Medical Rescue Therapy Research Articles

Hyperbaric Oxygen for Hospitalized patients with Ulcerative Colitis

One quarter of patients with ulcerative colitis will develop a severe acute exacerbation of disease during their lifetime. Despite high dose corticosteroids, half of these patients will fail subsequent medical rescue therapy, and half will require colectomy within 5 years. Dulai and colleagues report the results of a fascinating, double blind, sham controlled, proof of concept trial which demonstrated that administration of short term hyperbaric oxygen therapy (HBOT) at the point of presentation with severe UC was able to rapidly induce short term remission and avoid the need for urgent second line medical rescue therapy. Further dose finding studies are underway.

Long-Term Outcomes of Immunosuppression-Naïve Steroid Responders Following Hospitalization for Ulcerative Colitis.

Requirement for hospitalization in ulcerative colitis (UC) is a marker of severity of disease. However, the paradigm of when to escalate therapy in such patients and the benefits of early immunomodulator initiation is less well established. To examine the benefits of early therapy escalation in immunosuppression-naïve patients hospitalized with severe ulcerative colitis responsive to steroids. We identified hospitalized UC patients who were immunosuppression naïve at index hospitalization and responded to intravenous steroids, not requiring medical or surgical rescue therapy. The 'therapy escalated' group comprised of those who were initiated on immunomodulators within 3months of hospitalization. The need for colectomy at 12months was compared to the 'not escalated' group who remained on non-immunosuppressive therapy. Among 133 immunosuppressive naïve patients hospitalized for ulcerative colitis, 13 (9.8%) who responded to intravenous steroids and did not require rescue therapy underwent colectomy by 1year. Among 123 patients who escalated to either immunomodulators (n = 46, 37%) or remained on non-immunosuppressive therapy (92% on 5-ASA), there was no difference in the need for colectomy at 1year (10.8 vs. 7.8%; multivariate OR 1.29, 95% CI 0.35-4.74). There was also no difference in the time to colectomy between the two groups (p = 0.55). Immunosuppression-naïve ASUC patients who respond to intravenous steroids remain at risk for colectomy. Immunomodulator initiation by 3months did not reduce risk of colectomy at 1year. There is an important need for prospective studies identifying thresholds for therapy escalation in UC.

Sarcopenia is a Novel Predictor of the Need for Rescue Therapy in Hospitalized Ulcerative Colitis Patients.

Acute severe ulcerative colitis [ASUC] affects one in four patients with UC. Clinical parameters perform modestly in predicting the need for rescue therapy. Sarcopenia and visceral adiposity predict natural history in Crohn's disease, but the role of such metabolic factors on ASUC outcomes is unknown. The aim of this study was to define the effect of sarcopenia and visceral adiposity on outcomes in ASUC. We studied patients hospitalized for ASUC who underwent an abdominal CT scan during the hospitalization. Quantification of skeletal muscle mass and visceral adiposity was performed by radiologists blinded to the outcome. Sarcopenia was defined as a skeletal muscle index of <55 cm2/m2 for men and <39 cm2/m2 for women. The primary outcome of interest was need for medical or surgical rescue therapy. Our study included 89 patients with ASUC, among whom 39 [43.8%] patients required medical rescue therapy or surgery. Two-thirds of the cohort [70%] met the definition of sarcopenia [81% men, 48% women]. Patients with sarcopenia had similar disease characteristics and laboratory parameters to those with a normal muscle mass. However, a larger proportion of patients with sarcopenia required rescue therapy compared with those without (56% vs 28%, multivariable odds ratio [OR] 3.98, 95% confidence interval [CI] 1.12-14.1). Neither visceral [p = 0.23] nor subcutaneous adiposity [p = 0.53] predicted the need for rescue therapy. Sarcopenia as determined on abdominal CT was a novel predictor of need for rescue therapy in hospitalized UC patients.

