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GI function in critical illness and
managing intolerance
Kate Fetterplace BNut&Diet, PhD Candidate, APD Senior Dietitian, Clinical Lead, Royal Melbourne Hospital
@FetterplaceKate
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• Sponsored by Abbott
• Previously received honorarium/ sponsorship support from: – Baxter
– Fresenius Kabi
– Nestle
– Nutricia
– Abbott
Disclosures
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• Describe the prevalence of GI intolerance in critical care patients and the impact on outcomes
• Provide evidence-based approaches to manage GI intolerance in the critical care setting
• Nutrition interventions based on a patient’s specific GI intolerance
Objective
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Every critically ill patient staying
>48 h should be considered at risk for malnutrition
Consequences of critical illness
Singer et al Clin Nut 2019, Preiser JC et al Br J Anaesth 2014
Acute phase
Late period
Day 1 -2 Day 3-7
Late phase
Rehabilitation Or chronic
phase
Anabolism
Catabolism
Acute phase
Early period
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Nutrition and muscle loss
Muscle loss occurs when
Muscle breakdown is
> Muscle synthesis
Skeletal muscle loss is associated with worse clinical outcomes
Hurt RT et al Nutr Clin Pract. 2017, Wandrag L et al J Hum Nutr Diet. 2015
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Critical care nutrition guidelines
McClave S A et al, JPEN 2016, Singer et al Clin Nut 2019, CCPG Crit Care Nut 2015
ESPEN (2019) ASPEN (2016) Canadian (2015)
Early enteral nutrition (EN)
Early EN (within 48hrs) (Grade B)
Early EN (within 24–48hrs) (low level)
Early EN (within 24-48hrs)
Energy Indirect Calorimetry
Indirect calorimetry or 25-30kcal/kg
Insufficient data
Protein 1.3g/kg 1.2 – 2.0g/kg Insufficient data
Site of EN feed delivery
Gastric Gastric Gastric
Parenteral nutrition
Commence 3-7 days
Low risk >7 days Early PN in high risk
Early PN in high-risk
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How much protein
Ridley et al JPEN 2018
Mean (SD) protein provision: 0.6 (0.4) g/kg/day
Mean (SD) energy provision: 15 (8) kcal/kg/day
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Early EN
Improved outcomes
Support immune function
Modulates stress response
Maintains gut barrier function
Adequate nutrient delivery
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• Gastric residual volumes (GRV) > 500ml
• Uncontrolled shock, hypoxemia and acidosis
• Uncontrolled GI bleeding
• Bowel ischemia
• Bowel obstruction
• Abdominal compartment syndrome
• High output fistula without distal feeding access
Contraindications to early EN
Singer P et al Clin Nut 2019
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• Frequently occurs in critically ill
– More prevalent as the severity of illness increases
• Associated with adverse outcomes
– Diminished enteral nutrition provision
– Increased mortality
– Increased duration of admission to ICU
Gastrointestinal dysfunction
Deane et al Nut Clin Prac 2019
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Digestion and absorption of
nutrients
Enteric nervous system
Endocrine function
Immune function
Microbiome
Gut-brain axis
Nucleus Medical Media (2020). Gastrointestinal tract [Digital image]. Retrieved from https://ebsco-smartimagebase-com.ez03.infotrieve.com/gastrointestinal-tract/view-item?ItemID=25875
GI physiology and function
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Critical illness
Medical management
GI dysfunction in critical illness
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• Pre-existing medical problems (diabetes, Parkinson’s)
• Presenting problem (spinal core injury, burn injury, pancreatitis, intra-abdominal surgery)
Factors on admission
• Age, hyperglycaemia, hypokalaemia, pain
• Severity of illness, inflammation, gastrointestinal hormone (excessive or suppressed secretion)
Dynamic endogenous
factors
• Opiate analgesia, catecholamines/vasopressors
• Excessive volume resuscitation, electrolyte disturbances, intra-duodenal fat
Dynamic exogenous
factors
Risk factors for GI dysmotility
Deane et al Nut Clin Prac 2019
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Pathophysiological response
Vs.
