INTESTINAL FAILURE Dr Mike Stroud FRCP Senior Lecturer in Medicine & Nutrition Consultant Gastroenterologist Chair British Intestinal Failure Alliance

Intestinal Failure: Definition The reduction of functioning gut mass to below the minimum necessary for the absorption of nutrients and/or water & electrolytes Nightingale, 2001 Fleming & Remington, 1981 2

Types of Intestinal Failure Self-limiting intestinal failure Type 2 Significant & prolonged PN support (>28 days) Type 3 Chronic IF (long term PN support) short term medium term long term Lal et al. AP&T 2006:24;19-31

INTESTINAL FAILURE Type 1 Surgical ileus Critical illness GI problems Vomiting Dysphagia Pancreatitis GI obstruction Diarrheoa Oncology Chemo/DXT GVHD Type 2 Post surgery awaiting reconstruction ‘Disaster’ Crohns SMA Radiation Adhesions Fistulae Type 3 Short Bowel syndrome +/- other pathology Crohns +/-SBS Radiation+/-SBS Dysmotility Malabsorption Scleroderma CV Immunodef Inoperable obstruction Ca

Short Bowel Syndrome Group Common Uncommon Small intestinal resections Crohn's disease Post irradiation enteritis Repeated surgery for surgical comps Massive intestinal resection Infarction (SMA/SMV thrombosis) SMA embolus Massive volvulus Desmoid tumour EC fistula High output Bypass surgery Gastric bypass (obesity)

Types of short-bowel Jejunostomy Ileostomy Jejuno- colic Ileo- colic

Physiological changes with SBS Gastric emptying  with jejunostomy SB transit time  with jejunostomy Gastric secretions gastric acid (hypergastrinaemia) GI hormones gastrin, CCK, PYY, GLP-2

Problems in short-bowel patients Nutritional Macro-nutrient and energy deficiencies. Water and sodium losses Magnesium/potassium Vitamin and trace element deficiencies. Other Bile salt diarrhoea Gall stones oxalate absorption from colon and renal stones. D-lactic acidosis

Jejunal length (m) r = 0.96 p <0.001 Nightingale, 1990

Variability of intestinal length Technique Author n Small intestinal length (m) Mean Range Autopsy Bryant, 1924 3.0-8.5 Laparotomy Cook, 1974 6 421 3.2-5.2 Backman, 1974 32 643 4.0-8.5 Slater, 1991 38 500 3.0-7.8

Citrulline Permanent IF Transient IF 95% positive predictive value in distinguishing transient from permanent IF Long-term PN needed: Fasting plasma citrulline of less than 20 μmol/L at 2 years. For most types of failure we measure something to grade severity Gases, urea/creatinine, etc. Xylose not used. Crenn P et al. Gastroenterology 2000; 119: 1496-1505

Salt and water in SBS r = 0.96 p <0.001 Nightingale, 1990

Potassium & magnesium Potassium Magnesium Negative K balance when jejunum <50 cm Hyperaldosteronism in chronic Na deficiency Deficiency is common 40% jejunum-colon pts 70% jejunostomy pts No correlation between Mg balance & jejunal length

Treatment: High Output State Drink little hypotonic fluid Maximum 1L/day Drink a glucose-saline solution Drug therapy Antimotility Loperamide (up to 32mg QDS) Codeine phosphate (up to 60mg QDS) Antisecretory Omeprazole (40mg BD) ?Octreotide (50µg BD) Magnesium supplements Magnesium oxide Vitamin D Nutrition Low residue diet

Jejunum Hypotonic fluids Na Water, tea, coffee, fizzy drinks, soup Jejunal mucosa Unable to maintain a Na gradient >30-40mmol/L 17

Jejunum Decreasing fluid losses & increasing absorption Electrolyte Mix 100mmol/l Na Na X Na+ + H20 18

Sodium balance Patient with jejunostomy at 100 cm 50 loperamide codeine electrolyte 25 Sodium balance (mmol/day) electrolyte -25 -50 codeine loperamide & codeine -75 loperamide -100 ranitidine control -125 Nightingale JMD et al. Clin Nutr 1992; 11: 101-5

Stir into 1L water & chill overnight: enjoy the next day! E-mix recipe Ingredient Amount Note Glucose 20g 6 teaspoons Salt 3.5g 1 level 5ml teaspoon Sodium bicarbonate 2.5g 1 heaped 2.5ml teaspoon Stir into 1L water & chill overnight: enjoy the next day!

