Hypocaloric compared with eucaloric nutritional support and its effect
on infection rates in a surgical intensive care unit: a randomized
controlled trial1–5
Eric J Charles, Robin T Petroze, Rosemarie Metzger, Tjasa Hranjec, Laura H Rosenberger, Lin M Riccio,
Matthew D McLeod, Christopher A Guidry, George J Stukenborg, Brian R Swenson, Kate F Willcutts, Kelly B O’Donnell,
and Robert G Sawyer
ABSTRACT
Background: Proper caloric intake goals in critically ill surgical
patients are unclear. It is possible that overnutrition can lead to
hyperglycemia and an increased risk of infection.
Objective: This study was conducted to determine whether surgical
infection outcomes in the intensive care unit (ICU) could be im-
proved with the use of hypocaloric nutritional support.
Design: Eighty-three critically ill patients were randomly allocated
to receive either the standard calculated daily caloric requirement of
25–30 kcal $ kg–1 $ d–1 (eucaloric) or 50% of that value (hypo-
caloric) via enteral tube feeds or parenteral nutrition, with an equal
protein allocation in each group (1.5 g $ kg–1 $ d–1).
Results: There were 82 infections in the hypocaloric group and 66
in the eucaloric group, with no significant difference in the mean
(6SE) number of infections per patient (2.0 6 0.6 and 1.6 6 0.2,
respectively; P = 0.50), percentage of patients acquiring infection
[70.7% (29 of 41) and 76.2% (32 of 42), respectively; P = 0.57],
mean ICU length of stay (16.7 6 2.7 and 13.5 6 1.1 d, respectively;
P = 0.28), mean hospital length of stay (35.2 6 4.9 and 31.0 6 2.5
d, respectively; P = 0.45), mean 0600 glucose concentration (132 6
2.9 and 135 6 3.1 mg/dL, respectively; P = 0.63), or number of
mortalities [3 (7.3%) and 4 (9.5%), respectively; P = 0.72]. Further
analyses revealed no differences when analyzed by sex, admission
diagnosis, site of infection, or causative organism.
Conclusions: Among critically ill surgical patients, caloric provi-
sion across a wide acceptable range does not appear to be associated
with major outcomes, including infectious complications. The op-
timum target for caloric provision remains elusive. Am J
Clin Nutr 2014;100:1337–43.
INTRODUCTION
Appropriate nutrition intake in critically ill surgical patients is
a crucial aspect of care. Nutritional support is needed to over-
come stress-induced metabolic responses, prevent oxidative cel-
lular injury, and favorably modulate the immune response (1–3).
Malnutrition is associated with impaired immune function,
reduced ventilatory drive, weakened respiratory muscles, pro-
longed ventilator dependence, and increased infectious compli-
cations in critically ill patients (4, 5). Nutritional support is
believed to improve wound healing and gastrointestinal structure
and function, as well as reduce catabolism, complication rates,
and length of stay (1).
Am J Clin Nutr 2014;100:1337–43. Printed in USA. Ó 2014 American Society for Nutrition
Despite its attributes, nutritional support does have adverse
effects, suggesting a delicate balance between overfeeding and
underfeeding. Feeding intolerance is a less frequent occurrence
when patients receive trophic enteral feedings (6). However,
when goal enteral feeding is attempted and leads to high gastric
residual volumes, patients are at an increased risk of hospital-
acquired pneumonia, longer intensive care unit (ICU) stays, and
increased ICU mortality (7). When enteral nutrition is not pos-
sible, patients may receive supplemental parenteral nutrition,
although the appropriate timing of initiation and its role continue
to be debated (8–10). Parenteral nutrition is known to be asso-
ciated with increased infections, gut mucosal atrophy, hyper-
glycemia, and overall increased mortality in critically ill patients
(9, 11).
