Predicting complicated choledocholithiasis

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Association for Academic Surgery

Predicting complicated choledocholithiasis5 Kristy L. Kummerow, MD,a Julia Shelton, MD, MPH,a Sharon Phillips, MSPH,b Michael D. Holzman, MD, MPH,a William Nealon, MD,a William Beck, MD,a Kenneth Sharp, MD,a and Benjamin K. Poulose, MD, MPHa,* a b

Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee

article info

abstract

Article history:

Introduction: Management of choledocholithiasis and its complications is variable and often

Received 14 January 2012

requires transfer to a specialty facility. This study links patient-specific characteristics with

Received in revised form

the outcome measure of complicated choledocholithiasis to identify high-risk patients who

23 March 2012

may require expedited treatment or transfer to a higher level of care.

Accepted 17 April 2012

Materials and methods: Patients with a discharge diagnosis of choledocholithiasis (CDL) were

Available online 7 May 2012

identified from the 2009 Nationwide Inpatient Sample (NIS). Patient characteristics were identified associated with the primary outcome measure of complicated chol-

Keywords:

edocholithiasis (cCDL), defined as acute pancreatitis or cholangitis during the admission

Choledocholithiasis

for CDL. Predictors of mortality were also evaluated. Analysis was performed using

Cholangitis

complex-sample univariate and adjusted analyses.

Acute pancreatitis

Results: We identified 123,990 discharges with a diagnosis of CDL. The overall incidence of

Risk stratification

CDL was 314 per 100,000 NIS discharges. Forty-one percent of CDL discharges were for cCDL

Transfer

(acute pancreatitis 31%, cholangitis 12%). Risk factors for cCDL included age (risk increased

Access to care

0.8% per year), male gender (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.1e1.2),

Health disparities

alcohol abuse (OR 1.5, CI 1.3e1.8), diabetes (OR 1.1, CI 1.0e1.2), hypertension (OR 1.1, CI 1.0 e1.2), obesity (OR 1.2, CI 1.1e1.3), nonelective admission (OR 2.3, CI 2.0e2.6), and Asian/

Race

Pacific Islander race/ethnicity (OR 1.2, CI 1.0e1.5). Patients with cCDL had increased odds of mortality (OR 1.5, CI 1.2e2.0). Conclusions: Increased age, nonelective admission, and specific comorbid conditions are associated with cCDL, which has increased mortality. These factors can be used to identify patients needing timely access to treatment or transfer to a higher level of care. ª 2012 Elsevier Inc. All rights reserved.

1.

Introduction

Gallstone disease remains a widespread problem affecting about 10% of the United States population [1]. Of particular concern are complications of choledocholithiasis (CDL),

including pancreatitis and cholangitis, which carry mortality rates of 1%e3% and 10%, respectively [2e4]. Management of common duct stones varies widely, ranging from endoscopic retrograde cholangiopancreatography to surgical or percutaneous intervention, and often requires transfer of care to

5 Abstract to be presented at oral session during the 2012 meeting of the Academic Surgical Congress on Feb. 16th, 2012. * Corresponding author. D-5203 Medical Center North, VUMC, 1161 21st Avenue South, Nashville, TN 37232. Tel.: þ1 615 343 5613; fax: þ1 615 343 9485. E-mail address: [email protected] (B.K. Poulose). 0022-4804/$ e see front matter ª 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.jss.2012.04.034

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a specialty center where these modalities are readily available. We sought to identify risk factors for complicated choledocholithiasis in order to predict development of cholangitis or pancreatitis in patients with choledocholithiasis and to facilitate expedited treatment or transfer of high-risk patients to centers where definitive care can be provided.

2.

Materials and methods

2.1.

Study population

following data were obtained for study participants: age, gender, race/ethnicity, elective or emergent admission status, and presence of comorbid conditions with clinical relevance as related to gallstones or as confounding factors that may impact mortality. These included alcoholism, congestive heart failure, chronic lung disease, diabetes, obesity, hypertension, and renal failure. As a secondary outcome measure, risk factors for mortality were also identified by analysis of these demographic and comorbid conditions, as well as presence of complicated choledocholithiasis.