Parenteral fluids  nutrition Fluid & nutrition requirements are best considered separately “Standard IVN” bags will not be sufficient Bags need to be tailored to requirements Requirements alter daily until steady state Random urine Na: best measure of depletion

Recommended diet Jejunostomy patients Jejunocolic anastomosis Nutrient group Amount Note Energy High 30-60 kcal/kg/day Protein 0.2-0.25g N2/kg/day (80-100g protein) Fat Fibre Low Jejunocolic anastomosis Nutrient group Amount Note Energy High 30-60 kcal/kg/day Protein 0.2-0.25g N2/kg/day (80-100g protein) Fat Low/moderate according to degree of steatorrhoea Fibre Moderate/high Oxalate Low

Maximise macronutrients & electrolytes Enteral feeding Avoid elemental diets high osmolality (small molecules) low macronutrient & Na+ content high volume required to meet requirements No benefit over polymeric & will increase output Oral nutrition + supplements (? With added Na) Sometimes enteral nutrition useful Usually supplementary overnight enteral feed Occasionally impaired swallow X Aim Maximise macronutrients & electrolytes Minimise volume

Maximising GI function Fistuloclysis & enteroclysis Infusion of feed into distal limb of ECF or loop stoma Promotes intestinal adaptation before reconstructive surgery? Can replace IVN in selected patients

Manchester to London canoe Lifelong HPN Some patients can manage a good quality of life Full time work Holiday Challenge Manchester to London canoe

Surgical approaches Restorative surgery Fistula repair Restore intestinal continuity Intestinal lengthening Bianchi technique STEP Intestinal transplantation Small bowel ± colon Other abdominal organs +/-Abdominal wall

Intestinal lengthening STEP Bianchi technique Serial Transverse EnteroPlasty

Liver No liver

Glucagon-like Peptide 2 Naturally occurring 33 AA peptide Production Intestinal L cells (ileum & colon) Release stimulated by luminal nutrition Receptors Mainly in jejunum & proximal ileum Action Strong intestinotrophic properties  Bone density  Intestinal perfusion  Nutrient absorption  Mucosal proliferation  Cytoprotection

Teduglutide in HPN Patients Jeppesen et al, Gut 2011:60(7):902-914

Summary Understand the basic physiology Makes the management easy / possible Multidisciplinary approach essential Medications, diet, fluid intake Stoma care crucial Psychological issues should not be overlooked Optimise medical treatments Including PN were needed Surgical approaches Assess if any bowel can be brought back into continuity Long term outcome Balance life expectancy with quality of life for that patient Know your patients well to give them the best advice

Regional HPN & IF Networks

IF in Southampton Southampton has had NST for >25 years started by Prof Alan Jackson Long record (>20 yrs) as a regional centre for Type 3 HPN patients Increasing number of specialist Type 2 referrals since appointment of Andy King April 09 Specific 12 bedded IFU since Apr 2010 First Independent AHP PN prescribers in the UK (2007 with published audit confirming excellent outcomes which won National GSK Advanced Practice Award

The UHS Intestinal Failure Unit Opened April 2010 12 bed on Ward E8 within regional HPB surgical unit Adjacent to Surgical High Care IFU supported by extended multi-disciplinary healthcare team Majority Type 2/3 IF on IFU but no side rooms Some patients looked after in specialized areas e.g BM Tx/ITU IFU Nurse: patient ratio 1.25 wte nurses per bed 6 trained +2 assistants on an early shift 6 trained +1 assistant on a late shift 3 trained +2 assistants on a night.

