Internal and Emergency Medicine

https://doi.org/10.1007/s11739-018-1889-8

IM - ORIGINAL

Incidence, features, in‑hospital outcomes and predictors of in‑hospital

mortality associated with toxic megacolon hospitalizations
in the United States
Rajkumar Doshi1 · Jiten Desai2 · Yash Shah3 · Dean Decter4 · Shreyans Doshi5

Received: 5 March 2018 / Accepted: 5 June 2018

© SIMI 2018

Abstract
Toxic megacolon (TM) is a potentially fatal condition characterized by non-obstructive colonic dilatation and systemic tox-
icity. It is most commonly caused by inflammatory bowel disease (IBD). Limited data for TM are available demonstrating
incidence, in-hospital outcomes and predictors of mortality. We sought to investigate incidence, characteristics, mortality
and predictors of mortality associated with it. Data were obtained from the Healthcare Cost and Utilization Project (HCUP)’s
Nationwide Inpatient Sample (NIS) database from January 2010 through December 2014. An analysis was performed on
SAS 9.4 (SAS Institute Inc., Cary, NC). Patients below 18 years were excluded. A mixed-effects logistic regression model
was developed to analyze predictors of mortality. Thus, 8139 (weighted) cases of TM were diagnosed between 2010 and
2014. TM is more prevalent in women (56.4%) than in men (43.6%), with a mean age of onset at 62.4 years, affecting whites
(79.7%) more than non-whites. The most common reason for hospital admission included IBD (51.6%) followed by septice-
mia (10.2%) and intestinal infections (4.1%). Mean length of stay was 9.5 days and overall in-hospital mortality was 7.9%.
Other complications included surgical resection of the large intestine (11.5%) and bowel obstruction (10.9%). Higher age,
neurological disorder, coagulopathy, chronic pulmonary disease, heart failure, and renal failure were associated with greater
risk of in-hospital mortality. TM is a serious condition with high in-hospital mortality. Management of TM requires an inter-
disciplinary team approach with close monitoring. Patients with positive predictors in our study require special attention to
prevent excessive in-hospital mortality.

Keywords  Epidemiology · Inflammatory bowel disease · In-hospital outcomes · Predictors of mortality · Toxic megacolon

Electronic supplementary material  The online version of this Introduction

article (https​://doi.org/10.1007/s1173​9-018-1889-8) contains
supplementary material, which is available to authorized users. Toxic megacolon (TM) is a potentially fatal condition
defined as an acute colonic dilatation, greater than 6 cm in
* Rajkumar Doshi
raj20490@gmail.com diameter, of the transverse colon and loss of haustration on
radiologic examination in a patient experiencing a severe
1
Department of Internal Medicine, Renown Regional Medical attack of colitis [1, 2]. Although most commonly associ-
Center, School of Medicine, University of Nevada, 1155 Mill
ated as a complication of inflammatory bowel disease (IBD),
St, W‑11, Reno, NV 89502, USA
2
TM may also occur with infectious colitis, ischemic colitis,
Department of Internal Medicine, Nassau University Medical diverticulitis, and obstructive colon cancer. The mechanism
Center, East Meadow, NY, USA
3
involved in the development of TM remains unclear; how-
Department of Internal Medicine, Icahn School of Medicine ever, changes in colonic response to chemical mediators like
at Mount Sinai, James J. Peters VA Medical Center, Bronx,
NY, USA vasoactive intestinal polypeptides, substance P, leukotrienes,
4 and nitric oxide result in defective smooth muscle contrac-
Department of Cardiology, North Shore University Hospital,
Northwell Health, Manhasset, NY, USA tion and lowered basal pressure of the colonic lumen, which
5 may play an important role in the development of TM [3–6].
Department of Internal Medicine, HCA GME Consortium’s
Internal Medicine Program, University of Central Florida Recently, Clostridium difficile (C. diff) has been associated
College of Medicine, Gainesville, FL, USA with TM [7, 8]. TM has a reported lifetime incidence of 1

