Dr. Elizabeth Squirell

Acute severe ulcerative colitis

Admission orders, day-3 decision, infliximab or ciclosporin rescue, and when to call surgery

Reviewed October 2026 · For healthcare professionals. Follow your local protocols.

Tools: Acute severe UC (day 1 and day 3) · Mayo score

Is it this?

Truelove and Witts (as used by BSG 2025): at least 6 bloody stools a day plus at least one of:

  • temperature >37.8 °C
  • heart rate >90/min
  • hemoglobin <105 g/L
  • ESR >30 mm/h (the original 1955 marker)
  • or CRP >30 mg/L (the modern substitute, BSG 2019 Statement 15)

Rule out infection and other causes in parallel (C. difficile, CMV, enteric pathogens). Do not wait for results to start steroids.

First 24 hours: orders

  • IV corticosteroids now (adult doses):
    • methylprednisolone 60 mg IV daily (BSG: 30 mg every 12 h), or
    • hydrocortisone 100 mg IV every 6 h (ACG: 3 or 4 times a day).
    • Higher doses add nothing. Courses beyond 7–10 days add toxicity, not benefit (BSG 2025).
  • VTE prophylaxis with LMWH (or fondaparinux) unless a true contraindication. Rectal bleeding is not one: prophylaxis does not worsen colonic bleeding (BSG 2025; ACG Rec 47).
  • Bloods: CBC, CRP, electrolytes, creatinine, liver tests with albumin, magnesium and lipid profile (BSG baseline set; needed if ciclosporin becomes the rescue). Repeat CBC, electrolytes and CRP daily.
  • Stool: C. difficile testing (ACG Rec 46) and stool culture. If C. difficile is positive, treat it and continue steroids. First line: oral vancomycin 125 mg PO four times daily for 10 days. Fidaxomicin 200 mg PO twice daily for 10 days is an alternative (IDSA/SHEA 2021 prefers it), but coverage in Canada favours vancomycin: in Ontario, fidaxomicin is funded only through the Exceptional Access Program after vancomycin (failure, intolerance or a third episode). Not metronidazole (ECCO 2026). Vancomycin 500 mg four times daily (plus IV metronidazole 500 mg every 8 h) is the regimen for fulminant C. difficile: hypotension, shock, ileus or megacolon. Involve infectious diseases; follow local protocol.
  • Abdominal X-ray at admission for colonic dilatation (CT if perforation or collection is suspected).
  • Flexible sigmoidoscopy within 24 h (BSG 2025; ACG: within 72 h, preferably 24 h) to confirm severity, exclude other diagnoses and take biopsies, including for CMV. If CMV colitis is found in a steroid-refractory patient, treat it (ECCO 2026: antivirals for steroid-refractory CMV colitis; immunosuppression can usually continue); BSG suggests IV ganciclovir 5 mg/kg every 12 h. Involve virology.
  • Pre-rescue screening, sent on day 1 so results are ready by day 3 (BSG 2025):
    • hepatitis B (HBsAg, anti-HBc, anti-HBs) and hepatitis C
    • HIV
    • VZV IgG if no history of chickenpox, shingles or vaccination
    • TB risk assessment, chest X-ray and IGRA
  • Stool chart (frequency, blood) and serial CRP to monitor response (ACG key concept 50).
  • Diet: keep eating. No TPN for bowel rest (ACG Rec 49).
  • Don’t add oral 5-ASA to IV steroids (ECCO 2026 Rec 44); consider withholding it (BSG figure 4).

Avoid

  • Opioids, NSAIDs and drugs with anticholinergic effects (ACG key concept 51). AGA 2026 also advises avoiding opioids when possible.
  • Routine broad-spectrum antibiotics (ACG Rec 48; BSG 2025). Treat a proven infection.

Day 3: decide

Oxford (Travis) criteria on day 3 of IV steroids:

  • more than 8 stools that day, or
  • 3 to 8 stools with CRP >45 mg/L

predicted colectomy on that admission in 85% (Travis 1996).

  • Criteria met: start rescue therapy or proceed to colectomy. Decide with the surgeon today (ACG Rec 51; BSG GPS 44; Toronto consensus).
  • Criteria not met is not the same as response. If not clearly improving (BSG: fewer than 4 stools a day for 2 days, no blood), continue IV steroids and reassess daily. BSG does not recommend IV steroids beyond 7 days.
  • Ho index (stool frequency, colonic dilatation, albumin) adds prognostic information (Ho 2004).

