Delay in performing ERCP and adverse events increase the 30-day readmission risk in patients with acute cholangitis

ORIGINAL ARTICLE: Clinical Endoscopy

Delay in performing ERCP and adverse events increase the 30-day readmission risk in patients with acute cholangitis Udayakumar Navaneethan, MD, Norma G. Gutierrez, MD, Ramprasad Jegadeesan, MD, Preethi G.K. Venkatesh, MD, Mujtaba Butt, MD, Madhusudhan R. Sanaka, MD, John J. Vargo, MD, MPH, Mansour A. Parsi, MD, MPH Cleveland, Ohio, USA

Background: Readmission to the hospital within 30 days of discharge (30-day readmission rate) is used as a quality measure. Objective: To investigate the incidence and factors that contribute to readmissions in patients with acute cholangitis. Design: Retrospective cohort study. Setting: Tertiary-care referral center. Patients: Retrospective analysis of consecutive patients admitted to our center for acute cholangitis and ERCP. Intervention: ERCP. Main Outcome Measurements: Incidence and variables associated with 30-day readmission and 1-year mortality. Results: ERCP was successful in 98.8% of patients during the index admission. The 30-day readmission rate was 22.0%. Recurrence of cholangitis was the most common etiology for readmissions (37.8%). Readmission within 30 days was independently associated with failed ERCP or ERCP delayed for ⬎48 hours (odds ratio [OR] 2.47; 95% confidence interval [CI], 1.01-6.07), development of any after-ERCP adverse event (OR 11.0; 95% CI, 3.06-39.30), and the etiology of cholangitis (etiologies not related to stones) (OR 3.3; 95% CI, 1.17-9.18). Every 1-point increase in the Charlson Comorbidity Index score (OR, 1.33; 95% CI, 1.05-1.69) was associated significantly with 1-year mortality. In unadjusted analysis, 30-day readmission after ERCP was associated significantly with 1-year mortality (OR, 2.86; 95% CI, 1.16-7.07). This association, however, was not present after adjustment for other covariates. Limitations: Retrospective study. Conclusion: Delays in performing ERCP during the index admission, development of after-ERCP adverse events, and etiology of cholangitis not related to stones increased the risk of 30-day readmissions. (Gastrointest Endosc 2013;78:81-90.)

The importance of 30-day hospital readmission as a quality measure for hospitalized patients has been emphasized recently because of its significant negative conse-

quences.1-3 Twenty percent of all Medicare patients are readmitted to the hospital within the first 30 days after discharge, resulting in an annual cost of over 17 billion

Abbreviations: ASA, American Society of Anesthesiologists Physical Status Classification System; CCI, Charlson Comorbidity Index; PSC, primary sclerosing cholangitis.

Received October 31, 2012. Accepted February 1, 2013.

DISCLOSURE: The study was supported by a research grant from the Inflammatory Bowel Disease Working Group and an American College of Gastroenterology grant (both to U. Navaneethan). J. Vargo is a consultant for Olympus America. No other financial relationships relevant to this publication were disclosed.

Current affiliations: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA. Reprint requests: Mansour A. Parsi, MD, MPH, Head, Section for Advanced Endoscopy and Pancreatobiliary Disorders, Department of Gastroenterology and Hepatology, Digestive Disease Institute, Desk A30, The Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195.

Copyright © 2013 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2013.02.003

If you would like to chat with an author of this article, you may contact Dr Parsi at [email protected].

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dollars.4 Readmissions have a significant impact on the health care system, putting patients at risk for repeat testing and hospital-acquired infections and ultimately increasing the cost of health care.5 Mandatory reporting of the 30-day hospital readmission rates for 3 of the most common admitting diagnoses— heart failure, pneumonia, and acute myocardial infarction—is required by the Center for Medicare & Medicaid Services.6 In the future, we believe that more hospital readmissions will fall under this category of mandatory reporting. Furthermore, the expectations are that the 30-day readmission rate will be used as a quality outcome measure in the Patient Protection and Affordable Care Act of 2010 and will be linked to hospital reimbursement.7 Acute bacterial cholangitis is one of the reasons for hospital admissions nationwide, and biliary drainage to relieve the obstruction is the cornerstone of treatment of acute cholangitis.8-10 Biliary drainage usually is accomplished endoscopically with ERCP.8 Studies have been done to identify risk factors for readmission after discharge among patients with conditions such as congestive heart failure, chronic obstructive pulmonary disease, and pneumonia.11-13 However, our knowledge regarding risk factors associated with 30-day readmission for acute cholangitis is extremely limited. In clinical practice, we often observe that the most common reasons for 30-day readmission in patients with acute cholangitis who have undergone ERCP are stent occlusion or recurrence of cholangitis. The quality of care delivered during the initial admission may play a role in reducing readmissions. Understanding whether these readmissions result from procedural adverse events, delays in performing or inability to perform the procedures, or from other medical conditions is critical. A recently published study showed that delays in ERCP greater than 72 hours were associated with prolonged hospital stays and increased costs of hospitalization and composite clinical outcome (death, persistent organ failure, and/or intensive care unit stay).14 Given the importance of timing of ERCP on cholangitis outcomes, we wanted to know whether the timing of ERCP and other procedural factors during the initial hospitalization also impact the risk of subsequent readmissions. The aim of our study was to investigate the incidence and factors that predict the 30-day readmission rate in hospitalized patients with acute cholangitis who underwent ERCP. We also sought to study the association of 30-day readmission with 1-year mortality in patients with acute cholangitis.