Current guidelines detail the optimal delivery of nutritional
support and recommend providing 25–30 kcal $ kg–1 $ d–1 with
1.2–2 g protein $ kg–1 $ d–1. Yet, no published data have vali-
dated these standard daily caloric intake targets (2, 12, 13).
Although there is general consensus that excessive hypocaloric
(#25% recommended daily caloric intake) or hypercaloric
($125%) feeding should be avoided, controversy still exists
over what feeding targets should be (14). Particularly in patients
with a high severity of illness, attempting to provide full nutri-
tional support may correlate with adverse outcomes (15, 16).
New evidence suggests that outcomes may be improved in
patients who are “underfed.” Nevertheless, to our knowledge,
no study has yet randomly allocated critically ill patients to
1
From the Department of Surgery, University of Virginia Health System,
Charlottesville, VA (EJC, RTP, RM, TH, LHR, LMR, MDM, CAG, BRS,
KFW, KBO, and RGS), and the Department of Public Health Sciences,
University of Virginia School of Medicine, Charlottesville, VA (GJS).
2
EJC and RTP share first authorship on this article.
3
The work presented here is the original work of the aforementioned
authors and represents the authors’ views and not those of the institution
where the work was completed or that of any funding source.
4
Supported by grant 5-T32-AI-078875-03 from the NIH (principal inves-
tigator: RGS).
5
Address correspondence to EJ Charles, Department of Surgery, Univer-
sity of Virginia Health System, PO Box 800679, Charlottesville, VA 22908-
0679. E-mail: ec4wx@virginia.edu.
Received March 21, 2014. Accepted for publication August 11, 2014.
First published online September 3, 2014; doi: 10.3945/ajcn.114.088609.
1337
1338 CHARLES ET AL
eucaloric or hypocaloric feeds, for the length of their ICU ad-
mission.
This report describes a single-institution randomized con-
trolled trial testing the hypothesis that hypocaloric nutritional
support leads to better glycemic control, a decreased rate of
infection, shorter ICU and hospital stays, and decreased mortality
compared with eucaloric nutritional support in critically ill
patients.
SUBJECTS AND METHODS
Study design
This randomized controlled trial was conducted from 2008 to
2011 (initial recruitment date 1 March 2008) in the surgical ICU
at a tertiary care hospital. The Institutional Review Board for
Human Subjects Research at the University of Virginia (Protocol
13183) approved the study after ensuring that its design was in
accordance with the Declaration of Helsinki and the ethical
treatment of human subjects. Each patient or legally authorized
representative provided written informed consent before any
study procedures. After 50 patients were enrolled, the study was
reviewed by the independent data and safety monitoring officer
(Timothy L Pruett, University of Minnesota), and approval was
granted to continue the study.
Patients
We enrolled adult patients older than 18 y who were admitted
to the surgical ICU and were deemed appropriate for nutritional
support. Inclusion criteria were age $18 y, projected need for
artificial nutrition .48 h, and projected need for intensive care
stay .48 h as judged by the attending intensivist. Typical pa-
tients admitted to the surgical ICU included operative and
nonoperative trauma patients, as well as abdominal, vascular,
liver transplant, and orthopedic nontrauma surgical patients.
Exclusion criteria included age ,18 y, patients who had an
expected death or ICU discharge within 48 h, pregnancy, and
patients with a primary burn diagnosis.
Randomization
Patients were randomly allocated 1:1 by using a random
number sequence. Investigators were blinded to the preparation
of the randomization envelopes, and the randomization assign-
ment was determined by opening sequential opaque security
envelopes containing the randomization assignment.
Procedures
Before initiating nutritional support, daily caloric re-
quirements were calculated for each patient by using actual body
weight, unless the patient’s weight was greater than 130% of
ideal body weight, in which case an adjusted body weight was
used. For the purpose of this study, the eucaloric goal was 100% of
the calculated daily caloric requirement (25–30 kcal $ kg–1 $ d–1).
