Clinical Gastroenterology and Hepatology 2014;12:2063–2070

Increased Incidence of Critical Illness Among Patients With Inflammatory Bowel Disease: A Population-Based Study Ruth Ann Marrie,*,‡ Allan Garland,*,‡ Christine A. Peschken,*,‡ Carol A. Hitchon,* Hui Chen,§ Randall Fransoo,‡,§ and Charles N. Bernstein*,k *Department of Internal Medicine, ‡Department of Community Health Sciences, kInflammatory Bowel Disease Clinical and Research Centre, University of Manitoba, Winnipeg, Canada; and §Manitoba Centre for Health Policy, Winnipeg, Canada BACKGROUND & AIMS:

Little is known about how often, and for what reasons, patients with inflammatory bowel diseases (IBD) are admitted to the intensive care unit (ICU). We compared incidences of ICU admission, characteristics of critical illness, and mortality after ICU admission between patients with IBD and the general population.

METHODS:

We identified all persons with IBD in the province of Manitoba using a validated administrative definition of IBD for the period from 1984 to 2010. Cases were considered incident for IBD if their first health system contact for IBD was in 1989 or later. We identified a population-based control group, matched by age, sex, and geography (based on postal code). Case and control cohorts were linked to the Manitoba ICU database. We compared outcomes between groups using age- and sex-standardized rates, Cox proportional hazards models, and logistic regression models, adjusting for age, sex, comorbidity, and socioeconomic status.

RESULTS:

There were 8224 prevalent and 4580 incident cases of IBD. After adjustment, the risk for ICU admission was higher for patients with IBD than controls (hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.58–2.02). The risk of ICU admission was higher for patients with Crohn’s disease (HR, 2.31; 95% CI, 1.95–2.75) than ulcerative colitis (HR, 1.37; 95% CI, 1.13–1.65). From 2000 through 2010, age- and sex-standardized annual incidence rates for ICU admission in the prevalent IBD cohort ranged from 0.55% to 1.12%. Compared with controls admitted to ICUs, 1 year after ICU admission, mortality was 32% among patients with IBD.

CONCLUSIONS:

Patients with IBD have a higher risk for admission to the ICU than the general population, and increased mortality 1 year after admission. These findings underscore the potential severity of IBD.

Keywords: Administrative Data; Critical Illness; Incidence; Inflammatory Bowel Disease.

ealth care use in inflammatory bowel disease (IBD) is high, with more than 20% of the population being hospitalized annually.1 Care of critically ill patients in intensive care units (ICUs) is an important component of hospital care, consuming a disproportionate share of medical costs in industrialized countries.2,3 In IBD, an impaired intestinal barrier, malnutrition, an increased risk of thromboembolic disease,4,5 and the use of immune therapies that increase infection risk6 could increase the risk of critical illness, but the incidence of ICU admission is unknown. Which persons with IBD are at greatest risk of critical illness, and their outcomes after critical illness, also is unknown. We aimed to evaluate the incidence of ICU admission in the IBD population and matched controls from the general population using a large population-based data

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set. We also sought to describe the characteristics of IBD patients admitted to ICUs and subsequent mortality.

Methods Administrative Data We used population-based, anonymized, administrative data, from April 1, 1984, to March 31, 2010, from Abbreviations used in this paper: CD, Crohn’s disease; CI, confidence interval; HR, hazard ratio; IBD, inflammatory bowel disease; ICD, International Classification of Disease; ICU, intensive care unit; IRR, incidence rate ratio; OR, odds ratio; SES, socioeconomic status; UC, ulcerative colitis. © 2014 by the AGA Institute 1542-3565/$36.00 http://dx.doi.org/10.1016/j.cgh.2014.03.033

2064 Marrie et al

Manitoba, a Canadian province with a population of 1.2 million. The data were accessed at the Manitoba Centre for Health Policy. Manitoba has a universal health insurance plan that provides health care services to 98% of Manitobans.7 Every individual has a personal health identification number through which all hospital, physician, and prescription claims are captured electronically at the time of service. A population registry captures when an individual moves into or out of Manitoba, or dies.