13
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to 5% in patients with IBD [9–11], and nearly half the cases
of IBD with TM develop this complication within the first
3 months of their diagnosis [12]. Precipitating factors for
TM include medications, which reduce the motility of the
gut, such as narcotics and anticholinergic medications [13].
Additional factors may include: bacterial infections, elec-
trolyte derangements, such as hypokalemia, and diagnostic
procedures like barium enema and colonoscopy [13].
Systemic consequences of TM may include abnormal
renal function, electrolyte abnormality and hypoalbumine-
mia. In TM the colon loses its capacity to reabsorb salt and
water. In addition, the rate of potassium excretion into the
lumen may be markedly increased due to inflammatory diar-
rhea and steroid use leading to hypokalemia, contraction
metabolic alkalosis, and elevated serum levels of blood urea
nitrogen and creatinine, reflecting volume depletion [14].
Hypoalbuminemia develops eventually in approximately
75% of cases due to protein loss and decreased hepatic syn-
thesis due to chronic inflammation and malnutrition.
Prior to 1976, the mortality rate for TM was 27% in medi-
cally treated cases, however, as low as 19% in surgically
treated cases, which dropped dramatically to a mere 0–2% in
patients with IBD [11, 15, 16]. Early recognition and inten-
sive management of this condition may have contributed
to the reduced incidence and mortality of TM in IBD [11,
15, 16]. Patients with fulminant infection require surgical
intervention in up to 20% of cases, carrying mortality rates
between 35 and 80% [17–19]. Female gender, age more than
40 years, hypoalbuminemia, high blood urea nitrogen, and
low serum carbon dioxide levels are known to be associated
with high mortality in a previous study [10]. Colonic perfo-
ration is the most important predictor of mortality; 44% of
patients underwent emergent colectomy after perforation,
while only 2% of patients without perforation needed the
procedure [10].
The aim of this article is to observe demographics and
baseline characteristics for hospitalizations with TM, the fre-
quency of comorbidities, the primary cause of admission,
in-hospital outcomes, various infections, and predictors
of in-hospital mortality associated with TM. Additionally,
recent trends of hospitalization, in-hospital mortality, cost
of hospitalization, and length of stay were examined during
the study period.
Methods
Data source and study design
The National Inpatient Sample (NIS) database is publi-
cally available, all-payer database [20]. The NIS has been
described in earlier studies [21, 22]. Briefly, NIS con-
tains discharge data from a 20% stratified sample of U.S.
13
Internal and Emergency Medicine
Hospitals and is a part of the healthcare cost and utilization
project (HCUP), sponsored by the agency for healthcare
research and quality. The NIS constitutes data from 44 States
and 1000 United States hospitals participating in the HCUP,
representing 95% of the United States population. This study
utilized the NIS database from 2010 to 2014 using Interna-
tional classification of diseases, 9th revision, clinical modi-
fication (ICD-9 CM) diagnosis code 558.2 in any diagnostic
field in hospitalizations aged older than 18 years. This study
used Elixhauser comorbidities for baseline characteristics
[23]. For the primary reason for admission, Clinical Clas-
sification Software (single-level diagnostic codes) was used.
The ICD-9 CM codes used in this study for other in-hospital
outcomes and infections are explained in Supplementary
Table 1. (Supplementary Table 1) This study followed all
the required research practices recommended by the sponsor
[24]. Institutional review board approval was not required as
the NIS has deidentified hospitalizations.
Statistical analysis
Differences between categorical variables were tested
using the Chi-square test, and differences between continu-
ous variables were tested using the T test. Categorical data
are described as frequencies in percentages and continuous
data are described as mean ± standard deviation. A value
of p < 0.05 was considered significant. For trends, the Jon-
ckheere–Terpstra trend test was performed [21]. Discharge
weights were used to calculate the nationally representable
frequency. To examine and identify independent predictors
of in-hospital mortality with TM, a hierarchical, mixed-
effect, multivariate logistic regression model was used. The
variables included age, gender, race, teaching status, and
Elixhauser comorbidities. Finally, SAS 9.4 (SAS Institute
Inc., Cary, NC) was used to perform the analysis for this
study.
Results
A total of 8139 hospital admissions were included in this
study. Except for a slight increase in 2014, the overall
hospitalization frequency reduced over the study period
(Fig. 1). The mean age was 62.4 years, and the preva-
lence of TM increased as age increased (Supplementary
Figure 1). Higher prevalence was seen in hospitalizations
above 70 years of age. The study population was predomi-
nantly female (56.4%) and of white race (79.7%), followed
by blacks (10.1%). Most admissions were emergent or
urgent (84.5%) and primarily paid for by Medicare/Medic-
aid (64.3%). Most hospitalizations were admitted to urban
teaching hospitals (53.1%). It was noted that Americans in
southern regions had higher admissions with TM (44.9%).
Internal and Emergency Medicine