NSIFT - Standards of in Hospital Practice 2010: <20% good practice

UHS PN practice 2012/13 NSIFT involved in 99.6% of 427 patients PN use in 66% and oral enteral in 33%

Catheter Related Sepsis Following opening of IFU protocols developed for Ix and Rx of CRS in conjunction with microbiology. All cases of pyrexia in patients on PN are investigated Cases of infection in IF patients managed in conjunction with Microbiology which provides daily consultant-led clinical ward rounds (lead IF micro consultant Dr Adriana Basarab) 24 hour consultant microbiology on-call service with on-site specialist laboratory service. All cases audited within monthly ‘Root-Cause’ process.

UHS Catheter Related Sepsis Historical (cases/1000 PN days) IFU (cases/1000 PN days) Non-IFU 2005 - 08 10.01 2010-11 3.64 5.52 2011 – 12 1.28 8.06 2012 - 13 0.98 6.35

HPN patients Reading - 2 Bath - 1 Bristol - 1 Basingstoke - 6 Southampton - 34 Winchester - 3 Poole - 6 Worthing - 2 Chichester - 3 Dorchester - 2 Bournemouth - 8 IOW - 4 Portsmouth - 2

HPN Patients outcomes UKDDF 2012 Excellent quality outcomes CRS 1.42 per 1000 patient days catheter occlusion 0.31 per 1000 patient days.

IF outpatient clinics Weekly MDT clinic for Type 2 and 3 IF patients >10 years with joint med/surg review since 2009 Ad-hoc day-case review for urgent cases (although lack clinical examination/procedure room) Paediatric IBD/IF Transition clinic with Mark Beattie (President of BSPGHAN) every 6 months Joint small bowel transplant assessment clinics with Oxford (Prof Peter Friend + Mr Anil Vaidja) every 6 months (2 x transplants) Monthly OP clinic at Royal Bournemouth Hospital for Dorset IF patients Planning outreach clinic to serve Sussex patients if designated IF Regional out-patient experience published in 2010 ‘The value of multidisciplinary nutritional gastroenterology clinics for intestinal failure and other gastrointestinal patients’ Frontline Gastroenterology 2010; 1:178-181

Surgery for Intestinal Failure 44 patients over the 3 years 65% of patients were from the surrounding region Complex referrals: 30 enterocutaneous fistulae Of which 19 had laparostomies In 22 cases other organs were involved 5 urology 5 pancreatico-biliary 4 gastro-oesophageal 8 colorectal

Surgical Complexity 12 patients required interventional radiology placement of large bore drains in the acute phase of their illness to drain sepsis 5 patients had radiation enteritis 19 patients had had 3 laparotomies or more in the 3 months prior to transfer

Surgery - Outcomes No in-hospital or 1-year mortality 1 patient (2.2%) unexpected return to ICU 0f 30 patients who were TPN dependant 29 of patients are free of TPN (97%). 1 patient (3.3%) re-fistulated - this resolved spontaneously

SHIFNET The Southern Home Intestinal Failure Network Better Patient Care Shared protocols Clinical Governance Standardised audit Education Communication Website Northampton Milton Keynes Oxford Bucks Trust Stoke Newington London Reading Slough Bath Swindon Basingstoke Salisbury Winchester Southampton Dorchester Portsmouth Chichester Worthing Poole St Mary’s Bournemouth

Type 3 Intestinal Failure Case Presentation Dr Trevor Smith Nutrition Support & IF Team University Hospital Southampton

Case Presentation 2004 22 year old male Presented with life threatening acute abdomen SMA infarct Emergency laparotomy at local hospital

