Probiotics in the ICU. Who could benefit? Nadia J van Rensburg RD(SA) Groote Schuur Hospital, Cape Town

Transcription

1 Probiotics in the ICU. Who could benefit? Nadia J van Rensburg RD(SA) Groote Schuur Hospital, Cape Town

2 Outline Introduction: a brief overview Probiotics: Current guidelines Reviews and Meta-analyses IBD Surgery Critical illness Who could benefit from Probiotics?

3 Probiotics Pro latin / bios greek : For Life Hippocrates- death sits in the bowels bad digestion is the root of all evil 1900 s Gasbarrini et al, 2016; Gibson et al, 2017; Hill et al, 2014; Stravou et al, 2017; Wolff, et al, 2018

4 Probiotics Pro latin / bios greek : live microorganisms which, when administered in adequate amounts confer a health benefit on the host For Life onwards Gasbarrini et al, 2016; Gibson et al, 2017; Hill et al, 2014; Stravou et al, 2017; Wolff, et al, 2018

5 Probiotics Pro latin / bios greek : a substrate that is selectively utilized by host microorganisms conferring a health benefit For Life onwards Gasbarrini et al, 2016; Gibson et al, 2017; Hill et al, 2014; Stravou et al, 2017; Wolff, et al, 2018

6 Release bioactive compounds improve intestinal barrier fx & block pathogenic bacteria Endotoxin production & pathogens infections & multiple diseases Produce FA namely acetic acid, propionate & butyrate fuel to colonosites and modulate mucosal immunity Ghasias et al, 2016; Spanogiannopoulos et al, 2017; Stravou et al, 2017; Wolff, et al, 2018

7 Spatial and temporal aspects of the GUT microbiota 1-3 years

8 Composition of microbiota changes / adapts Environment Diet Antibiotics Disease/ inflammation or surgical preparations and procedures NORMAL FLORA DYSBIOSIS VS Ghasias et al, 2016; O Keefe et al, 2017

9

10 IBD SURGERY ESPEN/ ECCO ASPEN CPG Inducing remission & maintenance in UC 2017 E. coli Nissle 1917/ VSL#3 / Lactobacillus GG Pouchitis VSL#3 Strain & type not yet identified 2017 CRITICALLY ILL None 2009 Selective patient populations liver transplantation, trauma, pancreatectomy prevention of VAP, pseudomembranous colitis, & antibiotic-associated diarrhoea Strain & type not yet identified 2016 Saccharomyces boulardii considered unsafe Should be considered Strain & type not yet identified 2016 Saccharomyces boulardii considered unsafe Forbes et al, 2017; Weimann et al, 2017; McClave et al, 2016; Lherm et al, 2002; CPG, 2015

11

12

13 Probiotics: IBD Microbial balance dysbiosis Nutritional intake Enhanced gut barrier Fx & Immune response Mechanism Antagonisation of pathogenic bacteria ph inhibit bacterial adherence & translocation Durchschein et al (2016), Ghouri et al, 2014

14 Probiotics: IBD Crohn s disease: Few studies & poorly powered Not recommended Durchschein et al (2016), Ghouri et al, 2014

15 Probiotics: IBD Ulcerative colitis: Remission and other GI symptoms: Tursi et al (2007), VSL#3 significantly UC activity (mild-to-moderate) (3600 billion cfu/d) Improved PR bleeding & 15% more reinduction of remission in relapsing pts (controls vs placebo) (p=0,069) Bibiloni et al (2005), VSL#3 Two doses daily (3600 billion cfu/d) 77% achieved induced remission Zocco et al (2006), Lactobacillus GG cfu vs mesalazine 2400mg/d Lactobacillus GG significantly, although marginally more effective (85% vs 84% & 80%) in prolonging the relapse free time (p<0.05) Kruis et al (2004), E.coli Nissle 200mg/d vs mesalazine 1500mg/d Equivalent to mesalazine to maintain remission Durchschein et al (2016), Ghouri et al, 2014

16 Probiotics: IBD Ulcerative colitis: Pouchitis Gionchetti et al (2000), VSL#3 vs Ab Rx group 85% achieved remission vs none Gionchetti et al (2003), prevention VSL#3 vs placebo 30% less occurrence of acute pouchitis Significantly lower stool output Durchschein et al (2016), Ghouri et al, 2014

