Management of Acute Severe Colitis

1. Management of Acute Severe Colitis Dr Jayne Eaden Consultant Gastroenterologist, UHCW

2. Symptoms • Bloody diarrhoea (urgency & tenesmus) • Abdominal pain • Weight loss • Obstructive symptoms • Abdominal mass (esp RIF)

3. Warning Signs • Fever > 37.8 oC • Dehydration • Tachycardia (P>90), Hypotension • Abdominal pain and tenderness (beware toxic dilatation and perforation) • Patients can look well if been on steroids - beware

4. Other Signs • Mouth ulcers • Perianal disease • Erythema nodosum • Pyoderma gangrenosum • Eye disease • Arthropathy (large joints, asymmetrical and non-deforming)

8. Truelove & Witts Criteria Defines severe Ulcerative Colitis Bowels open > 6 times per 24 hours Plus any one or more of the systemic manifestations • Haemoglobin < 10.5 • ESR > 30 • Pulse rate > 90 • Temperature > 37.5

9. Differential Diagnoses • Bacterial infection • C. diff, Campylobacter, Salmonella, Shigella, E. coli 0157 • Viral infection if immuno-compromised (CMV) • Amoeba especially if travel history • Crohn’s colitis and ischaemia • Diverticulitis can occasionally mimic

10. Investigations on Admission Bloods • FBC • ESR & CRP • U&E, creat • LFT (albumin) • Blood cultures (if temp > 38°) • Glucose • (Mg+ and Cholesterol)

11. Investigations on Admission • Stool Culture and Microscopy • C. Diff (3 separate samples) • AXR: look for stool-free colon (indicates extent involved); severe disease indicated by mucosal oedema (thickened wall), mucosal islands, dilated small bowel loops, colonic dilatation (diameter > 6cm) • Inform the surgeons on call if the colon is dilated

12. Colectomy more likely if: -Mucosal islands present -Dilated small bowel loops

13. Investigations on Admission • Arrange a sigmoidoscopy and rectal biopsy. DO NOT prescribe bowel prep • should be done within 24 - 48 hours of admission • Avoid colonoscopy and barium enema in patients with acute, severe colitis

14. Daily Investigations • Bloods • FBC • U&E, creat (particularly watch the potassium) • LFT • CRP (a vital prognostic guide) • AXR for severe extensive colitis (any of fever, tachycardia, tenderness, dilatation on initial films) – in absence of these criteria less frequent AXR is OK • Results must be reviewed the same day (esp potassium) particularly if abdominal X-ray is requested.

15. Extra Investigations • In appropriate patients, send Amoebic Fluorescent Antibody test • Check CMV titre if patient is not responding after 3 days (EDTA sample)

16. Daily Monitoring • Temperature and pulse • Stool chart • Frequency • Colour / blood content • Estimate of volume (record even if only passed blood or mucus) • Abdo examination findings • tenderness, bowel sounds • Note increasing pulse / temp / abdominal pain or tenderness may indicate deterioration or frank perforation and requires appropriate urgent investigation and d/w SpR / consultant.

17. Management • Rehydrate with IV fluids • Correct electrolyte imbalance (in particular potassium) • Nutrition : Low residue diet (IV fluids if vomiting) • Inform colorectal surgeons & IBD nurse

18. Management • Corticosteroids: Hydrocortisone 100mg QDS IV until remission achieved. May use Predsol/Predfoam PR once or twice per day (mainly for distal disease) • Antibiotics (if febrile / toxic dilatation) • Severely anaemic patients (Hb < 9g / dl) should be considered for transfusion • DVT prophylaxis e.g enoxaparin 40mg od

19. Management • Look for and treat proximal constipation • If stop 5-ASA, restart on discharge DO NOT • Use opiates / codeine phosphate/ loperamide (may precipitate paralytic ileus, megacolon and proximal constipation) • Use anti-cholinergics

20. Travis Criteria After three days of intravenous hydrocortisone, the presence of either • Stool frequency > 8 times per 24 hours or • Stool frequency > 3 times + CRP > 45 gives an 85% likelihood of requiring colectomy on the same admission

21. The Management of Acute Severe UC: options for rescue....... If no improvement by day 3 make plans for day 5! • Surgery or • Cyclosporine or • Infliximab • MUST be discussed with a Consultant Gastroenterologist

22. Indications for colectomy • Toxic dilatation with failure to improve clinically / radiologically within 24 hrs • Perforation • Uncontrolled lower GI haemorrhage • Failure to respond after 3 days IV steroids • Deterioration at any stage

23. Acute severe UC:the role of cyclosporine • Only use if stool cultures negative • Toxic drug – safety is paramount • IV hydrocortisone is continued • Check Mg+ and ensure cholesterol >3 • Be aware of side effects (seizures) • Care in elderly / hypertensive / impaired renal function

24. Acute severe UC:the role of cyclosporine What dose? • 2mg/kg as IV infusion in 500mls glucose over 2-6 hrs • Monitor levels (100-200mcg/l trough) • Levels monitored at UHCW Mon-Fri • Rapid steroid wean once clinical response • If responded switch to oral after 3-5 days: • 5mg/kg/day in 2 divided doses

26. Acute severe UC:the role of cyclosporine – long term outcome • Clinical experience from Oxford • 76 pts from 1996-2003 followed 2.9 yrs • 54 received 4mg/kg, 22 oral 5mg/kg • 74% entered clinical remission and left hospital • BUT 65% relapse at 1 yr, 90% at 3 yrs • 58% of those came to colectomy at 7 yrs

28. Acute severe UC:the role of cyclosporine – exit strategy • Azathioprine naive vs refractory........ • Ideally check TPMT levels on admission • Commence Azathioprine at discharge • Wean off Cyclosporine after 6-8 weeks • Septrin 960mg alt days – prophylaxis against opportunistic infection • Early follow up to check remission and bloods

37. Acute severe UC:the role of infliximab – safety issues • Possible risk of lymphoma & malignancy • Increased if pt on other immunosuppressants • Infectious complications (VZV, candida) • Serious in 3% • TB reactivation (PPD & CXR required prior to treatment) • Interactions tacrolimus/ live vaccines

38. Acute severe UC:the role of infliximab – safety issues • Contraindications: • Sepsis • Significantly raised LFTs (x3), • Hypersensitivity to infliximab • Active TB • Pregnancy } avoid for 6 months after • Breast Feeding } stopping treatment • Cautions: • Previous TB • Hepatic Impairment • Renal Impairment • Heart Failure • Mouse allergies • > 14 weeks since last infusion

42. Infliximab for chronic active UC:can we predict who will respond? • Serum albumin <30g/l: 67% vs 23% colectomy OR 6.86 (1.03-45.6) p=0.05 (Lees et al APT 2007) • No effect of smoking status, age, stool frequency or disease extent

43. Management of acute severe UC:summary of evidence • Acute severe UC requires specialist care within an experienced MDT • Confirm diagnosis and exclude infection • Non responders should be identified early and salvage therapy considered • Controlled trials of cyclosporine vs infliximab are awaited

44. Management of acute severe UC:a multi disciplinary model Physicians Surgeons The Patient Combined approach Nurses Dieticians Pharmacists Radiologists Pathologists