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DOI: 10.4291/wjgp.v5.i4.579 © 2014 Baishideng Publishing Group Inc. All rights reserved.

MINIREVIEWS

Management of acute severe ulcerative colitis

Saurabh Kedia, Vineet Ahuja, Rakesh Tandon

Saurabh Kedia, Vineet Ahuja, Department of Gastroenterology, not responding to infliximab or cyclosporin should be
All India Institute of Medical Sciences, New Delhi 110029, India considered for colectomy.
Rakesh Tandon, Department of Gastroenterology, Pushpawati
Singhania Research Institute for Liver, New Delhi 110017, India © 2014 Baishideng Publishing Group Inc. All rights reserved.
Author contributions: All authors contributed to this paper.
Correspondence to: Dr. Rakesh Tandon, Head, Department
of Gastroenterology, Pushpawati Singhania Research Institute for Key words: Ulcerative colitis; Acute severe colitis; Intra-
Liver, Renal and Digestive Diseases, Press Enclave Marg, Sheikh venous steroids; Cyclosporin; Infliximab
Sarai II, New Delhi 110017, India. drrakeshtandon@hotmail.com
Telephone: +91-11-30611999 Fax: +91-11-29250548 Core tip: The mortality of severe ulcerative colitis has
Received: July 5, 2014 Revised: August 15, 2014 drastically reduced from 30%-60% in pre steroid era
Accepted: September 23, 2014 to 1%-2.9% at present. However these figures are for
Published online: November 15, 2014 specialist centers and at peripheral centers the mortal-
ity figures may be higher. The objective of this review
is to provide in depth information for what can be cat-
egorized as a gastrointestinal medical emergency with
Abstract the hope that informed clinical practices may translate
to superior patient care at tertiary as well as peripheral
The management strategy of acute severe ulcerative
centers treating ulcerative colitis. This review provides
colitis has evolved over the past decade from being en-
time bound framework, which looks at stepwise man-
tirely restricted to twin choices of intravenous steroids
agement of acute severe ulcerative colitis and explores
or colectomy to include colon rescue therapies like cy-
closporin as well as infliximab. However it still remains the recent concepts of choice between biologics and
a medical emergency requiring hospitalization and cyclosporin colon rescue therapies in case of steroid re-
requires care from a multidisciplinary team comprising fractory disease.
of a gastroenterologist and a colorectal surgeon. The
frame shift in management has been the emphasis on
Kedia S, Ahuja V, Tandon R. Management of acute severe ulcer-
time bound decision making with an attempt to curtail
ative colitis. World J Gastrointest Pathophysiol 2014; 5(4): 579-588
the mortality rate to below 1%. Intravenous corticoste-
roids are the mainstay of therapy. Response to steroids Available from: URL: http://www.wjgnet.com/2150-5330/full/v5/
should be assessed at day 3 of admission and partial/ i4/579.htm DOI: http://dx.doi.org/10.4291/wjgp.v5.i4.579
non-responders should be considered for alternative
medical therapy/surgery. Medical rescue therapies in-
clude intravenous cyclosporin and infliximab. Cyclospo-
rin is administered in a dose of 2 mg/kg per day and INTRODUCTION
infliximab is administered as a single dose intravenous
Acute severe ulcerative colitis (UC) is a medical emer-
infusion of 5 mg/kg. Approximately 75% patients have
short term and 50% patients have long term response
gency characterized by[1] (Table 1) presence of more than
to cyclosporin. Long term response to cyclosporin is 6 bloody stools/d along with any one of the following:
improved in patients who are thiopurine naïve and are tachycardia > 90 bpm, fever > 37.8 ℃, Hb < 10.5 gm/dL,
started on thiopurines on day 7. Infliximab also has a and/or ESR > 30 mm/h (Truelove and Witt’s criteria).
response rate of approximately 70% in short term and Other indices for defining severity include modified
50% in long term. Both cyclosporin and infliximab are Mayo’s classification[2], which is a combination of clinical
equally efficacious medical rescue therapies as dem- and endoscopic findings, and Montreal classification[3],
onstrated in a recent randomized control trial. Patients which is primarily based on Truelove and Witt’s criteria.