17 Probiotics: IBD Limitations Antibiotic resistance & bacterial translocation Inflamed colonic mucosa in severely ill IBD pts Too few data to clinically advice strain, dose, and frequency / duration of the probiotic therapy

18

19 Probiotics: Surgical considerations

20 Probiotics: Surgical considerations Peri-operative manipulations affecting the gut microbiome Stavrou et al, 2017

21 Probiotics: Surgical considerations Stavrou et al, 2017

22 Probiotics: Surgical considerations SIRS: anaerobic bacteria Lactobacilli & Bifido staphylococcus; Pseudonomas; C.diff; Enterobactariaceae; Candida Evolution of bacteria in SIRS DIVERSE SINGLE DEPLETED Increased bacteraemia and mortality rate p<0.05 Lack in diversity = increased post-operative infections & anastomotic complications Bo et al, 2014; Komatsu et al, 2015; Lui et al, 2011; Mangell et al, 2012; Stavrou et al, 2017; Shimzu et al, 2011

23 Probiotics: Surgical considerations Probiotics Meta-analysis 39% VAP, no effect on mortality Multi-strain pre-operative probiotics sepsis 38% / septic Cx & E.Coli with Bifidobacterium One size does not fit all L.plantarum LP299v no benefit Bo et al, 2014; Komatsu et al, 2015; Lui et al, 2011; Mangell et al, 2012; Stavrou et al, 2017; Shimzu et al, 2011; Siempos et al, 2014 Zhang et al, 2014

24

25 Significant decrease in SSI P= Xiang-Dong et al, 2018

26 Subgroup analysis Intervention Synbiotic (p=0.005) Administration route Oral; EN or Oral (p=0.04; p=0.003) Timing Peri-operatively (p=0.004) High or low dosage (p=0.008; p=0.007) More or less than 10 billion CFU per day Field of surgery Colorectal (p=0.03); Other abdominal (p=0.0009) Xiang-Dong et al, 2018

27 Effect on other surgical complications Xiang-Dong et al, 2018

28 Probiotics: Surgical considerations Limitations: Most trials had only a modest sample size (<100) Route, timing and type of pro-/synbiotics Challenge to give clinical advice Bias toward financial disclosure Xiang-Dong et al, 2018

29

30 Modulators of the microbiota in the critically ill Pathogens outcompete & alter the microbial composition C.Diff Mostly gram neg. aerobic species Proteobacteria?dysbiosis antibiotic use Poor/ inadequate nutrition Wolff et al, 2018

31

32 Probiotics: Critically ill Infections VAP, mortality, ICU & hospital LOS, diarrhoea, antibiotic days Dosage High >5x109 cfu vs Low <5x109 cfu Strains Lactobacillus Plantarum Lactobacillus rhamnosus GG

33 Probiotics: Critically ill Infections: 20% p=0.009

34 Probiotics: Critically ill VAP: 26% p=0.002

35 Probiotics: Critically ill Antibiotic days: 1.12 days p=0.0003

36 Probiotics: Critically ill No significance or no effect for Mortality ICU & hospital LOS Diarrhoea Similar results High >5x109 cfu vs Low <5x109 cfu Strains Lactobacillus Plantarum: 30% p=0.03 infectious complications Lactobacillus rhamnosus GG: although no significance alone Other Probiotics: 23% infectious complications

37 Probiotics: Critically ill Probiotics/ Synbiotics: Probiotics

38 Probiotics: Critically ill Limitations Publication bias for overall infections & LOS Larger, well-powered and definitive RCTs Small samples Subgroup analysis Variety of strains, time of/length of administration Guidelines ASPEN / CPG

39 Potential clinical relevance of the gut microbiota in ICU Dysbiosis Lack in diversity vs. overgrowth Sepsis Single pathogen vs. polymicrobial phenotypes Predict LOS

40 Who could benefit?

41 Who could benefit? IBD: Ulcerative colitis Pro/synbiotic supplementation peri-operatively Further well-designed, properly powered clinical trials to explore the proper mechanism of action South African based studies The research highlights the importance of early feeding in the surgical and critically ill patient maintain and treat the microbiome Possibly incorporate pro/synbiotic supplementation in the management of these patients Further well-designed, properly powered clinical trials to explore the proper mechanism of action

42 THANK YOU!