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265
19 Surgery for Fulminant Colitis
contraindicated in the fulminant setting because of the risk of perforation and risk
of precipitating toxic megacolon. However, a plain abdominal x-ray directly after
endoscopy may delineate the extent of disease (Box 19.1 ) .
19.3 Etiology
19.3.1 UC/Crohn’s Disease
Ulcerative colitis is still the commonest cause of fulminant colitis. The predomi-
nance of UC is however diminishing as Crohn’s disease is becoming more preva-
lent. Interestingly, the incidence of Crohn’s disease has risen worldwide, whereas
the incidence of UC has plateaued [ 11 ] . Six percent to 10% of patients with IBD
develop an episode of toxic colitis, and the risk of developing toxic megacolon is
highest early in the disease. Approximately 30% of the cases occur as their fi rst
presentation. It is important to appreciate that with the rise in the incidence of
Crohn’s disease, patients presenting with fulminant colitis are less likely to manifest
toxic megacolon because of the presence of transmural infl ammation but more
likely to develop localized perforation, fi stulae, and abscesses. These are less likely
to be apparent on plain x-rays and may require cross-sectional imaging (Fig. 19.2 ).
Fig. 19.1 CT scan of
Crohn’s colitis.
Abscess cavity containing
gas;
communication
between the bowel and
abscess cavity
Box 19.1: Predictive Factors for Poor Response to Medical Management
Day 3 on high-dose corticosteroid: >8 stools/day, CRP >45 mg/L [ • 8 ]
Temperature >37.5°C, HR >90 bpm, CRP >45 mg/L [ • 9 ]
Mucosal islands or transverse colonic diameter of >5.5 cm seen on AXR [ • 10 ]
Small bowel distension [ • 3 ]
Deep ulceration penetrating muscularis on endoscopy [ • 6 ]
266
K. Futaba et al.
19.3.2 Infective Colitis
A variety of organisms have been implicated in fulminant colitis caused by an infec-
tive agent: Clostridium diffi cile , Shigella , Salmonella , Campylobacter jejuni ,
E. coli-0157 , Amoebae , and Cytomegalovirus . Interestingly, fulminant infective
colitis is also recognized in horses, termed “colitis X,” which is often fatal within
24 h of diagnosis. It is also thought to be caused by clostridial organisms.
19.3.2.1 Clostridium Diffi cile
Over the past decade, there has been a substantial and international increase in the
incidence and severity of Clostridium diffi cile infection (CDI). Over a 30-month
period between 2003 and 2004 in Quebec, Canada, 38 out of 165 intensive care
admissions required emergency colectomy as a consequence of fulminant infective
colitis. CDI was becoming more frequent, severe, and refractory to treatment [ 12 ] .
The more virulent strain NAP1/027 was found to be responsible, causing outbreaks
in across three continents, including the United States, Canada, United Kingdom,
Japan, and the Netherlands. NAP1/027 strain was found to produce 15–20 times
more enterotoxin A and cytotoxin B than common strains, inducing an exaggerated
infl ammatory response.
In fulminant pseudomembranous colitis, there is progression of infl ammation
beyond and involving the muscularis propria, leading to loss of colonic tone result-
ing in passive dilatation of the colon, thus increasing the risk of perforation. This
Fig. 19.2 Colonic specimen
showing pseudopolyps
267
19 Surgery for Fulminant Colitis
has fast become the most common cause of toxic dilatation of the colon, requiring
regular surgical review to determine if the infection is settling or whether surgical
resection is required. This population of patients has an especially high mortality, as
they will usually harbor signifi cant comorbid disease. The most important risk
factor for the development of CDI is prolonged course of antibiotics, such as clin-
damycin, cephalosporins, and fl uoroquinolones. Other important risk factors are
immunosuppression, recent surgery, uremia, burns, chronic obstructive pulmonary
disease, intensive care admissions, use of proton pump inhibitors, and prolonged
hospital stay [ 13 ] .
Clinical manifestations of patients with fulminant CDI include a fl orid systemic
toxicity (fever, tachycardia, rigor, leukocytosis, and lactic acidosis) and acute
abdominal signs with or without abdominal distension. Up to 20% of patients may
not develop diarrhea due to severe colonic dysmotility [ 14 ] . Risk factors for patients
who are likely to develop fulminant colitis from CDI are: age over 65 years, raised
lactate between 2.2 and 4.9 mmol/L, leukocytosis (WCC >16), surgery within
30 days, history of IBD, or history of intravenous immunoglobulin treatment [ 15 ] .
