Enteral Nutrition Should Not Be Given to Patients on Vasopressor Agents

The gastrointestinal tract has been recognized to play an integral pathophysiologic role during critical illness. Clinical manifestations of acute gastrointestinal injury are common in critically ill patients and are associated with worse outcomes. A recent consensus statement by the working group on abdominal problems of the European Society of Intensive Care Medicine (ESICM) proposed grading acute gastrointestinal injury into four grades of increasing severity (1). A subsequent validation cohort study demonstrated that patients in these grades differed in blood pressure and the use of vasopressor agents, with higher grades associated with lower blood pressure and higher use of vasopressor agents. Importantly, these grades were associated with an incremental increase in mortality (2). Several important pathophysiologic alterations occur in the gastrointestinal tract during critical illness. The intestinal epithelial cells undergo accelerated apoptosis, which is associated with thinning of the mucus layer, resulting in impaired mucosal integrity (3). The intestinal microbiome undergoes a significant transition to a virulent pathobiome (3). As a result of breakdown in barrier defense, toxic mediators (pancreatic lipase and free fatty acids) gain access to the submucosa and are transported into the systemic circulation through lymphatic channels, contributing to the pathogenesis of multiple organ failure (3). This is further complicated by impairment in gastrointestinal motility, absorption, and secretion that negatively affect nutrient absorption and nutritional status. During enteral nutrition (EN), mesenteric blood flow is increased (4). A study involving healthy volunteers and acutely ill patients demonstrated an increase in mesenteric blood flow after an oral meal or nasogastric feeding, but not after parenteral nutrition (PN) (5). However, in patients receiving vasopressor agents, blood perfusion may not increase sufficiently to meet the demand, thus aggravating the injury in an already stressed bowel (6). In a porcine model of septic shock, norepinephrine and epinephrine diverted blood flow away from the mesenteric circulation and decreased microcirculatory blood flow in the jejunal mucosa and pancreas (7). In a cross-over study of eight patients with septic shock, epinephrine caused reduction in splanchnic flow and oxygen uptake, lowering of mucosal pH, and increase in hepatic vein lactate levels (8). Similar studies showed that vasopressin led to enteric and gastric hypoperfusion (9, 10). In a study of critically ill patients, the use of epinephrine and/or norepinephrine was associated with an increased plasma concentration of intestinal fatty acid–binding protein, which is released by injured enterocytes. Patients receiving more than 0.48 μg/kg/min of epinephrine and/or norepinephrine had higher fatty acid–binding protein concentrations than those who were on lower doses (11). When EN should be started in patients on vasopressor agents? Studies have shown that delayed EN in unselected ICU patients is associated with atrophic changes in the intestinal mucosa and that early EN mitigates against these changes. However, data regarding the clinical benefits of early EN in patients on vasopressor agents are limited. A retrospective study of mechanically ventilated patients requiring vasopressor agents found that early delivery of EN (within 2 d) was associated with lower mortality compared with late EN. However, the results of observational data should be interpreted cautiously because the observed associations may be influenced by residual unmeasured confounders. In addition, the study did not report the doses of vasopressor agents and did not provide data on the amount of feeding provided, on the rate of advancement of feeding or on the occurrence of bowel ischemia (12). Data from randomized controlled trials (RCTs) are also limited. Multiple meta-analyses showed that EN compared with late EN was associated with reduced mortality in unselected ICU patients (13–15). However, most included 1 College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.