REVIEW

CURRENT
OPINION Colonic ischemia: usual and unusual presentations
and their management
Ayah Oglat and Eamonn M.M. Quigley

Purpose of review
To provide an update on the epidemiology, pathophysiology, clinical presentation, and management of
colonic ischemia.
Recent findings
Formerly regarded as a rare cause of lower gastrointestinal hemorrhage, colonic ischemia is now
recognized to be the most common manifestation of intestinal vascular compromise. In contrast to ischemic
events in the small intestine wherein thrombotic and embolic events predominate, colonic ischemia typically
results from a global reduction in blood flow to the colon and no occlusive lesion(s) are evident. Several
risk factors for colonic ischemia have been identified and, together with an appropriate clinical
presentation and patient demographics, create a context in which the clinician should have a high level of
suspicion for its presence. Imaging with computerized tomography, in particular, may be highly supportive
of the diagnosis, which where appropriate can be confirmed by colonoscopy and colonic biopsy. For most
patients, management is supportive and noninterventional, and the prognosis for recurrence and survival
are excellent.
Summary
Colonic ischemia is a common cause of lower abdominal pain and hemorrhage among the elderly
typically occurring in the aftermath of an event which led to hypoperfusion of the colon. For most affected
individuals the ischemia is reversible and clinical course benign.
Keywords
colon, colonoscopy, computerized tomography, Escherichia coli 0157:H7, ischemia, ischemia-reperfusion
injury

INTRODUCTION of patients who present with colonic ischemia will

Colonic ischemia is the most common form of
ischemic vascular injury to the gastrointestinal tract
[1] and accounts for approximately 50% of all
instances of vascular compromise to the intestine
[2]. It results from a critical reduction in blood flow
to the colon because of anatomic and/or functional
changes in the mesenteric vasculature [3].
The clinical presentation is highly variable and
can be nonspecific. Among those who present with
severe life-threatening colonic ischemia resulting in
gangrene, multiorgan failure is likely to occur and
mortality rates are high. At the other end of the
spectrum are those who have a transient episode of
ischemia with relatively minor symptoms and in
whom a full recovery is to be expected. Clinicians
should have a low threshold of suspicion for colonic
ischemia in the appropriate clinical setting and
should be able to identify, at an early stage, that
minority of patients who require urgent surgical
intervention [4]. On the other hand, the majority
have a relatively acute, self-limited course, and
respond to conservative medical management. In
contrast, in the 20% of patients who require surgery
high rates of morbidity and mortality are to be
expected [5].
Colonic ischemia is most frequently encoun-
tered among elderly individuals with a history of
atherosclerotic vascular disease. The etiology of
colonic ischemia, however, is multifactorial and
Division of Gastroenterology and Hepatology, Lynda K and David M
Underwood Center for Digestive Disorders, Houston Methodist Hospital
and Weill Cornell Medical College, Houston, Texas, USA
Correspondence to Dr Eamonn M.M. Quigley, MD, FRCP, FACP, MACG,
FRCPI, Division of Gastroenterology and Hepatology, Houston Method-
ist Hospital, 6550 Fannin St, SM 1201, Houston, TX 77030, USA.
Tel: +1 713 441 0853; fax: +1 713 790 3089;
e-mail: equigley@tmhs.org
Curr Opin Gastroenterol 2017, 33:34–40
DOI:10.1097/MOG.0000000000000325

www.co-gastroenterology.com Volume 33  Number 1  January 2017

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

 Colonic ischemia presentations and management Oglat and Quigley
KEY POINTS
 Colonic ischemia is a common cause of lower
gastrointestinal hemorrhage in at-risk individuals.
 The etiology is typically nonocclusive and arteriography
is usually not indicated.
 Multiple risk factors ranging from comorbid medical
condition to therapeutic agents and various other
interventions have been identified.
 For most affected individuals colonic ischemia runs a
benign course; these individuals can be
managed conservatively.
 In a minority and, especially, those with right-sided
disease, transmural ischemia and related complications
may develop and surgery becomes necessary with
attendant morbidity and mortality.
multiple case series have demonstrated its associ-
ation with a number of identifiable risk factors.
