This document discusses enteral nutrition for patients on vasopressors. It provides an overview of how circulatory shock impacts the gut barrier and microbiota. Early enteral nutrition within 48 hours is recommended to maintain gut integrity, attenuate inflammation, and decrease complications. Recent observational studies and randomized trials show early enteral nutrition is well-tolerated and safe for patients on vasopressors, with low rates of new organ dysfunction. However, large randomized trials are still needed to determine optimal timing, dose and composition of enteral nutrition for patients in shock.

1. ENTERAL NUTRITION CAN BE GIVEN TO PATIENTS ON
VASOPRESSORS
PRESENTOR: Dr. Kanika Chaudhary

2. OVERVIEW
 Introduction
 The Consequences of Circulatory Shock on Gut Barrier and Immune Functions
 The Consequences of Circulatory Shock and Critical Illness on the Gut Microbiota
 Benefits of Enteral Nutrition
 Recommendations
 Evidences based on recent studies
 Conclusion and Future Insight
 References

3. INTRODUCTION
Critically ill patients are often hemodynamically unstable (or at risk of becoming
unstable) owing to hypovolemia, cardiac dysfunction, or alterations of vasomotor
function, leading to organ dysfunction, deterioration into multiorgan failure, and
eventually death.
Under resting and normal conditions, around 25% of cardiac output is located in the
splanchnic circulation. Shock is characterized by blood flow redistribution with
vasoconstriction at splanchnic circulatory level and in peripheral tissues, in an attempt
to maintain vital organs perfusion. This can give rise to an imbalance in the oxygen
supply/demand ratio at intestinal level, with resulting ischemia. The reported incidence
ranges between 0.3% and 8.5%, with mortality ranging from 46% to 100%.

4.  Enteral Nutrition Therapy (ENT) is part of the essential care of patients in the intensive
care unit (ICU). It is recommended, due to several studies that demonstrate better
outcomes, that nutritional support should be started 24 to 48 hours after admission to the
ICU, since the patient has been resuscitated and with hemodynamic stability.
 ENT, when applied properly and early at the correct time, reduces the incidence of
unfavourable outcomes in critically ill patients as well as the risk of infectious
complications and ICU length of stay.

5. The Consequences of Circulatory Shock on Gut Barrier and Immune Functions
 Circulatory shock reduced effective circulating blood volume hypotension reduced oxygen
deliverywidespread cellular and tissue hypoxia ensue.
 Small intestine villous blood flows in opposite directions: arterial blood flows upwards towards the villus
and venous blood flows towards the base. Oxygen is extracted as blood moves towards the villus.
 Early in shock, blood flow is diverted away from non-vital organs, such as the gut, to preferentially perfuse
vital organs like the brain, heart, and kidneysreduces splanchnic blood flowdiminishes oxygen
delivered to the villus tip, leaving it susceptible to ischemia.
 Also, critical illness pathophysiology and processes accelerate enterocyte apoptosis and impair mucosal
integrity, resulting in breakdown of barrier defense. As a result, toxic mediators are transported into the
systemic circulation through lymphatic channels and create downstream organ dysfunction like acute
respiratory distress syndrome (ARDS).

6.  In healthy individuals, tight junctions (TJ) link enterocytes and are selectively permeable to prevent
the unregulated passage of intraluminal contents. Claudins, MARVEL domain proteins (occludin
and tricellulin) and junctional adhesion molecules are common to all tight junctions. Zona
occludens (ZO) proteins help link TJs to the cytoskeleton.
 Many components of the tight junction are altered in circulatory shock. Bacterial activation of
myosin light chain kinase (MLCK) causes contraction of the actin–myosin ring and increases
permeability at the cell–cell junction.
 Systemic inflammation induced reduced expression of claudin or occludin proteins allow for
bacterial adherence, which increases permeability.
 Vermette et al. reviewed 15 studies and concluded (a.) serum and urine levels of claudins-2,3 and 4
correlated with severity of acute gastrointestinal injury, (b.) serum ZO-1 best stratified sepsis
severity and degree of organ dysfunction, and (c.) urinary claudins were a reliable measure of early
gastrointestinal injury.

