A randomized trial of supplemental parenteral nutrition in underweight and overweight critically ill patients: the TOP-UP pilot trial

Abstract

BackgroundNutrition guidelines recommendations differ on the use of parenteral nutrition (PN), and existing clinical trial data are inconclusive. Our recent observational data show that amounts of energy/protein received early in the intensive care unit (ICU) affect patient mortality, particularly for inadequate nutrition intake in patients with body mass indices (BMIs) of <25 or >35. Thus, we hypothesized increased nutrition delivery via supplemental PN (SPN) + enteral nutrition (EN) to underweight and obese ICU patients would improve 60-day survival and quality of life (QoL) versus usual care (EN alone).MethodsIn this multicenter, randomized, controlled pilot trial completed in 11 centers across four countries, adult ICU patients with acute respiratory failure expected to require mechanical ventilation for >72 hours and with a BMI of <25 or ≥35 were randomized to receive EN alone or SPN + EN to reach 100% of their prescribed nutrition goal for 7 days after randomization. The primary aim of this pilot trial was to achieve a 30% improvement in nutrition delivery.ResultsIn total, 125 patients were enrolled. Over the first 7 post-randomization ICU days, patients in the SPN + EN arm had a 26% increase in delivered calories and protein, whereas patients in the EN-alone arm had a 22% increase (both p < 0.001). Surgical ICU patients received poorer EN nutrition delivery and had a significantly greater increase in calorie and protein delivery when receiving SPN versus medical ICU patients. SPN proved feasible to deliver with our prescribed protocol. In this pilot trial, no significant outcome differences were observed between groups, including no difference in infection risk. Potential, although statistically insignificant, trends of reduced hospital mortality and improved discharge functional outcomes and QoL outcomes in the SPN + EN group versus the EN-alone group were observed.ConclusionsProvision of SPN + EN significantly increased calorie/protein delivery over the first week of ICU residence versus EN alone. This was achieved with no increased infection risk. Given feasibility and consistent encouraging trends in hospital mortality, QoL, and functional endpoints, a full-scale trial of SPN powered to assess these clinical outcome endpoints in high-nutritional-risk ICU patients is indicated—potentially focusing on the more poorly EN-fed surgical ICU setting.Trial registration NCT01206166 Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1736-8) contains supplementary material, which is available to authorized users.

Barriers and Solutions to Delivery of Intensive Care Unit Nutrition Therapy

“…There were no differences in treated infectious complications or 90‐day mortality between groups . In a recent randomized controlled pilot trial, adult ICU patients with acute respiratory failure whose body mass index was <25 or ≥35 were randomized for EN alone or SPN and EN . Over the first 7 days, SPN increased delivery of calories and protein by 26% and 22%, as compared with EN alone.…”

Supplemental Parenteral Nutrition: Review of the Literature and Current Nutrition Guidelines

“…SPN could simply be thought of as the addition of PN to EN (tube feeding or oral) to meet energy and protein goals. Published articles have referred to SPN as “parenteral nutrition added to EN when EN alone is insufficient.” Another definition is “step‐up approach when full enteral support is not possible or fails to meet caloric targets.” SPN may also be referred to as “Top‐Up” nutrition or bridge therapy. Whether the patient being treated is malnourished before initiation of SPN therapy should also be considered.…”

“…The 1A and 1B recommendation section points out that institution of care bundles for catheter care has reduced infection rates historically associated with central venous lines, and highlights the more recent trials of PN in the critically ill that have suggested that PN does not contribute to adverse events, particularly infectious complications . The authors of the recommendations suggest that further research is needed to “define the role of PN and its associated risks in a variety of clinical circumstances and patient populations.” 2A: Use PN in patients who are malnourished or at risk for malnutrition when a contraindication to EN exists or the patient cannot tolerate adequate EN.In the 2A section, the authors state that “PN becomes the preferred method for nutrition support in patients who need nutrition support and have contraindications to EN or who cannot meet their needs with EN alone.” 4A: Initiate PN after 7 days for well‐nourished, stable adult patients who have been unable to receive significant (≥50% of estimated requirements) oral or enteral nutrients. 4B: Initiate PN within 3–5 days in those who are nutritionally at risk and unlikely to achieve desired oral intake or EN. 4C: Initiate PN as soon as is feasible for patients with baseline moderate or severe malnutrition in whom oral intake or EN is not possible or sufficient. This important fourth section quotes a joint Academy of Nutrition and Dietetics/ASPEN malnutrition consensus characteristics article: “inadequate intake of nutrients is a known risk factor for the development of malnutrition.” The consensus recommendations authors emphasize the uncertainty of the timing of onset of starvation‐related malnutrition, resulting in the typical recommendation to start supplemental or full PN after 7 days in individuals who have not reached nutrition goals . The section also emphasizes the crucial importance of nutrition screening followed, if appropriate, by a full nutrition assessment to establish presence or absence of malnutrition: “Those individuals who are found to be moderately or severely malnourished should receive nutrition intervention at the earliest opportunity …”

“…Many international guidelines recommend early initiation of enteral nutrition (EN) in critically ill patients (and others for whom adequate oral intake is not achieved or impossible) . Everyone is taught “if the gut works, use it.” However, clinicians may not be aware that available information suggests that many patients receive only about 50% of prescribed daily calories from EN during the first 12 days in the ICU . It may be said, then, that the gut is in fact not working well enough to support adequate nutrition provision.…”

The Effect of Higher Protein Dosing in Critically Ill Patients: A Multicenter Registry‐Based Randomized Trial: The EFFORT Trial

“…While the analysis was underpowered, as evidenced by very wide CIs around point estimates, we point out that protein intake was the same in all patient groups. Moreover, another recent post hoc subgroup analysis did show a large survival advantage in the group of patients with a high NUTRIC score receiving supplemental PN compared with patients with high NUTRIC scores receiving only EN, whereas no signal of treatment effect of supplemental PN was observed in patients with low NUTRIC scores …”