These are an especially high risk group of patients, not least because they have usu-
ally presented with a preceding illness and developed CDI as a consequence of
antibiotic treatment. Early recourse to total colectomy and end ileostomy should be
considered.
The gold standard diagnostic test for CDI is the stool cytotoxin assay with sensi-
tivity of 67–100% and specifi city of 85–100%. However, as the test takes 1–3 days,
enzyme-linked immunosorbent assay (ELISA) is now most commonly used, which
quickly detects both toxin A and B with sensitivity of 92–94.5% and specifi city of
100%. These will provide a result within hours and allow treatment to start
promptly.
CT scans may show colonic wall thickening and colonic dilatation often with
ascites (Fig. 19.3 ) and are the most frequent investigation for these patients, with
early signs of peritonism. Endoscopic examination can demonstrate the classical
features of a diffuse colitis, marked mucosal edema, and pseudomembrane forma-
tion (Fig. 19.4 ) but is less commonly used since the widespread availability of
ELISA testing [ 12, 16 ] .
Fig. 19.3 CT scan of patient
with C. diffi cile colitis
showing typical colonic wall
thickening (mucosal
enhancement and submucosal
edema) with pericolic fl uid
268
K. Futaba et al.
Medical treatment for fulminant C. diffi cile colitis includes oral vancomycin
125–500 mg QDS +/− intravenous metronidazole 500 mg TDS, in addition to sup-
portive therapy and discontinuing the implicated antibiotics. Active vaccines and
immunotherapeutic strategies are currently under evaluation. The general indication
for colectomy is failure to respond to medical therapy (see Box 19.1 ). In patients
with CDI, additional indications for colectomy are signs of organ failure, shock,
requirement for vasopressor, worsening CT scan fi ndings despite medical treatment,
persistent toxic dilatation with focal tenderness, signs of peritonitis, or lack of
response to maximal appropriate medical management within 24–72 h. Lamontagne
et al. reported 30-day mortality of 58% in medically treated patients with severe CDI
in comparison to 34% treated surgically [ 12 ] . Importance of early diagnosis and
treatment and consideration for early surgery in these chronically debilitated patients
must be recognized. They are generally ill equipped to withstand prolonged periods
of poor nutrition combined with protein loss from the colon. At surgery, the colon is
typically edematous, distended with foci of necrosis, with or without perforation. As
with ulcerative colitis, cohort studies have shown that segmental resection and divert-
ing stoma are associated with higher mortality and the need for further surgery [ 17 ] .
Therefore, the procedure of choice is a subtotal colectomy with end ileostomy [ 16 ] .
19.3.3 Ischemic Colitis
With an increasing incidence in an aging population suffering from multisystem
vascular disease, ischemia must be considered when faced with an elderly patient
with colitis. In a cohort multicenter study, ischemic colitis represented only
Fig. 19.4 A typical
endoscopic picture of
pseudomembranous colitis
269
19 Surgery for Fulminant Colitis
2.5% of 364 cases [ 18 ] , but underdiagnosis is common because of relative rectal
preservation. Patients undergoing cardiac surgery present a special case because of
the use of inotropes and the use of aortic balloon pumps, both of which reduce an
already compromised gut perfusion. A degree of gut ischemia is probably universal
in this population, and ischemic colitis is not an infrequent complication.
Ischemic colitis should be considered and managed as part of a systemic disease.
Therefore, it is important to manage the risk and precipitating factors as well as the
colon. Optimizing cardiac function is essential, as isolated treatment of the ischemic
bowel is doomed to failure. At surgery, depending on the site of ischemia, it may be
worth preserving the rectal stump and considering ileorectal anastomosis as a two-
stage procedure. This is possible because of the relative preservation of rectal blood
fl ow. In general, a long rectal stump is advisable if reconstruction is to be consid-
ered. But ischemic colitis is the exception as ischemia may be worst in the sigmoid
colon. As the distal resection has to be through healthy bowel, the option to form a
mucus fi stula may not be available if the sigmoid colon is too affected to be
preserved.
19.4 Medical Treatment
The relationship between medical therapy and acute surgery has been the cor-
nerstone of managing fulminant ulcerative colitis for the last 40 years. However,
the introduction of novel therapeutic options has complicated this relationship.