Rescue: infliximab or ciclosporin

Infliximab Ciclosporin
Dose 5 mg/kg IV at weeks 0, 2, 6 2 mg/kg/day continuous IV infusion, then oral
Efficacy Equivalent to ciclosporin (CySIF; CONSTRUCT) Equivalent to infliximab
Prefer when Thiopurine already failed; maintenance on infliximab planned Anti-TNF already failed; centre experienced with levels
Check first Screening above (TB, HBV) Creatinine, BP, magnesium, cholesterol; drug levels
Then Continue infliximab for maintenance (ACG Rec 52) Bridge to thiopurine or vedolizumab (ACG Rec 53–54; BSG GPS 44)
  • Choose by local experience, prior thiopurine or anti-TNF failure, and albumin (ACG key concept 53).
  • Low albumin: ACG (key concept 57: albumin <25 g/L) and BSG (GPS 47) suggest considering intensified infliximab. PREDICT-UC (RCT) found no benefit of 10 mg/kg over 5 mg/kg or of accelerated over standard induction, and ECCO 2026 (Rec 46) finds insufficient evidence for routine intensified dosing. Discuss with your IBD attending.
  • JAK inhibitors (tofacitinib, upadacitinib): ACG 2025 says data are insufficient for routine use. BSG 2025 (GPS 48) says they may be considered in selected steroid-refractory patients, restricted in its text to those in whom conventional rescue is contraindicated or has failed. ECCO 2026 (practice point 2): consider when infliximab or ciclosporin has failed or cannot be given. Not first-line rescue; specialist decision, with surgery discussed.
  • Sequential rescue (infliximab then ciclosporin, the reverse, or a JAK inhibitor third line) only in highly selected patients at experienced centres after discussing surgery (ECCO 2026 Rec 47). BSG 2025 found insufficient evidence to recommend it; the Toronto consensus advises against it.
  • Responding to IV steroids? Plan maintenance before discharge: BSG 2025 (GPS 43) suggests a thiopurine or an advanced therapy; ECCO 2026 (practice point 1) suggests against a thiopurine or 5-ASA alone (ACTIVE trial).

When to call surgery

Situation Action
Admission Early joint review with colorectal surgery (BSG GPS 45; AGA 2026)
Day 3: failing IV steroids, or toxicity Surgical consultation (ACG key concept 52)
No response within 7 days of rescue Subtotal colectomy and ileostomy (BSG GPS 46)
Toxic megacolon, perforation, severe bleeding Emergency colectomy (ACG key concept 54)

Infliximab and ciclosporin do not increase postoperative complications; do not defer surgery because of them (ACG key concept 55).

Red flags

  • Toxic megacolon: colonic dilatation on X-ray with systemic toxicity. Repeat the X-ray and get surgical review for continued toxicity, severe pain, distension or falling albumin with edema (BSG daily checklist).
  • Perforation: CT is the preferred test when suspected (BSG 2025).
  • Massive bleeding or hemodynamic instability.

Pitfalls

  • Steroids delayed while stool results are pending.
  • No VTE prophylaxis “because of the bleeding.”
  • Screening for infliximab sent on day 3 instead of day 1, delaying rescue.
  • Reading “Travis negative” as response.
  • Patients already on steroids or advanced therapy may not meet Truelove and Witts. A 2026 Delphi consensus proposed new criteria for this group; they are not yet validated (Raine 2026).

Follow your local protocols for drug doses, renal adjustment and infusion orders.