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 Kedia S et al . Management of acute severe ulcerative colitis

Table 1 Modified Truelove and Witt’s criteria for classification

cytomegalovirus (CMV) colitis[12]. Endoscopic markers
of severity of ulcerative colitis of severe disease activity include hemorrhagic mucosa
with deep ulceration, mucosal detachment on the edge of
Mild Moderate Severe these ulcerations, and well like ulcerations[13].
Bloody stools per day <4 4-6 >6
Pulse < 90 bpm ≤ 90 bpm > 90 bpm Treatment
Temperature < 37.5 ℃ ≤ 37.8 ºC > 37.8 ℃
Hemoglobin > 11.5 gm/dL ≥ 10.5 gm/dL < 10.5 gm/dL
General management: In addition to specific therapy
ESR < 20 mm/h ≤ 30 mm/h > 30 mm/h these supportive measures are very important in the
CRP Normal ≤ 30 mg/dL > 30 mg/dL management of patients with acute severe UC. These
include: (1) Monitoring and replacement of intravenous
fluid and electrolytes to correct and prevent dehydration
However, Truelove and Witt’s criteria is the most widely or electrolyte imbalance as hypokalaemia/hypomagnesae-
accepted disease severity index in clinical practice. The mia can precipitate toxic dilatation[6]; (2) Anticholinergic,
term acute severe colitis is preferred over fulminant coli- antidiarrheal, non-steroidal anti-inflammatory drugs and
tis because the term fulminant is not well defined. It was opioid drugs should be promptly withdrawn as these may
coined in 1950 when it meant that single attack of UC precipitate colonic dilatation; (3) Malnourished patients
could lead to mortality within 1 year[4], which is no lon- should receive adequate nutritional support. Enteral nu-
ger relevant today. Approximately 20% UC patients with trition is most appropriate and is preferred over paren-
initial disease flares have severe UC[4], and about 15% pa- teral nutrition as it is associated with significantly fewer
tients have a severe attack at some stage of their disease[5]. complications than parenteral nutrition in acute colitis[14].
Megacolon refers to presence of dilated colon (> 5.5 There is no evidence that bowel rest with parenteral nu-
cm) on a plain abdominal X-ray film. Toxic megacolon trition alters the outcome[15]; (4) Flexible unprepared sig-
is presence of megacolon with signs of systemic toxicity moidoscopy and biopsy should be done to confirm the
(fever, tachycardia, hypotension, leukocytosis). The over- diagnosis of acute severe UC and exclude infections[16]
all lifetime incidence of toxic megacolon in patients with such as CMV. Presence of active CMV infection is indi-
UC is 1%-2.5%[6]. Prior to introduction of corticosteroid cated by presence of cytomegalovirus inclusion bodies
therapy, mortality with acute severe UC was reported to on colonic biopsies. However inclusion bodies are not
be upto 22%-75% within first year of diagnosis[7]. First very frequent even in patients with active disease with a
clinical trial of steroids for severe UC was performed sensitivity as low as 37.5%[17]. Special immunohistochemi-
in the 1950s and this trial reported a mortality of 7% in cal staining against immediate early antigens of CMV
patients treated with steroids compared with 24% in the increases the diagnostic sensitivity of histologic examina-
placebo group[8]. The mortality with severe UC has re- tion for CMV. In addition positive plasma real time PCR
duced to < 1% in specialist centers. assays for CMV DNA at levels > 20 copies/100 μL is
also an indicator of active CMV disease[18]. Presence of
active CMV disease requires treatment with ganciclovir,
APPROACH TO MANAGEMENT especially if the patient is slow to respond to convention-
Investigations required at admission al therapy; (5) Stool analysis (in atleast 3 stool samples) to
In addition to monitoring patient’s clinical feature and exclude co-existing C. difficile toxin is required especially
vital signs, all patients should have their full blood counts, in patients with history of prolonged hospitalization[19].
liver and kidney function tests, electrolytes including se- C. difficile infection co-existing with acute severe UC has
rum magnesium and inflammatory markers [C-reactive been associated with increased morbidity and mortality,
protein (CRP) and erythrocyte sedimentation rate (ESR)]. and requires appropriate antibiotic therapy (oral vanco-
At least 3 stool samples for Clostridium difficile (C. diffi- mycin or metronidazole)[20]; (6) There is increased risk of
cile) toxin should be obtained to rule out superimposed thromboembolic phenomena, in patients with active IBD
pseudo-membranous colitis[9]. A plain abdominal X-ray compared to controls, especially during disease flares[21].
should be done to exclude megacolon. Plain radiograph Therefore prophylaxis with subcutaneous low molecular
can also provide information about the extent of disease weight heparin is indicated to reduce the risk of throm-
and can also predict response to treatment. The distal dis- boembolism; (7) Topical corticosteroids or mesalazine
tribution of fecal residue can provide a rough estimate of may be administered if patient can tolerate and is able
disease extent as it correlates with the proximal extent of to retain them, although there have been no systematic
disease[10]. The predictors of poor response to treatment studies in acute severe colitis; (8) Antibiotics are indi-
on a plain abdominal radiograph are presence of mucosal cated only if infection is suspected or immediately prior
islands which are small, circular opacities that represent to surgery. Controlled trials of antibiotics such as oral
residual mucosa isolated by surrounding ulceration, or or intravenous metronidazole or ciprofloxacin in acute
presence of more than two gas-filled loops of small colitis have not shown any significant benefit in addition
bowel[11]. Flexible unprepared sigmoidoscopy with mini- to conventional therapy[22,23]; and (9) Blood transfusion is
mal air insufflation should be performed to confirm the indicated in patients with hemoglobin < 10 gm/dL[24].
diagnosis and exclude superimposed infection, especially In addition to these measures daily assessment