Inappropriate medical treatment can delay surgery, resulting in increased periopera-
tive morbidity and delayed recovery. An agreed unit policy has probably never been
more important.
Current guidelines for the management of severe UC are summarized in Box 19.2
[ 19 ] . Historically, patients with fulminant colitis were treated with intravenous ste-
roid for 5 days. If there was no improvement, the patient would be offered emer-
gency surgery. In 1996, Travis reported that 85% of patients who had more than
eight stools per day and CRP >45 mg/L after 3 days of intravenous corticosteroid
required colectomy during the same admission [ 8 ] . Recent systematic review
showed that overall response to steroid therapy for acute severe colitis from 1974 to
2006 was 67%. Approximately 27% proceeded to surgery in the short term, and
colectomy rate remained about the same over the 30 years, implying the steroid
therapy has little impact on the long-term course of the disease [ 20 ] . Novel therapies
can now be offered in selected patients. These treatments may also alter the long-
term disease outcome, but that is yet to be established. Now after 3 days, in patients
with an incomplete response to IV steroids, there are further treatment options avail-
able: intravenous ciclosporin (2 mg/kg/day) or infl iximab (5 mg/kg). Both treat-
ments have shown promising results in cohort studies, but as yet, no multicenter
RCT has been reported. A modifi ed version of a treatment algorithm recently sug-
gested in the literature for the management for severe/fulminant ulcerative colitis is
shown in Fig.
19.5 [ 21 ] .
270
K. Futaba et al.
In 1994, an RCT carried out on 20 patients with severe UC not responding to at
least 7 days of intravenous steroid therapy showed 82% (9/11) of patients treated
with ciclosporin improved in comparison to 0% (0/9) in the placebo group. Three
out of 11 patients in the ciclosporin group and 4 out of 9 patients in the placebo
Box 19.2: Guidelines for Management of Severe UC in Guidelines for
the Management of Infl ammatory Bowel Disease in Adults [ 19 ]
Assessment and monitoring:
Daily physical examination. Joint medical and surgical management. •
Recording of vital signs four times daily or more often if deterioration •
noted.
Stool chart – frequency, consistency, presence of blood. •
FBC, ESR/CRP, U&E, LFTs, albumin every 24–48 h. •
Daily abdominal radiography if colonic dilatation is detected. •
Management:
Intravenous fl uids and electrolyte replacement, with blood transfusion to •
maintain Hb > 10 g/dL.
Subcutaneous heparin for thromboprophylaxis (grade B). •
Nutritional support if malnourished (grade C). •
Intravenous corticosteroid (hydrocortisone 400 mg/day or methylpredni-•
solone 60 mg/day) (grade B).
Withdrawal of anti-cholinergic, anti-diarrheal agents, NSAID, opioids, •
which risk precipitating colonic dilatation.
Continuation of aminosalicylates once oral intake resumes. •
Topical therapy (corticosteroid/mesalazine) if tolerated and retained. •
Limited evidence (grade C).
Intravenous antibiotics only if infection is considered/immediately before •
surgery.
Immediate surgical referral if there is evidence of toxic megacolon (diam-•
eter >5.5 cm or cecum >9 cm). The greater the dilatation and the greater
the degree of toxicity, the sooner surgery should be undertaken, but signs
may be masked by steroid therapy (grade C).
Objective re-evaluation on the third day of intensive treatment. A stool •
frequency of >8/day or CRP >45 mg/L at 3 days appears to predict the
need for surgery in 85% of cases. Surgical review and input from specialist
colorectal nurse/stoma therapist is appropriate at this stage. There is no
benefi t from intravenous steroids beyond 7–10 days (grade B).
Consideration of colectomy or intravenous cyclosporin 2 mg/kg/day if •
there is no improvement during the fi rst 3 days (grade A).
The procedure of choice in acute fulminant UC or CD is a subtotal colec-•
tomy leaving a long rectal stump, either incorporated into the lower end of
the wound or exteriorized as a mucus fi stula, to facilitate later rectal exci-
sion and minimize the risk of intraperitoneal dehiscence (grade B).
271
19 Surgery for Fulminant Colitis
underwent colectomy [ 22 ] . Numerous RCTs have demonstrated that 4 mg/kg intra-
venous ciclosporin has no additional clinical benefi t over 2 mg/kg dose for severe
UC. Response rates in one cohort series showed response rate of 84.23% and
85.72% in 4 mg/kg and 2 mg/kg iv ciclosporin groups, respectively, at 8 days,
establishing 2 mg as the standard dose [
23 ] . Concern about signifi cant short- and
long-term toxicity with ciclosporin has prevented its widespread use: hyperten-
sion, renal failure, neurotoxicity, seizures in patients with low cholesterol and
magnesium, hepatotoxicity, and infection including pneumocystis . However, in
transplant centers, where the drug is widely used, experience is increasing in the
treatment of colitis.