Inflammatory Bowel Disease Cohort We identified the IBD population using a validated case definition.8 Manitobans who resided in the province for 2 or more years were identified as having IBD if they had 5 or more physician visits or hospitalizations with International Classification of Disease (ICD)-9-CM/ICD10 codes 555.xx/K50 (Crohn’s disease [CD]) or 556.xx/ K51 (ulcerative colitis [UC]) recorded as a diagnosis.8 People who resided in the province for fewer than 2 years were identified as having IBD if they had 3 or more separate contacts for these codes. Cases of IBD were classified further as CD or UC as described previously.8 All cases of IBD identified in this manner were included in our prevalent cohorts unless otherwise specified. The date of diagnosis (index date) was the date of the first health claim for either CD or UC. To identify incident cases we identified persons whose first claims for IBD occurred in 1989 or later, so that they had 5 or more preceding years without any IBD-related claims.

General Population Cohort We identified a matched general population control cohort, matched on sex, year of birth, and region of residence based on their 6-digit postal code (if a full postal code match was not possible we used the first 3 digits). We obtained up to 5 controls per case. We excluded individuals with any diagnostic codes for IBD. As part of a larger study we explored the incidence of ICU admission compared with controls among persons with demyelinating disease, rheumatoid arthritis, and related disorders, and therefore persons with codes for those diagnoses also were excluded (Supplementary Table 1). General population controls were assigned the same index dates as their matched cases, and were required to be alive on the index date.

Intensive Care Unit Database Since June 1999, the Winnipeg Regional Health Authority’s clinical ICU database has captured all admissions to adult ICUs in Winnipeg.9 These ICUs capture 93% of all high-intensity adult ICU admissions in Manitoba. The clinical ICU database has been linked to administrative data using the personal health identification number.

Clinical Gastroenterology and Hepatology Vol. 12, No. 12

The clinical database includes more than 60,000 records with prospectively collected clinical information on every admission, collected by trained abstractors using standardized data definitions and abstraction methods. Information captured includes the APACHE II acute physiology score,10 the Glasgow Coma Scale Score,11 the use of life support measures within the initial 2 days of ICU admission (mechanical ventilation, intravenous vasoactive agents, renal dialysis), length of stay, and up to 6 reasons for ICU admission.

Incidence of Critical Illness We estimated the incidence of critical illness, as measured by ICU admission, separately in persons with prevalent and incident IBD. We used data regarding special care units coded in hospital discharge abstracts.9 We considered ICU care as that provided in any of the 12 adult ICUs in Manitoba equipped to provide comprehensive critical care to patients.12 We estimated the incidence rate of ICU admission among prevalent IBD cohorts during the 10-year period from January 2000 to October 2009. Each year a new matched cohort was extracted from the general population as described earlier. Also, we estimated the 10-year cumulative incidence of ICU admission for this period. Results were age- and sex-standardized to the 2007 Canadian population. We compared the incidence of ICU admission between the IBD and matched cohorts using incidence rate ratios (IRRs) and calculated 95% confidence intervals (CIs) by bootstrapping. We used survival analysis to estimate the incidence of ICU admission among the cohort of incident cases of IBD. By using Kaplan–Meier analysis and log-rank tests we compared the time from the index date to the first ICU admission among the IBD and general population cohorts. Persons not admitted to the ICU were censored as of death, migration out of Manitoba, or the end of the study period (March 31, 2010), whichever came first. For multivariable analysis we used a Cox proportional hazards model in which the outcome was the first ICU admission and zero time was the index date. Model covariates were age at diagnosis, sex, socioeconomic status (SES), and comorbidity. By linking the postal code of residence to census data we obtained median household income, and this was divided into quintiles, separately for rural and urban residences. Based on hospital discharge ICD-9-CM/ICD-10 codes we classified comorbidity status using a modified version of the Charlson Comorbidity Index. The Charlson Comorbidity Index is a weighted summary index of 17 chronic conditions, and predicts health outcomes and use in patients admitted to ICUs.13 We collapsed the categories of diabetes with and without chronic complications because this distinction was inaccurate in Manitoba before 2006,14 and the human immunodeficiency virus/acquired immune deficiency syndrome category was not included owing to small numbers. We used a 5-year look-back period

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because this improves the prediction of health care use outcomes associated with comorbidity.15 For the regression analysis we used time-dependent covariates updated at 5-year intervals to account for possible secular changes in SES and comorbidity.

