Presentation on theme: "Treating the Challenging Inpatient with Complicated IBD: Case Studies"— Presentation transcript:
1 Treating the Challenging Inpatient with Complicated IBD: Case Studies Peter D.R. Higgins, MD, PhD, MScUniversity of Michigan
2 Today’s Cases Difficult inpatients The kind that are NOT eligible for clinical trialsLimited, if any, RCT data availableThere are frequently NO right answersManagement through general principles, art, analogy, and a bit of science
3 Complicated Crohn’s DIsease CASE 1Complicated Crohn’s DIsease
4 Case 1: Crohn’s Disease 23 year old male with CD x 4 years Ileal and segmental colonic locationFailed 5-ASA x 8m, Aza x 3 years, now referred after starting IFX monotherapy x 4mSlowly worsening RLQ pain, fevers x 2 monthsCT Scan orderedAdmitted with CRP 4.3, ESR 78, Albumin 2.2, Prealbumin 3 after scan result.
5 Long arrows: Active inflammatory TI stricture Short yellow arrow: retroperitoneal abscess cavity medial to the cecum
6 Coronal imagesLong arrows: Active inflammatory TI strictureShort yellow arrows: retroperitoneal abscess cavity medial to the cecum
7 Consultant NotesRadiology: 2.6 cm abscess medial to cecum, adjacent to long (15 cm) TI stricture with active inflammation. Unable to drain safely. Upstream SB dilated to 3.6 cm.Surgery: No emergent indication for surgery. Recommend maximize medical therapy to eliminate inflammation and eradicate all infection before elective surgery. Follow up in surgery clinic in 8 weeks.
8 Options? Continue anti-TNF? What are the anti-inflammatory options? Anti-microbial therapy?Surgical therapy?Will this situation recur?Will this damaged bowel be responsive to therapy?Discuss…
9 Medical Therapies Anti-TNF Systemic steroids Topical steroids EntocortImmunomodulatorsMethotrexateAzathioprineAbscess fertilizers
10 Anti-microbial therapy DrainageWould be optimal, not always possible60-84% can be drained in case series with 2+ attemptsAntibioticsCover gut bugs broadlyConsider iv for best bioavailabilityConsider early re-image (3-5d) if incomplete drainageLong term, re-image in 4-6 weeksWaljee, Chapter 135, Advanced Therapy of IBD text, ed. Bayless and HanauerFeagins, Kane, et al, CGH 2011:842
11 Is Surgery Avoidable? Usually not Penet rating complications occur close to stricturesIncreased pressure within and upstreamInflammation weakens wallsLikely to recur unless stricture fixedThere are exceptions – inflammatory stricturesCan you drain and start anti-TNF? 31% N=55Goal is generally to get patient to ELECTIVE surgeryNguyen, Sandborn, et al. CGH 2012: 400-4
12 Goals for pre-op visit Eradicate infection Control mucosal inflammationEven better, control transmural inflammationLimit/reduce length of resection“neoadjuvant” anti-TNF therapy?Prevent new fistulas, abscessesBoost nutritional status – Prealb, AlbBoost functional status – “Pre-hab”
13 Treating the challenging inpatient with complicated IBD: Case studies Hans Herfarth, MD, PhDUniversity of North Carolina at Chapel HillChapel Hill, North Carolina
14 Case 227 yo female patient, hospitalized for refractory ulcerative colitisPMHx: Diagnosis of ulcerative pancolitis 2.5 years agoInitial therapy with steroids and 5-ASA without improvement, start of infliximab.Allergic reaction with shortness of breath, chest pain during maintenance therapyStart of 6-MP, remission for 18 months until 3 weeks before hospitalization.2 weeks before hospitalization start of oral steroids (40 mg prednisolone) without success
15 Case 2 (cont'd) Time of consult: 8-10 bloody bowel movements/day, no feverPhysical exam: Abdomen soft, non-tenderMedication: Start of 60 mg methylprednisolone iv yesterday.Labs:WBC 11.9 x10 9th/L, HGB 8.9 g/dl, platelets 550,000 x10 9th/L,CRP 9.4 mg/dl.