The hypocaloric target was 50% (12.5–15 kcal $ kg–1 $ d–1) of the
calculated daily caloric requirement. Both groups had a protein
intake goal of 1.5 g $ kg–1 $ d–1.
All patients were evaluated before the initiation of nutritional
support to determine their risk for refeeding syndrome. Patients
were considered at risk if they had a history of significant alcohol
abuse, a 5% weight loss in the preceding 30 d or 10% loss in the
preceding 6 mo, or poor caloric intake for at least 7 d before
initiation of nutritional support or if their premorbid diet/weight
history was unavailable. Patients at risk for refeeding syndrome
who were randomly allocated to the eucaloric group had initial
goals set at 12.5–15 kcal $ kg–1 $ d–1 and 1.5 g protein $ kg–1 $
d–1 for at least 2 d. Electrolytes were closely monitored and
replaced. According to institutional protocol for all patients re-
ceiving nutritional support, advancement to full feeding did not
occur until electrolyte abnormalities resolved.
Enteral nutrition was initiated at 25 mL/h and advanced by
25-mL increments 3 times daily until the desired goal rate was
achieved. For patients fed into the stomach, gastric residuals were
checked 4 times a day. Prokinetic agents were permitted. Post-
pyloric rather than gastric feeding tubes were used at the dis-
cretion of the attending intensivist. No immune-enhancing
enteral formulas were used to limit confounding variables.
In accordance with institutional policy and American Society
for Parenteral and Enteral Nutrition standards, patients were
considered for parenteral nutrition if they were severely mal-
nourished and could not receive enteral feeding. Otherwise, all
other patients were started on enteral feeds. Any patient who
demonstrated continued intolerance of enteral feeds after 5–7 d
was started on parenteral nutrition. It is not routine at our
institution to supplement enteral nutrition with parenteral nu-
trition to meet caloric goals. Adequacy of nutritional support
was determined by measurement of nitrogen balance.
An insulin infusion was initiated for any patient with blood
glucose greater than 150 mg/dL and adjusted in accordance to the
ICU treatment protocol. For those patients receiving continuous
infusion therapy, the number of units of insulin received per day
was determined by reviewing nursing records.
Data were abstracted from the electronic medical record.
Glucose data were reported as mean overall glucose for the study
inclusion dates and mean glucose at 0600, reported as the glucose
value nearest 0600 on every day of the study. Infection data were
abstracted from a previously described prospectively collected
ICU infections database from the general surgery, trauma, and
transplantation services. US Centers for Disease Control and
Prevention criteria were used to define infections (17, 18). For
example, to diagnose pneumonia, the following were necessary:
a properly collected specimen with isolation of a predominant
organism, production of purulent sputum, a new or changed
infiltrate on chest radiograph, and a quantitative endotracheal
suction specimen with $104 colony-forming units/mL.
Study endpoints
The primary study endpoint was the development of a hospital-
acquired infection. Secondary outcomes included glucose con-
trol, as defined by morning glucose values and daily insulin
requirements, ICU length of stay, hospital length of stay, and all-
cause in-hospital mortality.
Statistical analysis
Preliminary data from 309 ICU patients showed a 67% in-
fection rate. Therefore, by using a conservative estimate of at
least a 50% infection rate in the control group, we estimated
 HYPOCALORIC VS EUCALORIC NUTRITIONAL SUPPORT
a sample size of 58 patients in each study arm (a total of 116
patients) to detect a 50% reduction in infection rate. Because this
is a pilot study, it was not designed or powered to detect
a mortality difference.
Differences in demographic characteristics between the
hypocaloric and eucaloric groups were compared by using
a Student’s t test and Wilcoxon rank-sum test for continuous
variables, as well as the Wald x2 test and Fisher exact test for
categorical variables. Bivariable logistic regression analysis and
the Wald x2 test were used to estimate the relative odds of
hospital-acquired infection and associated 95% CIs for the ORs.