Diagnosis should be suspected clinically and its
presence and severity confirmed, were appropriate,
by serologic, radiologic, and colonoscopic findings.
EPIDEMIOLOGY
In the general population, the incidence of colonic
ischemia has been estimated to be between 7.2 and
&&
16.3 cases per 100 000 person-years [6,7 ]. However,
these incidence rates may well be underestimates as
they are based primarily on instances occurring
among hospitalized patients who have undergone
colonoscopic confirmation; it is highly likely that a
significant proportion of patients with colonic
ischemia of a mild and transient nature either never
present to medical attention, are undiagnosed based
on the spectrum of their clinical presentation, or
misdiagnosed, on a clinical basis, as inflammatory
or infectious colitis [1,8]. In addition, it has been
suggested that studies of incidence and prevalence
that are based on the prior or current World Health
Organization International Classification of Dis-
eases (ICD), ICD-9 and ICD-10, may also encounter
misclassification and, therefore, under-diagnosis
&&
[7 ].
These diagnostic and classification shortcom-
ings notwithstanding, colonic ischemia is currently
the third most common cause of a lower gastroin-
testinal bleed accounting for about 12% of lower
gastrointestinal bleeding cases requiring hospitaliz-
ation [9]. Mortality rates range from 4 to 12% in
&&
large series [10 ]. In population-based studies there
is a female predominance among reported instances
of colonic ischemia [11].
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PATHOPHYSIOLOGY
Colonic ischemia is the result of acute or chronic
reduction in colonic blood supply to a level that is
insufficient to maintain metabolic demand. Colonic
ischemia can be generally classified into occlusive
ischemic disease which includes embolism and arte-
rial or venous thrombosis or insufficiency; and non-
occlusive disease caused by alterations in the
systemic circulation that globally reduce perfusion
in the absence of an identifiable thrombotic or
embolic lesion on angiography or major vessel
&& &
occlusion [10 ,12 ]. In the majority of cases an
exact cause cannot be identified, a major vascular
occlusion cannot be identified and circumstantial
evidence points to an episode of global hypoperfu-
sion resulting in nonocclusive ischemia operating at
the level of smaller vessels [8,13].
Depending on the severity of the injury, the
ischemic damage can be reversible or irreversible.
In reversible disease, there are subepithelial hemor-
rhage and edema that subsequently resorb and lead
to ulceration of the overlying mucosa which is
visible as an acute colitis. Irreversible manifestations
include gangrene and fulminant colitis. Chroni-
cally, fibrosis can ensue and strictures form [10 ].
&&
When hypoxic conditions persist, activation of
an inflammatory cascade leads to the release
of cytokines; these proinflammatory cytokines
together with bacterially derived endotoxin increase
membrane permeability and ultimately result in
mucosal ulceration. The net consequence of these
events is a disruption of colonic epithelial barrier
function and the promotion of bacterial transloca-
tion to the portal and systemic circulations. If the
individual survives the acute event and circulation is
restored, reperfusion injury results with the acti-
vation of complement and the production of reac-
tive free radicals which are collectively highly
damaging at the cellular level and lead to apoptosis
of colonic epithelial cells [3].
ANATOMIC PATTERNS AND
DISTRIBUTION
The arrangements of the vascular anatomy and
resultant patterns of blood flow to the colon and
rectum explain the segmental nature of colonic
ischemia. The vascular supply to the colon involves
three main vessels: the superior mesenteric artery
(SMA), which supplies the right colon and a portion
of the proximal transverse colon, the inferior mes-
enteric artery (IMA) which supplies the mid to distal
transverse, descending, sigmoid colon, and rectum
and superior hemorrhoidal artery which provides a
dual blood supply to the rectum in addition to IMA.
It is very important to emphasize, however, that
www.co-gastroenterology.com 35
Large intestine
vascular anatomy can be variable between individ-
uals [8,14]. The splenic flexure and sigmoid colon
are the two regions that have been previously con-
sidered to be anatomically vulnerable, watershed
areas due, first, to their location at the junction
between two vascular supplies and, second, to a
potentially limited collateral blood flow. They have
been regarded, therefore, as those locations most
susceptible to ischemic insult. The clinical and func-
tional significance of these anatomic points has
been questioned as recent studies have downplayed
the prevalence of these ‘classic’ presentations by
failing to demonstrate that instances of colonic
ischemia are predominant in these locations [5,14].