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 Kedia S et al . Management of acute severe ulcerative colitis

Acute severe UC
(Truelove Witt's critetia)
IV hydrocortisone 100 mg
Day 1 every 6 hourly or i.v.
methylprednisolone 60
mg/d

Complete responders: Stool

Oral steroids, Add AZA
frequency < 3/d
when steroid dose < 20
mg/d
Classify response according Incomplete responders; Stool
Day 3
to Oxford criteria frequency 3 - 8/d and CRP < 45 mg/L
Medical rescue
Non responders therapy or
Stool frequency > 8/d or 3 - 8/d and colectomy
CRP > 45 mg/L

Complete responders: Switch

to oral steroids, add AZA when
steroid dose < 20 mg/d
Day 4-7
Incomplete/non responders:
Medical rescue therapy or
colectomy

Figure 1 Algorithm for treatment decisions for patients with acute severe ulcerative colitis on intensive steroid therapy. AZA: Azathioprine.

of patients’ clinical status should be done in follow- Predictors of response to steroids

ing manner: (1) Physical examination is required daily Response to steroids is indicated by improvement in pa-
to evaluate abdominal and rebound tenderness. Joint tients’ symptoms (decreased stool frequency, urgency and
collaboration between medical and surgical team is re- rectal bleeding, improved stool consistency, reduction in
quired for appropriate management of such patients; abdominal pain, and improvement in general well being)
(2) Vital signs should be recorded four times daily and and improved laboratory parameters (reduced CRP and
more often if deterioration is noted; (3) A stool chart ESR and improvement in hemoglobin and albumin).
which records the number and character of bowel At day 3 of admission, response to steroids should
movements, including the presence or absence of blood be measured by assessing stool frequency and CRP lev-
and liquid versus solid stool should be properly main- els (Figure 1). In the landmark study by Travis et al[10],
tained; (4) Measurement of blood count, CRP, serum which included patients with 51 episodes of severe UC,
electrolytes, serum albumin, liver function tests, and presence of more than 8 stools/d or 3-8 stools/d plus a
glucose should be done every 24 h; and (5) Abdominal CRP > 45 mg/L at day 3 predicted a colectomy rate of
radiographs should be done daily, especially in patients 85%. In another prospective study by Lindgren et al[27]
in whom there are signs of colonic distension and/or which included 97 episodes of severe UC, the following
there is significant deterioration in clinical condition or mathematical model was devised to predict colectomy:
laboratory parameters. number of stools⁄d + 0.14 × CRP (mg ⁄L) ≥ 8 predicted
a colectomy rate of 72%.
Therefore regular assessment of response to steroids
CORTICOSTEROIDS is of paramount importance in treating patients with
Corticosteroids are the mainstay of therapy for acute acute severe UC. In a group of 80 patients who under-
severe UC. Steroids are given intravenously with meth- went emergency colectomy for severe UC between 1994
ylprednisolone given in a dose of 60 mg/d or hydrocor- and 2000 in Oxford[28], patients with significantly longer
tisone 100 mg every 6 h. Treatment duration is usually duration of preoperative medical therapy (> 8 d) were
limited to 7 to 10 d; continuing corticosteroid treatment more likely to have major post-operative complications.
beyond that period carries no additional benefit[25]. True- Therefore at day 3 of admission, in cases of non
love and Jewell published the first clinical trial of intrave- response to steroids according to above mentioned cri-
nous corticosteroids for acute severe UC in 1974[26]. Of teria (stool frequency > 8/d or stool frequency 3-8/d
49 patients treated with intravenous steroids, 36 (73%) and CRP > 45 mg/L) other treatment options or sur-
achieved complete remission by day 5. In a recently pub- gery should be considered. In cases of partial response,
lished systematic review of 1991 patients from 1974 to therapy should be continued till day 5-7, and if the
2006[25], overall response to steroids was 67%. The overall patient still does not respond, other therapies/surgery
short-term colectomy rate was 29% (565/1991) and mor- should be considered (Table 2). In patients who respond
tality was 1%. to steroids, oral steroids should be started after 5-7 d of