Inability to satisfactorily deliver caloric and protein load to patients
(feeding intolerance)
No universally accepted definition
GI Dysfunction
Reintam Blaser et al Acta Anaesthesiol Scan 2014
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43 different definitions
3 main categories
– ‘Large’ gastric residual volumes
– Presence of GI symptoms
– Inadequate delivery of enteral nutrition
Definition of feeding intolerance
Reintam Blaser et al Acta Anaesthesiol Scan 2014
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Prevalence of feeding intolerance
0
10
20
30
40
50
60
70
80
GI symptoms(including large
GRVs)
Large GRValone
GI symptomsalone
Inadequate EN Total
Pre
vale
nce
of
FI %
pooled proportion (%)
Reintam Blaser et al Acta Anaesthesiol Scan 2014
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Author (n) Definition Prevalence Outcomes
Mentec 2001
153 GRV 150m -500ml (x2) or > 500ml or vomit
43% Increased ICU mortality OR 1.48, longer ICU LOS (23 vs 15 days)
Lam 2007
272 Vomiting or regurgitation GRV > 250ml
57% Longer ICU LOS (19 vs 12 days)
Nguyen 2007
95 + match controls
GRV > 250ml NA Longer ICU LOS (18 vs 11 days)
Reintam 2008
264 EN discontinued (vomiting, large GRVs, ileus, severe diarrhoea, abdo pain or distention
47% Increased mortality 90 day (58 vs 17%)
Shimizu 2011
63 Free gastric drainage >300 ml during Post-pyloric feeding
22% Increased mortality (64 vs 20%) Increased incidence of bacteraemia
Outcomes associated with feeding intolerance
Reintam Blaser et al Acta Anaesthesiol Scan 2014
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Treatment & management
GI dysfunction
Assessment of GI
Function
Determine underlying
cause
Treatment and
monitor
Optimise nutrition provision
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GI dysfunction
Region Organ dysfunction Signs and symptoms
Upper GI dysmotility
Stomach and/or small bowel
vomiting, regurgitation, large GRV
Lower GI dysmotility
Large bowel dilation or dysmotility
bowel distention, and pain, prolonged period of non-defecation
Diarrhoea Small and/or large bowel +/- biliary system
at least 3 stools per day (type 5-7) or >300ml
Deane et al Nut Clin Prac 2019, Plummer et al Curr Opin Crit Care 2019
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3 major physiological functions:
– Fasting motility pattern to intermittently expel ingested non–nutrient material
– Prepare ingested solid nutrient material (chyme)
– Storage nutrient and regulating the delivery to the Small intestine
• ideally to match the absorptive capacity
Stomach
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• Coordinated effort between the fundus, antrum, pyloric sphincter and duodenum
• Regulated by:
• Gastrointestinal electrical activity – interstitial cells of Cajal
• Neural – intrinsic modulation by the enteric nerves and extrinsic input via the vagal nerves (CNS)
• Feedback from the nutrients and volume in the stomach and small bowel (small feedback loop)
Gastric emptying
Deane et al Nut Clin Pract 2019
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• Delayed GE is observed in a significant proportion of critically ill (possibly up to 80%)
• Changes in hormones and neurotransmitters
• Nutrient-simulated feedback mechanisms are heightened
• Marked increase in pyloric tone
Gastric emptying in critical illness
Deane et al Nut in Clin Pract 2019
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Critical care nutrition guidelines ESPEN (2019) ASPEN (2016) Canadian (2015)
Measuring GRV 7 days Early PN in high risk
Early PN in high-risk
McClave S A et al, JPEN 2016, Singer et al Clin Nut 2019, CCPG Crit Care Nut 2015
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• GRV – surrogate measures for gastric emptying
• GRV > 250 ml – relative sensitive marker of delayed gastric emptying
Gastric residual volumes
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329 patients randomised
Control 200ml GRV
vs
Intervention 500ml
No increase in adverse outcomes
GRV during EN in critically ill: REGANE
Montejo et al Int Care Med 2010
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• 452 ventilated ICU patients
– Control (intolerance vomiting or GRV > 250ml)
– Intervention (no monitoring, intolerance = vomiting)
• No different in VAP or other outcomes (mortality, duration of ventilation)
• Higher rates of vomiting – intervention
Reignier et al JAMA 2013
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• 6 studies
• Monitoring of GRV may not affect ventilator associated pneumonia in medical ICU patients
• Mechanically ventilated surgical patients may still benefit from lower thresholds (250ml)
Kuppinger et al Nutrition 2013