Navaneethan et al

Take-home Message ● ●

Readmission to the hospital within 30 days of discharge (30-day readmission rate) is used as a quality measure. Delay in performing ERCP during the index admission is associated with 30-day readmissions. Patients who develop after-ERCP adverse events are also at risk of readmissions.

January 2001 to August 2012. The medical records of all identified patients were manually reviewed. Patients without evidence of acute cholangitis on chart review were excluded. For the analysis of readmissions, only the index ERCP procedures were included. Patients who died during the initial hospitalization were excluded from the readmission analysis. Demographic, clinical, and procedural data and information on adverse events were collected. The study was approved by the Cleveland Clinic Institutional Review Board.

Inclusion and exclusion criteria The major inclusion criterion was the presence of acute cholangitis as the indication for ERCP. Diagnosis of acute cholangitis was based on the presence of fever, leukocytosis, abdominal pain, and jaundice with or without the presence of purulent drainage during ERCP and/or positive blood cultures in patients with risk factors for intermittent biliary obstruction, such as those with cholelithiasis or strictures. In our hospital, most patients with acute cholangitis are admitted to the gastroenterology service. However, some patients are admitted to general internal medicine, general surgery, or hepatobiliary surgical services. Patients admitted to any service after discharge were considered as readmissions and were included in the final analysis. Admissions were excluded if patients left against medical advice.

Demographic and clinical variables

The Cleveland Clinic electronic medical records database was queried to identify patients referred to our hospital for acute cholangitis who underwent ERCP from

Data collected included readmission within 30 days of discharge and relevant demographic, clinical, and laboratory test values. Collected variables during the index admission included age, sex, smoking status, body mass index, etiology of cholangitis, Charlson Comorbidity Index scores (CCI), the presence of systemic inflammatory response syndrome, American Society of Anesthesiologists Physical Status Classification System (ASA) scores, use of anti-platelet agents (eg, aspirin and/or clopidogrel), use of statins, history of cholangitis, the presence of purulent bile at the index ERCP, failure of ERCP, serum bilirubin levels, the presence of positive blood cultures, the presence of cirrhosis, the Child-Pugh-Turcotte score at admission, and the time of ERCP in relation to time of admission (doorto-ERCP time). Failed ERCP was defined as a procedure in which biliary cannulation could not be accomplished. We

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METHODS Patients

Navaneethan et al

assessed for statin use in our cohort of patients based on the hypothesis that statin use may decrease cholangitis readmissions and improve its long-term outcome. This hypothesis is derived from a previous study in which statin use decreased the risk of gallstone disease and cholangitis.15 In addition, the pleiotropic effects of statins have been shown to modify inflammatory cell signaling on the immune response to infection.16,17 We obtained information on whether the admission to the hospital and performance of ERCP happened during regular working hours or after hours. Regular working hours was defined as any time between 8 AM and 5 PM during weekdays. Any other time and weekends and/or holidays during which there is lack of full support staff was classified as after hours. Data on therapeutic procedures during ERCP such as sphincterotomy, precut sphincterotomy, papillary balloon dilation, biliary stricture dilation, biliary stent placement, type of stent placement, bile duct injections, number and diameter of stents placed, and stone extraction also were evaluated. Pancreatic duct injection was defined as opacification of any portion of the pancreatic duct by contrast material. The number of pancreatic injections and the use of pancreatic duct stents were recorded. After-ERCP adverse events were defined based on the American Society for Gastrointestinal Endoscopy workshop.18 These included pancreatitis, bleeding, perforation, hypoxia, abdominal pain, cholecystitis, hypotension, and bradycardia. The other variables obtained included length of initial index hospital stay, the presence of renal insufficiency (defined as a serum creatinine level ⬎1.9 mg/dL), and requirement for intensive care unit stay during the index hospitalization. ERCP procedures were performed by 1 of 8 experienced interventional endoscopists by using standard endoscopic equipment. The endoscopic treatment of bacterial cholangitis in our practice includes wireguided biliary cannulation; minimizing contrast material injection, biliary sphincterotomy (dependent on the endoscopist and clinical presentation), and sweeps of the bile duct. Biliary and pancreatic stent placement during the ERCP procedures was performed at the endoscopist’s discretion.

Outcome measurement The primary study outcomes were the incidence and etiology of all-cause readmission to our hospital within 30 days of discharge. The secondary outcome was to study variables associated with 30-day readmissions and 1-year mortality.