In one of the largest series, Brandt et al. [14]
analyzed the anatomical distribution of ischemia in
313 patients with colonoscopically or surgically and
pathologically confirmed colonic ischemia. The most
commonly affected segment was the left colon
(32.6%), followed by the distal colon (24.6%), right
colon (25.2%), and entire colon (7.3%). The frequen-
cies of dominant hepatic and splenic flexure involve-
ment were much lower at 1.23 and 4.8%, respectively.
The sigmoid was involved in 20.8% of all cases [14].
It is important to note that anatomical location
(in terms of the specific segment involved) has
prognostic implications. Many studies have shown
that ischemic injury to the right colon has a poor
prognosis [14,15] being associated with a five-fold
higher rate of surgery, and twice the mortality rate
compared with patients with other involved
locations [14,15].
Colonic phlebosclerosis or phlebosclerotic col-
itis is a rare form of ischemic colitis due to occlusion
of the veins in the colonic wall and adjacent mes-
entery. It usually affects the right colon and is most
common among Asian populations [16].
CLINICAL PRESENTATION
Most patients with colonic ischemia present with
sudden onset of mild-to-moderate lower abdominal
pain associated with an urge to defecate and result-
ing in the passage of maroon or bright red blood per
rectum or frank bloody diarrhea. However, these
symptoms are not specific for colonic ischemia
and can be observed with infectious colitis and
inflammatory bowel disease in addition to a variety
&
of other entities [8,12 ]. One infectious agent that
can mimic colonic ischemia very closely and may,
indeed owe some of its features to ischemia, is
&
Escherichia coli 0157:H7 [17 ,18]. Ischemic features
have also been reported in association with cytome-
galovirus and hepatitis virus infections [19–21];
here again, vascular compromise has been impli-
cated.
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Several studies have provided data on the pre-
senting symptoms of colonic ischemia. One of the
largest, a retrospective study involving 401 patients,
reported that the most common presenting symp-
toms were abdominal pain (87%), rectal bleeding
(84%), diarrhea (56%), and nausea (30%) [22]. Mild
to moderate lower abdominal pain typically pre-
ceded bleeding. In patients with right-sided colon
involvement, pain has been notably severe and
hematochezia or rectal bleeding were remarkable
&&
for their rarity [10 ,14,15,22,23]. In colonic ische-
mia it is important to note that, despite the occur-
rence of bloody diarrhea and hematochezia, profuse
blood loss, or the need for transfusion, are rare
&&
[10 ,14,22,23].
Data on the short-term and long-term outcomes
following an episode of colonic ischemia appear at
first glance conflicting. Thus, in their meta-analysis
of 22 studies involving 2923 patients, Sun et al.
&&
[24 ] reported an overall rate for adverse outcomes
of 22% which rose to 48% for those with predom-
inant involvement of the right colon. Other nega-
tive predictors identified in this review included
male gender, peritonitis, shock, arterial hypoten-
sion, tachycardia, and absence of rectal bleeding
&&
[24 ]. Others report a more benign course; Long-
streth and Yao [22], in their large single-center
study, reported an overall rate for surgical resection
of 8% and mortality of just 4%. Furthermore, they
did not encounter any instances of chronic colitis
over a follow-up period which exceeded 2.5 years
and only one patient required dilation for a colonic
stricture [22]. These contrasting differences in out-
come may be explained largely on the basis of
patient selection. Thus, Nagata et al. [25] reported
an especially benign course for those managed as
outpatients; only 5% rebled and 2% died when
followed for almost 2 years.
ETIOLOGY AND RISK FACTORS
Elderly patients afflicted by multiple comorbidities
including, in particular, significant atherosclerotic
vascular disease or end stage renal disease, are con-
sidered to be at the highest risk for ischemic colitis.