Table 1  Demographics and baseline characteristics for hospitaliza-

tions with toxic megacolon in the Unites States: 2010–2014
Variable name Frequency (N = 8139)

Age (years) 62.4±17.2

Gender
 Male 43.6%
 Female 56.4%
Racea
 White 79.7%
 Black 10.1%
 Hispanic 6.6%
Fig. 1  Hospitalizations with toxic megacolon in United States  Asian/pacific Islander 1.4%
 Native american 0.4%
 Other 1.8%
Additionally, the most common comorbidities were fluid
Admission ­typeb
and electrolyte disorder (69.1%), hypertension (49.7%),
 Elective 15.5%
anemia (23.5%), weight loss (20.5%), uncomplicated
 Non-elective 84.5%
diabetes (18.3%), and renal failure (13.1%). (Table  1).
Primary expected ­payerc
Gastrointestinal disorders like ulcerative colitis and
 Medicare 56%
Crohn’s disease were the most common primary reasons
 Medicaid 8.3%
for admissions (51.6%). Other top reasons included sep-
 Private insurance (including HMOs and 29.5%
ticemia (10.2%) and intestinal infection (4.1%) (Table 2).
PPOs)
Identifiable infections and their frequencies are included
 Self-pay 3.1%
in Table 2. C. diff is the most common infection associ-
 Other 3.1%
ated with TM. The infections listed represent only those
Median household income for patient’s ZIP c­ oded
caused by bacteria present in high-enough frequencies to
 0–25 percentile 28%
be detected and calculated. As a result, 3.25% is listed as
26-50 Percentile 26.5%
“Other.”  51–75 percentile 24.8%
In-hospital mortality was the primary outcome. All-  76–100 percentile 20.7%
cause in-hospital mortality was 7.9% for this study cohort. Teaching status of ­hospitale
In-hospital mortality associated with TM decreased sig-  Rural 13%
nificantly between 2010 and 2014 (Fig.  2). The mean  Urban (non-teaching) 33.9%
length of stay was 9.5 days and did not change during  Urban (teaching) 53.1%
the study period (Table 3, and Supplementary Figure. 2). Hospital region
Additionally, the mean hospitalization cost increased dur-  Northeast 19.9%
ing this study period (Supplementary Figure. 3). A total  Midwest 19.9%
of 57.5% hospitalizations who survived were discharged  South 44.9%
to home. Other in-hospital outcomes such as resection  West 15.3%
of large intestine were seen in 11.5% hospitalizations. Hospital bed ­sizef
Bowel obstruction was seen in 10.9% of hospitalizations,  Small 14.2%
active fistulizing disease or intra-abdominal abscess was  Medium 21.8%
observed in 3.3%, and active stricturing disease was noted  Large 64%
in 2.8%. Finally, though least common, lower gastrointes- Comorbidities
tinal bleeding and rectum or perianal surgery was noted in  Diabetes mellitus (uncomplicated) 18.3%
2.4% of hospitalizations (Table 3).  Diabetes mellitus (with chronic complica- 4.3%
In the multivariate predictor model for in-hospital mor- tions)
tality with TM, higher age was associated with greater risk  Hypertension 49.7%
of mortality. Also, neurological disorders, coagulopathy,  Liver disease 4.2%
chronic pulmonary disease, congestive heart failure, and  Fluid and electrolytes disorder 69.1%
renal failure were also independent predictors of in-hospital  Other neurological disorder 6.3%
mortality. In contrast, female gender, hypertension, and iron Obesity 6.6%
deficiency anemia were associated with reduced risk of in-  Peripheral vascular disease 6%
hospital mortality (Table 4).

