Early Enteral Nutrition in Trauma: Is There Still Any Doubt?
Curr Trauma Rep
Early Enteral Nutrition in Trauma: Is There Still Any Doubt?
Keith R. Miller 0
Jason W. Smith 0
Brian G. Harbrecht 0
Matthew V. Benns 0
0 Department of Surgery, Trauma/ Critical Care, University of Louisville , Louisville, KY 40202 , USA
1 Keith R. Miller
Early enteral nutrition support has been standard in the care of the injured patient for nearly three decades. The Eastern Association for the Surgery of Trauma (EAST) provided the most recent management recommendations for nutritional support of trauma patients in 2004. Simply stated, the recommendation provided by the authors described the superiority of support via the enteral route within the first 72 h of injury when feasible. This statement implied that both the timing of initiation and route of support had potential to impact patient outcomes. The American Society of Parenteral and Enteral Nutrition (ASPEN) in conjunction with the Society of Critical Care Medicine (SCCM) published a broader set of guidelines in 2009 and 2016 that generally agreed with the EAST recommendations and were applicable to critically ill patients. The superiority of the enteral route for delivery of nutritional support has been theorized to be associated with the non-nutritional benefits of substrate provision at the level of the gastrointestinal tract within a 72-h therapeutic window. These concepts, at least in part, were the product of trials performed by surgeons in the setting of severe trauma and are now applied broadly to critically ill patients. However, as is clearly stated in the above guidelines, there are significant limitations inherent in the available literature. The breadth of literature in clinical nutrition has been plagued with issues including small trial size, the presence of multiple confounding variables, diverse control groups, and heterogeneous
Critical care; Intensive care; Nutrition; Enteral nutrition; Parenteral nutrition; Permissive underfeeding
patient populations. Trials examining the role of early enteral
nutrition support in injured patients have similar limitations.
Over the last decade several significant trials have been
conducted examining questions regarding nutrition support in the
ICU, many of which conflict with historical findings. As a
result of these trials, the practice of clinical nutrition is
evolving rapidly. The objectives of this review include the
following: discussion of the historical perspective on nutrition
support in the setting of trauma, brief summary of existing data
and more recent trials of importance, and how these trials may
impact longstanding dogma.
Early enteral nutrition support has been the mainstay of care in
the critically injured trauma patient for decades. BEarly^ has
generally implied the initiation of enteral support within 48 to
72 h of the initial insult, be that injury or admission to the ICU
for a variety of illnesses. Guidelines specific to the trauma
patient have not been revised since the Eastern Association
for the Surgery of Trauma (EAST) published a review of the
evidence in 2004 [
]. Two broader sets of guidelines, in
2009 and recently in 2016, have since been published by the
American Society of Parenteral and Enteral Nutrition in
conjunction with the Society of Critical Care Medicine suggesting
an evidence-based approach to the nutritional care of the
critically ill patient [
2 , 3
]. Within these guidelines, trauma
patients are included but are only rarely individually addressed.
In the interval between the 2004 EAST guidelines and the
2016 revised ASPEN guidelines, very few studies have been
published addressing specifically the benefit of early enteral
support in trauma patients. The available literature for review
is limited by patient heterogeneity, small numbers, alterations
in ICU care over time, and variable control groups. Most
recommendations are made based on extrapolation from
mixed populations of critically ill patients that include sepsis,
post-cardiac, and medical ICU patients. Despite these
limitations, decisions in nutrition support in critically ill and
injured patients continue to be necessary and the available
data can assist clinicians in these decisions. In addition,
surgeons and physicians caring for injured and critically ill
patients should be aware of several recent large clinical trials
published in the last decade (in journals not typically
reviewed by the trauma surgeon).
Three options exist for nutrition support in the critically ill
patient: no support, enteral nutrition (EN), and parenteral
nutrition (PN). The teleological argument has traditionally
suggested that during illness and injury, appetite is diminished as
a protective mechanism due to the inability to utilize substrate
and the risk of increased metabolic demand in the stress state.
Therefore, early nutrition support of any kind could have
adverse consequences. The alternative perspective would
suggest that due to the hypermetabolic, catabolic state of severe
illness and trauma, provision of substrate (either EN or PN)
during times of increased demand could improve outcome. In
fact, following critical illness, multiple observational trials
have suggested that cumulative caloric debt is a powerful
prognostic predictor [
]. Thus patients that received fewer
calories had poorer outcomes. Proponents of early nutrition
support suggest that through early initiation of EN or PN, the
caloric debt is decreased and outcomes improved. However,
an alternative perspective would suggest that due to the
observational nature of these trials, patients with higher morbidity
and mortality are more likely to be intolerant of nutrition
support and thereby quickly accumulate larger caloric deficits.