Statistical analysis Descriptive statistics were computed for all factors. These included medians, 25th and 75th percentiles, range or mean and standard deviation (SD) for quantitative variables, and frequencies and percentages for categorical factors. Continuous data are summarized as mean and SD. Categorical data are summarized as frequency and group www.giejournal.org

Cholangitis and readmissions

percentage. Apparently normally distributed continuous variables were analyzed by using a t test (age, body mass index, bilirubin level, CCI score, ASA score), and continuous variables that were not apparently normally distributed such as Child-Pugh-Turcotte score were analyzed by using the nonparametric (Wilcoxon) rank sum test. Variables analyzed by t test are presented as mean values with SD, whereas the variables analyzed by Wilcoxon rank sum test are presented as median values with interquartile range (IQR). Differences between patients who were readmitted within 30 days and those who were not readmitted within 30 days were compared. Logistic regression models were built for 30-day readmission by selecting from the various covariates associated with the end point at the 0.10 significance level. The covariates in the final model included door-to-ERCP time, CCI score, pancreatic duct stent placement, etiology of cholangitis, and the presence of after-ERCP adverse events. We used the door-toERCP time of greater than 48 hours as the definition for delayed ERCP because it had the best predictive ability on univariate analysis. Failed and delayed ERCP procedures were combined as one variable. Logistic regression models were built for 1-year mortality by selecting from the various covariates associated with the end point at the 0.05 significance level. The covariates in the final model included 30-day readmission of any etiology, ASA score, CCI score, cholangitis-related 30-day readmission, and intensive care unit stay during the index hospitalization. The odds ratios (OR) for variables analyzed as continuous (eg, age and body mass index) or ordinal categorical variables not analyzed as dichotomous indicate that the multiplicative factor is applied as a factor to the odds for each designated quantity increase (eg, unit increase in CCI score, 5-year units of age). P values ⬍ .05 were taken as nominally statistically significant. It is recognized that there was multiple testing of outcome data arising from individual patients. The P values for the univariate statistical tests are not corrected for multiple testing, because those tests were taken as exploratory. The subsequent multivariate logistic regression analyses were considered the main definitive results because they determined those variables independently associated with 30-day readmission and 1-year mortality, after we adjusted for the contributions of the other variables. Because there were 2 definitive multivariate models constructed, the method of Bonferroni would remove statistical significance from nominally significant multivariate findings unless the P value was ⬍ .025. The uncorrected P values are presented, and it is noted wherever statistical significance would be removed by the correction for multiple testing.

RESULTS A query of the Cleveland Clinic electronic medical report database from January 2001 through August 2012 identified 202 patients with acute cholangitis who were Volume 78, No. 1 : 2013 GASTROINTESTINAL ENDOSCOPY 83

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TABLE 1. Selected clinical characteristics of the study cohort (n ⴝ 168) Variable Age, median (IQR), y

No. (%) 62.0 (52-72)

Male

94 (55.9)

Thirty-day readmission rate

37 (22.0)

Etiology of cholangitis Bile duct stone

65 (38.7)

Primary sclerosing cholangitis

45 (26.8)

Cancer

28 (16.7)

Benign stricture

20 (11.9)

Other

10 (5.9)

Cirrhosis

29 (17.3)

One-year mortality rate

25 (14.9)

Index hospitalization to gastroenterology service

111 (66.1)

Index hospitalization to intensive care unit

12 (7.1)

History of biliary tract disease

48 (28.6)

IQR, Interquartile range.

referred to our hospital. After chart review, 30 patients were excluded because of absence of confirmation of acute cholangitis. An additional 4 patients who died during the index hospital admission were excluded from the readmission analysis. ERCP was successful in 98.8% of patients during the index hospitalization. Overall, 37 patients (22.0%) were readmitted within 30 days of discharge. Twenty-three of these patients (62.2%) were discharged from the gastroenterology service during the index hospitalization. Table 1 highlights the characteristics of the study cohort. After-ERCP adverse events were bleeding (n ⫽ 2), perforation (n ⫽ 1), abdominal pain (n ⫽ 4), hypoxia (n ⫽ 4), and after-ERCP pancreatitis (n ⫽ 3). Two patients who failed ERCP underwent percutaneous transhepatic biliary drainage. The reason for ERCP failure was edematous ampulla in both patients.

tal status at index admission, and door-to-ERCP time (⬎48 hours) were not associated with 30-day readmission on univariate analysis. The median serum bilirubin level was higher in patients with delayed ERCP compared with those who had ERCP within 48 hours of admission (6.7 mg/dL [IQR 4.1-11.2] vs 4.2 mg/dL [IQR 2.5-7.7); P ⫽ .01). Comparison of various factors in patients with and without delayed ERCP is summarized in Table 4. The admission service (gastroenterology vs others) and location (intensive care unit vs regular nursing unit) did not have a significant effect on 30-day readmission. Figure 1 shows the timing of ERCP and readmissions in the study cohort.

Multivariate analyses Variables with P ⬍ 0.1 were selected as candidates for the multivariate model building as previously described. These factors included door-to-ERCP time (⬎48 hours or failed ERCP), CCI score, pancreatic duct stent placement, etiology of cholangitis (not stone related) and the presence of after-ERCP adverse events. Readmission within 30 days was independently associated with failed or delayed ERCP (OR 2.47; 95% confidence interval [CI], 1.01-6.07), development of any afterERCP adverse events (OR 11.0; 95% CI, 3.06-39.30), and etiology of cholangitis not stone related (OR 3.3; 95% CI, 1.17-9.18). On correction for multiple testing with the Bonferroni method, nominal statistical significance would remove door-to-ERCP time ⬎48 hours or failed ERCP as a significant variable for 30-day readmissions. Other factors including CCI score and pancreatic stent placement did not have any significant associations with readmission (Table 5).