2.3. Adult inpatients with a discharge diagnosis of CDL were identified from the 2009 Association for Healthcare Research and Quality Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) database based on the 2009 International Classification of Diseases, ninth revision (ICD-9) codes. The NIS is the largest all-payer inpatient database available, representing 20% of all nonfederal discharges in the United States. Data were included from 1050 hospitals in 44 states, representing greater than 39 million discharges [5]. Of those patients identified, an individual discharge was designated as a CDL discharge if age at admission was at least 18 y and an ICD-9 diagnosis code for CDL (574.3e574.9) was noted. Discharges were identified as complicated choledocholithiasis (cCDL) if the patient also had a diagnosis of acute pancreatitis (576.1) or cholangitis (577.0). Discharges with a diagnosis of chronic pancreatitis (577.1), pancreatitis not related to gallstones (i.e., idiopathic, drug-related), pancreatic pseudocyst (577.2), obstruction of bile duct without stone (576.2), and complications of liver transplantation (996.82) were excluded. Malignancies of the pancreas, gall bladder, bile duct, or liver were also excluded from analysis using HCUP Clinical Classification Software categories.

2.2.

Comparison and outcome variables

Demographic and comorbid conditions were analyzed for patients with choledocholithiasis and those with cholangitis or acute pancreatitis in addition to choledocholithiasis. The

Statistical analysis

Statistical analyses were performed in SAS version 9.1.3 (SAS Institute Inc, Cary, NC) using complex sample analysis. Univariate analyses were performed using t-test or c2 statistics to compare patient demographics and comorbidities for the primary outcome measure of cCDL. Risk factors for cCDL were further evaluated using a multivariate complex sample logistic regression model that incorporated variables achieving significance of P < 0.05 on univariate analysis. In the multivariate models, age was analyzed first as a continuous variable and then as a categorical variable using the following age groups: 18e24, 25e34, 35e44, 45e54, 55e64, and >65 years. This study was deemed exempt by the Vanderbilt University Institutional Review Board.

3.

Results

Using the 2009 NIS, we identified 123,990 discharges with a diagnosis of CDL. The overall cumulative incidence of CDL was 314 per 100,000 NIS discharges for 2009. Patients with complicated choledocholithiasis comprised 41% of the sample (pancreatitis 31%, cholangitis 12%). Of note, some discharges carried diagnoses of both pancreatitis and cholangitis. Demographic data for the study population are described in Table 1. Mean age for patients with choledocholithiasis without pancreatitis or cholangitis was 56.5  0.36 y (mean  SE), with 67% female. For the cCDL group, mean age

Table 1 e Demographic characteristics of study population.

Mean age (y) Female (%) Elective admission (%) Comorbid condition (%) Congestive heart failure Chronic lung disease Diabetes mellitus Hypertension Obesity Renal failure

Uncomplicated choledocholithiasis* n ¼ 73,064

Acute pancreatitisy n ¼ 38,953

Cholangitisy n ¼ 15,121

56.5 67.2 14.0

57.6 63.8 6.8

69.1 53.7 6.9

6.8 13.2 15.0 43.8 12.1 7.2

6.8 12.8 17.2 48.8 14.7 7.7

12.5 15.4 21.8 59.2 9.5 11.9

* Includes all Nationwide Inpatient Sample 2009 discharges with a discharge diagnosis of choledocholithiasis without a concomitant diagnosis of acute pancreatitis or cholangitis. y Includes all Nationwide Inpatient Sample 2009 discharges with concomitant diagnosis of choledocholithiasis and either acute pancreatitis or cholangitis.

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was 60.3  0.40 y, with 62% female. Female patients comprised a greater percentage of patients with both acute pancreatitis and cholangitis. The mean age for acute pancreatitis was younger than for cholangitis. Distributions of race/ethnicity were statistically different between discharges for choledocholithiasis without acute pancreatitis or cholangitis and those with cCDL. Whites and Asians/Pacific Islanders were slightly more likely than blacks or Hispanics to have cCDL. With the exception of chronic lung disease, which was similar among patients with or without complicated choledocholithiasis, all comorbid conditions evaluated were more common in patients with cCDL. Choledocholithiasis was more common in older patients (Fig. 1). Older age was also found to be a predictor of cCDL among all patients with choledocholithiasis. This was significant as a continuous variable, where after the age of 18, the risk of cCDL increased by 0.8% per year of age. In the multivariate analysis, age was included as a categorical variable by decile (Fig. 2). For each increase in age decile there was a concomitant increase in the odds of cCDL. Most of this difference can be attributed to the increase in cholangitis among older patients, which was present in 18% of CDL discharges for patients >65 y versus 3%e12% in the younger age groups (Fig. 1). By contrast, the proportion of patients with acute biliary pancreatitis among all patients with choledocholithiasis remained stable across all age deciles, ranging from 29% to 32% (Fig. 1). Other risk factors for complicated choledocholithiasis included male gender (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.1e1.2), alcohol abuse (OR 1.5, CI 1.3e1.8), diabetes (OR 1.1, CI 1.0e1.2), hypertension (OR 1.1, CI 1.0e1.2), obesity (OR 1.2, CI 1.1e1.3), nonelective admission (OR 2.3, CI 2.0e2.6), and Asian/Pacific Islander race/ethnicity (OR 1.2, CI 1.0e1.5). Mortality in patients with choledocholithiasis was primarily predicted by complicated choledocholithiasis and age (Table 2). Patients with cCDL had 1.56 times greater odds of mortality than those with uncomplicated CDL (CI 1.22e1.99). Older age predicted mortality, with increasing age deciles trending toward increasing likelihood of death. Statistical significance was achieved for patients 55 y and older. For patients older than 65 y, the odds of mortality increased 35000