A systematic review looking at infl iximab therapy in UC showed that it was more
effective than placebo for the treatment of moderate to severe UC (NNT 3–5). Short-
term response was 65% with infl iximab and 33% with placebo. Long-term remis-
sion at approximately 9 months was achieved in 33% of patients treated with
infl iximab compared to 14% in placebo group [
24 ] . One RCT from Scandinavia
comparing infl iximab (5 mg/kg) and placebo on day 4 postinitiation of intravenous
steroid therapy showed colectomy rate of 29% (7/24) and 67% (14/21) in infl iximab
and placebo groups, respectively, at 90 days ( p = 0.017) [ 25 ] . However, a recent
study from Italy showed that although infl iximab may reduce the need for urgent
colectomy in steroid-refractory patients, the risk of elective colectomy, in the long
term, is not modifi ed [ 26 ] .
Fulminant Ulcerative Colitis
Oral Ciclosporin for 3 months
Start Azathioprine 2mg /kg
before dischage
Intravenous steroids
(iv Hydrocortisone 100mg qds or
iv methylprednisolone 60mg od)
Ciclosporin 2mg/kg
Continue lnfliximab
iv Infliximab 5mg /kg
Thiopurine nalve
No Response
Unstable
No Response
Response
Response
Incomplete Response
SURGERY
SURGERY
SURGERY
Fig. 19.5 Possible treatment algorithm for the management for severe/fulminant colitis [ 21 ]
272
K. Futaba et al.
There are currently no guidelines as to which therapy to offer and specifi cally no
timelines to guide duration of medical therapy. In addition, only anecdotal data are
available as to the crossover use of ciclosporin and infl iximab. One retrospective
study looking at only 19 patients with severe corticosteroid-refractory UC who
failed treatment with either ciclosporin or infl iximab achieved remission for a short
period of time in approximately one third of patients using acute salvage therapy by
crossing over to the other drug. However, serious adverse events occurred in 16%,
including one death, suggesting that the risks of acute salvage therapy may out-
weigh the benefi ts [
27 ] . We would not advocate this approach on the present
evidence.
The challenge for surgery is to determine how surgical intervention can be
planned alongside this increasingly complex medical therapy. It is diffi cult to com-
ment as to the timing of surgery, with these novel therapies becoming available, as
the evidence is lacking. Our current policy is to preferentially offer novel therapies
to patients who have made an incomplete response to medical therapy. Patients with
evidence of progression (extending colitis) or those with signifi cant comorbidity
would be guided toward early surgery. It will be interesting to see the results of a
UK-wide multicenter RCT currently being carried out, comparing the use of infl ix-
imab and ciclosporin in steroid resistant ulcerative colitis (CONSTRUCT).
19.5 Surgery
In 1967, Goligher suggested that early surgery may present considerable advantage
in those patients with severe UC failing to respond rapidly to intensive medical
treatment [ 28 ] . A report from Canada recently showed that UC patients whose sur-
gery was performed more than 6 days after their emergency admission had signifi -
cantly increased likelihood of in-hospital death (adjusted OR 2.12) compared to
those who had early surgery. They also showed that postoperative mortality was
lower in hospitals performing higher volume surgery [ 29 ] . This indicates that the
timing of surgery remains key, and early surgery remains the safest option for the
patient. Surgical assessment should be sought at the time of admission. Delaying
surgery in the acute setting may allow patients to avoid surgery all together, but this
is still a minority. For many patients, interval surgery will be performed because of
further relapses or uncontrollable symptoms. These are important factors to bear in
mind when counseling patients. One must still not wait too long with hopeful expec-
tation of response in patients with fulminant colitis. We are currently in the process
of evolving new therapeutic algorithms for fulminant UC, but the benefi ts of novel
medical treatments need to be better defi ned and the risks to the patients minimized.
Surgery remains a safe and effective treatment for this condition.