Age represents an important risk factor as up to 90%
of all instances of ischemic colitis occur in patients
&&
over 60 years of age [10 ,14]. Not surprisingly, given
the progressive aging of our general population, the
incidence of colonic ischemia has increased in
&&
recent years [7 ]. Colonic ischemia occurs most
frequently in the context of global hypoperfusion
related to hypotension, hypovolemia, or heart fail-
ure [26].
However, colonic ischemia may develop in
younger individuals who are less likely to have
Volume 33  Number 1  January 2017
 Colonic ischemia presentations and management Oglat and Quigley
classic cardiovascular risk factors [3,27]; among
these individuals, colonic ischemia has been associ-
ated with a diverse array of underlying causes and
risk factors [27,28]. Indeed, the occurrence of
colonic ischemia in a younger patient without pre-
disposing factors for atherosclerosis, such as diabe-
tes, hyperlipidemia, hypertension, and tobacco use,
should prompt a search for attributable, uncommon
causes. Among such etiological and predisposing
risk factors identified in retrospective studies or
clinical reports have been smoking, hematologic
and hypercoagulation disorders (e.g., thrombo-
philia), medications, colonic obstruction, irritable
bowel syndrome, chronic constipation, colonic dis-
tension, abdominal fat accumulation, connective
tissue disease, and infectious processes
&& && & &
[6,7 ,10 ,17 ,18–21,29–32,33 ]. Instances have
also been reported in endurance runners [34,35].
Iatrogenic causes include complications of surgical
interventions and aortic and vascular surgeries, in
particular [36], or vascular compromise arising from
an undue increase in intraluminal pressure during
colonoscopy [37,38].
Chronic obstructive pulmonary disease (COPD)
has also been implicated, not only as a predictor of a
more severe disease course, but also as a risk factor for
colonic ischemia, per se, and has been reported to be
associated with a two-fold to four-fold increase in risk
for colonic ischemia. Although some of this increased
risk can be attributed to factors associated with COPD,
such as cigarette smoking and comorbid cardiovas-
cular disease, it has been suggested that COPD may
independently increase risk of colonic ischemia by
mediating systemic inflammation [24 ,39].
&&
Several pharmacologic agents have been associ-
ated with the occurrence of colonic ischemia. These
include antihypertensives, vasoconstrictors, anti-
psychotics, oral contraceptives, antidiarrheal
agents, immunosuppressive medications, and illicit
drugs, such as cocaine, amphetamine, and pseudoe-
phedrine [40–47]. Many pathophysiologic mechan-
isms have been ascribed to medication-associated
colonic ischemia. Common mechanisms include
vasoconstriction, an alteration in intravascular
volume resulting in a reduction in blood flow,
hypercoagulability, and thrombogenesis, direct
endothelial damage and an increase in intraluminal
pressure in the colon. The Federal Drug Adminis-
tration Adverse Event Reporting System (FAERS)
database identifies agents associated with colonic
ischemia and can be utilized to search for a sus-
&
pected causative agent [33 ]. It is important to note
that in many cases of medication-related colonic
ischemia, a specific pathophysiology cannot be
identified. In others, such as in the case of cocaine
and related drugs, wherein sympathomimetic
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effects including vasoconstriction are considered
critical, the mechanism underlying the induction
of colonic ischemia is clear. One of the most widely
publicized instances of drug-induced colonic ische-
mia related to the 5-hydroxytryptamine-3 (5-HT3)
receptor antagonist alosetron hydrochloride. On
the basis of its effects on receptors in the enteric
nervous system, this drug had effects on both vis-
ceral sensation and gut motility and was approved
for patients with diarrhea-predominant irritable
bowel syndrome (D-IBS) [48]. However, reports of
instances of ischemic colitis [49] (as well as severe
constipation) among those receiving alosetron led
to its initial withdrawal by the Food and Drug
Administration [50]. It was later restored for use
in severe diarrhea-predominant IBS, but in the con-
text of an extensive risk management programme
[51,52]. The true role of alosetron in these instances
of colonic ischemia remains somewhat unclear
given the demonstration, in some epidemiological
studies, that IBS, per se, is associated with an
increased risk for colonic ischemia, possibly because
of symptom overlap [6]. Furthermore, instances of
colonic ischemia have been remarkably rare when
alosetron has been administered under the risk
management programme [51,52].