Sa1782 - Sarcopenia is a Novel Predictor of Need for Medical or Surgical Rescue Therapy in Acute Severe Ulcerative Colitis

Sa1782 - Sarcopenia is a Novel Predictor of Need for Medical or Surgical Rescue Therapy in Acute Severe Ulcerative Colitis

Su1808 - Mural Stratification on CT Scan Independently Predicts Need for Medical or Surgical Rescue Therapy in Acute Severe Ulerative Colitis

Su1808 - Mural Stratification on CT Scan Independently Predicts Need for Medical or Surgical Rescue Therapy in Acute Severe Ulerative Colitis

Post-Operative Morbidity and Mortality of a Cohort of Steroid Refractory Acute Severe Ulcerative Colitis: Nationwide Multicenter Study of the GETECCU ENEIDA Registry

Despite the increased use of rescue medical therapies for steroid refractory acute severe ulcerative colitis, mortality related to this entity still remains high. We aimed to assess the mortality and morbidity related to colectomy and their predictive factors in steroid refractory acute severe ulcerative colitis, and to evaluate the changes in mortality rates, complications, indications of colectomy, and the use of rescue therapy over time. We performed a multicenter observational study of patients with steroid refractory acute severe ulcerative colitis requiring colectomy, admitted to 23 Spanish hospitals included in the ENEIDA registry (GETECCU) from 1989 to 2014. Independent predictive factors of mortality were assessed by binary logistic regression analysis. Mortality along the study was calculated using the age-standardized rate. During the study period, 429 patients underwent colectomy, presenting an overall mortality rate of 6.3% (range, 0-30%). The main causes of death were infections and post-operative complications. Independent predictive factors of mortality were: age ≥50 years (OR 23.34; 95% CI: 6.46-84.311; p < 0.0001), undergoing surgery in a secondary care hospital (OR 3.07; 95% CI: 1.01-9.35; p = 0.047), and in an emergency setting (OR 10.47; 95% CI: 1.26-86.55; p = 0.029). Neither the use of rescue medical treatment nor the type of surgical technique used (laparoscopy vs. open laparotomy) influenced mortality. The proportion of patients undergoing surgery in an emergency setting decreased over time (p < 0.0001), whereas the use of rescue medical therapy prior to colectomy progressively increased (p > 0.001). The mortality rate related to colectomy in steroid refractory acute severe ulcerative colitis varies greatly among hospitals, reinforcing the need for a continuous audit to achieve quality standards. The increasing use of rescue therapy is not associated with a worse outcome and may contribute to reducing emergency surgical interventions and improve outcomes.

Acute severe ulcerative colitis: latest evidence and therapeutic implications.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of the colorectum which results from a complex interplay between environmental, genetic and microbial factors. One-fifth of patients with UC will experience an acute flare requiring hospitalization. This is a medical emergency and requires prompt recognition and multidisciplinary management. In patients who fail first-line therapy after approximately 3-5 days of intravenous steroids, medical rescue therapy is indicated with either infliximab (IFX) or cyclosporine (CsA). Optimal dosing strategies for IFX are uncertain, with several retrospective studies suggesting an association between an intensified or accelerated IFX induction regimen and lower colectomy rates, although prospective studies are warranted. In patients not responding to medical rescue therapy, or in those with fulminant colitis, urgent colectomy is indicated. Longer prognosis is suboptimal, with half of patients requiring colectomy within 5 years of presentation with acute severe UC (ASUC).

Surgery of acute severe ulcerative colitis. Subtotal colectomy: when and how to do it?

The aim of this review is to focus attention on the role of surgery in the management of acute ulcerative colitis (UC). UC is a chronic inflammatory disease of the mucosa of the large intestine. We have examined the data from the literature of the past 20 years and we have analyzed the role of emergency surgery. A medical literature search was conducted using Medline, Embase, Ovid Journals, and Science Direct. Acute severe colitis (ASC) occurs in 12–25% of patients affected by UC. Patients with ASC should be managed by a multidisciplinary team. Aggressive medical or surgical treatment is undertaken with the final aim of reducing mortality. Intravenous corticosteroids are the mainstay of therapy. Medical rescue therapy based on cyclosporine or infliximab should be considered if there is no response to corticosteroids after 3 days. In the event that there has been no response to medical rescue therapy after 4–7 days, the patient must undergo urgent colectomy surgery. Prolonged observation is counterproductive as over time it increases the risk of toxic megacolon and of perforation burdened with a very high mortality rate. The best possible treatment is represented by subtotal colectomy with ileostomy and preservation of a long rectal stump. Emergency colectomy is characterized by high morbidity and low mortality rates.