Reasons for delayed ERCP in patients readmitted within 30 days Door-to-ERCP time was ⬎48 hours in 13 patients (35.1%) who were readmitted within 30 days of discharge. In 11 of 13 patients, hemodynamic instability precluded ERCP for 48 hours. Two patients who had cancer metastatic to the bile duct (primary breast and colon carcinoma) were admitted for fever of unknown origin, and cholangitis was recognized after 48 hours of hospitalization.

Readmission diagnoses

Univariate comparisons of categorical and procedural variables between index admissions with and without 30day readmission are summarized in Tables 2 and 3. CCI score, pancreatic stent placement, etiology of cholangitis (bile duct stones were less likely and etiologies not related to stones, including primary sclerosing cholangitis (PSC)/ cancer/benign strictures, were more likely), and development of any after-ERCP adverse events were associated with 30-day readmission. Higher ASA scores, altered men-

Among the 37 readmissions, recurrence of cholangitis was the most common etiology, occurring in 14 of 37 patients (37.8%). The underlying etiologies for recurrent cholangitis in this group of patients were stent occlusion (n ⫽ 8), incomplete clearance of biliary stones during index ERCP (n ⫽ 3), and both stent occlusion and incomplete clearance of stones during index ERCP (n ⫽ 2). In 1 patient, the underlying etiology for recurrence of cholangitis remained unknown. Other reasons for readmission were further management of cirrhosis or its complications such as encephalop-

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Univariate analyses

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TABLE 2. Demographic and clinical characteristics during index hospitalization and 30-day readmission No 30-day readmissions n ⴝ 131 (78.0%)

30-day readmissions n ⴝ 37 (22.0%)

P value

OR (95% CI)

61 (50-72)

64.5 (52.8-71.5)

.93

0.99 (0.89-1.11)

74 (56.5)

20 (54.1)

.79

0.91 (0.44-1.89)

26.3 (23.1-29.4)

25.9 (22.3-28.1)

.64

0.92 (0.65-1.30)

Smoking, no. (%)

33 (25.2)

11 (29.7)

.65

1.23 (0.51-2.96)

Primary sclerosing cholangitis, no. (%)

37 (28.2)

8 (21.6)

.86

1.07 (0.48-2.39)

Cirrhosis, no. (%)

22 (16.8)

7 (18.9)

.81

1.27 (0.43-2.41)

Systemic inflammatory response syndrome, no. (%)

23 (17.6)

9 (24.3)

.39

1.47 (0.61-3.52)

0

27 (20.6)

6 (16.2)

1

31 (23.7)

5 (13.5)

2

18 (13.7)

5 (13.5)

3

32 (24.4)

9 (24.3)

ⱖ4

22 (16.8)

12 (32.4)

2 (1-3)

3 (1-6)

0 (0)

2 (5.4)

Variable Age, median (IQR), y* Male, no. (%) BMI, median (IQR), kg/m2†

Charlson Comorbidity Index, no. (%)

Charlson Comorbidity Index, median (IQR)

.27

.04

1.20 (1.01-1.42)

ASA score, no. (%) 1 2

1 (0.7)

1 (2.7)

3

82 (62.6)

19 (51.4)

4

44 (33.6)

14 (37.8)

5

3 (2.3)

1 (2.7)

ASA score, median (IQR)

.07

3 (3-4)

3 (3-4)

.29

0.75 (0.44-1.28)

7.2 (2.1)

7.5 (2.7)

.13

1.03 (0.80-1.65)

4 (3.1)

4 (10.8)

.07

3.82 (0.91-16.08)

30 (22.9)

6 (16.2)

.38

0.65 (0.25-1.70)

Regular hours, no. (%)

67 (51.1)

14 (37.8)

.15

1.76 (0.82-3.78)

After hours, no. (%)

57 (43.5)

21 (56.8)

ⱕ48 h

103 (78.6)

24 (64.9)

.09

1.99 (0.90-4.41)

⬎48 h

28 (21.4)

13 (35.1)

4.4 (2.5-8.1)

5.2 (2.3-8.7)

.43

1.03 (0.96-1.11)

1.0

Child-Pugh-Turcotte score in cirrhotic patients, mean (SD)‡ Altered mental status, no. (%) Anti-platelet medications at admission, no. (%) Timing of admission‡

Door-to-ERCP time, no. (%)

Before-ERCP bilirubin level, median (IQR) Positive blood cultures Gram positive, no. (%)

9 (6.9)

2 (5.4)

Gram negative, no. (%)

24 (18.3)

7 (18.9)

6 (4.6)

8 (21.6)

.001

9.03 (2.55-32.04)

2.3 (2-3)

2.3 (1.6-2.8)

.22

0.76 (0.48-1.18)

7 (5.3)

2 (6.5)

1.0

1.00 (0.20-5.05)

Presence of any after-ERCP adverse event, no. (%) Length of index hospital stay, median (IQR) ICU stay during index hospitalization, no. (%)

OR, Odds ratio; CI, confidence interval; IQR, interquartile range; BMI, body mass index; ASA, American Society of Anesthesiologists Physical Status Classification System; ICU, intensive care unit. *OR reported for every 5-y increase in age. †OR reported for every 1-kg/m2 increase in BMI. ‡Data not available for all patients.

