Management of Diarrhea in Critical Ill Patients CCSSA Congress Sun City 20. October 2017

Transcription

1 Management of Diarrhea in Critical Ill Patients CCSSA Congress Sun City 20. October 2017 Prof. em Rémy Meier MD University of Basel Gastro-Center Obach Solothurn, Switzerland

2 Outline Definition of diarrhea The burden of diarrhea Causes of diarrhea Management of diarrhea New option to prevent and treat diarrhea

3 The diagnosis and management of diarrhea in the ICU can be a challenge!!!

4 Introduction I Diarrhea is a common and prevalent problem in the ICU The causes are complex and multifactorial - Bacterial - Medication (eg prokinetics, laxatives, antibiotics) - Predisposing diseases - Enteral feeding

5 Introduction II The reported incidence varies a lot The most common infectious cause is Clostridium difficile (10-20%) Among medication the antibiotic associated diarrhea is the most common cause The use of enteral nutrition was thought to be a major cause of diarrhea, but there is no evidence to support this anymore

6 Definition of diarrhea The major problem is the definition! There are 33 different definitions reported

7 Definitions of diarrhea Definitions based on frequency (>2 stools, >3 stools, >4 stools) Definitions based on consistency (unformed, liquid) Definitions based on weight (>200g, >300g) Definitions based on duration (>1day, >2days) Combination of frequeny and consistency s

8 Definition of diarrhea Subjective measures - Stool frequency - Consistency When are they clinically relevant Objective measures - Stool weight - Stool volume These are often difficult to obtain

9 Definition of diarrhea Scoring systems combining different variables are popular today Scoring systems have shown good validity and inter-rater reliability Whelan et al, Eur J Clin Nutr 2004

10 Causes of diarrhea Medication - Laxantives - Antibiotics - Prokinetics Infectious causes - C. difficile Predisposing illness - Diabetes - Bacterial overgrowth - Gallsalt loosing syndrome - Severe hypoalbuminia - Malabsorption diseases Enteral nutrition

11 Medication A common cause are hyperosmolar medications - 61% of the cases! Antibiotics - can cause diarrhea by changing the microbial compostion in the gut - can cause overgrowth of C. difficile Edles et al, Am J Med 1990 Guenter et al, JPEN 1991 Bliss et al, J Clin Nutr 1992

12 Osmolality of selected Medication Drug (mosm/kg) Acetaminophen elixir 5400 Diphenoxylate susp KCl elixier (sugar-free) 3000 Chloral hydrate sirup 4400 Furosemide (oral) 3938 Metoclopramide 8350 Multivitamin liquid 5700 Sodium Phosphate 7250

13 Diarrhea management in the ICU I 1. Make a proper diagnosis of diarrhea - Is it really diarrhea? - Has diarrhea consequences for the patient? 2. Check medication treatments - Laxantives, prokinetics - Antibiotics - Others (Magnesium, Sorbitol!) 3. Look for infectious causes - C. difficile (If postitive antibiotic treatment) 4. Check for predisposing illness - Diabetes - Bacterial overgrowth - Gallsalt loosing syndrome - Hypoalbuminia - Malabsorption diseases

14 Diarrhea management in the ICU II 5. Treat the underlying disease or infectious causes 6. Stopp medications causing diarrhea if it is posible 7. Dilute medication to make them isotonic 8. Changing the administration route of medication from enteral to intravenously 9. If there is no infectious cause try an antidiarrheal agent (eg Loperamide) Cave!!! Avoid managements that reduce optimal nutritional support

15 Incidence of diarrhea in tube fed patients 2-68% A 46% incidence was reported using subjective data A 10% incidence was reported using objective data

16 Diarrhea in tube fed patients in the ICU Prevention and treatment of diarrhea Try to change delivery of EN Try to change the type of formula - Fibre containing formulas - Peptide formulas - Fat-modified formulas with MCT Try probiotics

17 Diarrhea in tube fed patients in the ICU Management of diarrhea with uncertain effects - Changing the flow rate of enteral nutrition - Changing the osmolality of the enteral formula - Formula composition (Peptide diets are not better tolerated than polymeric diets) Peptide formulas are limited for patients with severely impaired GI-function

18 Delivery modes of enteral nutrition EN can be delivered as continuous infusion or as bolus The results on diarrhea are conflicting: - Bolus vs continuous (164 trauma patients)*: - Bolus reached the 100% nutritional goal faster - No difference in the occurence of diarrhea - Bolus vs continuous (60 elderly patients)**: - Continuous feeding had a reduction of diarrhea of 30% Bolus vs continuous (105 elderly patients)***: - No difference in diarrhea * MacLeod et al, J Trauma 2007 ** Ciocon et al, JPEN 1992 *** Lee and Auyeung, Age Ageing 203

19 Bolus vs continuous feeding A systemic review 6 trials included No significant difference Martinez et al, JBI Database of Systematic Reviews and Implementation 2014

20 Fibre Soluble and non soluble fibre Fermentable and non fermentable fibre A subgroup is called prebiotics, able to stimulate beneficial Gut bacteria