18 Case 2 (cont'd)Therapeutic options in the setting of no response to steroids in active UC and pregnancy:InfliximabAdalimumabGolimumabCyclosporineColectomy with ileostomy
19 Cyclosporine Therapy of UC in Pregnancy 3 case reports, 3 case series with 2, 5 and 8 patients8 patients7-Pan-UC1 Left sided UCPregnancy week 6-27Iv cyclosporine for 5-17 days (1 patient oral), then switch to oral cyclosporine (2 patients + AZA7/8 patients with response to therapy.One patient after 17 days switch to IFX with response (later on Dx of CD)7/8 pregnancies conducted to term.1 death at week 22 (cyclosporine started week 10; mother with protein-S defect).Two newborns premature.Branche et al. 2009
20 Surgical management of Therapy Refractory UC in Pregnancy 11 case reports with 1 or 2 patients, 4 case series with 4, 5, 7 and 9 patientsCase series before 2000 , especially around the 1970’s significant mortality of mothers or infantsCase series Mayo 2006 (Dozois et al. 2006):5 patients with UC.All with subtotal colectomy at first (1), second (3) and third trimester (1)No complications after surgery or during delivery.
21 In-Hospital Management and Birth Outcomes in Pregnancy in 2 Tertiary Care Centers (Mount Sinai, NYC, Chicago)Time period : 11 patients with UC, 6 patients with CD, 1 patient with ICHospitalization and treatment with hydrocortisone n=18, cyclosporine n=5, start of 6-MP/AZA n=3.15 pat. 83% response to medical therapy, 3 (17%) colectomy. 1 patient in cyclosporine group spontaneous abortion week 15.Average weight (g)p<0.0001p<0.0001Reddy et al. 2008
22 Outcome case UC pregnancy Start of cyclosporine 2 mg/kg bw . Aim trough level >200 <400 ng/ml. Continuation of 6-MP Continuation of iv steroidsPatient improved after 2 days with decrease of bowel movements. Switch to oral steroid taper on day 3. Switch on day 7 to oral cyclosporine (6 mg/kg body weight).Continuation of oral cyclosporine + 6-MP for 3 months, then continuation of 6-MP onlyUncomplicated vaginal delivery week 36, baby with normal weight
23 Severe ulcerative colitis CASE 3Severe ulcerative colitis
24 Case 3: Severe Ulcerative Colitis 19 year old female with UC x 4 months3 m on 5-ASA, various types and doses1 m on Aza 2.5 mg/kgTPMT 13.2C diff infection found 3 weeks agoFlagyl x 10 days, better on days 5-10Then worsened22 bloody BM daily, low-grade fevers
25 Admitted CDTOX negative WBC 12.2, ESR 33, CRP 9.2 HR 95, BP 122/78 IV methylprednisolone 60 mg dailySmall improvementsDay 2 scope - severe UC, no CMVEnd of day 3: 15 BM/day, CRP 6.9
26 Options? Prognosis? What are the rescue therapy options? How to dose/frequency of dosing?Where will drug go? How to monitor levels?Implications of surgery on fertility?What are long-term risks/benefits?Discuss….
27 An Extreme Paucity of Data… A fair amount of trial and errorTrial and failure, learn from your mistakesIFX can leak out of colon into stool in surprisingly large amountsCRP is invariably high, and falls with therapyRetrospectively developed prognostic indices helpIf steroids are not working by day 3, will not workIn the CYSIF trial, IFX ~ Cyclo at 90 days
28 What Various IBD Centers Do Operate at Day 4Rescue with Cyclosporine (decreasing)Rescue with IFXDose high (10 mg/kg)Dose often (5 mg/kg q 72h until CRP <1)Hybrids of theseUM protocol:
29 Pain in Crohn’s Disease Case 4Pain in Crohn’s DiseaseHans Herfarth, MD, PhDUniversity of North Carolina at Chapel HillChapel Hill, North Carolina
30 Case 440 yo female patientDiagnosis of Crohn‘s disease (CD) at age 24 Intermittent treatment with steroids and 5-ASA for 10 yearsCD flares up with severe colitis, steroid refractory. Initiation of infliximab and 6-MP. Remission after 2nd infusion of infliximab.3 months later diagnosis of fibromyalgia. No effects of pregabalin, start of pain management by outside pain clinic.