7. The Consequences of Circulatory Shock and Critical Illness on the Gut Microbiota
 Commensal organisms live in symbiosis with their host. The combination of commensal (nonvirulent)
organisms, IgA, thick mucus layer, an acidic gastric environment, and peristalsis resist pathogenic
bacterial colonization.
 Critical illness pathophysiologic processes and clinical interventions alter the gut ecological system to
(a.) increase microbial immigration,
(b.) impair microbial clearance
(c.) change environmental growth conditions
 Gut hypoperfusion impairs mucosal integrity to increase bacterial and their product elimination through
mesenteric lymphatics (alters microbial elimination) and increases mucosal inflammation (changes
environmental growth condition).
 Clinical ICU interventions such as gastric acid suppression and diminished oral intake, further impair
microbial elimination and promote acid-intolerant bacteria and create stress condition of nutrient scarcity,
respectively. As a result, a healthy gut microbiota consisting of predominantly Firmicutes and
Bacteroidetes is decimated and replaced by pathogenic Proteobacteria.

8.  Altered mucosal oxygen gradient and thinning of the intestinal mucosal layer that occur in circulatory
shock favor Pseudomonas aeruginosa and Escherichia coli growth
 Perturbations of intestinal epithelial homeostasis in critical illness increased pro-inflammatory cytokine
production, gut barrier dysfunction, and cellular apoptosis multiple organ failurerapid change in the
microbiome, known as dysbiosis.
 Dysbiosis has numerous consequences for the host. Virulent pathogens interact with epithelium, with or
without invasion, and induce the release of mucosal-derived cytokines, which travel through mesenteric
lymphatics to perpetuate inflammation and generate multiple organ dysfunctions. Gut-induced
inflammation has been associated with more gastrointestinal complications, more organ dysfunction and
infections, and greater mortality rate.

9. Benefits of Enteral Nutrition
1) Maintaining structural/functional gut integrity, thus attenuating intestinal permeability
2) Attenuate oxidative stress and inflammatory response, while maintaining humoral
immune responses
3) Decreased bacterial translocation
4) Modulation of metabolism to decrease insulin resistance
5) In endotoxic and septic shock, enteral feeding improved hepatic artery and portal vein
blood flow, superior mesenteric artery blood flow, intestinal mucosal microcirculatory flow,
hepatic microcirculatory flow, hepatic and intestinal tissue oxygenation, and hepatic energy
store

10. 6) EN promotes enterocyte secretion of mucin-2 protein, which maintains a mucus layer
and helps flush pathogens, and resistin-like molecule-b secretion into the submucosa,
which pro motes CD-4 T cell recruitment driving host defense mechanisms including
epithelial cell proliferation.
7) EN promotes commensal bacteria to protect against enteric pathogens by (a.) direct
competition for nutrients,(b.) production of antibacterial peptides, and (c.) bile salt
modification rendering them harmful to other microorganisms
and driving mucus production.
8) Better clinical outcomes were observed, such as improved wound healing reducing the
severity of illness, complications, and ICU Length of stay (LOS)

11. RECOMMENDATIONS
 2016 Surviving Sepsis Campaign: International Guidelines for Management of Sepsis
and Septic Shock
1. We suggest the early initiation of enteral feeding rather than a complete fast or only
IV glucose in critically ill patients with sepsis or septic shock who can be fed
enterally.
(weak recommendation, low quality of evidence)
2. We suggest either early trophic/hypocaloric or early full enteral feeding in critically
ill patients with sepsis or septic shock; if trophic/hypocaloric feeding is the initial
strategy, then feeds should be advanced according to patient tolerance.
(weak recommendation, moderate quality of evidence)

12.  2016 Guidelines for the Provision and Assessment of Nutrition Support Therapy
in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and
American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.)
1. We recommend that nutrition support therapy in the form of early EN be initiated
within 24–48 hours in the critically ill patient who is unable to maintain volitional
intake.
(Quality of Evidence: Very Low)

13. 1. If oral intake is not possible, early EN (within 48 h) in critically ill adult patients
should be performed/initiated rather than delaying EN
Grade of recommendation: B-strong consensus (100% agreement)
2. If oral intake is not possible, early EN (within 48 h) shall be performed/initiated in
critically ill adult patients rather than early PN
Grade of recommendation: A-strong consensus (100% agreement)
 2019 ESPEN guideline on clinical nutrition in the Intensive care unit

14. EVIDENCES BASED ON RECENT STUDIES

15. Krezalek MA, Yeh A, Alverdy JC, et al: Influence of nutrition therapy on the
intestinal microbiome. Curr Opin Clin Nutr Metab Care 2017;20:131–137
Provision of even 20% of nutrition via EN can prevent dysbiosis, attenuate loss
of gut barrier function, and innate immunity