Improved outcome of acute severe ulcerative colitis while using early predictors of corticosteroid failure and rescue therapies

Background and aimIntravenous corticosteroids remain the first line therapy for severe attacks of ulcerative colitis although up to 30–40% of patients do not respond to treatment. The availability of alternative therapies to colectomy and the knowledge of early predictors of response to corticosteroids should have improved the clinical outcomes of patients with severe refractory ulcerative colitis. The aim of the study is to describe the current need, way of use, and efficacy of rescue therapies, as well as colectomy rates in patients with severe ulcerative colitis flares. MethodsBetween January 2005 and December 2011, all patients admitted in three referral centres for a severe ulcerative colitis flare who received intravenous corticosteroids were identified and clinical and biological data were accurately collected. Patients were followed-up until colectomy, death, or date of data collection. ResultsSixty-two flares were included. Initial efficacy of intravenous corticosteroids (mild activity or inactive disease without rescue treatment, at day 7 after starting intravenous corticosteroids) was achieved in 50% of flares, and rescue therapies were used in 27 episodes (43%). After a median follow-up of 18 months, the colectomy rate was 6.5%. Failed oral corticosteroids for the index flare were the only baseline feature that predicted the need for rescue therapy and colectomy. ConclusionsThere is a marked reduction in the colectomy rate and an increased use of medical rescue therapies as compared to historical series. Patients worsening while on oral corticosteroids for a moderate flare are at high risk of rescue therapy and colectomy and, therefore, should be directly treated with rescue therapies instead of attempting intravenous corticosteroids.

Adjuvant use of antibiotics with corticosteroids in inflammatory bowel disease exacerbations requiring hospitalisation: a retrospective cohort study and meta‐analysis

Patients hospitalised with an exacerbation of inflammatory bowel disease (IBD) often receive antibiotics in addition to intravenous steroids. However, their efficacy in this setting is unclear. To ascertain if the addition of antibiotics to intravenous steroids modifies short and long-term clinical outcomes. Our study included IBD patients hospitalised between 2009 and 2014 who received intravenous (IV) steroids with or without adjuvant antibiotics. Outcomes of interest included length of stay (LOS), need for medical and surgical rescue therapy during the hospitalisation, and at 90 and 365 days. A meta-analysis of previously published randomised trials was additionally performed. A total of 354 patients were included [145 ulcerative colitis (UC); 209 Crohn's disease (CD)]. In CD, combination of IV steroids and antibiotics did not change need for in-hospital medical rescue therapy, surgery or hospitalisations at 1 year but was associated with greater LOS (6.1 vs. 4.6 days, P = 0.02). In UC, patients receiving antibiotics were less likely to require in-hospital medical rescue therapy [odds ratio (OR): 0.42, 95% confidence interval (CI): 0.19-0.93] but experienced no statistically significant differences in LOS, in-hospital surgery, re-hospitalisations or surgery by 1 year. A meta-analysis of three relevant randomised trials demonstrated no difference in clinical improvement with antibiotics over placebo (OR: 1.08, 95% CI: 0.50-2.32). The addition of antibiotics to intravenous steroids for treatment of IBD exacerbations was associated with a reduced need for in-hospital medical rescue therapy in ulcerative colitis without significant long-term benefit, and did not affect short- or long-term outcomes in Crohn's disease.

Surgical and medical treatment in patients with acute severe ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease of the mucosa of the colorectum. The treatment of UC depends on the severity of symptoms and the extent of the disease. Acute severe colitis (ASC) occurs in 12-25% of patients with UC. Patients with ASC must be managed by a multidisciplinary team. Medically or surgically aggressive treatment is carried out with the final aim of reducing mortality. Intravenous administration of corticosteroids is the mainstay of the therapy. Medical rescue therapy based on cyclosporine or infliximab should be considered if there is no response to corticosteroids for 3 days. If there has been no response to medical rescue therapy after 4-7 days, the patient must undergo colectomy in emergency surgery. Prolonged observation is counterproductive, as over time it increases the risk of toxic megacolon and perforation, with a very high mortality rate. The best potential treatment is subtotal colectomy with ileostomy and preservation of the rectum. Emergency surgery in UC should not be seen as a last chance, but can be considered as a life-saving procedure. Colectomies in emergency setting are characterized by high morbidity rates but the mortality is low.

