Critical Care Controversies
Enteral nutrition is rarely an urgent topic of discussion during the initial resuscitation of a critically ill patient in the emergency department (ED) resuscitation bay, yet it is a cornerstone of subsequent critical care and recovery from critical illness. While the gastrointestinal tract should not be prioritized over the management of a critically ill patient’s airway, breathing and circulation, it is important to understand the pathophysiological role the gut plays during critical illness. Critically ill patients with shock sustain visceral hypoperfusion and ischemia-reperfusion injury, where the intestinal epithelium is subject to apoptosis, mucosal atrophy edema and loss of tight junctions between enterocytes. This breakdown of gut barrier function can lead to bacteria and endotoxin crossing the mucosa, which augments cytokine release and fuels the systemic inflammatory response and multiorgan dysfunction. Whether enteral nutrition should be started in patients requiring vasopressor support is a controversial topic in critical care and is often fiercely debated during rounds in the intensive care unit (ICU). What are the arguments for and against feeding critically ill patients requiring vasopressors?
1. Enteral nutrition prevents dysbiosis, or pathologic changes in the microbiome, that contributes to cytokine release and multiorgan dysfunction.
2. Enteral feeding helps maintain the structural integrity of the intestinal epithelium, mitigating intestinal permeability and bacterial translocation.
3. Early enteral feeding (<48 hours) was associated with lower mortality compared with late enteral nutrition in a large cohort (n = 1174) of critically ill patients requiring mechanical ventilation and vasopressor support (Am J Crit Care 2010).
4. In a large database study of over fifty-two thousand ventilated patients in shock, early enteral nutrition (<48 hrs) compared to late enteral nutrition was associated with lower 28-day mortality in the low-dose (0.1 mcg/kg/min) and medium-dose (0.1-0.3 mcg/kg/min) norepinephrine groups, and showed no difference in mortality for patients on high-dose (>0.3 mcg/kg/min) norepinephrine (Clin Nutr 2019).
5. In a study of nearly three thousand mechanically ventilated patients, only 59 percent of ICU patients received adequate total calories and protein (Crit Care Med 2010).
6. Non-occlusive bowel necrosis typically occurs late in the course of critical illness, not at the initiation of feeds, suggesting that impaired intestinal mucosal perfusion can occur without evidence of systemic shock.
1. Mesenteric blood flow is increased during enteral nutrition, which could perpetuate bowel ischemia, if intestinal perfusion is unable meet the increased oxygen demand.
2. Vasopressors, particularly epinephrine, divert blood to the central circulation through vasoconstriction and have been shown to lower mucosal pH and increase hepatic vein lactate levels.
3. The use of epinephrine and norepinephrine is associated with increased intestinal fatty acid-binding protein concentrations, which is released from damaged enterocytes.
4. Most randomized controlled trials studying the target volume of tube feeds have excluded patients requiring high doses of vasopressors (>30 mcg/min norepinephrine). The PermiT and EDEN trials showed no mortality difference in patients receiving trophic versus target rates of tube feeds, suggesting that advancing tube feeds does not portend a survival benefit.
5. The NUTRIREA-2 trial randomized mechanically ventilated patients in shock to parenteral versus enteral nutrition and found no difference in the primary outcome of mortality or hospital-acquired infection. The enteral nutrition group demonstrated an increase in the rate bowel ischemia as a secondary outcome; however, the median norepinephrine dose in the enteral nutrition group was very high (0.56 mcg/kg/min).
The Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN) guidelines recommend withholding tube feeds in the setting of “hemodynamic compromise or instability,” which they define as patients undergoing catecholamine initiation or requiring escalating doses of vasopressors. They suggest starting enteral nutrition once the patient is resuscitated and shock has been controlled, although the vasopressor dose defining a safety threshold is unclear. These guidelines are based on expert consensus, as the data for patients on high-dose vasopressors is limited. Virtually all studies examining early enteral nutrition in patients on low- or moderate-dose vasopressors suggest early enteral nutrition is both safe and beneficial, particularly at a trophic rate. Ultimately, the decision to initiate enteral nutrition or advance enteral feeding to meet energy expenditure for critically ill patients requiring vasopressors is up to the clinician, particularly in patients receiving high doses of catecholamines. When enteral nutrition is initiated for vasopressor-dependent patients, it is imperative to monitor for signs of gastrointestinal intolerance or hypoperfusion with attention to nasogastric tube output, worsening lactic acidosis or escalating catecholamine doses.
1. Arabi Y and McClave SA. Enteral nutrition should not be given to patients on vasopressor agents. Crit Care Med2020;48(1):119-121.
2. Cahill NE et al. Nutrition therapy in the critical care setting: What is “best achievable” practice? An international multicenter observational study. Crit Care Med 2010;38(2):395-401.
3. EDEN Trial. Initial trophic vs full enteral feeding in patients with acute lung injury. JAMA 2012;307(8):795-803.
5. NUTRIREA-2 Trial. Enteral versus parenteral early nutrition in ventilated adults with shock: a randomized, controlled, multicenter, open-label, parallel-group study. Lancet 2018;391:133-143.
6. Ohbe H et al. Differences in effect of early EN on mortality among ventilated adults with shock requiring low-, medium-, and high-dose noradrenaline: A propensity-matched analysis. Clin Nutr 2019 Feb 15. [Epub ahead of print]
7. PermiT Trial. Permissive underfeeding or standard enteral feeding in critically ill adults. New Engl J Med2015;375(25):2398-2408.
8. Wishchmeyer PE. Enteral nutrition can be given to patients on vasopressors. Crit Care Med 2020;48(1)122-125.