Adjusted ORs for the primary outcome were calculated by using
multivariate logistic regression to control for risk of refeeding,
which showed a statistically significant difference between the 2
groups, and the percentage of goal calories received. Statistical
significance was indicated by using an a level of 0.05.
Differences in mean values for glucose control variables
(mean glucose values and mean insulin requirements), hospital
length of stay, and ICU length of stay were assessed by using
bivariable linear regression. The difference in the relative odds of
FIGURE 1. Participant flow diagram. ICU, intensive care unit.
1339
in-hospital death between the 2 groups was also assessed by using
bivariable logistic regression and the Wald x2 test. To determine
the efficacy of treatment randomization, we compared several
treatment characteristics. Group means were compared by using
a Wilcoxon rank-sum test. Subgroup analysis of the primary and
secondary outcomes was completed comparing the trauma with
the nontrauma population and men with women. All calculations
were performed with SAS 9.3 (SAS Institute Inc).
RESULTS
Of 2892 admissions to the surgical/trauma ICU between
March 2008 and November 2011, a total of 83 patients were
enrolled and randomized, 41 to hypocaloric and 42 to eucaloric
feeding. As shown in Figure 1, details of the randomization of
patients, as well as the reasons for exclusion and reasons for
study end, are presented. Analysis for all patients was completed
on an intention-to-treat basis. Because of slow enrollment, this
study was closed before the full planned enrollment of 116
patients.
1340 CHARLES ET AL

There were no statistically significant differences between the TABLE 2

2 groups in terms of Acute Physiology and Chronic Health Treatment characteristics1
Evaluation II score, age, sex, height, weight, admission diagnosis Hypocaloric Eucaloric P
(trauma compared with nontrauma), or the number of comor- Variable (n = 41) (n = 42) value
bidities (Table 1). The percentage of patients at risk for re-
Daily nutritional intake (kcal) 982 6 612 1338 6 92 0.019
feeding syndrome was higher in the eucaloric group, and thus Daily nutritional intake (kcal/kg) 12.3 6 0.7 17.1 6 1.1 0.0002
we controlled for refeeding risk when describing our primary Daily protein intake (g) 86 6 6 83 6 6 0.75
outcome. Daily protein intake (g/kg) 1.1 6 0.1 1.1 6 0.1 1.00
The treatment characteristics of patients in both arms of the Days in the study (n) 12.6 6 2.8 10.4 6 1.1 0.99
study are summarized in Table 2. There was a statistically Days in the study (n) 9.0 (4–14)3 8.0 (5–16) —
significant difference in the mean (6SE) amount of nutritional Days of CRRT use (%) 7.3 6 2.9 8.6 6 4.0 0.61
support provided to each group, 12.3 6 0.7 compared with 17.1 Days of ventilator use (%) 66.5 6 4.1 67.3 6 4.3 0.74
Days receiving insulin infusion (%) 30.8 6 6.2 35.0 6 6.0 0.67
6 1.1 kcal $ kg–1 $ d–1, P = 0.0002. The mean protein received
Days using TPN (%) 20.7 6 4.9 22.6 6 5.1 0.75
daily by each group was not significantly different (1.1 g/kg for Nutrition goal attained (%) 81.0 6 4.5 73.0 6 4.7 0.17
each group). There were no statistically significant differences Protein goal attained (%) 69.9 6 4.2 70.8 6 4.9 0.78
identified between the 2 groups when analyzed for percentage of 1
Continuous variables were compared by using Student’s t test and the
days of key ICU treatment interventions that may influence
Wilcoxon rank-sum test. Categorical variables were compared by using the
nutrition such as renal replacement therapy, mechanical venti- Wald x2 test and Fisher exact test. CRRT, continuous renal replacement
lation, insulin infusion, or total parenteral nutrition. therapy; TPN, total parenteral nutrition.