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TABLE 3. Procedural characteristics during index hospitalization and 30-day readmission No 30-day 30-day readmission readmission P n ⴝ 131 (78.0%) n ⴝ 37 (22.0%) value

Variable

OR (95% CI)

Etiology of cholangitis, no. (%) Bile duct stone

58 (44.3)

7 (18.9)

.007

0.29 (0.12-0.72)

Primary sclerosing cholangitis

37 (22.9)

8 (21.6)

.001

3.45 (1.39-8.33)

Cancer

17 (3.0)

8 (21.6)

Benign strictures

14 (10.7)

6 (16.2)

5 (3.8)

8 (21.6)

Purulent bile at ERCP, no. (%)

57 (43.5)

10 (27.0)

.11

Multiple contrast material injections into biliary system at ERCP, no. (%)

27 (20.6)

9 (24.3)

.91

Balloon dilatation during ERCP, no. (%)

48 (36.6)

16 (43.2)

.46

Multiple bile duct contrast material injections at ERCP, no. (%)

27 (20.6)

9 (24.3)

.91

1.06 (0.38-2.92)

9 (6.9)

6 (16.2)

.11

3.58 (0.22-58.71)

41 (31.3)

7 (18.9)

.06

4 (3.1)

0

.58

67 (51.1)

21 (56.8)

.67

4 (3.1)

1 (2.7)

96 (73.3)

30 (81.1)

7 (5.3)

3 (8.1)

83 (63.4)

26 (70.3)

Covered metal stent, no. (%)

3 (2.3)

0 (0)

Uncovered metal stent, no. (%)

3 (2.3)

1 (2.7)

Pancreatic duct stent, no. (%)

6 (4.6)

Not related to bile duct stone

Other (ampullary adenoma; Caroli’s disease; choledochojejunostomy, idiopathic)*

More than 2 pancreatic duct contrast material injections at ERCP, no. (%) Biliary sphincterotomy, no. (%) Pancreatic sphincterotomy, no. (%)

1.06 (0.38-2.92)

Type of cannulation, no. (%) Guidewire Precut sphincterotomy Bile duct stent, no. (%) Multiple plastic biliary stents, no. (%) Single plastic biliary stent, no. (%)

.44

1.03 (0.96-1.11)

6 (16.2)

.02

4.1 (1.22-13.50)

10 (10, 10)

10 (10, 10)

.26

0.78 (0.51-1.20)

Choledocholithiasis with incomplete bile duct clearance at index ERCP, no. (%)

14 (5.3)

3 (5.3)

.80

0.89 (0.37-2.16)

Biliary balloon dilation without subsequent biliary stent placement, no. (%)

27 (20.6)

5 (16.1)

.41

78 (56.9)

24 (64.9)

Total diameter of biliary stents, median (IQR), F

Timing of ERCP†, no. (%) Regular hours

.50 After hours

51 (37.2)

0.76 (0.35-1.66)

12 (32.4)

OR, Odds ratio; CI, confidence interval; IQR, interquartile range. *Choledochojejunostomy, idiopathic. †Data not available for all patients.

athy (n ⫽ 7) as well as upper GI bleeding (n ⫽ 4), abdominal pain in the setting of chronic pancreatitis (n ⫽ 2), renal insufficiency (n ⫽ 2), postoperative ileus (n ⫽ 1), subdiaphragmatic abscess (n ⫽ 2), chronic cholecystitis (n ⫽

1), pancreatic cancer (n ⫽ 2), and management of primary cancer (colon and breast cancer) (n ⫽ 2). Both patients with pancreatic cancer who were readmitted had abdominal pain that did not respond to oral narcotics.

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TABLE 4. Demographic and clinical characteristics of patients who had ERCP performed before and after 48 hours ERCP timing <48 h* n ⴝ 127 (75.6%)

ERCP timing >48 h or failed n ⴝ 41 (24.4%)

P value

63 (52-74)

61 (46.5-70)

.22

70 (55.1)

23 (56.1)

.79

26.7 (22.8-29.2)

25.1 (23.4-28.5)

.63

Smoking, no. (%)

35 (27.6)

10 (24.4)

.77

Primary sclerosing cholangitis, no. (%)

34 (26.8)

11 (26.8)

1.0

Charlson Comorbidity Index, median (IQR)

2 (1-3)

3 (1-3)

.84

ASA score, median (IQR)

3 (3-4)

3 (3-4)

.79

4.2 (2.5-7.7)

6.7 (4.1-11.2)

.01

Gram positive

9 (7.0)

3 (7.0)

.34

Gram negative

21 (16.3)

10 (23.3)

13 (10.2)

4 (9.8)

1.0

2.3 (1.6-2.8)

2.8 (2.3-3.4)

⬍.001

Variable Age, median (IQR), y Male, no. (%) 2

BMI, median (IQR), kg/m

Before-ERCP bilirubin level, median (IQR) Positive blood cultures, no. (%)

Presence of any after-ERCP adverse event, no. (%) Length of index hospital stay, median (IQR), d

IQR, Interquartile range; BMI, body mass index; ASA, American Society of Anesthesiologists Physical Status Classification System.

