Inpatient Management of Acute Severe Ulcerative Colitis
Acute severe ulcerative colitis (ASUC) is a potentially life-threatening presentation of ulcerative colitis that in nearly all cases requires inpatient management and coordinated care from hospitalists, gastroenterologists, and surgeons. Even with ideal care, a substantial proportion of patients will ultimately require colectomy, but most patients can avoid surgery with intravenous corticosteroid treatment and if needed, appropriate rescue therapy with infliximab or cyclosporine. In-hospital management requires not only therapies to reduce the inflammation at the heart of the disease process, but also to avoid complications of the disease and its treatment. Care for ASUC must be anticipatory, with patient education and evaluation starting at the time of admission in advance of the possible need for urgent medical or surgical rescue therapy. Here we outline a general approach to the treatment of patients hospitalized with ASUC, highlighting the common pitfalls and critical points in management.
© 2019 Society of Hospital Medicine
Infliximab
Infliximab is an intravenously-administered anti-TNF monoclonal chimeric antibody that is effective both for outpatient treatment of moderate to severe UC and inpatient treatment of ASUC.1 It is relatively contraindicated in patients with untreated latent tuberculosis, demyelinating disease, advanced congestive heart failure, or uncontrolled infection.
The optimal dosing strategy for infliximab in ASUC is unknown. Infliximab clearance in the setting of ASUC is increased, partly because it is bound to albumin, which is often low in ASUC, and partly because it is excreted in the stool.60,61 As a result, accelerated loading doses may be more successful than a typical loading schedule,62 and most clinicians use alternative dosing strategies.63 Our typical approach for ASUC is an initial dose of 10 mg/kg rather than 5 mg/kg, with an additional 10 mg/kg dose 48-72 hours later if an adequate clinical response is lacking. Patients who respond to infliximab can continue to use the drug as an outpatient for maintenance of remission.
Cyclosporine
Cyclosporine is a fast-acting immunosuppressive agent that acts primarily via T-cell inhibition. Although older literature used a dose of 4 mg/kg per day, a randomized trial demonstrated similar response rates to a dose of 2 mg/kg per day.64 Patients receiving treatment with cyclosporine, which is given as a continuous infusion, must be monitored for toxicities. These can include potentially severe infection, seizures (often associated with low total cholesterol or hypomagnesemia), electrolyte abnormalities, renal impairment, hypertension, hypertrichosis, tremor, and others.65
Before initiation of treatment, serum cholesterol levels should be obtained to screen for low total cholesterol that may portend risk of seizures on the drug. Additionally, baseline creatinine and magnesium should be established. While on treatment, daily serum cyclosporine levels and electrolytes including magnesium should be measured. Patients who respond to intravenous cyclosporine must be transitioned to oral cyclosporine and have stable drug levels before discharge. Unfortunately, oral cyclosporine has not been shown to be as effective as long-term maintenance therapy. Therefore, cyclosporine can only be used as a “bridge” to another therapy. Historically, thiopurines like azathioprine or mercaptopurine have been used for this purpose because they are effective for the treatment of UC but may require months to have a full therapeutic effect. There have been promising reports of using vedolizumab similarly.66,67 Vedolizumab is a monoclonal antibody that selectively blocks lymphocyte trafficking to the gut that, like thiopurines, has an onset of action that is significantly longer than calcineurin and TNF inhibitors.
COLECTOMY
Colectomy should be considered as a second- or third-line therapy for patients who fail to respond to intravenous corticosteroids. In an analysis of 10 years of data from the Nationwide Inpatient Sample, mortality rates for colectomy in this setting varied from 0.7% at high volume centers to 4% at low volume centers.68 Therefore, if a patient is not hospitalized at a center with expertise in colectomy for UC, transfer to a specialized center should be considered. Colectomy should be performed promptly in all the patients who have failed rescue therapy with infliximab or cyclosporine or have opted against medical rescue therapy. Surgery should be performed emergently in patients with toxic megacolon, uncontrolled colonic hemorrhage or perforation.