In planning surgery, one must consider the overall condition of the patient, the
condition of the bowel at surgery, and the probable pathological cause of colitis. The
surgical treatment of choice in fulminant colitis remains a subtotal colectomy and
end ileostomy [ 30 ] . This allows speedy removal of the majority of affected bowel in
273
19 Surgery for Fulminant Colitis
a critically ill patient, resulting in clinical resolution of the colitis in almost all
patients. Avoiding proctectomy simplifi es the operation and reduces complications
related to pelvic surgery.
Many groups are exploring a laparoscopic approach in selected patients [
31 ] .
Some report earlier discharge, less adhesions facilitating future pelvic and restor-
ative pouch surgery following laparoscopic total colectomy in patients with fulmi-
nant colitis [ 32 ] . The high risks of operative perforation in the acutely ill patient
preclude this being advocated more widely at the present time. However, Crohn’s
colitis is less susceptible to perforation and perhaps more suitable for a laparoscopic
approach. It may be that in a selected group, early surgery enabling a laparoscopic
approach could be advocated. There are no studies advocating a primary restorative
procedure for these patients. Following surgery and full recovery, many of these
patients will request a restorative proctocolectomy [ 33 ] . Therefore, in our own prac-
tice at colectomy, we advocate leaving a long rectal stump as this makes subsequent
pelvic dissection for reconstruction safer (Box 19.3 ).
In addition to the complications associated with major surgery in a critically ill
patient, there are additional, potentially serious complications, most importantly,
pelvic sepsis from rectal stump “blowout.” You may also see adrenal insuffi ciency
and portal vein thrombosis occurring in these patients, and preventative medical
measures are required [
7 ] .
There are a number of options available to try and reduce the occurrence of pel-
vic sepsis: exteriorization of rectal stump as a mucus fi stula, exteriorization above
the abdominal fascia, or incorporation into the bottom of the wound. These options
should always be considered if a secure closure of the stump is not possible. Our
preference is to bring out a separate mucus fi stula, as wound infection is a signifi -
cant problem if the stump is incorporated into the wound. Diffi culties arise if there
is ischemia or necrosis in the sigmoid colon. In these cases, a lower resection in the
Box 19.3: Operative Tips for Surgical Management of Fulminant
Ulcerative Colitis
Operative tips for fulminant colitis:
Timing of surgery is central.•
Patient mentally prepared –
Minimize delay following failed medical therapy –
In fulminant colitis, the bowel is very friable. Careful handling. •
Omentum may be covering a small perforation. Therefore, avoid dissec-•
tion and excise en bloc.
Subtotal colectomy with end ileostomy is the operation of choice.•
Leave rectal stump long. –
Avoid laparoscopic procedure if unstable, grossly distended, or •
peritonitic.
274
K. Futaba et al.
upper rectum is probably advisable. This will make subsequent pelvic dissection
hazardous, and stenting of the ureters may be advisable.
Alternatively, rectal decompression can be carried out by inserting a rectal tube
or Heald anal stent at the end of the procedure. These measures probably do not
reduce the risk of rectal stump sepsis but ensure it is identifi ed quickly and treated
at an early stage.
There is an increased risk of postoperative complications in patients receiving
preoperative steroid therapy [
34 ] . These patients must be given adequate steroid
cover in the postoperative period to avoid adrenal insuffi ciency. There is confl icting
evidence regarding association of postoperative complications with preoperative
infl iximab therapy. At present, there appears to be an association with surgery for
chronic UC, but not for Crohn’s disease [ 35 ] . Concerns remain about the conse-
quences of other immunosuppressive agents in the postoperative period, but data
from Crohn’s patients are largely reassuring [ 36 ] . Nonetheless, antibiotic cover for
patients undergoing surgery for fulminant colitis should be routine (Box 19.4 ) .
19.6 Conclusion
Although the surgery for fulminant colitis has changed little in recent years, the
complexity of these patients has increased. More aggressive medical therapy can
delay surgery in a critically ill patient, and changing patient populations have broad-
ened the differential diagnosis. Careful monitoring of these patients by a multidis-
ciplinary team remains central to their safe management.
Box 19.4: Key Points in Postoperative Management
Postoperative key points:
Reduce steroids gradually •
Monitor fl uid balance and electrolyte closely•
Ileostomy fl ux –
If septic, consider rectal stump complications•
Perforation –
Infl ammation –
Consider restorative proctocolectomy as outpatient •
Key Points
Presentation•
Bloody diarrhoea, urgency – “Truelove & Witts” criteria; 30% fi rst pre- –
sentation of CUC.
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