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 Kedia S et al . Management of acute severe ulcerative colitis

[38]
Table 2 Ten year follow up of patients of Oxford cohort Table 3 Long term response rates to cyclosporin
categorized at day 7 of intensive therapy
Initial response 74%
Parameter Complete responders Incomplete responders 1 yr 65% relapsed
Colectomy rate at 1 yr 5% 54% 3 yr 90% relapsed
Number requiring 6/19 (32%) 10/13 (76.9%) 7 yr 58% colectomy rates
colectomy
Maximum steroid free 3.5 yr < 1 yr
remission
However, one of the major limitations associated with
cyclosporin use is its side effect profile. The short-term
side effects are a cause of concern because cyclosporin
intensive therapy.
is generally used as bridge to immunomodulators. These
There are several other studies which have predicted
include minor side effects, which occur in 31%-51% pa-
response to steroids in acute severe UC. Ho et al[29], in
tients, including tremors, paresthesias, malaise, headache,
a retrospective study found that, number of stools/day
abnormal liver function tests, gingival hyperplasia and
(score 1-4); hypoalbuminaemia < 3 mg/dL (score 1) and
hirsutism. Major complications are reported in 0%-17%;
colonic dilatation > 5.5 cm (score 4) were useful in pre-
including hypertension, renal impairment, infections and
dicting colectomy as 85% of patients with a score ≥ 4
neurotoxicity[36]. Cyclosporin therapy in UC is associated
required colectomy. In another study by Ananthakrishnan
with a mortality rate of approximately 1.8%-3.5%[36].
et al[30], anemia, malnutrition, need for blood transfusion Therefore, following points should be considered before
and total parenteral nutrition would independently pre-
starting cyclosporin therapy.
dict colectomy. Radiological markers which can predict
Cyclosporin should not be used if cholesterol < 115
colectomy include the presence of mucosal islands on
mg/dL or magnesium < 1.4 mEq/L. It should also be
a plain abdominal radiograph which is associated with a
avoided in presence of hypertension, renal impairment,
75% colectomy rate[31], and presence of an ileus (indicated
epilepsy, sepsis, age > 80 years. Magnesium, cholesterol,
by 3 or more small bowel loops of gas) which is associ-
and creatinine should be measured at baseline and within
ated with 73% colectomy rate[11]. In a study, presence of
48 h of starting cyclosporin.
deep ulcers on endoscopy after gentle air insufflation
Cyclosporin should be administered in a dose of 2
identified 42/49 patients who required colectomy[32].
mg/kg per day intravenously aiming for levels 150-250
ng/mL[37].
CYCLOSPORIN Oral microemulsion 4 mg/kg twice daily can be alter-
natively considered.
Two controlled clinical trials established the efficacy of
Blood Pressure and renal function should be moni-
intravenous cyclosporin (fungal calcineurin inhibitor) as tored and cyclosporin should be stopped if serum creati-
medical rescue therapy for acute severe UC not respond- nine rises > 25%.
ing to intravenous corticosteroids. In the first landmark Cyclosporin should be stopped if there is no im-
trial by Lichtiger et al[33] 9 out 11 patients in the cyclospo- provement in 7 d.
rin (4 mg/kg per day) group had a response vs none of In responders intravenous cyclosporin (Figure 2)
9 placebo treated patients. The trial was terminated early should be switched to oral cyclosporin 4 mg/kg per day
for ethical reasons because of marked response to cyclo- twice daily. Monitoring of trough levels (150-250 ng/mL)
sporin. Of nine placebo treated patients 5 patients were should be regularly done. Azathioprine should be started
crossed over to cyclosporin and all five responded. In an- along with oral cyclosporin. Cyclosporin should be
other study 73 patients were randomized to 4 mg/kg vs 2 stopped after 3 mo.
mg/kg of intravenous cyclosporin[34]. Response rates at 8 Infective complications with cyclosporin can be
d were similar in both groups (83% and 82% respectively), avoided by minimizing concomitant immunosuppressants
with 9% and 13% colectomy rate in 2 and 4 mg/kg group and by using prophylactic antibiotics when indicated.
respectively. Therefore, cyclosporin dose of 2 mg/kg per Regarding long term efficacy of cyclosporin (Table 3)
day has become the standard in clinical practice. Another several cohorts have been evaluated long term colectomy
European study compared intravenous cyclosporin (4 in patients treated with cyclosporin. In the retrospective
mg/kg) with intravenous steroids and found similar re- cohort from Oxford, 42% patients could avoid colectomy
sponse rates between the two groups (64% vs 53%)[35]. after 7 years[38]. Overall, approximately 50% patients will
Therefore cyclosporin monotherapy may be preferred avoid colectomy over a period of 2-3 years[39,40]. Immu-
over steroids in patients who have high chances of side- nomodulators when used with cyclosporin can decrease
effects with steroids including patients with osteoporosis, the colectomy rate, thus improving the long term efficacy
poorly controlled diabetes and those who are susceptible of cyclosporin. In a study by Cohen et al[41] probability
to steroid-psychosis. Overall, pooled results from con- of avoiding colectomy at long-term follow-up (5.5 years)
trolled and non-controlled trials show response rates with was 66% in patients receiving cyclosporin and azathio-
intravenous cyclosporin to vary from 76% to 85%, with prine/mercaptopurine compared with 40% in those who
median time to response being 4 d[35]. received cyclosporin alone. Further studies in this regard

