GI function in critical illness and

managing intolerance

Kate Fetterplace BNut&Diet, PhD Candidate, APD Senior Dietitian, Clinical Lead, Royal Melbourne Hospital

@FetterplaceKate

• Sponsored by Abbott

• Previously received honorarium/ sponsorship support from: – Baxter

– Fresenius Kabi

– Nestle

– Nutricia

– Abbott

Disclosures

• 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

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

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

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

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

Early EN

Improved outcomes

Support immune function

Modulates stress response

Maintains gut barrier function

Adequate nutrient delivery

• 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

• 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

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

• 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

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

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

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

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

Treatment & management

GI dysfunction

Assessment of GI

Function

Determine underlying

cause

Treatment and

monitor

Optimise nutrition provision

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

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

• 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

• 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

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

• GRV – surrogate measures for gastric emptying

• GRV > 250 ml – relative sensitive marker of delayed gastric emptying

Gastric residual volumes

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

• 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

• 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

• Accelerate gastric emptying

• Bypass the stomach

• Parenteral nutrition

Management of gastric dysmotility

• 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

• 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

• 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

• Fat

• Energy density

• Osmolarity

• ? Possibly protein

Considerations with enteral nutrition

Effect of EN on gastric emptying

Kar et al JPEN 2016

Larger volume retained in the stomach of 2.0kcal/ml

• 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

• 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

• 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

• 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

• No therapeutic drug agents

• Control infections

• Requirement for parenteral nutrition depending on severity and length of time

Management of SB dysmotility

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

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

• 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

• 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

• Prevalence 14 -21 % of critically ill

• Causes:

– Osmotic

– Secretory

– Exudative

– Motility

Diarrhoea

Pitta JPEN 2019

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

Enteral nutrition

• Osmolarity

• Infusion modality and speed

• Type of protein

• Fibre

Nutritional management strategies

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

Polymeric versus peptide formula

Critical Care Nutrition: Systematic Review 2018

No difference between groups for clinical outcomes

• 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

Fibre versus no fibre

Critical Care Nutrition: Systematic Review 2018

The type of fibre may matter

• 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

Emerging role of the microbiota in the ICU

Wolff et al Crit Care 2018

• 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

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

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

Thank you!

@FetterplaceKate