Number of discharges (weighted frequency)

30000

25000

20000

Uncomplicated Acute Pancreatitis Cholangitis

15000

10000

5000

0

18-24.9

25-34.9

35-44.9

45-54.9

55-64.9

>=65

Age (decile)

Fig. 1 e Distribution of choledocholithiasis discharges by age category. “Uncomplicated” denotes inpatient admissions for choledocholithiasis without concomitant acute pancreatitis or cholangitis.

Fig. 2 e Multivariate regression analysis predicting complicated choledocholithiasis among 2009 NIS discharges with a diagnosis of choledocholithiasis. Complicated choledocholithiasis includes discharges with choledocholithiasis and either acute pancreatitis or cholangitis during the admission for choledocholithiasis. LCL [ lower confidence limit; UCL [ upper confidence limit. Race variables are compared to the reference variable “white race.” Ages are compared to the reference variable “age 18e24.9 y.”

28-fold when compared with patients aged 18e24.9 (95% CI 6.8e118.3). Interestingly, no comorbid condition was a significant predictor of mortality in patients with choledocholithiasis, and hypertension appeared to be slightly

Table 2 e Multivariate regression analysis predicting mortality among 2009 Nationwide Inpatient Sample discharges with a diagnosis of choledocholithiasis. Variable Complicated CDL* Alcoholism Diabetes mellitus Hypertension Obesity Race White Black Hispanic Asian/Pacific Islander Native American Other Unknown Nonelective admission Male gender Age decile 18e24.9 y 25e34.9 y 35e44.9 y 45e54.9 y 55e64.9 y 65 y

Odds ratio (95% confidence interval) 1.56 1.23 1.14 0.66 0.84

(1.22e1.99)y (0.61e0.50) (0.87e1.49) (0.51e0.85)y (0.54e1.30)

1.25 0.86 1.05 1.26 1.03 0.75 1.24 1.05

Ref (0.75e1.05) (0.58e1.35) (0.62e1.76) (0.30e5.21) (0.54e2.08) (0.50e1.13) (0.85e1.81) (0.83e1.33)

Ref 0.78 (0.11e5.54) n/az 4.31 (0.93e19.98) 8.47 (1.94e36.93)y 28.36 (6.80e118.34)y

Ref ¼ reference values. * Includes discharges with choledocholithiasis and either acute pancreatitis or cholangitis during the admission for choledocholithiasis. y Statistically significant. z Age category for which no mortalities were documented.

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protective in this model. No disparities in mortality were noted based on race/ethnicity, gender, or elective versus nonelective admission status.

4.

