy is safe and that non-operative management is associated with increased complications. The role of cholecystostomy remains unclear but in our study was associated with increased length of stay and high rates of cholecystectomy at readmission. Efforts must be made to promote the implementation of current guidelines and advocate for operative treatment for pregnant patients with acute cholecystitis.

Footnotes

Authors’ Contributions

J.L.W.: Conceptualization and writing—original draft. A.S.: Formal analysis. T.W.C.: Writing—review and editing. L.H.: Conceptualization, formal analysis, and writing—review and editing.

Funding Information

No external funding was used to support this study.

Author Disclosure Statement

The authors have no conflicts of interest to disclose.

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