How do our findings compare with those of other recent trials on nutritional support in the critically ill? In the Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) trial,61
which was conducted in two hospitals (involving seven different ICUs) with patients recruited to receive early or late parenteral supplementation of enteral feeding (if the enteral route alone was not meeting their nutritional target). The investigators found an association between supplemental PN delivered within 48 hours after admission (compared with supplemental PN delayed until after 8 days) and an increased number of new infectious episodes and days of mechanical ventilation. These differences were found both for the large subgroup of cardiac surgical patients and for other critically ill patients. However, the need of many patients for nutritional support, the high target energy intake and the practice of using tight
care potentially challenging. Post hoc analysis suggested a dose–response relationship between an
increased amount of parenteral supplementation and an increased rate of infectious episodes.64Despite
important differences between the CALORIES and the EPaNIC trials (research question evaluated, patients studied, nutrition and other care practices), our results potentially support the hypothesis that among patients receiving early PN/supplementation, the dose administered may be more associated with harm than the route of delivery.
In a trial conducted at two ICUs, Heidegger et al.62found no difference in the rate of infection between
day 8 and day 28 among patients receiving individually optimised PN to supplement inadequate enteral
intake on day 4 and patients receiving EN only. In a trial conducted at 31 ICUs, Doig et al.65studied
patients with relative contraindications to early enteral feeding and found no differences in 60-day mortality or the incidence of infection but fewer days of mechanical ventilation in patients receiving early PN than those with standard care. However, in the standard care group, 27% received early PN and 41% received no nutritional support.
There are two major and contradictory perspectives when it comes to how much to feed critically ill
patients in the early phase. One perspective maintains that overfeeding is potentially harmful,61,66a second
that underfeeding is potentially harmful67–69and a third that there is no difference between underfeeding
and standard feeding.70–72Still others argue that any effect of nutritional support is likely to be seen only
in selected patients who are at greater nutritional risk as a result either of pre-existing malnutrition, obesity or of the nature of their presenting illness. In the CALORIES trial, in both groups, the amount of nutrition delivered was below target but similar to that seen in previous studies in which nutritional targets were
also commonly not met.67,73,74This suggests that there are substantial practical and organisational obstacles
for both routes of feeding. Other research, more recently, has suggested that it is adequacy of protein
intake, rather than simply energy intake, which requires to be supported in critical illness.70
Previous economic analyses report cost savings with the use of the enteral route, rather than the parenteral route, in critically ill patients.3,75,76However, these results need to be interpreted with caution,
as no incremental cost-effectiveness results were provided. A few economic analyses performed only cost-minimisation analysis because there were no differences in outcome between the parenteral and enteral routes. These studies have suggested that the parenteral route may significantly reduce total costs
of hospital care.65,77A few other studies have performed economic analysis of nutritional support in
critically ill patients but the treatment comparators were different from those in the CALORIES trial. For example, use of early PN compared with late PN in critically ill patients was associated with higher costs
and no additional clinical benefit.78Early nutrition compared with standard enteral nutrition was found
cost-effective for patients admitted to ICUs.79
Compared with previous economic analyses, our analysis undertook an integrated, full economic evaluation to provide a direct comparison of early nutritional support via the parenteral route compared with the enteral route and extrapolated to lifetime cost-effectiveness results. A key advantage of the integrated economic evaluation, undertaken as part of the CALORIES trial, is that individual-level data on quality of life and resource use were collected prospectively. The quality-of-life data were collected at
90 days and at 1 year post-randomisation with the EQ-5D-5L version.38Hence the cost-effectiveness
analysis was able to incorporate any quality-of-life differences between the treatment groups into the final measures of cost-effectiveness. The quality-of-life results also showed that, for both treatment groups and
time points, patients’ average quality of life (which was between 0.65 and 0.68) was substantially lower
than that for the age–gender-matched general population (approximately 0.81)59and similar to previous
estimates for general ICU survivors.80In the CALORIES trial, at 1 year post-randomisation, about 30–40%
of responders reported‘severe’ or ‘extreme’ problems with mobility and/or undertaking usual activities
The findings of our study support previous analyses that nutritional support via the parenteral route is more costly. The results of Doig et al.,65that early PN is cost saving, are in contrast with both our
integrated economic analysis and another recent costing analysis, by Vanderheyden et al.,78reporting
increased treatment costs attributable to PN. However, clinical indication and population groups are different across these studies. The CALORIES trial compared costs and QALYs in critically ill adults for
whom either route was indicated. Doig et al.65addressed the financial consequences of administering
PN to patients who were unable to receive early enteral nutrition because of short-term relative
contraindications and Vanderheyden et al.78assessed costs of early PN compared with late PN to critically
ill patients who were able to receive enteral nutrition.
In drawing any comparisons between nutrition studies, it must always be noted that the CALORIES trial asked a different research question in a different population of critically ill patients to other studies. the CALORIES trial does, however, suggest that modern, early nutritional support via the parenteral route, as typically utilised in critical care units in the NHS, is neither more harmful nor more beneficial than via the enteral route and is unlikely to be cost-effective.