DIAGNOSIS
Serologic testing
Serologic assessment is not sensitive or specific for
diagnosing colonic ischemia; however, it plays an
essential role in determining disease severity and
triaging patients. Elevated levels of laboratory
markers suggest inadequate global perfusion or non-
&&
specific tissue injury [5,10 ]. Severe disease is typ-
ically associated with elevated levels of blood urea
nitrogen (BUN), creatinine, white blood cell (WBC)
count, and lactate dehydrogenase (LDH), and lower
levels of bicarbonate, hemoglobin, and albumin in
the peripheral blood. It is important to note that
there is no consensus regarding the status of sero-
&&
logic testing in predicting outcome [5,8,10 ]. In
addition, stool studies including testing for bacterial
pathogens such as Clostridium difficile toxin and
Escherichia coli 1057-H7, as well as stool examination
for ova and parasites, should be performed to rule
out an infectious etiology.
Imaging
The diagnosis of colonic ischemia is ultimately
made, first, based on clinical suspicion triggered
by the nature of the presenting symptoms, the
presence of known risk factors, second, supported
www.co-gastroenterology.com 37
Large intestine
by a combination of serologic and imaging findings,
and, finally, confirmed by endoscopic and histopa-
&&
thological findings [3,8,10 ,11]. Although various
imaging modalities have been employed in the
assessment of patients with suspected colonic ische-
mia, including plain abdominal films, barium
enema, computerized tomography (CT) scan, and
magnetic resonance imaging (MRI), a definitive
diagnosis cannot be made solely on the basis of
imaging because of the nonspecificity of radiologic
findings.
Plain abdominal films are not sensitive or
specific for colonic ischemia but are important to
obtain to exclude other differential diagnoses and
exclude perforation with evidence of pneumoperi-
toneum (both spontaneous and related to colono-
&
scopy) [12 ]. Suggestive findings on plain abdominal
films include the ‘thumbprinting sign’ indicative of
mucosal edema, which appears as gas-filled, dis-
tended colon surrounded by rounded densities
&
[12 ].
Barium enema, though used in the past, is no
longer employed in the diagnosis of acute colonic
ischemia, not only because of the superior perform-
ance of other imaging modalities but also because of
the potential to exacerbate ischemia and lead to
perforation due to the associated rise in intraluminal
pressure exerted in the colon. Barium enema may
have some utility in the assessment of strictures
related to chronic ischemia or arising in the after-
math of an acute event [2].
Where such expertise is available, ultrasonogra-
phy has been reported to have a role in diagnosis;
one study reported a positive predictive value of
87.5% for this imaging modality in the diagnosis
of colonic ischemia [53].
CT scan is nowadays considered the primary
noninvasive modality in the assessment of colonic
&
ischemia [12 ,54,55]. CT scan is used to exclude
alternate diagnoses such as diverticulitis, in deter-
mining the anatomical location and extent of
involved colon, to assess the severity and phase of
the ischemic injury and to identify complications
such as transmural ischemic injury leading to per-
foration.
The acuity of the event and timing of the dam-
age can also be estimated. Acute ischemia is associ-
ated with the presence of pericolic fluid and a lack of
clear demarcation of the affected areas. In chronic
ischemia, pericolic fluid is absent and the bowel wall
appears irregular with circumferential thickening
because of nonuniform fibrosis.
There are two manifestations of vascular damage
that are apparent on CT imaging. In the acute
ischemic phase, the bowel wall appears ‘paper-thin’
with a dilated lumen. When effective reperfusion
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occurs, the large bowel wall appears thickened due
to the presence of edema and hemorrhage with
&
consequent lumen caliber reduction [12 ,54].
The demonstration of colonic pneumatosis and
an absence of large bowel enhancement on contrast-
enhanced CT is highly suspicious of irreversible
&
ischemia and necrosis [12 ,54].
One variant of colonic ischemia that may be
identified on CT is the rare ‘mass-forming’ type. This
CT appearance mimics a tumor and typically
involves the right colon and affects elderly individ-
&
uals [56 ].