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 Internal and Emergency Medicine

Table 1  (continued) Table 2  Top primary reasons for hospitalizations with toxic megaco-

lon in the United States 2010–2014
Variable name Frequency (N = 8139)
Diagnosis Frequency
 Valvular disease 3.2% (N = 8139)
 Alcohol abuse 2.6%
 Coagulopathy 13.5% Gastrointestinal disorders (Ulcerative Colitis, Crohn’s 51.6%
Disease, etc.)
 Chronic pulmonary disease 18.9%
Septicemia 10.2%
 Congestive heart failure 9.3%
Intestinal infection 4.1%
AIDS 0.1%
Diseases of white blood cells 3.1%
 Deficiency anemia 23.5%
Acute and unspecified renal failure 3%
 Chronic blood loss anemia 1.5%
Fluid and electrolyte disorders 2.1%
 Drug abuse 2.3%
Regional enteritis and ulcerative colitis 1.8%
 Renal failure 13.1%
Leukemia 1.3%
 Peptic ulcer disease excluding bleeding 0.1%
Multiple myelomas 1.3%
 Weight loss 20.5%
Maintenance chemotherapy or radiotherapy 1.3%
Frequencies in mean or % Pneumonia 1.3%
HMO healthcare maintenance organization, PPO preferred provider Infection Associated with TM
organization, AIDS acquired immuno deficiency syndrome  Overall infection 14.8%
a
 104 missing  Clostridium difficile 11.25%
b
 2 missing  E. coli 0.1%
c
 3 missing  Pseudomonas 0.1%
d
 42 missing  Campylobacter 0.1%
e
 7 missing
f
Frequencies in %
 
This represents a quartile classification of the estimated median
household income of residents in the patient’s ZIP code. These values TM Toxic megacolon
are derived from ZIP Code-demographic data obtained from Claritas.
The quartiles are identified by values of 1–4, indicating the poorest to
wealthiest populations. Because these estimates are updated annually;
the value ranges vary by year. http://www.hcupu​s.ahrq.gov/db/vars/
zipin​c_qrtl/nisno​te.jsp

Discussion

This study demonstrates the prevalence of TM using the NIS

database between 2010 and 2014. The highest prevalence
of TM is found in females, white race, and those hospital-
ized in southern regions of the U.S. Various comorbidities
present in TM hospitalizations were also analyzed. C. diff
infection presented with the highest prevalence. This study
demonstrates the prevalence of various in-hospital outcomes
including all-cause in-hospital mortality with TM, which is
very high. Age, coagulopathy, iron deficiency anemia, and
renal failure are strong predictors of in-hospital mortality.
Furthermore, while a decreasing trend for in-hospital mor-
tality is observed, the length of stay and healthcare cost are
shown to significantly increase.
Initially TM was thought to be a complication only of
IBD. Although, TM may complicate any number of kinds
of colitis, including: inflammatory, ischemic, infectious,
radiation, and pseudomembranous. Recently, owing to the
increasing use of antibiotics, the incidence of C. diff infec-
tion, which is one of the major etiologies for TM, has been
increasing. Also, patients with IBD who develop C. diff
Fig. 2  Trend of In-hospital mortality with toxic megacolon from
2010 to 2014. Jonckheere–Terprstra trend test for in-hospital mortal-
ity p =< 0.01 
have a worse clinical course and are at increased risk of
TM [25]. As per the description of Jalan et al., the diag-
nostic criteria of toxic megacolon include (a) radiographic
evidence of colonic dilatation of more than 6 cm especially
in the transverse colon; (b) any three of the following: fever
(> 38.6 °C, 101.5 °F), tachycardia (> 120 beats/min), leu-
kocytosis (> 10.5 × 103/µL), or anemia; and (c) any one of
the following: dehydration, altered mental status, electrolyte
abnormality, or hypotension [26]. Treatment of TM has cer-
tain goals: (a) to reduce colonic distention to prevent perfo-
ration, (b) withdraw C .diff-causing antibiotics, (c) correct

