Table 1 Summary of evidence in predefined subtopics related to gastrointestinal dysfunction (what we know). More details on the literature behind statements in this table are presented in Supplement 2 Table S3

 i.

Clinical assessment

Can GI symptoms* and/or clinical signs be used to monitor GI function in critically ill patients?

- There is no gold standard for monitoring of GI function in critically ill.

- GI symptoms and clinical signs may be used, and the number of GI symptoms is associated with increased mortality.

- GI symptoms/signs have not been clearly correlated with other objective methods quantifying GI function.

 ii.

Imaging

Can imaging be used to monitor GI function in critically ill?

- No validated imaging method for bedside monitoring.

- GI ultrasound is promising but requires further study.

 iii.

Laboratory (including biomarkers)

Can biomarkers be used to monitor GI function in critically ill?

- No biomarker is validated for clinical use.

- Host-, disease- and analytics-related factors may influence potential biomarkers of interest.

- Most of the studies assess biomarkers of mesenteric ischaemia or organ dysfunction.

 iv.

Absorption of nutrients

Can absorption of nutrients be measured to monitor GI function?

- No method to measure absorption is available for routine clinical use.

 v.

Barrier function

Can barrier function be measured to monitor GI function?

- No valid method to measure barrier function is available for routine clinical use.

 vi.

Others (including intra-abdominal pressure (IAP))

Which other monitoring methods can be used to monitor GI function?

- IAP can be easily measured and gives a numeric value reflecting abdominal compartment.

- Association with GI function is unclear.

- Grossly elevated and increasing IAP may necessitate discontinuation or reduction of EN.

 vii.

Prokinetics

-Do prokinetics improve upper GI motility in critically ill?

- Do prokinetics improve lower GI motility in critically ill?

- Does combined treatment of upper and lower GI intolerance improve GI motility in critically ill?

- Do prokinetics improve other clinically relevant outcomes?

Gastric emptying:

- Erythromycin accelerates gastric emptying and may be superior to metoclopramide.

- The effect of combination metoclopramide and erythromycin is sustained for longer than either drug alone.

Lower GI dysmotility: insufficient data.

Combined treatment of upper and lower GI motility: insufficient data

Uncertainty with regards to:

- Recommended dose of erythromycin (3 × 100 mg vs 200–250 mg) and therapy duration.

- Repeated treatment with gastroprokinetics.

- Definition of lower GI intolerance/dysmotility.

- Effect on morbidity and mortality.

 viii.

Laxatives

Do laxatives improve GI function, morbidity and mortality in critically ill patients?

- Possible benefit of prophylactic therapy (polyethylene glycol, lactulose) regarding time to defaecation, but not regarding complications.

- Polyethylene glycol probably better than lactulose, suggested to reduce the incidence of Ogilvie’s syndrome.

 ix.

Post-pyloric feeding

Does post-pyloric feeding improve GI function, morbidity and mortality in critically ill patients receiving EN?

- Post-pyloric feeding may reduce the number of patients who develop ventilator-associated pneumonia.

- Mostly small studies in patients without feeding intolerance.

- Heterogeneity of intervention, i.e. different location of tubes (duodenal and jejunal) pooled.

 x.

Others

Which other management improves GI function, morbidity and mortality in critically ill?

- None confirmed in critically ill in general.

- In postoperative patients, ERAS protocol and epidural analgesia may improve GI motility.

- Beneficial effect of any specific (e.g. restrictive) fluid management strategy on GI function has not been proven.

 xi.

GI function and nutrition

Does EN improve GI function, morbidity and mortality in critically ill?

- EN may preserve GI immunity and attenuate proinflammatory changes and bacterial overgrowth.

- The quantity of nutrients absorbed with EN during critical illness is uncertain.

- EN has not been shown to improve patient-centred outcomes.

 xii.

The role of the gut in multiple organ failure

What is the evidence on the role of the GI dysfunction in the development and course of MOF?

Indirect evidence supports a role of GI dysfunction in the development/perpetuation of MODS suggested by associations between the severity of GI dysfunction and organ failures.

 xiii.

Microbiome

What is the evidence on the role of the microbiome in GI dysfunction?

Observational data have shown an association between critical illness (severity) and change of the intestinal microbiome as compared to the healthy state (‘dysbiosis’). Change in microbiome is suggested to be associated with GI dysfunction and clinical outcome but has yet to be confirmed by adequately powered studies.

 xiv.

Bacterial translocation/mucosal integrity

What is the evidence on bacterial translocation/mucosal integrity in GI dysfunction?

Reported associations between the presence of enteric bacteria or bacterial products in the circulation, presumably related to gut dysfunction and poor outcome. Gut microbiota or related products (e.g. DAMPs in lymphatic ducts, endotoxins in portal blood) may trigger distant organ damage in GI dysfunction.

 xv.

GI hormones

What is the evidence that endogenous GI hormones are important in modulating GI dysfunction?

A decrease in the plasma concentration of orexigenic hormones (e.g. ghrelin) and an increase of anorexigenic hormones (e.g. PYY) during the early phase have been observed. No direct correlation with the GI function has been reported.

 xvi.

Bile acid signalling

What is the evidence on bile acid signalling in GI dysfunction?

Bile acid signalling as a mechanism of GI dysfunction has not been studied in adult critically ill patients, but increased levels of bile acids in circulation are associated with adverse outcome.

 xvii.

Others

What is the evidence on other mechanisms in GI dysfunction?

Bowel oedema and bowel distension have not been studied in critically ill patients. Bowel oedema impaired motility in experimental study.