Management of severe ulcerative colitis.

Acute severe steroid-refractory ulcerative colitis (ASUC) provides challenges for physicians and surgeons who manage these patients. When a patient is diagnosed with ASUC, they should be admitted for inpatient management including intravenous corticosteroids, venous thromboembolism prophylaxis, oral or enteral feeding if tolerated, and exclusion of infection including Clostridium difficile. Failure to improve by day 3 of corticosteroids requires escalation to medical rescue therapies such as infliximab or cyclosporine, or surgical management with colectomy. This chapter will review management of ASUC with a focus on the medical rescue options available.

Algorithm for managing severe ulcerative colitis.

Acute severe ulcerative colitis as defined by Truelove Witt's criteria is a medical emergency which requires hospitalization. Patient requires close clinical monitoring with assessment of daily vital parameters, stool frequency, serum electrolytes and daily abdominal examination Intravenous corticosteroids are the mainstay of therapy. Approximately two thirds of patients will respond to steroids. Response to steroids should be assessed at day 3 of admission and partial/non-responders should be considered for alternative medical therapy/surgery. Medical rescue therapies include intravenous cyclosporin and infliximab. This article provides an time bound step up algorithm for management of acute severe ulcerative colitis.

Pediatric ulcerative colitis: a practical guide to management.

Ulcerative colitis (UC) is a chronic inflammatory disorder of the gastrointestinal tract of unknown etiology that frequently presents in the pediatric population. The evaluation of pediatric UC involves excluding infection, and a colonoscopy that documents the clinical and histologic features of chronic colitis. Initial management of mild UC is typically with mesalamine therapy for induction and maintenance. Moderate UC is often initially treated with oral prednisone. Depending on disease severity and response to prednisone, maintenance options include mesalamine, mercaptopurine, azathioprine, infliximab, or adalimumab. Severe UC is typically treated with intravenous corticosteroids. Corticosteroid nonresponders should either undergo a colectomy or be treated with second-line medical rescue therapy (infliximab or calcineurin inhibitors). The severe UC patients who respond to medical rescue therapy can be maintained on infliximab or thiopurine, but 1-year remission rates for such patients are under 50 %. These medications are discussed in detail along with the initial work-up and a treatment algorithm.

Management of acute severe ulcerative colitis.

The management strategy of acute severe ulcerative colitis has evolved over the past decade from being entirely restricted to twin choices of intravenous steroids or colectomy to include colon rescue therapies like cyclosporin as well as infliximab. However it still remains a medical emergency requiring hospitalization and requires care from a multidisciplinary team comprising of a gastroenterologist and a colorectal surgeon. The frame shift in management has been the emphasis on time bound decision making with an attempt to curtail the mortality rate to below 1%. Intravenous corticosteroids are the mainstay of therapy. Response to steroids should be assessed at day 3 of admission and partial/non-responders should be considered for alternative medical therapy/surgery. Medical rescue therapies include intravenous cyclosporin and infliximab. Cyclosporin is administered in a dose of 2 mg/kg per day and infliximab is administered as a single dose intravenous infusion of 5 mg/kg. Approximately 75% patients have short term and 50% patients have long term response to cyclosporin. Long term response to cyclosporin is improved in patients who are thiopurine naïve and are started on thiopurines on day 7. Infliximab also has a response rate of approximately 70% in short term and 50% in long term. Both cyclosporin and infliximab are equally efficacious medical rescue therapies as demonstrated in a recent randomized control trial. Patients not responding to infliximab or cyclosporin should be considered for colectomy.