TABLE 5. Independent predictors of 30-day hospital readmission: results of the multivariate analyses Variable

OR (95% CI)

P value

Charlson Comorbidity Index (per 1 unit)

1.15 (0.94-1.40)

.18

Door-to-ERCP time ⬎48 h or failed*

2.47 (1.01-6.07)

.04

Etiology of cholangitis, not related to stones

3.30 (1.17-9.18)

.02

Any after-ERCP adverse event

11.0 (3.06-39.3)

⬍.001

Pancreatic stent

3.00 (0.78-11.6)

.11

OR, Odds ratio; CI, confidence interval. *On correction for multiple testing with the Bonferroni method, nominal statistical significance would remove door-to-ERCP time ⬎48 h or failed ERCP as a significant variable.

Figure 1. Timing of ERCP and readmissions in our cohort. Patients with ERCPs that were performed more than 48 hours after the index admission had more readmissions.

Readmission and subsequent mortality In unadjusted analysis, 30-day readmission after ERCP was associated with a higher risk of a multiplicative increase in the odds for 1-year mortality (OR 2.86; 95% CI, 1.16-7.07). In addition, readmission related to cholangitis, higher ASA score, median CCI score, altered mental status, and intensive care unit stay during the index hospitalizawww.giejournal.org

tion all were associated with a higher risk of 1-year mortality (Table 6). After adjustment for factors associated with 30-day readmission, 30-day readmission was no longer significantly associated with a higher risk of 1-year mortality (OR 2.15; 95% CI, 0.77-6.02). Every 1-point increase in CCI score (OR 1.33; 95% CI, 1.05-1.69) was independently associated with 1-year mortality (Table 7).

DISCUSSION Quality improvement efforts need to be concentrated on preventing readmissions because these have significant Volume 78, No. 1 : 2013 GASTROINTESTINAL ENDOSCOPY 87

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TABLE 6. Demographic and clinical characteristics of patients with 1-year mortality No long-term death within 1 y n ⴝ 143 (85.1%)

Long-term death within 1 y n ⴝ 25 (14.9%)

P value

OR (95% CI)

61 (52-72)

64 (44-78)

.65

1.03 (0.91-1.17)

80 (55.9)

14 (56.0)

.99

1.00 (0.43-2.36)

26.3 (23.3-28.9)

23.2 (21.5-29.3)

.23

0.75 (0.47-1.20)

Smoking, no. (%)

38 (26.6)

6 (24.0)

.88

0.92 (0.31-2.69)

Primary sclerosing cholangitis, no. (%)

38 (26.6)

7 (28.0)

.95

0.97 (0.38-2.49)

Cirrhosis, no. (%)

23 (16.1)

6 (24)

.39

0.82 (0.57-1.43)

Child-Pugh-Turcotte score in cirrhotic patients, mean (SD)§

7.1 (2.4)

7.9 (2.1)

.46

1.12 (0.83-1.50)

Systemic inflammatory response syndrome, no. (%)

25 (17.5)

7 (28.0)

.26

1.91 (0.72-5.09)

0

32 (22.4)

1 (4.0)

1

32 (22.4)

4 (16.0)

Variable Age, median (IQR), y* Male, no. (%) 2

BMI, median (IQR), kg/m †

Charlson Comorbidity Index, no. (%)

2

20 (14.0)

3 (12.0)

3

36 (25.2)

5 (20.0)

ⱖ4

22 (15.4)

12 (48.0)

2 (1-3)

3 (2-6)

1

1 (0.7)

1 (4.0)

2

2 (1.4)

0 (0)

3

93 (65.0)

8 (32.0)

4

45 (31.5)

13 (52.0)

5

1 (0.7)

3 (12.0)

3 (3-4)

4 (3-4)

.015

2.47 (1.19-5.12)

Charlson Comorbidity Index, median (IQR)

.007

⬍.001

1.45 (1.18-1.78)

ASA score, no. (%)

ASA score, median (IQR) Altered mental status, no. (%)

.001

4 (2.8)

4 (16.0)

.018

6.57 (1.53-28.30)

32 (22.4)

4 (16.0)

.79

0.76 (0.24-2.40)

ⱕ48 h

106 (74.1)

21 (84.0)

.29

0.55 (0.18-1.69)

⬎48 h

37 (25.9)

4 (16.0)

4.5 (2.4-8.2)

4.6 (3.2-8.3)

⬎.99

1.00 (0.91-1.09)

Gram positive

10 (7.0)

1 (4.0)

.94

Gram negative

27 (18.9)

4 (16.0)

2 (1.4)

0 (0)

1.0

Anti-platelet medications at admission, no. (%) Door-to-ERCP time, no. (%)

Before-ERCP bilirubin level, median (IQR) Positive blood cultures, no. (%)

After-ERCP bleeding, no. (%) After-ERCP pancreatitis, no. (%)

3 (2.1)

0 (0)

1.0

Median length of stay (IQR)‡

2.3 (2-2.8)

2.6 (2-3.2)

.21

1.37 (0.84-2.24)

Prolonged length of index hospital stay (⬎10 d, 90th percentile), no. (%)

18 (12.6)

7 (28)