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 Kedia S et al . Management of acute severe ulcerative colitis

Adequate response:
Switch to oral CsA,
Cyclosporine add AZA at day 7 d
(In AZA naive Assess response
patients) at day 4-7

Inadequate
Colectomy
response

Single dose
Infliximab infusion Assess response
at 5 mg/kg at day 4-7 Adequate response:
Infliximab dose at
2 and 6 wk, AZA to
be continued

Figure 2 Algorithm for medical rescue therapy after failure of response to intravenous steroids.

have shown that in patients already on immunomodula- skin test or Interferon gamma release assays for latent
tors at the time of admission with acute severe UC, the tuberculosis.
likelihood of needing a colectomy following treatment Long term follow up data up to 3 years in infliximab
with cyclosporin is higher than among those in whom treated severe UC patients are available. Two studies
immunomodulators are started after admission[40]. with follow up data of 1 year show colectomy rates of
Therefore, cyclosporin is more beneficial in pa- approximately 25% at 1 year in infliximab treated pa-
tients with acute severe UC who are thiopurine naïve at tients[45,46]. In another Swedish study, colectomy rate at 3
the time of admission. In patients who are already on years in infliximab treated patients was 50% as compared
thiopurine at the time of admission, the outcome with to placebo (76%)[47].
cyclosporin would be less favourable and other medical There are no exclusive trials of other anti TNF
options or surgery needs to be considered. agents for acute severe UC. However, there are few trials
of adalimumab in moderate to severe active UC which
showed efficacy of adalimumab over placebo. Reinisch
INFLIXIMAB et al[48] showed that adalimumab induced remission in
Infliximab the chimeric monoclonal antibody against 18.5% patients as compared to 9.2% patients in placebo
tumor necrosis factor (TNF) alpha has been found to group (P = 0.031). In another study Sandborn et al[49], in
have a favorable response in patients with steroid refrac- a similar group of patients showed efficacy of adalim-
tory acute severe UC. In an open label study of 6 steroid umab over placebo (16.5% vs 9.3%, P = 0.019) in induc-
refractory severe UC patients[42], single infusion of in- ing remission.
fliximab in a dose of 5 mg/kg showed marked clinical
improvement at day 7 in all patients. Four out of these 6
patients were in long term remission at median follow up CYCLOSPORIN VS INFLIXIMAB
of 5.5 mo. Later a randomized placebo controlled trial Before the landmark randomized trial CYSIF (Cyclospo-
of 45 patients (24 infliximab and 21 placebo) showed rin With Infliximab in Steroid-refractory Severe Attacks
that a colectomy rate at 3 mo was significantly lower in of Ulcerative Colitis) between cyclosporin and infliximab
infliximab group as compared to placebo group (29% vs there was limited evidence to suggest any difference in
67%, P = 0.017)[43]. The maximum benefit of infliximab efficacy of cyclosporin and infliximab. In a retrospective
was seen in patients with moderately severe disease than review of two cohorts (43 treated with cyclosporin and
in those with most severe disease. Prior exposure to thio- 49 treated with infliximab) there was lower short term
purines does not seem to affect the outcome of patients colectomy rate in the cyclosporin group[50]. The CYSIF
treated with infliximab[43]. Other factors which may ad- trial[51] randomized 111 thiopurine naïve patients with se-
versely affect outcome with infliximab include increased vere UC after 5 d of Ⅳ steroids to cyclosporin (2 mg/kg
baseline CRP (> 20 mg/L), concomitant steroid use, per day for 8 d followed by 4 mg/kg per day orally) and
disease duration ≤ 3 years and baseline Mayo score ≥ infliximab (5 mg/kg iv infusion at 0, 2 and 6 wk). Patients
10[44]. Screening for infections and immunization history who responded at day 7 received oral azathioprine and
should be obtained prior to initiating infliximab therapy. tapered steroids from day 8. The response to treatment
Screening tests which need to be done include hepatitis B at day 7 was seen in approximately 85% patients in both
serology, HIV serology, chest radiograph and tuberculin groups. Colectomy rates at day 98 were also similar be-

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 Kedia S et al . Management of acute severe ulcerative colitis