As shown in Table 3, details of the primary infectious out- 2
Mean 6 SE (all such values).
3
comes between both groups are presented. There were 82 in- Median; IQR in parentheses (all such values).
fections in the hypocaloric group and 66 in the eucaloric group,
with no statistically significant difference in the mean number of
infections per patient (2.0 6 0.6 and 1.6 6 0.2, respectively; P = Results of secondary outcomes are summarized in Table 4. No
0.50) or the percentage of patients acquiring infection [70.7% statistically significant differences occurred between groups in
(29 of 41) and 76.2% (32 of 42); P = 0.57; adjusted OR: 0.82 mean ICU length of stay (16.7 6 2.7 and 13.5 6 1.1 d, re-
(95% CI: 0.28, 2.39)]. There were also no statistically significant spectively; P = 0.28), mean hospital length of stay (35.2 6 4.9)
differences between the hypocaloric and eucaloric groups in the and 31.0 6 2.5 d, respectively; P = 0.45), or inpatient mortality
percentage distributions of infection types or types of causative [7.3% (3 of 41) and 9.5% (4 of 42), respectively; P = 0.72].
organism. Glucose values and insulin usage were not different between
groups. Further subgroup analyses revealed no differences when
analyzed by sex (men compared with women) and trauma
TABLE 1 compared with nontrauma (data not shown).
Demographic characteristics1 When patients who developed an infection were compared
Hypocaloric Eucaloric with patients who did not develop an infection, there was no
Variable (n = 41) (n = 42) P value statistically significant difference between the mean percent-
age of goal kilocalories received (P = 0.21; 79% goal kcal for
Age (y) 50.4 6 2.8 2
53.4 6 2.7 0.45 any infection; 70% goal kcal for no infection). Again com-
Age (y) 51.0 (38–63)3 52.5 (45–61) —
paring patients who did and did not develop an infection, there
Male sex [% (n)] 68.3 (28) 73.8 (31) 0.58
White race [% (n)] 90.2 (37) 90.2 (37) 1.00 was no statistically significant difference between the per-
Height (cm) 174.0 6 1.6 176.5 6 1.4 0.09 centage of days with primary parenteral nutrition (P = 0.12;
Actual body weight (kg) 97.9 6 4.6 88.0 6 3.4 0.10 25% compared with 13%, respectively) or the percentage of
BMI (kg/m2) 32.9 6 2.0 28.1 6 0.9 0.18 days receiving enteral nutrition (P = 0.99; 67% compared with
Ideal body weight (kg) 69.9 6 1.9 72.4 6 1.8 0.23 67%, respectively). In univariate analysis, patients who re-
Refeeding risk at 31.7 (13) 54.8 (25) 0.03 ceived less than 80% of their goal kcal were not at increased
admission [% (n)] risk of developing an infection compared with those who re-
Trauma admission 68.3 (28) 59.5 (25) 0.41
ceived 80% or more of their goal (P = 0.13; OR: 0.47; 95%
[% (n)]
APACHE II score 16.6 6 0.9 17.3 6 0.8 0.58 CI: 0.18, 1.26).