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• Accelerate gastric emptying
• Bypass the stomach
• Parenteral nutrition
Management of gastric dysmotility
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• Metoclopramide – dopamine antagonist, 5HT3 receptor antagonist, 5HT4 agonist
– IV 10mg TDS
• Erythromycin – Motilin agonist, increases antral activity
– IV 70mg – 200mg BD
• Combined therapy is most effective
• Accelerate gastric emptying when delayed
Promotility agents
Nguyen et al Crit Care Med 2006, Ritz MA et al Int Care Med 2005, Lewis et al Crit Care 2016
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• Erythromycin – cardiac toxicity, tachyphylaxis, and bacterial resistance
• Metoclopramide – dyskinesia, more frequently in the elderly
• Both agents have been associated with QT prolongation
Potential adverse effects
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• Generally used when prokinetics failed
• Insertion is challenging
• Systematic review – 14 trials (1109 patients)
– Lower rates of pneumonia (RR 0.65 CI 0.5-0.84)
– Possibly increased nutrient delivery (MD 7.8 %, CI 1.4 -14)
– No clear effects on other outcomes
Small bowel feeding
Alkahawaja S et al Cochrane database 2015
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• Fat
• Energy density
• Osmolarity
• ? Possibly protein
Considerations with enteral nutrition
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Effect of EN on gastric emptying
Kar et al JPEN 2016
Larger volume retained in the stomach of 2.0kcal/ml
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• Systematic review: 8816 patients (25 studies)
• Insufficient evidence to determine if EN is better or worse than PN
– Mortality (30 days) (RR 1.02, CI 0.92 to 1.13)
– EN may reduce sepsis (RR 0.59, CI 0.37 to 0.95)
– PN may reduce vomiting (RR 3.42, CI 1.15 to 10.2)
PN versus EN
Lewis SR et al Cochrane database syst rev 2018
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• Predominant site for digestion and absorption
• SB motility has 2 major functions – Mixing and propulsion
– Dependent on the presence of nutrients
Controlled by:
• Presence of nutrients in the small bowel
• Intrinsic pathways (enteric nerves)
• Parasympathetic pathways (vagus nerve)
Small bowel motility
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• Minimal data
• Significant variability in critically ill
• Small cohorts studied
– SB transit time was 2 fold longer in critically ill traumatic brain injury patients
SB motility in critical illness
Deane et al Nut Clin Prac 2019
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• Surgical insult
– Activation of inhibitory spinal reflex arcs
– Endocrine and inflammatory cytokines augment inhibitory neurotransmitters
• Opioids
• Changes in microbiome
• Stress or pain
• Fluid and electrolytes
Causes of SB dysmotility in critical illness
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• No therapeutic drug agents
• Control infections
• Requirement for parenteral nutrition depending on severity and length of time
Management of SB dysmotility
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Type Description Examples Management Type I IF
Acute
Often self-limiting, and
resolves with minimal
medical management
Days
• Acute nausea or vomiting
• Acute ileus following surgery
• May require short
term PN
Type II IF
Prolonged
Acute
Signs of GI dysfunction
are prolonged
Often in metabolically
unstable patients
Weeks
• Prolonged paralytic ileus
• Significant gastrointestinal dysmotility
• Intraabdominal sepsis
• High output stoma or fistula
• Severe mucositis
• PN support
• Control sepsis and
other organ
dysfunction
Type III IF
Chronic
Often occurs in
metabolically stable
patients
Months to years
• Short bowel syndrome
• Chronic GI dysmotility disorders
• Extensive small bowel mucosal
disease such as radiation enteritis
• Home PN
• Restore nutritional
status
• Optimise GI function
where possible
Management of intestinal failure
Klek S et al Clin Nut 2016
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Functions:
• Provide a condition for fermentation of fibre and undigested nutrients
• Absorb water from faeces • Excrete
Control by:
• Not dependent on the presence of nutrients to stimulate motility
• Large propulsive contractions sweep through the colon periodically
Large bowel
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• May occur in 20 – 70% of critically ill
• Small studies on transit time: – markedly slower in critically ill (10 [8.5 -13] days)
compared to healthy controls (1.2 days [0.0 -1.9] days)
• Paralysis of the lower intestine is defined as failure to pass stool for ≥ 3 days
Large bowel dysmotility in critically ill
Deane et al Nut Clin Prac 2019