Letter: acute severe ulcerative colitis - should all patients be treated equally? Authors' reply

We would like to thank Barreiro-de Acosta and Gisbert for their interest in our article.1, 2 The mortality we observed in the elderly acute severe ulcerative colitis (ASUC) population was striking, with a 13-fold and 28-fold increased risk of death in those patients over 60 in 2008 and 2010 respectively.2 This higher mortality in the elderly has been previously reported and was recently summarised in a review of mortality in ulcerative colitis (UC).3 In addition, our finding of increasing mortality in patients with comorbidities might go some way in explaining the higher mortality in elderly patients. It is of note, however, that age and comorbidity have previously been shown to be independent risk factors for mortality in UC.4 A recent report by Charpentier et al. suggests that elderly UC patients' presentations are phenotypically different, with milder disease at presentation, but with earlier progression to colectomy when compared with younger patients;5 could this be relevant in the increased mortality observed? As patients survive longer and present with evermore complex comorbidities, these findings will certainly be relevant in future ASUC management. We would also agree that it is important to at least consider medical rescue therapy in all ASUC patients failing steroid therapy as we have not demonstrated increased short-term mortality when compared with surgery.2 Similar to Nørgård et al.,6 we have demonstrated, in unpublished work from this cohort, that there is no increase in short-term complications in patients who undergo surgery following rescue medical therapy.7 However, it is important to emphasise that our follow-up extends only to hospital discharge. The cornerstone of high-quality care in ASUC continues to be a multidisciplinary approach, with decisions being made promptly and with the appropriate involvement of all members, including patients. The authors' declarations of personal and financial interests are unchanged from those in the original article.2

Surgical outcomes in steroid refractory acute severe ulcerative colitis: the impact of rescue therapy

The advent of rescue medical therapy (cyclosporin or infliximab) and laparoscopic surgery has shifted the paradigm in managing steroid refractory acute severe ulcerative colitis (ASUC). We investigated prospectively the impact of rescue therapy on timing and postoperative complications of urgent colectomy and subsequent restorative surgery for steroid refractory ASUC. All consecutive presentations of steroid refractory ASUC at the Royal Brisbane Hospital (1996-2009) were entered in the study. Data collated included demographics, clinical and laboratory parameters on admission, medical therapy and operative and postoperative details. Steroid refractory ASUC patients undergoing immediate colectomy were compared with those failing rescue therapy and requiring same admission colectomy. Of 108 steroid refractory ASUC presentations, 19 (18%) received intravenous steroids only and proceeded directly to colectomy. Rescue medical therapy was instituted in 89 (82%) patients with 30 (34%) failing to respond and proceeding to colectomy. There was no significant difference in the median time from admission to colectomy for rescue therapy compared with steroid-only cases (12 vs 10 days, P = 0.70) or 30-day complication rates (27%vs 47%, P = 0.22). The interval from colectomy to a subsequent restorative procedure was significantly longer for patients who failed rescue therapy (12 vs 5 months, P = 0.02). Furthermore 30-day complications following pouch surgery were significantly higher in patients who failed rescue therapy (32%vs 0%, P = 0.01). Rescue therapy in steroid refractory ASUC is not related to delay in urgent colectomy or increased post-colectomy complications.

P543 Better response rates to anti-TNFa than cyclosporin in steroid refractory acute severe colitis: data from the UK IBD audit