APACHE II score 17 (13–20) 17 (14–20) —
Total comorbidities 2.2 6 0.3 2.5 6 0.3 0.39
Coronary artery disease 17.1 (7) 11.9 (5) 0.50 DISCUSSION
[% (n)]
Few studies have been conducted to challenge the notion that
Diabetes mellitus [% (n)] 19.5 (8) 14.3 (6) 0.53
Ventilator dependence 68.3 (28) 57.1 (24) 0.29 critically ill patients benefit from receiving the same caloric
[% (n)] intake recommended for patients in the acute care setting. Since
1
its publication in 1997, many clinicians have referred to the
Continuous variables were compared by using Student’s t test and the
consensus statement by the American College of Chest Physi-
Wilcoxon rank-sum test. Categorical variables were compared by using the
Wald x2 test and Fisher exact test. APACHE II, Acute Physiology and cians to determine caloric goals for critically ill patients. “Ad-
Chronic Health Evaluation II. ministering 25 total kilocalories per kilogram usual body weight
2
Mean 6 SE (all such values). per day appears to be adequate for most patients” (12). It is
3
Median; IQR in parentheses (all such values). unknown from current literature what effect this level of caloric
 HYPOCALORIC VS EUCALORIC NUTRITIONAL SUPPORT 1341
TABLE 3
Primary infection results1
Variable Hypocaloric (n = 41) Eucaloric (n = 42) P value OR (95% CI)

Total no. of infections 82 66 0.72 —

Infections per patient (n) 2.0 6 0.62 1.6 6 0.2 0.50 —
Any infection [% (n)]3,4 70.7 (29) 76.2 (32) 0.57 0.76 (0.28, 2.01)
ICU-acquired infection [% (n)]3,5 56.1 (23) 57.1 (24) 0.92 0.96 (0.40, 2.28)
Infection site [% (n)]
Pneumonia 43.9 (18) 47.6 (20) 0.73 0.86 (0.36, 2.04)
Central line 4.9 (2) 4.8 (2) 0.98 1.03 (0.14, 7.65)
Bloodstream 24.4 (10) 19.1 (8) 0.56 1.37 (0.48, 3.92)
Urinary tract 14.6 (6) 14.3 (6) 0.96 1.03 (0.30, 3.50)
Wound 12.2 (5) 7.1 (3) 0.44 1.81 (0.40, 8.10)
Causative organism [% (n)]
Gram negative 53.7 (22) 42.9 (18) 0.33 1.54 (0.65, 3.67)
MRSA 2.4 (1) 4.8 (2) 0.58 0.50 (0.04, 5.74)
Escherichia coli 7.3 (3) 7.1 (3) 0.98 1.03 (0.20, 5.41)
Anaerobe 12.2 (5) 9.5 (4) 0.7 1.32 (0.33, 5.31)
Fungus 14.6 (6) 14.3 (6) 0.96 1.03 (0.30, 3.50)
1
Continuous variables were compared by using Student’s t test and the Wilcoxon rank-sum test. Categorical variables
were compared by using the Wald x2 test and Fisher exact test. Bivariable logistic regression and the Wald x2 test were used
to estimate the relative odds of hospital-acquired infection and associated 95% CIs. ICU, intensive care unit; MRSA,
methicillin-resistant Staphylococcus aureus.
2
Mean 6 SE (all such values).
3
Adjusted ORs for the primary outcome were calculated by using multivariate logistic regression to control for risk of
refeeding and the percentage of goal calories received.
4
Adjusted P = 0.41; OR: 0.82; 95% CI: 0.28, 2.39.
5
Adjusted P = 0.61; OR: 0.78; 95% CI: 0.31, 2.00.

support might have on glucose control and infectious outcomes,
particularly during critical illness. To address this issue, we
conducted a single-institution pilot study to evaluate the differ-
ences in infectious outcomes between critically ill patients
randomly allocated to receive either the standard daily recom-
mendation of 25–30 kcal $ kg–1 $ d–1 or 50% of that amount.
These results failed to identify any difference in outcomes be-
tween critically ill surgical patients enrolled to each group.
Current literature supports the following recommendations for
providing nutritional support to critically ill adults: the enteral
route is preferred; nutrition should be initiated as soon as pos-
sible, ideally within 24–48 h of ICU admission; and postpyloric
feeding should be considered (2, 12, 13). Patients should be in
the semirecumbent position, have their tube feeds titrated up to
80% of goal rate within 72 h, and have gastric residuals moni-
tored (19). Motility agents should be used and enteral nutrition
should be continued unless residuals .500 mL are encountered
(2, 13). There is also literature that supports providing increased
protein for patients receiving continuous renal replacement
therapy or hemodialysis, as well as monitoring and controlling
glucose levels closely (2, 20).