16. EN can trigger activation of anti-inflammatory vagal-cholinergic pathway via
Cholecystokinin-mediated receptor stimulation in shock states
Lubbers T, de Haan JJ, Luyer MD, et al: Cholecystokinin/cholecystokinin-1
receptor-mediated peripheral activation of the afferent vagus by enteral nutrients
attenuates inflammation in rats. Ann Surg 2010;
252:376–382

17. Observational studies since 2017 primarily evaluating early enteral nutrition (EN) in shock

18. Randomized controlled studies since 2017 primarily evaluating early enteral nutrition (EN) in shock

20. EFFECT OF VASOPRESSORS ON DIGESTIVE SYSTEM CIRCULATION
EFFECT OF VASOPRESSORS ON DIGESTIVE SYSTEM CIRCULATION

21. CONCLUSIONS AND FUTURE INSIGHT
• Circulatory shock turns on the ‘‘gut motor,’’ which perpetuates inflammation through loss
of TJ integrity and bacterial dysbiosis, which generate dysregulated immune responses.
• Early EN, may maintain enterocyte barrier function and provide substrate for bacteria to
limit dysbiosis to prevent dysregulated immune responses.
• Recent observational and RCT data show early EN is well-tolerated and safe whereby the
incidence of NOMI and NOBN is low.
• Emerging observational and pilot RCT data suggest benefit from early EN in shock.
• Large-scale RCTs comparing different EN doses in circulatory shock are lacking.
• Future research testing the role of EN in shock is needed to identify optimal EN timing,
dose, and composition.

22. TAKE HOME MESSAGE

23. REFERENCES
• Wischmeyer PE. Enteral Nutrition Can Be Given to Patients on Vasopressors. Crit Care Med. 2020
Jan;48(1):122-125. doi: 10.1097/CCM.0000000000003965. PMID: 31414992
• Simo Es Covello LH, Gava-Brandolis MG, Castro MG, Dos Santos Netos MF, Manzanares W, Toledo
DO. Vasopressors and Nutrition Therapy: Safe Dose for the Outset of Enteral Nutrition? Crit Care Res
Pract. 2020 Feb 10;2020:1095693. doi: 10.1155/2020/1095693. PMID: 32104602; PMCID:
PMC7035530.
• Barash, M., Patel, J.J. Gut Luminal and Clinical Benefits of Early Enteral Nutrition in Shock. Curr
Surg Rep 7, 21 (2019)
• Krezalek MA, Yeh A, Alverdy JC, et al: Influence of nutrition therapy on the intestinal microbiome.
Curr Opin Clin Nutr Metab Care 2017; 20:131–137
• Bruns BR, Kozar RA: Feeding the postoperative patient on vasopressor support: Feeding and pressor
support. Nutr Clin Pract 2016;31:14–17
• Merchan C, Altshuler D, Aberle C, et al: Tolerability of enteral nutrition in mechanically ventilated
patients with septic shock who require vasopressors. J Intensive Care Med 2017; 32:540–546

24. • Ohbe H, Jo T, Matsui H, Fushimi K, Yasunaga H. Differences in effect of early enteral nutrition on
mortality among ventilated adults with shock requiring low-, medium-, and high-dose noradrenaline: a
propensity-matched analysis. Clin Nutr. 2019.
• Ohbe H, Jo T, Yamana H, Matsui H, Fushimi K, Yasunaga H. Early enteral nutrition for cardiogenic or
obstructive shockrequiring venoarterial extracorporeal membrane oxygenation: a nationwide inpatient
database study. Intensive Care Med.2018;44(8):1258–65.
• Ewy M, Aqeel M, Kozeniecki M, et al. The impact of enteral feeding on vasoactive support in septic
shock: a retrospective observational study. Aspen nutrition science and practice conference:Phoenix,
Arizona, March 23–26, 2019. J Parenter Enter Nutr. 2019;43:445.
• Patel JJ, Kozeniecki M, Peppard WJ, Peppard SR, Zellner-Jones S, Graf J, Szabo A, Heyland D. A phase
III pilot randomized controlled trial comparing early trophic enteral nutrition to ‘No Enteral Nutrition’ in
mechanically ventilated patients with septic shock. American society of parenteral and enteral nutrition
2019 nutrition science and practice conference, 2019, Phoenix,Arizona.
REFERENCES

25. • Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and
Septic Shock: 2016
• 2016 Guidelines for the Provision and Assessment of Nutrition Support Therapy in the
Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American
Society for Parenteral and Enteral Nutrition (A.S.P.E.N.)
• 2019 ESPEN guideline on clinical nutrition in the Intensive care unit
REFERENCES

26. THANK YOU