.14

2.21 (0.83-5.91)

Readmission within 30 d, no. (%)

27 (18.9)

10 (40.0)

.022

2.86 (1.16-7.07)

Cholangitis-related readmission within 1 mo, no. (%)

9 (6.3)

5 (20.0)

.038

3.72 (1.13-12.23)

ICU stay during index hospitalization, no. (%)

5 (3.5)

5 (20%)

.01

6.23 (1.67-23.28)

OR, Odds ratio; CI, confidence interval; IQR, interquartile range; BMI, body mass index; ASA, American Society of Anesthesiologists Physical Status Classification System; ICU, intensive care unit. *OR reported for every 5-y increase in age. †OR reported for every 1 kg/m2 increase in BMI. ‡OR reported for every 1 d for length of stay. §Data not available for all patients.

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Navaneethan et al

Cholangitis and readmissions

negative clinical and economic consequences. In patients admitted for acute cholangitis, the reasons for readmissions remain largely unknown. We observed that among 172 hospitalizations for acute cholangitis, 1 in 5 patients were readmitted within 30 days of discharge, and readmissions were related to both recurrence of cholangitis and comorbidities. We observed that patients with acute cholangitis who had a delayed ERCP (door-to-ERCP time ⬎48 hours) had a ⬎2-fold increased risk for readmission. It should be pointed out that the associated conditions that led to delays in ERCP, such as hemodynamic instability or unrecognized cholangitis, and not necessarily delayed biliary drainage per se, may be contributing to the higher readmission rate in these patients. We also observed that patients with delayed ERCP had higher serum bilirubin levels. Although it could not be determined with certainty, it is possible that these patients became sicker with time. Higher serum bilirubin levels have been associated with worse clinical outcomes in patients with acute cholangitis.19,20 To our knowledge, no previous study has addressed the issue of timing of ERCP and risk of readmissions. We took 48 hours as the cut-off for delayed ERCP because it had the best predictive value on univariate analysis. We also believe that early ERCP, within 24 hours, may not be possible in all cases because patients often need resuscitation and optimization of hemodynamic status before ERCP. Although this is the first study assessing the association of delayed ERCP with risk of early readmission, prior studies have suggested that delayed ERCP can have negative consequences in patients with acute cholangitis.8,14,21 For example, a previous study showed that delayed ERCP (⬎24 hours of admission) is associated with longer length of hospital stay.21 Two subsequent studies suggested that delayed ERCP (⬎3 days) is associated with worse clinical

outcomes.8,14 Although there is no evidence-based support for the timing of biliary drainage, the Tokyo guidelines, based on expert opinion, recommend biliary drainage in moderate to severe cholangitis as soon as possible.22 In our patient cohort, development of any after-ERCP adverse events was associated with 30-day readmission. Interestingly, readmissions in this group of patients were not because of the adverse events per se, but were for other reasons, the most common of which was recurrence of cholangitis and comorbidities. In a previous study, adverse events after ERCP were shown to be related to comorbidities.23 It is possible that the same factors that increase the risk of adverse events may influence early readmission rates. It also may be suggestive of delayed recovery after an adverse event in patients with comorbidities undergoing emergent ERCP for acute cholangitis. This information can be used to modify discharge policies for patients with specific comorbidities and help plan closer outpatient follow-up of those at high risk for readmission. Our study showed that patients who are admitted for acute cholangitis in the setting of cancer, PSC, and other etiologies not related to stones are at increased risk for readmission. Patients with PSC have underlying liver disease, which may increase the risk of readmission. However, we did not see any relationship between cirrhosis or its severity and readmission risk. Additionally, the cholangitisrelated readmissions in our cohort of patients with PSC were not related to inadequate drainage of intrahepatic bile ducts, which could increase the readmission risk. The presence of comorbidities based on CCI scores can be a predictor of readmission in other medical conditions or procedures such as chronic obstructive pulmonary disease, congestive heart failure, or coronary artery bypass surgery.12,13,24 In our study, although the median CCI score was higher in patients who were readmitted within 30 days, after adjustment for other covariates, CCI score was no longer associated with higher risk of readmission. We did observe that patients with comorbidities were more likely to die at 1 year. It is reasonable to attribute the higher risk of 1-year mortality in patients with more comorbidities to a composite effect of all comorbidity-related admissions. This study has several limitations, including its retrospective design. We obtained information only on readmissions to hospitals within our system. There is a possibility that some patients could have been admitted to other hospitals outside of our system. However, in practice, patients admitted to outside hospitals are transferred back to our hospital, and hence we believe that we have captured nearly all readmissions. In addition, all confounders may not be completely adjusted for by multivariate modeling. In this study, only 2 patients had failed ERCP. The effect of failed ERCP on the risk of readmission in patients with acute cholangitis warrants further investigations. Despite these limitations, the current study has identified

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Volume 78, No. 1 : 2013 GASTROINTESTINAL ENDOSCOPY 89

TABLE 7. Independent predictors of 1-year mortality: results of the multivariate analyses

OR (95% CI)

P value

All-cause 30-d readmission

2.15 (0.77-6.02)

.14

ASA score ⬎3

1.78 (0.61-5.17)

.29

Charlson Comorbidity Index (per 1 unit)

1.33 (1.05-1.69)

.01

Cholangitis-related readmission within 30 d

2.09 (0.46-9.47)

.34

ICU stay during index hospitalization

4.41 (0.78-24.8)

.09

Variable

OR, Odds ratio; CI, confidence interval; ASA, American Society of Anesthesiologists Physical Status Classification System; ICU, intensive care unit.