“Cut and Shut ?” Extensive intestinal ischaemia Extensive SB and colonic resection End Jejunostomy 20cm from DJ flexure Mucous fistulae to ‘50cm’ colon • Discharged home after long admission, including ITU with multi-organ failure

Medical Issues: 2004-2008 High stomal losses (5-6 l/day) Limited oral intake Antisecretory and antimotility agents Dietary manipulation 6 litre iv fluid requirement 4 litres PN & 2 litres 0.9% saline 555 mmol sodium per day Weight stable at 67kg BMI 20 Unable to gain weight; physically very weak

Medical Issues: 2004-2006 Behavioural problems Depressed/socially isolated Psychiatry review in UHS and community ?related to cerebral damage during critical illness Recurrent line infections Multiple interruptions to nutrition IFALD ALT 72; ALP414; Bili 10 Osteoporosis

Therapeutic options considered Intestinal lengthening procedure Only 20cm of jejunum therefore not possible Intestinal transplantation assessment Assessed in Cambridge Turned down because of mental health issues

Therapeutic interventions in Southampton Taurolidine line locks Significant reduction in admissions for line sepsis

J Saunders, M Naghibi, T Smith, A King, Z Leach and M Stroud Taurolidine significantly reduces the incidence of catheter related blood stream infections in patients on home parenteral nutrition. J Saunders, M Naghibi, T Smith, A King, Z Leach and M Stroud Southampton NIHR Biomedical Research Centre, Southampton General Hospital, Southampton, UK.

Southampton indications for taurolidine

Results *per 1000 patient days HPN

Therapeutic interventions in Southampton Taurolidine line locks Significant reduction in admissions for line sepsis Reconstructive surgery Re-anastamosis of jejunum to remaining colon 20cm + 50cm colon High risk of intractable diarrhoea Distal colostomy considered

Surgery in 2008 4 years after initial event Anastamosed 20 cm of jejunum to 30cm of colon End sigmoid colostomy Uneventful recovery 12 days in hospital HPN dependent IF team not very optimistic that surgery would radically change prognosis: nutritional balance, line complications, liver

Life after surgery: 2009 Stoma losses ↓ >50% IV fluids requirements ↓ to 4.1L per day LFTs normalised Weight gain no change to PN protein/energy Functional improvement Huge improvement in QOL

Results Date June 2006 May 07 Nov 08 Surgery Jan 2009 July 2009 Weight (kg) 67.5 67.7 66.9 70.5 75 BMI 20.8 20.6 21.8 23.1 Fluid input (litres) 6.1 4.1 Stoma output (litres) 5-6 3.5 2.5 2 ALT iu/l 72 67 14 16 23 ALP iu/l 414 152 94 96 104 Bil mmol/l 10 8 11 Urine Na mmol/l 10-78 10-57 - 85

Mechanisms underlying the benefits of jejuno-colic anastamosis Improved sodium & water resorption Decreases in hyperaldersteronism ↓ urinary potassium losses ↑ potassium availability to form lean body mass Adaptive small bowel changes GLP2 peptide from colon ↑ absorptive capacity Reduced small bowel transit times Peptide YY acting as a ‘colonic brake’ Nitrogen & energy recovery by the rejoined colonic segment

Progress in 2009 Clinically and subjectively much improved Transplant assessment Reviewed in joint clinic in Southampton Admitted for assessment in Oxford Deemed unnecessary But, why did he have a mesenteric infarct?

Patent Foramen Ovale

Current health 2010-2014 HPN dependent, but rarely uses saline Eating, with manageable stomal losses Maintains healthy weight Decreased line infections fewer connections and taurolidine Last admission for CRS May 2012 after fighting...... Better quality of life Time off IV infusions Expert in poisonous snakes and spiders!! Has avoided transplantation

Current health 2010-2014 LFTs – normal Micronutrient screen – normal Bone health Osteoporosis treated with IV Zolendronic acid T score now -1.8 T score -2.7 in 2006 Mental health Stable, with easy access to CMH team