Characteristics of Critical Illness in Incident Cohorts We reviewed clinical data for ICU admissions in our incident cohorts from 2000 through 2010. Based on the admission diagnoses, the primary reason for ICU admission was categorized independently by 2 reviewers (C.N.B., R.A.M.) as follows: (1) infection, (2) exacerbation or complications secondary to the underlying IBD, and (3) other acute serious illness unrelated to IBD.16 The following diagnoses were classified as complications: pulmonary embolism, sepsis of gastrointestinal origin, gastrointestinal bleeding, and bowel perforation. Disagreements were resolved by consensus. For categoric variables we reported frequency (percentage) whereas we reported means (SD) or medians (interquartile range) for continuous variables. We compared the characteristics of critical illness between the IBD and general populations using chi-square tests for categoric variables and analysis of variance or Kruskal–Wallis tests for continuous variables. By using multivariable logistic regression we initially compared

the risk of being admitted for infection for the 2 populations, adjusting for age at ICU admission, sex, SES, comorbidity, year of ICU admission, and disease duration. Second, we included the use of corticosteroids and immunomodulatory and immunosuppressive therapies (Supplementary Table 2) in the year before admission (yes vs no) in the model. We report odds ratios (ORs) and 95% CIs (shown in parentheses) for the observed associations.

Mortality For the first ICU admission among persons with IBD and their controls, we estimated age- and sexstandardized mortality rates in the ICU, in the hospital, at 30 days after ICU admission, and at 1 year after ICU admission. Because of small numbers in the incident cohort we limited this analysis to the prevalent cohorts. The Vital Statistics Death Database captures information from all provincial and territorial vital statistics registries for all deaths in Canada.17 By using ICD coding we categorized underlying causes of death as of December 31, 2009, as resulting from infection, IBD, or other illness. This study was approved by the University of Manitoba Health Research Ethics Board and the Manitoba Health Information Privacy Committee. Statistical analyses were conducted using SAS (version 9.2; SAS Institute, Inc, Cary NC).

Table 1. Characteristics of Incident IBD Cohorts and General Population Controls at the Index Date

Characteristic Female, n (%) Mean age at diagnosis, y (SD) Urban region of residence, n (%) SES, n (%) Rural 1 (lowest rural) Rural 2 Rural 3 Rural 4 Rural 5 (highest rural) Urban 1 (lowest urban) Urban 2 Urban 3 Urban 4 Urban 5 (highest urban) Not calculatedb Modified Charlson index, n (%) 0 1 >1 to 3 >3 to 5 >5

General populationa (n ¼ 25,034)

IBD (n ¼ 4580)

CD (n ¼ 2241)

UC (n ¼ 2339)

13,286 (53.1) 37.5 (17.4) 16,637 (66.5)

2459 (54.3) 38.5 (18.1) 3009 (65.6)

1275 (56.9) 35.9 (17.5) 1496 (66.8)

1184 (50.6) 40.9 (18.3) 1513 (64.7)

1083 1700 1689 1842 1961 2887 3402 3603 3507 3040 319

(4.3) (6.8) (6.7) (7.3) (7.8) (11.5) (13.6) (14.4) (14.0) (12.1) (1.3)

204 317 299 366 364 448 625 660 665 590 42

(4.45) (6.92) (6.52) (8.06) (7.99) (9.78) (13.6) (14.4) (14.5) (12.9) (0.92)

24,387 184 350 45 67

(97.4) (0.74) (1.4) (0.18) (0.27)

4380 74 108 11 7

(95.6) (1.6) (2.4) (0.24) (0.15)

