Nutrition in the intensive care unit: from the acute phase to beyond

Abstract

Recent randomized controlled trials (RCTs) have shown no benefit but dose-dependent harm by early full nutritional support in critically ill patients. Lack of benefit may be explained by anabolic resistance, suppression of cellular repair processes, and aggravation of hyperglycemia and insulin needs. Also early high amino acid doses did not provide benefit, but instead associated with harm in patients with organ dysfunctions. However, most studies focused on nutritional interventions initiated during the first days after intensive care unit admission. Although the intervention window of some RCTs extended into the post-acute phase of critical illness, no large RCTs studied nutritional interventions initiated beyond the first week. Hence, clear evidence-based guidance on when and how to initiate and advance nutrition is lacking. Prolonged underfeeding will come at a price as there is no validated metabolic monitor that indicates readiness for medical nutrition therapy, and an adequate response to nutrition, which likely varies between patients. Also micronutrient status cannot be assessed reliably, as inflammation can cause redistribution, so that plasma micronutrient concentrations are not necessarily reflective of total body stores. Moreover, high doses of individual micronutrients have not proven beneficial. Accordingly, current evidence provides clear guidance on which nutritional strategies to avoid, but the ideal nutritional regimen for individual patients remains unclear. In this narrative review, we summarize the findings of recent studies, discuss possible mechanisms explaining the results, point out pitfalls in interpretation of RCTs and their effect on clinical practice, and formulate suggestions for future research.

Keywords: Amino acid; Critical illness; Glucose; Intensive care; Macronutrients; Micronutrients; Nutrition.

Fig. 1

Evolution in nutritional practice in relation to large-scale randomized controlled trials. This graph presents multivariable regression of the start day of EN alone, PN alone, and EN in combination with PN from 2007 to 2018 in Europe, with 2007 as the reference year. Studies potentially influencing the actual dynamics of feeding practices are shown in the left. Data based on NutritionDay (16,032 patients admitted to 1389 intensive care units ([43], reproduced with permission). The reference (zero days) is set at the intercept of a multivariate model for year 2007 and does not represent real days since admission. EN enteral nutrition, PN parenteral nutrition, x axis days, y axis years

Fig. 2

Suggested pragmatic feeding strategy for ICU patients. In the hyperacute phase of critical illness, no nutrition is necessary. In patients developing spontaneous hypoglycemia, intravenous glucose is initiated to treat hypoglycemia. After initial stabilization, EN is started, when possible, considered “early” if started within 48 h. If EN is not possible and no non-nutritional energy is provided, low-dose glucose may need to be considered. If tolerated, EN is progressively increased toward target over several days. If EN is not possible or insufficient, PN should likely be initiated between days 4 and 8, and progressively increased toward target. The exact duration of the different phases shown in the figure is not known and likely varies individually. As full feeding should be avoided in the first days after ICU admission, it seems prudent to ensure sufficient micronutrient intake by maintenance doses of micronutrients, provided as long as the patient does not receive sufficient macronutrient intake via oral or enteral nutrition (unlike PN, standard commercial EN formulations contain micronutrients). If a patient develops hypophosphatemia upon initiation or increase of feeding, temporarily reducing macronutrient intake while correcting electrolyte abnormalities (in particular potassium and phosphate) is advised. Similarly, in patients developing a new severe insult (e.g., a new septic shock) during ICU stay while receiving full feeding, temporarily reducing or stopping macronutrient intake seems prudent. ¹Reasons to delay EN [40]. ²No nutrition if high non-nutritional intake (e.g., propofol, citrate, glucose-containing solutions). ³Consider non-nutritional intake. ⁴A drop in phosphate by at least 0.16 mmol/l to below 0.65 mmol/l after initiating medical nutrition therapy. ⁵Coverage of increased basal needs according to ESPEN micronutrient guidelines [51]. EN enteral nutrition, PN parenteral nutrition, ICU intensive care unit

Fig. 3

Potential mechanisms for the lack of benefit by early full feeding in critical illness. This figure is a reproduction and adaptation from [4], under the Creative Commons Attribution 4.0 International License, (http://creativecommons.org/licenses/by/4.0/)