31 Case 2 (cont'd)Now admission with increased diarrhea (8-10 BMs daily), non-bloody and severe abdominal pain (10 out of 10).Previous medication before admission:For CD: Infliximab q 8 weeks, last infusion 4 weeks ago and 6-MP (1.2 mg/kg bodyweight).For fibromyalgia: Fentanyl patch 25 mcg/hr and oxycodone/acetaminophen 7.5 mg/325 mg 3-4 tablets daily as needed.Physical exam: No fever, abdomen soft, diffusely tender on deep palpation, no rebound tenderness.After admission: Patient is on hydromorphone 4 mg iv q 4 hours
32 Possible Reasons for Recurrent IBD Symptoms (Pain, Diarrhea) FlareStricture, AbscessInfection (e.g. C. diff, CMV)Bacterial overgrowthNarcotic Bowel SyndromeIBS
33 Case 2 (cont'd) Workup Laboratory: CBC, CRP, calprotectin normal CT-abdomen with oral contrast: Normal, no dilated loops, no abscessUpper-GI endoscopy and colonoscopy:
35 Possible Reasons for Recurrent IBD Symptoms (Pain, Diarrhea) FlareStricture, AbscessInfection (e.g. C. diff, CMV)Bacterial overgrowthNarcotic Bowel SyndromeIBS
36 Use of Narcotics in Hospitalizations for IBD 117 patients with IBD (exclusion of postoperative pat. (up to 1 month) and pat. with abscesses.70. 1% receiving pain medications at admission ( median 12 mg in first 24 hours, median daily later on 7.5 mg/day.7.7 % PCA pumpRisk Factors for Inpatient Narcotic UseOdds ration95% confidence interval [CI]Narcotics prior to admission5.41.5 – 19.0Smoking4.31.2 – 15.6Psychiatric diagnosis2.20.4 – 11.6Long et al. 2012
37 Diagnostic Criteria for Narcotic Bowel Syndrome Chronic or frequently recurring abdominal pain that is treated with acute high-dose or chronic narcotics and all of the following:The pain worsens or incompletely resolves with continued or escalating dosages of narcotics.There is marked worsening of pain when the narcotic dose wanes and improvement when narcotics are re-instituted (soar and crash).There is a progression of the frequency, duration, and intensity of pain episodes.The nature and intensity of the pain is not explained by a current or previous GI diagnosis.Grunkemeier et al. 2007
38 Detoxification Protocol for Narcotic Bowel Syndrome (1) Reduction of morphine doseTreatment of anxietyTreatment of withdrawal symptomsStart of medications for long term control of abdominal painPhysician – Patient RelationshipDays ………..Grunkemeier et al. 2007
39 Detoxification Protocol for Narcotic Bowel Syndrome (2) Effective communication with the patient is essential.Explanation of rationale/benefit of stopping the narcoticsExplanation of the withdrawal program.Affirmation of the patient’s pain and an explanation of the underlying pathophysiology of NBS (i.e. altered motility and/or visceral hypersensitivity).Total narcotic daily dose should be converted to morphine equivalents using an appropriate calculator and the 24 hours total drug dose reduced by 10-33% q 24 hours. In inpatients setting administration of morphine as continuous infusion (not PRN).Grunkemeier et al. 2007
40 Detoxification Protocol for Narcotic Bowel Syndrome (3) Start of TCA (e.g. desipramine, mg/qhs) or SNRI (e.g. duloxetine mg. qd) for immediate and long terms pain control and to help manage psychological comorbidities.Mirtazepine (15-30 mg. qhs) can be considered instead of or in addition to a TCA or SNRI if nausea is a prominent feature.For withdrawal symptoms clonidine (start with 0.1 mg bid)For anxiety benzodiazepine (e.g. lorazepam 1 mg q 6 hours)For constipation e.g. PEG g bidGrunkemeier et al. 2007
41 Narcotics discontinued Outcome after Discontinuation of Narcotics in IBDNarcotics discontinuedn=22Narcotics continuedn=17Medically adherent100 %53 %Surgically adherent94 %Mod/severe pain27 %82 %None/mild clinical symptoms80 %24 %Hanson et al. 2009