Background: For over thirty years high dose steroids followed by colectomy if required has been the mainstay of treatment for active ulcerative colitis (UC). Recently we have seen the introduction of second-line medical therapies such as anti-TNFa and cyclosporin with the hope of avoiding the need for surgery if first line medical therapy fails. Methods: Using a cohort of UC patients from round two (2008) and three (2010) of the UK inflammatory bowel disease (IBD) audit respectively we aim to assess the outcomes of patients receiving second-line medical therapies. We audited 3049 patients with UC from the 2010 round of the UK IBD audit of which 1071 were considered to have acute severe UC (ASUC). 202 Sites audited a median of 18 UC patients per site that were admitted with IBD between 1/09/09 and 31/08/10. The results of this were compared against the results from the 2008 UK IBD audit which collected data on 2981 UC patients of which there were 863 with ASUC. 209 sites audited a median of 17 UC patients per site that were admitted with IBD between 1/09/07 and 31/08/08. Results: Between rounds there was no significant change in mortality in the ASUC population, 1.2% (10/863) in 2008 vs 0.7% (7/1071) in 2010 (p < 0.3) additionally response rates to first line steroids were similar between rounds 61.1% (498/815) in 2008 vs 58.8% (602/1024) in 2010 (p < 0.4). Significantly more patients are receiving second-line medical therapy 47.3% (150/317) in 2008 vs 57.6% (243/422) in 2010 (p < 0.01). Of the patients failing first line therapy significantly less underwent surgery in 2010: 51.4% (163/317) vs 41.0% (173/422) (p < 0.005). The response rates to anti-TNFa were significantly better than to cyclosporin in both rounds: 75% (39/52) vs 45.9% (45/98) in 2008 (p < 0.005); 81.4% (79/97) vs 60.3% (88/146) in 2010 (p < 0.005). There was a significant difference in response rates to cyclosporin between rounds 45.9% (45/98) in 2008 vs 60.3% (88/146) in 2010 (p < 0.03). Among patients receiving secondline medical therapies there was no significant difference in mortality either between treatments or rounds. Conclusions: In this unselected population, patients consistently respond significantly better to anti-TNFa than cyclosporin. There has been a significant increase in the number of patients receiving rescue medical therapy and an overall decrease in the number of patients receiving rescue surgery. Interestingly, response rates to cyclosporin are improving which could be a reflection of more established protocols for its use.

P544 Does measuring IFX and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease impact clinical management? A Canadian experience

Background: For over thirty years high dose steroids followed by colectomy if required has been the mainstay of treatment for active ulcerative colitis (UC). Recently we have seen the introduction of second-line medical therapies such as anti-TNFa and cyclosporin with the hope of avoiding the need for surgery if first line medical therapy fails. Methods: Using a cohort of UC patients from round two (2008) and three (2010) of the UK inflammatory bowel disease (IBD) audit respectively we aim to assess the outcomes of patients receiving second-line medical therapies. We audited 3049 patients with UC from the 2010 round of the UK IBD audit of which 1071 were considered to have acute severe UC (ASUC). 202 Sites audited a median of 18 UC patients per site that were admitted with IBD between 1/09/09 and 31/08/10. The results of this were compared against the results from the 2008 UK IBD audit which collected data on 2981 UC patients of which there were 863 with ASUC. 209 sites audited a median of 17 UC patients per site that were admitted with IBD between 1/09/07 and 31/08/08. Results: Between rounds there was no significant change in mortality in the ASUC population, 1.2% (10/863) in 2008 vs 0.7% (7/1071) in 2010 (p < 0.3) additionally response rates to first line steroids were similar between rounds 61.1% (498/815) in 2008 vs 58.8% (602/1024) in 2010 (p < 0.4). Significantly more patients are receiving second-line medical therapy 47.3% (150/317) in 2008 vs 57.6% (243/422) in 2010 (p < 0.01). Of the patients failing first line therapy significantly less underwent surgery in 2010: 51.4% (163/317) vs 41.0% (173/422) (p < 0.005). The response rates to anti-TNFa were significantly better than to cyclosporin in both rounds: 75% (39/52) vs 45.9% (45/98) in 2008 (p < 0.005); 81.4% (79/97) vs 60.3% (88/146) in 2010 (p < 0.005). There was a significant difference in response rates to cyclosporin between rounds 45.9% (45/98) in 2008 vs 60.3% (88/146) in 2010 (p < 0.03). Among patients receiving secondline medical therapies there was no significant difference in mortality either between treatments or rounds. Conclusions: In this unselected population, patients consistently respond significantly better to anti-TNFa than cyclosporin. There has been a significant increase in the number of patients receiving rescue medical therapy and an overall decrease in the number of patients receiving rescue surgery. Interestingly, response rates to cyclosporin are improving which could be a reflection of more established protocols for its use.

OC-165 No increase in surgical complication in patients treated with rescue therapy for acute severe ulcerative colitis: data from the UK IBD audit

IntroductionHigh dose steroids followed by colectomy if required remains the mainstay of treatment for active ulcerative colitis (UC). Recently we have seen the introduction of second-line medical therapies with the...