21 Intestinal bacteria and fibre Soluble fibre Bacterial fermentation - Short chain fatty acids (Butyrate, Acetate, Proprionate) and H 2, CO 2 - Reduction of the ph in the colon

22 SCFA absorption SCFA - H + Na + SCFAH SCFAH H + Na + SCFA are potent promoters for sodium and water absorption in the colon E. Cabré, Fibre Consensus

23 The clinical and physiological effects of fibre-containing enteral formulae: Systematic review and meta-analysis 43 randomized controlled trials Reduction of the diarrhea incidence OR 0.68, 95% CI: Fibre were generally well tolerated Elia et al, Aliment Pharmacol & Ther 2008

24 Elia et al, Aliment Pharmacol & Ther 2008

25 Partially hydrolysed guar gum (PHGG) PHGG is 100% soluble and 100% frementet PHGG has shown to reduce the incidence of ETF-induced diarrhea Best results with 20g PHGG per day Cave: More than 20g/day can result in more diarrhea

26 Fibre supplemented EN in medical and surgical patients (n=100; t>5 days) Incidence of diarrhea Fibre-free (n=50) 30% P< g/l PHGG (n=50) 12% yes No Homann et al, JPEN 1994

27 Fibre supplemented EN in medical and surgical patients (n=100; t>5 days) Incidence of flatulence Fibre-free (n=50) 8% P< g/l PHGG (n=50) 22% yes No Homann et al, JPEN 1994

28 Fibre supplemented EN in critically ill septic patients (n=25; T>6 days) * *22 g/l of partially hydrolized guar gum Spapen et al, Clin Nutr 2001

29 Control of diarrhea by PHGG in ICU on enteral nutrition Prosp. rand. controlled trial (N=20) Nr liquid stools Day 1 Day 4 Study group 2.0 ± ± 0.7 * Control group 1.2 ± ± 0.8 ** *p<0.01; **p<0.05 Rushdi et al, Clin Nutr 2004

30 Peptide formulas Peptide formulas had no effect on diarrhea compared with polymeric formulas They are seldom used If everything fails they can be tried Howatt-Larssen et al, JPEN 1992 Heimburger et al, Nutrition 1995

31 Fat modified formulas Fat can contribute to feeding intolerances Fat can delay gastric emptying MCT containing formulas have shown to increase feeding tolerance and an increase in caloric and protein intake Qui et al, JPEN 2015

32 Probiotics Definition Live microorganisms which when administered in adequate amounts confer a health benefit on the host FAO (Food and Agriculture Organization of the UN) and WHO

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34 Probiotics to prevent antibiotic associated diarrhea Rand, db, Placebo-controlled trial Lactobacillus casei vs Placebo N=135 Probiotics Placebo Diarrhea 12% 34%* Cl difficile 0% 17%* Risk reduction 22%, NT 5 *p=0.001 Hickson et al, BMJ 2007

35 Probiotics for the prevention of AAD and the treatment of Clostridium difficile disease Meta-analysis (31 studies) Probiotics significantly reduced the relative risk of AAD (25 studies) RR 0.43 (95%: ), p<0.001 Probiotics had a significant efficacy for CDD (6 studies) RR 0.59 (95%: ) p<0.005 Saccharomyces boulardii, Lb rhamnosus GG, and probiotic mixtures) significantly reduce the development of AAD Only Saccharomyces boulardii is effective for CDD treatment McFarland, Am J Gastroenterol 2006

36 Probiotics for prevention and treatment of antibiotic induced diarrhea Systematic review and Meta-Analysis 82 randomized controlled studies with Lb, Bifidus, Saccharomyces boulardii, Streptococcus Probiotics reduce significantly the relative risk of AAD (63 Studien) RR 0.58 (95%: ), p<0.001 Number to treat 13 (95%: 10,3-19.1) Unclear: Which is the best probiotic for the different antibotic Hempel et al, JAMA 2012

37 Risks for the patients Increased risk of complications in specific patients groups (e.g. endocarditis, abscess). 20 case reports of adverse events in 32 patients for Lb rhamnosus GG and Saccharomyces boulardii 53 trials in which 4131 patients received probiotics - Most trials showed no effect or a positive effect on outcome - Only 3 trials showed increased complications (non-infectious) in liver transplant and severe pancreatitis patients No complications reported with Bifidobacteria! Whelan an Myers, Am J Clin Nutr 2010

38 Complications with Saccharomyces bouldardii - Review- 57 cases with Saccharomyces boulardii fungiaemias 60% were in a ICU 71% had enteral or parenteral nutrition 26 patients got Sb treatment 17 patients died Mumoz et al, Clin Infect Dis, 2005

39 Probiotics and enteral nutrition Canadian Clinical Practice Guidelines Pooling the results from 8 trials that reported patients who developped diarrhea, probotics had no effect (RR 0.95, 95% CI 0.80, 1.13, p=0.54) nutrition.com, 2013

40 Summary and Conclusion Verify if the patient has diarrhea (Definition!!) Search for the cause of diarrhea Treat the cause of diarrhea Change medication Try a specific fibre formula (PHGG) Don t stopp feeding the patients For the future probiotics are an option for preventing and treatment of diarrhea (efficacy and safety has to be more clear)