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• Prophylactic bowel protocols
• Severe cases – intestinal pseudo-obstruction
– Neostigmine
• Nutritional management
– Severe cases PN
Management of large bowel dysmotility
Oczkowski et al Crit Care Med 2017
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• Prevalence 14 -21 % of critically ill
• Causes:
– Osmotic
– Secretory
– Exudative
– Motility
Diarrhoea
Pitta JPEN 2019
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Diarrhoea
Aetiology
Disease related Specific
Non specific
Medication –related
Antibiotic
Osmolality
Feeding related
Osmolality
Specific intolerance
Bacterial contamination
Infectious Bacterial
Viral
Reintam Blaser R Cur Ppin Care 2015, Pitta MA JPEN 2019
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Enteral nutrition
• Osmolarity
• Infusion modality and speed
• Type of protein
• Fibre
Nutritional management strategies
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Critical care nutrition guidelines ESPEN (2019) ASPEN (2016) Canadian (2015)
Fibre versus non-fibre
NA Commercial mixed fibre formula should not be used routinely Consider for persistent diarrhoea (low level)
Insufficient data to support routine use of fibre EN
Probiotics NA Cannot make a recommendation for the routine use of probiotics
The use of probiotics should be considered
Polymeric versus peptide
NA Standard polymeric formula Consider small peptide for persistent diarrhoea
Whole protein formula should be used
Continuous versus bolus
Continuous rather than bolus EN should be used (Grade: B)
Continuous for high risk patients or signs of intolerance
Insufficient data to recommend continuous over other methods
McClave et al, JPEN 2016, Singer et al Clin Nut 2019, CCPG Crit Care Nut 2015
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Polymeric versus peptide formula
Critical Care Nutrition: Systematic Review 2018
No difference between groups for clinical outcomes
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• Systematic review assessed the benefits of semi-elemental diets in multiple conditions
– Very small studies and limited data in critical care
• Theoretical concepts support the use of peptide-formula
• Possibly beneficial in pancreatic insufficiency
Polymeric versus Peptide
Alexander et al World J Gast Pharm Ther 2016, McClave et al JPEN 2016
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Fibre versus no fibre
Critical Care Nutrition: Systematic Review 2018
The type of fibre may matter
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• 120 mechanically ventilated patient
• Intervention: 1.0kcal/ml multi-fibre
• Control: 1.0kcal/ml
• Fibre free – slight reduction in overall GI complications
• Fibre formula – significantly lower diarrhoea score and possibly great nutrition provision
Fibre versus fibre free
Yagmurdur et al Asia Pac Clin Nutr 2016
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Emerging role of the microbiota in the ICU
Wolff et al Crit Care 2018
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• Gastrointestinal dysfunction occurs frequently in the critically ill
• Identify the underlying cause
• Nutrition interventions must be tailored to the cause of the dysfunction
Summary of key points
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Patient admitted to ICU who is MV
Does the patients have any of the following? • GRV > 500ml • Uncontrolled shock, hypoxemia and acidosis • Uncontrolled GI bleeding • Bowel Ischemia • Bowel obstruction • Abdominal compartment syndrome • High output fistula without distal feeding access
Commence enteral nutrition support within 24-48hrs
Well nourished Await resolution
up to 3- 7 day
Malnourished commence PN 48 -72 hours
Assess if the GI tract is functioning and if it is safe to commence EN
Monitor GI function: Symptoms and GRV (250 – 500ml)
No
Monitor for 48 hours
Yes
Resolved Not resolved
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Nutrition support in critical ill patients
Stomach dysmotility (delayed gastric emptying)
• Prokinetics • NJT • Reduce energy
density of EN • Reduce osmolality
EN
Small bowel dysmotility (ileus)
PN if not resolved in 3-7 days
Large bowel dysmotility (pseudo-obstruction)
Monitor GI function
• GRV > 250 ml • Vomiting
• High GRVs • Abdominal
distention • Dilated SB
loops radiology confirmation
Diarrhoea (malabsorption, infection, antibiotics)
• Abdominal distention
• Dilated large bowel loops with radiological confirmation
• Neostigmine • PN if not
resolved 3-7 days
• 3 bowel action • >300ml
Consider: • Fibre versus no
fibre EN • Semi- elemental • Osmolarity
Treat underlying cause
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Thank you!
@FetterplaceKate