Table 4 Mortality according to day of surgery after intensive

therapy within 48 h will decrease the morbidity and mor-
steroid therapy tality of this condition.
Other complications include perforation which is the
Timing of surgery Number of Mortality most serious complication of severe UC. Risk factors
Total emergency surgeries = 72 patients include inappropriate total colonoscopy and delaying treat-
Overall 51 8 ment of toxic megacolon. Diagnosis of perforation can
≤ 5d 17 0/17
>5d 34 8/34
often be delayed as abdominal signs can be masked when
patient is on steroids. Therefore, patients with severe UC
should be monitored closely for abdominal signs and on
tween cyclosporin and infliximab (18% vs 21%, P = 0.66). the slightest suspicion abdominal radiographs should be
Treatment failure at day 98 was also similar, seen in 60% obtained. Other complication includes severe hemorrhage.
patients in the cyclosporin group vs 54% in the infliximab
group. There was no clear evidence of superiority of any SURGERY
one therapy over other.
Therefore choosing between cyclosporin and inflix- Surgery is the final option for patients with severe UC
imab depends upon physician and patient preferences not responding to medical therapy. Other indications for
as both appear to be equally efficacious in the setting of surgery include toxic megacolon, perforation and severe
acute severe colitis. haemorrhage. The decision for surgery should not be
delayed as this increases the morbidity and mortality of
surgery. In a study performed at our center, the mortal-
SWITCHING BETWEEN INFLIXIMAB AND ity of emergency surgery was very high if the interven-
tion was delayed beyond 5 d following non-response to
CYCLOSPORIN
intravenous steroid therapy (Table 4)[56]. In another study
In cases of non-response to infliximab or cyclosporin, from Oxford, higher surgical complication was noted if
switching to either therapy is associated with significant surgery was delayed beyond 8 d of medical therapy[28].
morbidity and mortality and is not recommended. In Therefore management of severe UC requires close col-
the largest study of 86 patients on this aspect, 65 pa- laboration between surgeon and gastroenterologist so
tients were administered infliximab after cyclosporin that appropriate decisions can be taken without delay.
and 21 patients had cyclosporin after infliximab. Thirty Most centers advocate a 3 step surgery in emergency
three percent patients underwent colectomy within 3 setting. The surgical procedure of choice in acute setting
mo and 1/3 rd of the patients had adverse effects in is sub-total colectomy and ileostomy, with the rectum
form of infections[52]. left in situ. The whole of rectum and inferior mesenteric
artery should be preserved, which facilitates further sur-
TACROLIMUS gery. The bowel can either be closed in subcutaneous fat
or brought forward as mucous fistula, depending upon
Tacrolimus is also a calcineurin inhibitor with mechanism the surgeon’s decision. Subtotal colectomy is a safe pro-
of action similar to that of cyclosporin. A randomized cedure even in critically ill patients[57,58] and will relieve the
trial of tacrolimus included 27/60 patients with severe patient from burden of severe colitis, thus allowing the
UC[53]. In this trial partial response was seen in 67% pa- patient to normalise health and nutrition. Reconstructive
tients, although complete remission was not seen on any surgery is best performed approximately 6 mo after pri-
patient. However, further case series have shown results mary surgery[59]. The second step consists of ileal pouch
similar to that of cyclosporin[54,55]. formation and defuctioning temporary ileostomy. In the
final step ileal pouch anal anastomosis (IPAA) is done