Discussion

This study using the HCUP NIS data evaluated risk factors for complicated choledocholithiasis, specifically acute pancreatitis and cholangitis. We found that age was the most significant risk factor for complications of choledocholithiasis and mortality during admission for choledocholithiasis. Age has previously been identified as a risk factor for acute suppurative cholangitis in a retrospective review of 343 patients with bile duct stones [6]. Further, Sugiyama and Atomi [7] and Csendes et al. [8] found that severe cholangitis related to common duct stones occurred more frequently in elderly patients. In a retrospective study of 528 patients with gallstone disease, Venneman et al. found that patients with complicated gallstone disease (defined as acute pancreatitis, acute cholecystitis, or obstructive jaundice), were older than patients with uncomplicated gallstone disease [9]. The present study corroborates these findings using a nationwide database that reflects 39 million inpatient discharges. Comorbid conditions including alcoholism, obesity, diabetes, and hypertension were found to be more common in patients with complicated choledocholithiasis than those without complicated choledocholithiasis. Obesity has previously been linked to increased severity of biliary pancreatitis in a prospective study of 250 patients [10]. That study did not evaluate the potential confounding impact of diabetes, which is closely linked to obesity in terms of epidemiologic distribution, and which we found also increased the likelihood of complicated choledocholithiasis in our sample population. The association between alcoholism and complicated choledocholithiasis may reflect miscategorization of patients with alcoholic pancreatitis as having biliary pancreatitis based on a concomitant diagnosis of choledocholithiasis; however, it may also reflect a propensity toward pancreatitis of any type in alcoholic patients or potentially an association between poor nutritional status, which is common in alcoholic patients, and development of complicated choledocholithiasis. When complications of choledocholithiasis were accounted for in our multivariate analysis, none of the above-mentioned comorbid conditions impacted mortality. Hence age and presence of complicated choledocholithiasis were the most important clinical predictors of death from common bile duct stones in this population. Identification of patients with common bile duct stones who are at higher risk of pancreatitis or cholangitis can help identify patients who may benefit from early treatment or expeditious transfer to an appropriate hospital setting. Our group has previously demonstrated that the hospital location at which a patient receives care for choledocholithiasis impacts his or her treatment [11]. Patients treated in urban settings are more likely to receive an intervention for choledocholithiasis than patients treated in rural hospitals. Further, endoscopic treatment is more frequently employed in urban hospitals, while surgery with common bile duct exploration is a more common intervention for patients who are

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treated at rural hospitals. The process of transferring patients to higher levels of care where more advanced or more definitive management of choledocholithiasis is available can be quite unwieldy, involving delays in care, costs of transportation and repeated laboratory tests and imaging, and significant patient and family frustration. The ability to quickly identify patients at higher risk of complications and death secondary to common bile duct stones could inform early treatment and/or transfer to a facility where essential interventions are available, potentially reducing morbidity and mortality associated with choledocholithiasis and its treatment. This study is limited in several ways. First, we use an inpatient database to identify patients with choledocholithiasis, which fails to capture patients who are managed on an outpatient basis either with no intervention or at outpatient surgery/procedure centers. While little data are available regarding the volume of patients with choledocholithiasis who are treated as outpatients, from our experience this disease is largely managed by inpatient admission, so we expect that most cases are captured by the NIS database. Secondly, we rely on the accuracy of medical coding to appropriately identify patients with choledocholithiasis, acute pancreatitis, and cholangitis, which may not accurately or completely reflect a specific patient’s hospital course. For example, an admission for sepsis secondary to cholangitis might be coded with the ICD-9 codes for choledocholithiasis and sepsis but not cholangitis, which would result in this being miscategorized as an uncomplicated choledocholithiasis admission in this particular study. While this could significantly impact the validity of our results, such coding errors are likely to be equitably distributed between our exposure groups, which would negate the potential impact of miscoded diagnoses on our study conclusions. Further, we presume that for discharges with concomitant diagnoses of choledocholithiasis and either cholangitis or pancreatitis, the common bile duct stone was the etiology of cholangitis or pancreatitis. This fails to differentiate patients for whom pancreatitis results from alcoholism, as discussed above, or from an endoscopic procedure that was done to treat choledocholithiasis, which occurs after about 2%e7% of endoscopic retrograde cholangiopancreatography procedures [12]. Finally, while this study proposes some criteria that can be used to stratify risk in patients with choledocholithiasis, our use of the NIS limits us to demographic risk factors only. Specific clinical indices for patients with gallstone pancreatitis, including vital signs and laboratory values, have been shown to be very effective in predicting need for a higher level of care within a facility and to predict mortality [13,14]. Chart review of large institutional or multi-institutional databases could help us more clearly delineate objective risk factors for complicated choledocholithiasis and mortality that should prompt early treatment or transfer to a specialty center. In conclusion, this study uses a nationwide inpatient data set to identify risk factors for complicated choledocholithiasis among patients admitted with common bile duct stones. It also outlines predictors of mortality in patients with choledocholithiasis. In both analyses, older age emerges as the most significant risk factor for cholangitis, pancreatitis, and death, with the most marked rise in mortality occurring after 55 y of age. Early recognition and treatment of these high-risk

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patients at a center equipped with advanced endoscopic and operative capabilities may improve outcomes.

references

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