Of those that have addressed the issue of proper dosing of
nutritional support in the recent past, results are inconclusive, but
a push toward less is more has garnered some recent attention.
Arabi et al (21) published their results of a cohort study to de-
termine whether morbidity and mortality are affected by caloric
intake and concluded that increased hospital mortality, ICU and
hospital lengths of stay, infection rates, and mechanical venti-
lation duration were associated with near-target caloric intake
(.64.6% of goal). These findings are consistent with a study
published by Krishnan et al (16), which found that caloric intake
between 33% and 66% of recommended was beneficial to

TABLE 4
Secondary outcomes1
Variable Hypocaloric (n = 41) Eucaloric (n = 42) P value OR (95% CI)
2
ICU length of stay (d) 16.7 6 2.7 3
13.5 6 1.1 0.28 —
Hospital length of stay (d) 35.2 6 4.9 31.0 6 2.5 0.45 —
Mortality [% (n)] 7.3 (3) 9.5 (4) 0.72 0.75 (0.16, 3.58)
Glucose control variables
Mean overall glucose (mg/dL) 133 6 2.8 138 6 2.7 0.22 —
Mean 0600 glucose (mg/dL) 132 6 2.9 135 6 3.1 0.63 —
Mean insulin (units/d) 36.9 6 8.3 39.3 6 12.2 0.87 —
1
Bivariable linear regression was used to compare differences in mean values. Relative odds of in-hospital mortality
was assessed by using bivariable linear regression and the Wald x2 test.
2
ICU, intensive care unit.
3
Mean 6 SE (all such values).
1342 CHARLES ET AL
clinical outcomes. Permissive underfeeding is currently recom-
mended for critically ill obese patients and may be associated
with lower mortality rates (22). And although limited to par-
enteral nutrition alone, a randomized controlled trial published
in 2000 by McCowen et al (23) found that hypocaloric paren-
teral nutrition can help avoid overfeeding, hyperglycemia, and
infectious complications. For enteral nutrition, a goal of only
15 kcal $ kg–1 $ d–1 has been described as beneficial in nonobese
multiple-trauma patients (24).
The EDEN Randomized Trial compared initial trophic feeding
with full enteral feeding for the first 6 d of nutritional support in
patients with acute lung injury. Outcomes of that study showed
no differences between groups in terms of ventilator-free days,
60-d mortality, or infectious complications (6). A previous ran-
domized controlled trial by Rice and colleagues (25) also con-
cluded that no clinical benefit existed from initial trophic feeds
other than fewer incidences of gastrointestinal intolerance. A 1-y
follow-up study to the EDEN trial analyzing physical and cog-
nitive functioning and quality of life failed to demonstrate any
difference between patients who received initial trophic or full
enteral feeding (26). In the Tight Caloric Control Study, when
indirect calorimetry was used to calculate energy targets, com-
pared with using the consensus statement from the American
College of Chest Physicians, there was a statistically significant
increase in total infection rate, length of time on mechanical
ventilation, and ICU length of stay (27).
The results of our study failed to find any significant differ-
ences between treatment arms. The optimum target remains
undetermined, and future studies are needed to identify outcome
differences. Even when the caloric goal is set at 25–30 kcal $ kg–1
$ d–1, many patients do not actually achieve this amount, es-
pecially within the first 7 d of ICU admission. This may be at-
tributable to interruptions in feeding for procedures or to rate
titration. In the absence of any complicating factors such as
refeeding risk, patients can be started at their target feeding goal
rate. This is an option supported by the findings of a study by
Desachy et al (28), which would improve total caloric intake.