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Table 3  In-hospital outcomes for hospitalizations with toxic megaco- Table 4  Predictors of In-Hospital Mortality with Toxic Megacolon
lon in the United States 2010–2014
Variable name Odds ratio (95% p value
Variable Frequency in % confidence interval)

In-hospital mortality 7.9% Age 1.03 (1.02–1.05) < 0.01

Length of stay (mean days) 9.5 ± 12.2 Female vs Male 0.82 (0.55–0.21) 0.31
Disposition Race
 Routine 57.5%  White Referent
 Transfer to short-term hospital 1.6%  Black 1.27 (0.62–2.59) 0.51
 Transfer to ­othera 16.3%  Other 0.91 (0.51–1.62) 0.74
 Home health care 16.6% Teaching status of the hospital
 Against medical advice 0.1%  Rural Referent
 Died 7.9%  Urban (non–teaching) 1.19 (0.61–2.30) 0.61
Other In-hospital Outcomes  Urban (teaching) 1.43 (0.76–2.70) 0.27
 Active fistulizing disease or intra-abdominal 3.3% Comorbidities
abscess  Diabetes mellitus (uncomplicated) 0.85 (0.50–1.43) 0.54
 Active stricturing disease 2.8%  Diabetes mellitus (with chronic 1.08 (0.47–2.47) 0.86
 Bowel obstruction 10.9% complications)
 Perianal abscess 0.1%  Hypertension 0.64 (0.42–0.96) 0.03
 Unspecified lower GI bleeding 2.4%  Liver disease 0.59 (0.17–2.04) 0.40
 Resection of large intestine 11.5%  Fluid and electrolytes disorder 1.23 (0.79–1.92) 0.36
(procedure code)  Other neurological disorder 1.98 (1.06–3.71) 0.03
 Rectum/Perianal Surgery 2.4%  Obesity 0.54 (0.19–1.54) 0.24
 Other surgery of large intestine 0.5%  Peripheral vascular disease 1.69 (1.93–3.10) 0.09
 Post-operative wound complication including 1%  Valvular disease 1.90 (0.83–4.32) 0.13
infection, dehiscence, and fistula
 Alcohol abuse 1.18 (0.32–4.26) 0.80
a
 Includes skilled nursing facility (SNF), intermediate care facility  Coagulopathy 2.67 (1.69–4.20) < 0.01
(ICF), another type of facility  Chronic pulmonary disease 1.57 (1.01–2.45) 0.04
 Congestive heart failure 1.71 (1.01–2.91) 0.04
 Deficiency anemia 0.48 (0.29–0.81) < 0.01
fluid and electrolyte disturbances, and (d) treat toxemia and
 Chronic blood loss anemia 1.06 (0.23–5.01) 0.94
precipitating factors. Broad-spectrum intravenous (IV) anti-  Drug abuse 1.12 (0.24–5.15) 0.89
biotics and IV steroids should be initiated. In case medical  Renal failure 2.47 (1.51–4.04) < 0.01
management fails to improve the condition, subtotal colec-  Weight loss 1.49 (0.96–2.30) 0.07
tomy is an alternate option. Management of toxic megacolon
is an interdisciplinary task that requires close interaction of
gastroenterologists, surgeons, and critical care specialists
from the very beginning. inflammatory condition of the colon can predispose to severe
Fluid and electrolyte disorders, hypertension, iron defi- inflammation of the smooth muscle layer, which paralyzes
ciency anemia, weight loss, and chronic pulmonary disease the colonic smooth muscle [29]. It is still questionable, how-
are the top comorbidities associated with TM. IBD remains ever, if pancolitis increases the relative risk of TM compared
the primary admission diagnosis for TM; septicemia and to the regional involvement of colon.
intestinal infections are the second and third most common Reported in-hospital mortality among IBD patients is
causes for admission. Among all the infectious etiologies, only 0.9% [30]. However, data on in-hospital mortality in
C. diff is most commonly associated with TM (76%). This recent years are not available. This study finds in-hospital
may be associated with increasing use of the antibiotics. mortality rate for TM to be 7.9%. Age, coagulopathy, iron
Antibiotics maintaining C. diff should be withdrawn imme- deficiency anemia, and renal failure are strong predictors of
diately after diagnosis of TM. It is still possible that C. diff in-hospital mortality. However, as suggested by Greenstein
infection can further complicate IBD in some cases. Case et al. [10], female gender is not an independent risk factor for
reports have suggested the role of fulminant C. diff in the mortality. Coagulopathy and anemia can be limiting factors
presentation of TM [27]; however, the increasing incidence for urgent surgery, and can also complicate the post-oper-
of pseudomembranous colitis infection [7] requires attention ative hospital course [31, 32]. Consistent with Greenstein
due to the high, associated mortality rates (38–80%) [28]. et al. [10], age is one of the strongest predictors of mortality
It has become evident in previous studies that almost any in this study, which shows age > 40 years as an independent