TOXIC MEGACOLON AND OTHER restoring normal continuity.
There appears to be a strong association of prolonged
COMPLICATIONS OF SEVERE UC use of immunosuppression and poor wound healing
Toxic megacolon may be defined as colonic dilatation of after surgery which may manifest as wound dehiscence,
more than 5.5 cm along with signs of systemic toxicity. infection following intestinal leak or a pelvic abscess fol-
Lifetime incidence of toxic megacolon in patients with lowing anastomotic leak. Long-term preoperative steroid
UC varies from 1%-2.5% and approximately 5% severe use has been found to be a significant risk factor for
UC patients who are hospitalized may develop toxic anastomotic leak. Immunosuppressive agents (azathio-
megacolon[6]. Risk factors include dyselectrolytemia, full purine and 6-mercaptopurine) have not been associated
bowel preparation and medications (antidiarrheal, anti- with increased postoperative complications. When used
cholinergic, and opiods)[6]. Earlier identification of this alone, cyclosporin has not been associated with increased
condition, prompt institution of medical therapy (nil per postoperative complications. The use of infliximab (IFX)
oral, intravenous broad spectrum antibiotics, fluid and and its impact on postoperative course is debatable and is
electrolyte management, and intensive therapy) and low a subject of intense interest. Two studies have identified
threshold of surgery in cases of non-response to medical a relationship between IFX and postoperative complica-

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 Kedia S et al . Management of acute severe ulcerative colitis

tions in IPAA patients. The first report came from Mayo drawl of drugs promoting colonic dilatation and adequate
Clinic[60] which included a retrospective survey of 47 nutritional support are important adjuncts in the manage-
patients who received preoperative IFX and 254 who did ment of severe UC. Intravenous corticosteroids are the
not. In the multivariate analysis, IFX was independently first line therapy for severe UC, and approximately two
associated with increased risk of pouch-related and infec- thirds of patients respond. Response to steroids should
tious complications. The authors concluded that IFX was be assessed at day 3, and in non-responders/partial re-
a surrogate for critical patients who were at a higher risk sponders, medical rescue therapy or surgery should be
for postoperative complications. The second study by considered. Efficacy of both cyclosporin and infliximab
Mor et al[61], had a case control design. It suggested that in this setting is comparable as shown in a recent ran-
patients who had preoperative IFX were 3.5 times more domized trial. A close coordination between gastroenter-
likely to experience an early postoperative complication as ologist and surgeon is required for optimal management
compared to control patients. IFX-exposed patients were of severe UC. Surgery is always an option after failure
nearly 14 times more likely to suffer infectious complica- of IV steroids, and all patients should be given an option
tions. Other studies, which have not been in agreement of surgery. A time bound strategy is required to manage
with the conclusion of above-mentioned studies, include such patients and surgery should not be delayed beyond
a large retrospective review of 413 patients with UC and 5 d of intensive therapy, as a delay increases surgical mor-
CD over a 14-year period[62]. This study did not find any bidity and mortality.
association between IFX and postoperative complica-
tions. The study faced certain criticisms, which included a
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