The fact that 54.8% (25 of 42) of patients in the eucaloric arm
were determined to be at risk for refeeding syndrome definitely
affected the mean daily caloric intake for that group, causing
them to fall short of their goal. Supplementing enteral nutrition
with parenteral nutrition sooner than 5–7 d is an option to in-
crease the percentage of goal calories received, although this
practice is not supported by outcomes in the Early Parenteral
Nutrition to Supplement Insufficient Enteral Nutrition in In-
tensive Care trial (29). Results of that study demonstrated that
allowing hypocaloric feeding in the ICU during the first 7 d of
admission decreased the rate of new infections and increased the
likelihood of early alive-discharge. A post hoc analysis of this
study again concluded that combining early parenteral nutrition
with enteral nutrition to reach caloric intake goals delays re-
covery (30). In contrast, however, the findings of a study by
Petros et al (31) concluded that hypocaloric feeding was asso-
ciated with more nosocomial infections in medical ICU patients
during the first 7 d. The interpretation of these results in com-
parison to our study is complicated by the differences in the
delivery of nutritional support, such as the addition of parenteral
nutrition by day 3 in the Petros et al study, the cohort of patients
(surgical/trauma ICU compared with medical ICU), and the
overall infection and mortality rates. The outcomes of both
studies validate the notion that future studies are needed to de-
termine whether hypocaloric feeding may be appropriate for
certain cohorts of critically ill patients.
To focus our analysis on caloric intake, we had protein pro-
vision goals the same for both groups. Although our data failed to
reveal any statistically significant outcome differences between
patients with hypocaloric feeding goals and those with eucaloric
feeding goals, it may be that optimizing nutritional support is not
so much a factor of caloric intake but of protein provision.
Several limitations should be noted for this study. First, all
patient enrollment and data collection occurred in a single sur-
gical ICU. Set up as a pilot study, this allowed for feasibility of
enrollment, data gathering, and analysis. Second, the sample size
of the study was small. Although we achieved adequate patient
randomization, opening the study to multiple institutions could
improve enrollment and the generalizability of the findings.
Third, the study was closed before the targeted enrollment was
completed because of low volume, increasing the possibility that
type II error may result from lack of power. A difference in the
number of infections may have been seen with full enrollment.
Unfortunately, with limited prior research on hypocaloric feed-
ing, there was a misconception held by family members signing
consent that patients would be intentionally starved if randomly
allocated to the hypocaloric arm. Overcoming this fear was
challenging, and consent was often difficult to obtain. Despite
these limitations, the results of the study can inform the design of
future multicenter studies that would have larger enrollments.
Patients and their family members now have data to review
showing that hypocaloric feeding is a reasonable alternative to
eucaloric feeding and should not imply intentional starvation.
Subsequent studies could also allow for diagnosis-specific sub-
group analyses and the identification of patients with certain
illnesses who might benefit from varying levels of hypocaloric
nutritional support.
In conclusion, we performed a randomized controlled trial to
evaluate the benefit of hypocaloric nutritional support in the
treatment of critically ill surgical patients. Although limited by
a small sample size, we failed to show significant differences in
outcome between patients with eucaloric or hypocaloric feeding
goals in terms of glucose control, infection rates, ICU and
hospital lengths of stay, and mortality. Further research is nec-
essary to determine whether specific subsets of critically ill
patients might benefit from different levels of caloric provision.
We thank the NIH; the Department of Surgery at the University of Virginia
Health System, Charlottesville, VA; and the entire staff of the Surgical,
Trauma, Burn Intensive Care Unit for their hard work and dedication to
the successful completion of this project.
The authors’ responsibilities were as follows—RM, TH, LHR, GJS, BRS,
and RGS: designed the research; RM, TH, LHR, LMR, MDM, CAG, KFW,
KBO, and RGS: conducted the research; EJC, RTP, LHR, CAG, GJS, BRS,
KFW, KBO, and RGS: analyzed data; EJC, RTP, and RGS: wrote the man-
uscript; and EJC: had primary responsibility for the final content. All authors
read, revised, and approved the final manuscript. No conflicts of interest
were reported.
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