13

risk factor for mortality. In early reviews, reported mortal-
ity rates ranged between 19 and 27%; however, mortality
is 7.9% in this study [15]. Early diagnosis due to the avail-
ability of computed tomography [33] makes it easier to start
early and effective treatment [34]. Advances in surgical stag-
ing and minimally invasive techniques have also improved
outcomes in recent years [35, 36].
The most common complications are colon resection and
bowel obstruction followed by active fistulizing disease and
intra-abdominal abscess. Many patients underwent early
intervention because of a reported 5-fold increase in mor-
tality after free perforation following late treatment [37].
Interestingly, the median length of stay and the total hos-
pitalization cost have increased between 2010 and 2014.
There is controversy regarding the timing of surgery and a
lack of sufficient evidence to choose between conservative
and surgical approaches. Advanced early surgical procedures
are becoming more popular, but may lead to increases in
associated healthcare cost. More data are required to deter-
mine peri-operative complications and hospital-acquired
infections related to surgical treatment modalities [38].
Limitations
There exist several limitations inherent in any retrospective
study and a large database. The use of such administrative
data sets has its own limitations; the data only include in-
hospital stays and each hospitalization was not followed lon-
gitudinally, and was subject to misclassification. Moreover,
the data were not specifically collected to answer a research
question. The NIS considers each hospitalization as a sepa-
rate entry, so it was not possible to separate index cases
from readmissions, which could result in an overestimation
of the number of admissions. However, the analysis included
a large number of hospitalizations, and lacked the selection
bias associated with clinical trials. Despite these limitations,
the inclusion of a huge number of hospitalizations from vari-
ous demographic and socioeconomic backgrounds, with all
types of insurances, and from academic and nonacademic
institutions, leads to highly generalizable results, which rep-
resent a “real-world” population.
Conclusion
In conclusion, the trend of TM hospitalizations is decreasing
with decreasing trends in associated mortality. Interestingly,
however, the cost associated with TM is increasing. IBD
remains the main reason for TM hospitalization. Further-
more, C. diff might be associated with TM as the prevalence
is higher in TM hospitalizations. Finally, high in-hospital
mortality and high-risk patients require special attention to
prevent added in-hospital cost.
13
Internal and Emergency Medicine
Funding None.
Compliance with ethical standards 
Conflict of interest  The authors declare that they have no conflict of
interest.
Statement of human and animal rights  This article does not contain
any studies with human participants or animals performed by any of
the authors.
Informed consent  Informed consent was not required as the data were
obtained from NIS. It has deidentified hospitalization data.
Data availability statement  The data that support the findings of this
study are openly available in Healthcare Cost and Utilization Project’s
website at https​://www.hcup-us.ahrq.gov/nisov​ervie​w.jsp. Reference
Number: 19.
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