Cholangitis and readmissions

potential targets for intervention in order to decrease readmission rates in those with acute cholangitis. To conclude, delays in performing ERCP during the index admission and development of after-ERCP adverse events appears to be associated with 30-day readmissions. Further studies are needed to confirm these findings and help develop strategies to decrease readmission rates in patients with acute cholangitis.

Navaneethan et al

1. Ashton C, Kuykendall D, Johnson M, et al. The association between the quality of inpatient care and early readmission. Ann Intern Med 1995; 122:415-21. 2. Balla U, Malnick S, Schattner A. Early readmissions to the department of medicine as a screening tool for monitoring quality of care problems. Medicine 2008;87:294-300. 3. Benbassat J, Taragin M. Hospital readmissions as a measure of quality of health care: advantages and limitations. Arch Intern Med 2000;160: 1074-81. 4. Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicare fee-for-service program. N Engl J Med 2009;360:1418-28. 5. US Department of Health & Human Services; Centers for Medicare & Medicaid Services. Medicare fact sheet: quality measures for reporting in fiscal year 2009 for 2010 update. Baltimore (MD): US Dept of Health & Human Services; 2008. 6. Epstein AM. Paying for performance in the United States and abroad. N Engl J Med 2006;355:406-8. 7. Straube B, Blum JD. The policy on paying for treating hospital-acquired conditions: CMS officials respond. Health Aff (Millwood) 2009;28: 1494-7. 8. Boender J, Nix GA, de Ridder MA, et al. Endoscopic sphincterotomy and biliary drainage in patients with cholangitis due to common bile duct stones. Am J Gastroenterol 1995;90:233-8. 9. Leung JW, Chung SC, Sung JJ, et al. Urgent endoscopic drainage for acute suppurative cholangitis. Lancet 1989;1:1307-9.

10. Hui CK, Liu CL, Lai KC, et al. Outcome of emergency ERCP for acute cholangitis in patients 90 years of age and older. Aliment Pharmacol Ther 2004;19:1153-8. 11. Jasti H, Mortensen E, Obrosky D, et al. Causes and risk factors for rehospitalization of patients hospitalized with community-acquired pneumonia. Clin Infect Dis 2008;46:550-6. 12. Almagro P, Cabrera FJ, Diez J, et al; Working Group on COPD of the Spanish Society of Internal Medicine. Comorbidities and short-term prognosis in patients hospitalized for acute exacerbation of COPD. The ESMI study. Chest. Epub 2012 Apr 5. 13. Roberts CM, Lowe D, Bucknall CE, et al. Clinical audit indicators of outcome following admission to hospital with acute exacerbation of chronic obstructive pulmonary disease. Thorax 2002;57:137-41. 14. Khashab MA, Tariq A, Tariq U, et al. Delayed and unsuccessful endoscopic retrograde cholangiopancreatography are associated with worse outcomes in patients with acute cholangitis. Clin Gastroenterol Hepatol 2012;10:1157-61. 15. Bodmer M, Brauchli YB, Krähenbühl S, et al. Statin use and risk of gallstone disease followed by cholecystectomy. JAMA 2009;302:2001-7. 16. Thomsen RW, Riis A, Kornum JB, et al. Preadmission use of statins and outcomes after hospitalization with pneumonia: population-based cohort study of 29,900 patients. Arch Intern Med 2008;168:2081-7. 17. Gupta R, Plantinga LC, Fink NE, et al. Statin use and sepsis events in patients with chronic kidney disease. JAMA 2007;297:1455-64. 18. Cotton PB, Eisen GM, Aabakken L, et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc 2010;71:446-54. 19. Salek J, Livote E, Sideridis K, et al. Analysis of risk factors predictive of early mortality and urgent ERCP in acute cholangitis. J Clin Gastroenterol 2009;43:171-5. 20. Hui CK, Lai KC, Yuen MF, et al. Acute cholangitis—predictive factors for emergency ERCP. Aliment Pharmacol Ther 2001;15:1633-7. 21. Chak A, Cooper GS, Lloyd LE, et al. Effectiveness of ERCP in cholangitis: a community-based study. Gastrointest Endosc 2000;52:484-9. 22. Miura F, Takada T, Kawarada Y, et al. Flowcharts for the diagnosis and treatment of acute cholangitis and cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg 2007;14:27-34. 23. Alkhatib AA, Hilden K, Adler DG. Comorbidities, sphincterotomy, and balloon dilation predict post-ERCP adverse events in PSC patients: operator experience is protective. Dig Dis Sci 2011;56:3685-8. 24. Hannan EL, Zhong Y, Lahey SJ, et al. 30-day readmissions after coronary artery bypass graft surgery in New York State. JACC Cardiovasc Interv 2011;4:569-76.

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ACKNOWLEDGMENT We would like to thank Jeffrey Hammel for help with statistical analysis. REFERENCES