Sources

  1. Rubin DT, et al. ACG Clinical Guideline Update: Ulcerative Colitis in Adults. Am J Gastroenterol 2025;120:1187–1224. PMID 40701556 Rec 46–51 (C. difficile testing, pharmacologic VTE prophylaxis, no routine antibiotics, no TPN for bowel rest, methylprednisolone 60 mg/day or hydrocortisone 100 mg 3–4 times daily, rescue at day 3). Key concepts 48–57 (sigmoidoscopy within 72 h, preferably 24 h; avoid NSAIDs, narcotics and anticholinergics; surgical consult at day 3; JAK inhibitors not routine; consider IFX intensification if albumin <25 g/L).
  2. Moran GW, et al. British Society of Gastroenterology guidelines on inflammatory bowel disease in adults: 2025. Gut 2025;74(Suppl 2):s1–s101. PMID 40550582 GPS 40–48 and figure 4: Truelove and Witts with CRP >30 mg/L, baseline bloods incl. magnesium and lipids, sigmoidoscopy within 24 h with CMV biopsies, LMWH, pre-rescue screening, day-3 Oxford criteria, rescue options, colectomy if no response within 7 days of rescue.
  3. Gisbert JP, Chaparro M, Verstockt B, et al. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment. J Crohns Colitis 2026;20(7). PMID 42413123 Replaces the 2022 ECCO UC guidelines (ASUC is now in the medical document). Rec 43 IV steroids first line; Rec 44 suggest against adding oral 5-ASA to IV steroids; Rec 45 infliximab or ciclosporin rescue; Rec 46 insufficient evidence for routine intensified infliximab, individualised dosing can be considered; Rec 47 third-line sequential rescue only in highly selected patients at experienced centres; practice point 1 after IV-steroid response, against maintenance with a thiopurine or 5-ASA alone; practice point 2 consider a JAK inhibitor if infliximab or ciclosporin has failed or cannot be given.
  4. Yanai H, Ellul P, Verstockt B, et al. ECCO Guidelines on the Prevention, Diagnosis, and Management of Infections in Inflammatory Bowel Disease. J Crohns Colitis 2026;20(7). PMID 42417116 Statements 11–12: CMV testing on tissue (IHC and/or PCR) in ASUC; antivirals considered in steroid-refractory CMV colitis; immunosuppression can usually continue. Statements 21–23: two-step C. difficile testing; oral vancomycin or fidaxomicin first line, not metronidazole; IBD therapy need not routinely stop.
  5. Cohen-Mekelburg S, et al. AGA Clinical Practice Update on Inpatient Management of Adults With Inflammatory Bowel Disease: Expert Review. Gastroenterology 2026;170:408–417. PMID 41579011 Methylprednisolone 60 mg or equivalent; reassess at 72 h; early surgical consultation; VTE prophylaxis; C. difficile and CMV assessment; avoid opioids when possible.
  6. Bitton A, et al. Treatment of hospitalized adult patients with severe ulcerative colitis: Toronto consensus statements. Am J Gastroenterol 2012;107:179–194. PMID 22108451 Canadian (CAG) consensus: escalate to infliximab or ciclosporin after 72 h of failed IV steroids; sequential ciclosporin and infliximab not recommended.
  7. Travis SP, et al. Predicting outcome in severe ulcerative colitis. Gut 1996;38:905–910. PMID 8984031 Day 3: >8 stools, or 3–8 stools with CRP >45 mg/L, predicted colectomy in 85%.
  8. Truelove SC, Witts LJ. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J 1955;2:1041–1048. PMID 13260656 Original severity criteria.
  9. Williams JG, et al. Infliximab versus ciclosporin for steroid-resistant acute severe ulcerative colitis (CONSTRUCT). Lancet Gastroenterol Hepatol 2016;1:15–24. PMID 27595142 Infliximab 5 mg/kg at 0, 2, 6 weeks vs ciclosporin 2 mg/kg/day IV up to 7 days then oral; no difference in effectiveness or colectomy.
  10. Laharie D, et al. Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids (CySIF). Lancet 2012;380:1909–1915. PMID 23063316 Treatment failure 60% ciclosporin vs 54% infliximab (P=0.52).
  11. Choy MC, et al. Intensified versus standard dose infliximab induction therapy for steroid-refractory ASUC (PREDICT-UC). Lancet Gastroenterol Hepatol 2024;9:981–996. PMID 39236736 10 mg/kg first dose not superior to 5 mg/kg (day-7 response 65% vs 61%); no difference in 3-month colectomy between intensified, accelerated and standard induction.
  12. Ho GT, et al. Predicting the outcome of severe ulcerative colitis: development of a novel risk score. Aliment Pharmacol Ther 2004;19:1079–1087. PMID 15142197 Stool frequency, colonic dilatation and hypoalbuminaemia over days 1–3 predict steroid failure.
  13. Johnson S, et al. IDSA/SHEA 2021 focused update guidelines on management of Clostridioides difficile infection in adults. Clin Infect Dis 2021;73:e1029–e1044. PMID 34164674 Table 1: initial episode fidaxomicin 200 mg twice daily for 10 days (preferred) or vancomycin 125 mg four times daily by mouth for 10 days; fulminant: vancomycin 500 mg four times daily plus IV metronidazole 500 mg every 8 h.
  14. Ontario Ministry of Health. Exceptional Access Program: reimbursement criteria for frequently requested drugs (January 1, 2025). Fidaxomicin (Dificid 200 mg) is considered only in patients who meet the criteria for vancomycin and have had a third or later episode within 6 months of vancomycin, vancomycin failure, or allergy or intolerance to oral vancomycin. Oral vancomycin for uncomplicated C. difficile has been available through Ontario Drug Benefit Limited Use criteria since September 30, 2019. KHSC practice (Dr. Squirell, October 2026): vancomycin first line because of coverage in Canada.
  15. Butler TD, Segal JP. Guideline review: 2025 BSG guidelines on inflammatory bowel disease in adults, part 2: ulcerative colitis. Frontline Gastroenterol 2025. PMID 42273203 Summary of BSG 2025 ASUC advice. Its JAK wording ('conventional rescue therapy and surgery is contraindicated') is narrower than the guideline itself (GPS 48: may be considered in selected steroid-refractory patients; text: where conventional rescue is contraindicated or has failed).
  16. Raine T, et al. New diagnostic criteria for acute severe ulcerative colitis in the modern treatment era: a modified Delphi consensus. Clin Gastroenterol Hepatol 2026 (online July 2026). PMID 42486394 Proposed criteria for patients already on steroids or advanced therapy; not yet validated.
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