The Unresolved Questions of Nutritional Support in the ICU: Now or Later, More or Less, Enteral or Parenteral?

 

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Two divergent recommendations recently published by ESPEN and ASPEN [1] [2] have stressed the need for more research regarding the indication for supplemental parenteral nutrition (PN) in critically ill patients who are not achieving their calorie target in the first 48 hours after admission. In a recent paper, Casaer et al. [3] suggest that early PN may be detrimental for these patients, a view which is contrary to the ESPEN guidelines. However, the topic has to be analyzed cautiously since the consequences of such an assertion could significantly affect patient outcome if misunderstood.

In fact, the idea of assessing the added value of supplemental parenteral to enteral nutrition is older than the guidelines (Casaer et al. recruited patients from August 2007 while the ESPEN guidelines were published in 2009), and was suggested in an early article published by the Van den Berghe group [4]. Then, PN was added to progressive enteral feeding in order to achieve a calorie target of around 1800 kcal/day. With this approach, the authors described an improvement in survival of patients receiving both intensive insulin therapy and supplemental parenteral nutrition. In this publication [4], the addition of early supplemental parenteral nutrition was the recommendation of the group at that time.
Since that time, many prospective, randomized studies have been published comparing various nutritional interventions/protocols, including underfeeding vs. targeted (i. e. according to a predetermined caloric goal) nutritional support (Arabi et al., [5]), trophic enteral (10 mL/h administered through the nasogastric tube) vs. targeted enteral feeding (Rice et al., [6]), tight calorie control vs. liberal nutritional support (Singer et al., [7]), and supplemental PN vs. a regular regimen (Heiddeger et al., [8]). These studies are summarized in [Fig. 1] and are compared to the range of measurements of energy expenditure published in the last 30 years [9]. The figure shows that – despite the title – the Arabi and Rice studies compare underfeeding to more severe underfeeding, whereas Casaer compared underfeeding without PN to early overfeeding with PN. Singer compared underfeeding to slight overfeeding and Heiddeger compared supplemental parenteral nutrition within the range to enteral nutrition alone resulting in negative energy balance. Looking at the studies in this manner suggests that achieving an appropriate calorie input may indeed impact the outcome. Thus, Heiddeger (energy administration close to ideal target) described an improvement in days of ventilation and in the rate of infection, Arabi and Rice (energy administration below ideal target) found no significant difference between the groups. The study from our group (energy administration slightly above ideal target) found an increase in infection and ICU stay, but also a significant improvement in hospital survival, while Casaer (energy administration above ideal target) described an increase in infection and days of ventilation. As a matter of fact, administrating between 24 to 36 kcal/kg/day with the addition of parenteral nutrition as described by Casaer et al. is not considered the standard of care for cardiothoracic patients after surgery having a short ICU stay (60 % of the studied population). Another confusing aspect of the Casaer study is the APACHE II score, which appears disproportionately high for the described low mortality. In fact, the APACHE II score has not been validated for use in open heart surgery patients and is better assessed by other scores [10].

The main point of confusion appears to relate to the fact that early nutrition has become synonymous with adequate nutrition. Most authors use predictive formulae which include the weight of the patient, despite the fact that these equations are recognized to be very inaccurate [11]. In addition, the energy-protein target is not static during a patient's stay in the ICU, but is influenced – and therefore changes – by numerous factors including the presence or absence of sepsis, level of sedation or of stress [12]. Protein administration is typically underestimated despite its recognized importance. In the Arabi, Rice, Casaer, Singer and Heiddeger studies, protein intake was respectively of 43, 55, 60, 75 and 90 g/day when recommended levels should be up to 100 g/d. In the control groups, the intake was approximately 47, 6.8, 15, 60 and 60 g/day, respectively. These variations in calorie and protein intake make the studies difficult to compare so that no conclusions may be drawn regarding the question of early versus late as well as parenteral versus enteral feeding.

Therefore, it is not apparent from the Casaer study to conclude which component of their nutritional support was responsible for the increased observed morbidity, i. e. early parenteral nutrition, low protein intake or overfeeding. Ideally, future studies should concentrate on one component of the debate, while keeping all other parameters close to current recommendations. Thus, for example in the Casaer study, PN should be administered to supplement enteral nutrition using energy expenditure measured by indirect calorimetry as the target and at the same time ensuring adequate protein intake. Otherwise, the hypothesis cannot be demonstrated.

Finally, however, the importance of the Casaer study lies in the fact that more clinicians are being made aware of the nutritional priorities of critically ill patients, just as the studies from the Leuven group raised awareness of the importance of glucose control. Despite the pitfalls of the Casear study, it provides a welcome impetus to the goal of improving nutritional care of the critically ill patient.

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