86 154 148 183 161 232 337 333 328 257 22

(3.8) (6.8) (6.6) (8.2) (7.2) (10.3) (15.0) (14.8) (14.6) (11.5) (0.98)

118 163 151 183 203 216 288 327 337 333 20

P valuea .45 .98 .33 .03

(5.0) (7.0) (6.4) (7.8) (8.7) (9.2) (12.3) (14.0) (14.4) (14.2) (0.85) 3

HR

95% CI

1.0 1.81

1.60–2.04

1.0 0.51

0.47–0.55

1.0 4.69 13.3 1.22 0.89 0.80 1.19 0.97 1.88 1.72 1.46 1.27 1.0 0.64 1.0 1.47 1.68 1.12

4.12–5.33 11.7–15.1 1.00–1.49 0.73–1.08 0.66–0.97 0.99–1.43 0.79–1.20 1.60–2.19 1.47–2.01 1.24–1.70 1.07–1.50 0.46–0.88

1.25–1.72 1.49–1.90 0.88–1.42

by those aged 40 to 59 years (HR 1.69; 95% CI, 1.38–2.07); it was lowest among persons aged 60 years and older (HR 1.42; 95% CI, 1.17–1.73).

Intensive Care Unit Admission in Prevalent Cohorts From 1984 to 2010, we identified 8224 persons with IBD. The crude 10-year average annual incidence of ICU admission was 0.74% (95% CI, 0.67%–0.81%) for IBD. It was 0.80% (95% CI, 0.70%–0.90%) in CD and 0.67% (95% CI, 0.58%–0.77%) in UC. From 2000 through 2010, the age- and sex-standardized annual incidence of ICU admission ranged from 0.55% to 1.12% in IBD, and from 0.35% to 0.59% in the matched general population controls. In CD, the annual incidence varied from 0.58% to 1.39%, whereas the incidence in UC tended to be lower, ranging from 0.42% to 0.82% (Supplementary Figure 1). As compared with controls, the standardized incidence of ICU admission was consistently higher in the IBD cohorts. In 2009, for example, the IRR for IBD was 1.81 (95% CI, 1.22–2.46). The crude 10-year cumulative incidence of ICU admission was 5.88% (95% CI, 5.30%–6.47%) in IBD, and was 3.45% (95% CI, 3.34%–3.56%) in the control cohort. After age- and sex-standardization, the cumulative incidence of ICU admission was 1.5-fold higher in IBD overall than in the general population (IRR, 1.52; 95% CI, 1.36–1.68). In CD, the cumulative incidence was 6.31% (95% CI, 5.46%–7.15%) and it was 5.44% (95% CI, 4.63%–6.25%) in UC. When compared with the general population, the cumulative incidence was relatively higher in CD (IRR, 1.72; 95% CI, 1.48–2.01) than in UC (1.28; 95% CI, 1.10–1.46).

Characteristics of Incident Intensive Care Unit Admissions: 2000 to 2010 At the time of the first ICU admission the IBD population was younger and had less comorbidity than controls, but similar use of mechanical ventilation, vasoactive drugs, and renal replacement therapy within the first 2 days of admission (Table 3). Patients with CD were younger at admission, and had higher APACHE II acute physiology scores than those with UC or controls, and were more likely to require mechanical ventilation. Patients with CD also had longer hospital stays than those with UC or controls. Findings were similar when all ICU admissions in 2000 to 2010 were considered rather than just incident ICU admissions (data not shown). The most common reason for admission in IBD was other acute illness unrelated to the underlying disease, followed by disease-related reasons such as infection (Table 4). In IBD, the most common other reasons for admission were diseases of the circulatory system (63.3%), and diseases of the respiratory system (11.7%). In controls, other acute illness was also the most

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Table 3. Characteristics of Incident IBD and General Population Cohorts at the First ICU Admission in the Winnipeg Regional Health Authority in the Interval From 2000 to 2010