Multiphasic CT (or magnetic resonance) angiog-
raphy can be used to identify and rule out vascular
occlusion as a cause of colonic ischemia; however it
is not recommended as part of the routine evalu-
ation because the majority of cases are caused by a
low flow state resulting in nonocclusive ischemia
and colonic blood flow has typically returned to
normal by the time of presentation [57]. CT angiog-
raphy has a utility in isolated right colon ischemia to
exclude obstruction of SMA resulting in acute mes-
&
enteric ischemia [55,58 ].
Colonoscopy
By providing direct observation of the mucosa and
permitting tissue biopsy for histological examin-
&&
ation [3,8,10 ], colonoscopy has the potential to
provide a definitive diagnosis, if imaging provides
nonspecific findings, the diagnosis remains in ques-
tion or if the patient is not improving with medical
&&
management [3,8,10 ]. Where appropriate, colono-
scopy should be performed early, typically within
48 h of presentation, in suspected colonic ischemia
to confirm the diagnosis. However, it is important to
emphasize that colonoscopy should not be per-
formed in patients with signs of peritonitis or
gangrene.
Management
There is a paucity of evidence-based information on
the appropriate management of colonic ischemia.
Treatment is usually individualized based on the
depth of colonic mural ischemia and hemodynamic
&&
status [3,8,10 ,59].
For those patients who are hemodynamically
stable and do not have signs of peritonitis, suppor-
tive medical management remains the cornerstone
of management. Components of this approach have
included the correction of any underlying cause, the
withdrawal of any offending agent, bowel rest, intra-
venous fluid replacement, optimization of blood
pressure and cardiac output, and the administration
of broad-spectrum antibiotics. Of these, the status of
Volume 33  Number 1  January 2017
 Colonic ischemia presentations and management Oglat and Quigley
bowel rest and antibiotics can be questioned as they,
like most aspects of the management of this dis-
order, are based more on theoretical concepts rather
than real clinical evidence and need to be tested
prospectively in a formal fashion. Patients should be
assessed for signs of adequate end organ perfusion
and periodically monitored for changes in abdomi-
&&
nal pain, mental status, and urine output [3,8,10 ].
The primary challenge in the management of
colonic ischemia is timely diagnosis. Perioperative
morbidity and mortality rates are high among those
who require colonic resection and may reach as high
as 50%. Surgical management and resection of non-
viable colon is reserved for patients with gangrene of
the colon and peritonitis. Risk factors for perioper-
ative complications and overall mortality include:
first, those instances of colonic ischemia that
develop in the immediate aftermath of cardiac or
aortic surgery, second, the length of the time inter-
val between presentation and surgery, and third,
certain laboratory parameters, such as leukocytosis
and lactic acidosis [60,61]. In addition, multiple
retrospective studies have shown that prognosis
for those with involvement of the right colon is
inferior in comparison to those instances wherein
ischemia is left-sided [60–62].
Clinical indications for surgery include the
development of peritoneal signs on clinical exam-
ination and of CT findings indicative of transmural
involvement with infarction. Though earlier
recourse to surgery has been advocated based on
the severity of the endoscopic findings [63], this
approach has not been subjected to rigorous evalu-
ation.
Among those who follow a more chronic and
indolent course, fibrosis and stricturing may
develop and require colonoscopic dilation or surgi-
cal resection should obstructive symptoms develop.
CONCLUSION
Formerly regarded as a rather rare disorder [64],
colonic ischemia/ischemic colitis is now appreci-
ated as a common and under-recognized disorder
which most typically develops in the context of low
blood flow to the colon. Its presentation can vary
from a mildly symptomatic and reversible disorder
to fulminant colitis with colonic infarction with an
associated high mortality. A much broader spectrum
of risk-factors and causative agents is now recog-
nized [65] and the clinical context in which the
clinician should suspect this disorder expanded
and refined. Conventional views on the anatomical
distribution of colonic ischemia have been ques-
tioned and a number of risk factors have been
identified. Abdominal imaging and colonoscopy
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remain the cornerstones of its diagnosis and for
most affected patients complete recovery can be
expected with a conservative noninterventional
approach.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
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Volume 33  Number 1  January 2017