MANAGEMENT OF SEVERE COLITISThe patient with severe colitis refractory to maximal oral treatment with prednisone, oral aminosalicylate drugs, and topical medications, or the patient who presents with toxicity, should be treated for 7-10 days with intravenous steroids. Failure to demonstrate significant improvement within 7-10 days is an indication for either colectomy or treatment with intravenous cyclosporine in specialized centers.

The patient who continues to have severe symptoms despite optimal doses of oral steroids (40-60 mg daily of prednisone), oral aminosalicylates (4-6 g of sulfasalazine or 4.8 g of mesalamine), and topical medications, should be hospitalized for further treatment [78] [79] [80] [81] [82] . The mainstay of therapy at this point is intravenous steroids in a daily dose equivalent to 300 mg of hydrocortisone or 48 mg of methylprednisolone if the patient has received steroids in the prior month, or perhaps intravenous adrenocorticotropic hormone if the patient has not recently received steroids [82] [83] [84] . There is no benefit to treatment with a much higher daily dose of steroids [85] . The clinical impression that continuous infusion is preferable to bolus therapy has not been subjected to a controlled trial. Controlled trials of antibiotics, however, have demonstrated no therapeutic benefit from the use of either oral vancomycin [86] , or intravenous metronidazole [81] when added to intravenous steroids.

There is a prevalent tendency to place patients with severe colitis almost routinely on total parenteral nutrition. Controlled studies on this subject, however, show no benefit from this maneuver [87] [88] , which may even be detrimental by depriving the colonic enterocytes of the short-chain fatty acids vital to their metabolism and repair [89] . However, total parenteral nutrition may be useful as a nutritional adjunct in patients with severe nutritional depletion.

There are no studies to demonstrate that an oral aminosalicylate is of clinical benefit in this setting either, so it is generally withheld if the patient is nil per os, but it may be continued if the patient is eating and has been tolerating this drug. Likewise, no controlled studies have confirmed any incremental benefit of topical medications in this setting, but they are still often prescribed if they can be retained and tolerated. Because the failure rate of medical therapy in patients hospitalized for severe colitis is approximately 40% [90] , these patients should be followed closely in conjunction with a surgeon experienced in the management of patients with inflammatory bowel disease. In patients with either toxic signs (fever, leukocytosis, or worsening symptoms) or megacolon, medications with anticholinergic or narcotic properties should be avoided for fear of worsening colonic atony or dilation. Patients who do not improve significantly after 7-10 days [80] [82] of maximal medical therapy are unlikely to benefit from prolongation of this medical treatment and should either be referred for surgery (see below) or offered treatment with an investigational therapy such as intravenous cyclosporine. In one placebo controlled double-blind trial, 80% of patients treated with intravenous cyclosporine in a dose of 4 mg/kg/day improved and were able to avoid colectomy in the acute stage [91] . However, approximately one-third of this group required colectomy within the ensuing 6 months [92] , so additional follow-up that includes quality of life and cost-benefit assessment is necessary to determine the long-term value of this drug.

Patients with toxic megacolon should be treated as above; in addition they should be kept nil per os, have a small bowel decompression tube if a small bowel ileus is present, and instructed to rotate into the prone [93] or knee-elbow [94] position frequently to aid in evacuation of bowel gas. Broad spectrum antibiotics are usually used empirically in these patients. The duration of medical treatment of megacolon is controversial; some experts advocate surgery within 72 h if no significant improvement is noted [95] , whereas others take a more watchful stance if no toxic symptoms are present [93] . All agree, however, that any clinical, laboratory, or radiologic deterioration on medical therapy mandates immediate colectomy.


So Many Advances in Medicine, So Many Yet to Come