Characteristic Female, n (%) Mean age at admission, y (SD) Disease duration, y, mean (SD) ICU length of stay, d, mean (SD) Hospital length of stay, d, mean (SD) APACHE II acute physiology score, mean (SD) Glasgow Coma Scale Score, median (IQR) Mechanical ventilation, n (%) Vasoactive agents, n (%) Dialysis, n (%) Urban region of residence, n (%) SES, n (%) Rural 1 (lowest rural) Rural 2 Rural 3 Rural 4 Rural 5 (highest rural) Urban 1 (lowest urban) Urban 2 Urban 3 Urban 4 Urban 5 (highest urban) Not calculatedc Modified Charlson Index, n (%) 0 1 >1 to 3 >3

General population (n ¼ 473) 91 (46.9) 64.7 (14.6) 4.6 (7.2) 19.3 (30.4) 10.6 (7.1) 15 (15–15) 194 (41.0) 164 (34.7) 12 (2.5) 349 (73.8)

IBD (n ¼ 194) 91 58.8 7.73 4.75 27.7 10.9 15 91 74 7 144

(46.9) (17.2) (5.0) (7.13) (43.4) (7.06) (15–15) (46.9) (38.1) (3.61) (74.2)

14 17 28 34 27 80 75 75 64 53 6

(2.9) (3.6) (5.9) (7.2) (5.7) (16.9) (15.9) (15.9) (13.5) (11.2) (1.3)

12 (6.2)

107 133 163 70

(22.6) (28.1) (34.5) (14.8)

82 54 43 15

CD (n ¼ 109) 63 54.5 8.0 5.1 32.0 12.0 15 59 37

(5.7) (7.2) (5.1) (20.6) (16.5) (10.8) (13.4) (12.4)

28 64.2 7.3 4.2 22.1 9.6 15 32 37

(32.9) (14.6) (5.3) (6.0) (25.0) (6.2) (15–15) (37.6) (43.5)

b

b

81 (74.3)

63 (74.1)

b

8 (9.4)

b

b

b

11 14 10 40 32 21 26 24

(57.8) (17.9) (4.8) (7.9) (53.0) (7.5) (15–15) (54.1) (33.9)

UC (n ¼ 85)

7 8 7 23 18 13 15 11

b

(6.4) (7.3) (6.4) (21.1) (16.5) (11.9) (13.8) (10.1) b

P valuea .05 1 to 3 >3 to 5 >5

General population controls (n ¼ 794) 309 62.4 6.75 579

(38.9) (15.4) (4.8) (72.9)

IBD (n ¼ 293)

CD (n ¼ 164)

UC (n ¼ 129)

137 57.6 6.00 211

96 54.2 6.42 117

41 61.9 5.46 94

(46.7) (17.6) (5.0) (72.0)

31 (3.9)

17 (5.8)

b

b

45 55 47 133 130 127 103 78

(5.7) (6.9) (5.9) (16.8) (16.4) (16.0) (13.0) (9.8)

20 17 13 40 57 43 37 32

b

(6.8) (5.8) (4.4) (13.6) (19.4) (14.7) (12.6) (10.9)

(58.5) (18.0) (5.0) (71.3)

6 (3.6)

b

(7.9) (7.3) (4.9) (18.9) (17.7) (15.9) (12.2) (8.5)

.020

.76 .77

10 (7.7)

b

13 12 8 31 29 26 20 14

(31.8) (16.1) (5.0) (72.9)

P valuea

b b

13 (10.1) b

22 24 15 12 21

b

(17.0) (18.6) (11.6) (9.3) (16.3) b

5 of the IBD cohort, and shown as n (%) of other admissions. b Suppressed owing to small size of patient group and to protect patient confidentiality.

Supplementary Table 5. Reasons for First ICU Admission Among Cohorts of Patients With IBD and Matched Controls From the General Population Admitted in the Period From 2000 to 2010, Stratified by Age Group

Reason Age

Increased incidence of critical illness among patients with inflammatory bowel disease: a population-based study.

Little is known about how often, and for what reasons, patients with inflammatory bowel diseases (IBD) are admitted to the intensive care unit (ICU). ...
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