These opposing perspectives would define the fundamental
question regarding nutrition support in the critically ill patient
Interestingly, trauma surgeons were at the forefront as
proponents of the early nutrition support movement that
characterized the 1990s and permeates all disciplines today. Moore
et al. in 1986 demonstrated that severely injured trauma
patients (ATI > 15) undergoing laparotomy with concurrent
jejunostomy placement and early initiation (at 18 h post
laparotomy, goal in 72 h) of enteral support fared better with
regard to septic complications (pneumonia, abscess) when
compared to controls with no supplemental nutrition [
Proponents of early enteral nutrition have suggested that there
is a therapeutic window (lasting anywhere from 24 to 72 h
from the time of insult) whereby nutrition support can
positively impact outcomes and improve future
gastrointestinal tolerance. The initial study by Moore et al. was followed
by a second study from the same group that suggested a
physiologic advantage through anti-inflammatory mechanisms as
the etiology of the differences observed. Acute phase reactants
(alpha 1-antitrypsin and orosomucoid) were decreased in the
enteral nutrition (EN) group when compared to parenteral
nutrition (PN) in abdominal trauma patients [
]. Kudsk et al.
demonstrated similar findings with regard to decreased acute
phase reactants in a trial examining EN versus PN in 68
trauma patients [
]. These studies, as highlighted in the 2004
EAST recommendations, supported reduced risk of septic
and infectious complications in patients receiving EN post
injury when compared to either PN or no support control
groups. These findings, in part, led to the concept of
Bnonnutritional^ benefits of early EN.
The non-nutritional benefits of early EN have long been
purported as the underlying mechanism contributing to the
observed outcome differences when the enteral route is
compared to the parenteral route or no support groups. There are
several proposed advantages of enteral nutrition over
parenteral nutrition. First, the maintenance of gastrointestinal
structural integrity, and mucosal perfusion allow for the
preservation of barrier function of the GI tract. Second, the
maintenance of immune function as well as the preservation of
gastrointestinal-associated lymphatic tissue (GALT) mass
preserves both the systemic and locoregional immune response to
infectious and inflammatory stimuli. The concept of the
gastrointestinal tract serving as the Bmotor of sepsis^ is an old
]. This principal implies that the vulnerable
ecosystem within the gut involves dynamic interplay between
microbiome and human host. This homeostasis depends on
multiple variables within a delicate system and is dependent
upon intact barriers separating the visceral lumen from the
lymphatic, portal and, ultimately, systemic circulation (host
from outside world). These principles theoretically explained
the advantages of EN over PN despite the reduction in caloric
deficit achieved through both interventions. Finally, the notion
that early initiation of enteral nutrition improves future
gastrointestinal tolerance alludes to the therapeutic window
following injury. Evidence for improved gastrointestinal motility
with the initiation of early EN is lacking in trauma patients
and has been demonstrated predominately in the setting of
major burn injuries and acute care surgical patients [
Following severe trauma, ischemia, hypoxia, and sepsis, the
gastrointestinal barrier function is disrupted .
Derangements in visceral physiology can lead to alteration
in GI cellular structure such as uncoupling of tight junctions,
thinning of visceral mucous layers, and increased mucosal cell
membrane permeability. Due to these changes in GI
permeability, traditional studies have focused on assessing whether
or not bacterial translocation occurs from the GI tract
following critical illness, trauma, and shock. These studies to date
have been mixed and inconclusive. However, more current
thinking identifies that increased permeability of the intestinal
barrier to bacterial cell fragments, free bacterial DNA
fragments, and necrotic intestinal cellular debris are enough to
activate both the local and systemic inflammatory processes
following critical illness and injury. This activation can lead to
worsening of the inflammatory response or, if persistent, can
lead to a reduction in the body’s ability to fight off future
inflammatory/infectious stimuli. Increased permeability does
not tell the complete story, however, as variables such as
electrolyte concentrations and pH within the gastrointestinal
lumen can significantly affect the overall virulence and
distribution of the host microbiome [
]. These alterations in host
physiology can directly impact the interaction between the
host and the microbiome which can subsequently lead to
remote organ dysfunction and failure. A more thorough
discussion of these findings are beyond the scope of this manuscript,
but the end result is selection of more virulent strains of GI
bacteria while at the same time compromising the organs’
ability to contain that bacterium away from the host organism.
EN has been suggested to be more efficacious in the
maintenance of the structural integrity of the gastrointestinal tract
when compared to PN. Mucosal atrophy has been observed in
the absence of intraluminal substrate on serial small bowel
biopsy in acute pancreatitis and restored with the initiation
of EN [
]. Animal studies have demonstrated restoration of
GALT and intestinal IgA levels with administration of EN
following PN-induced atrophy [
]. EN has also been shown
to reduce mucosal atrophy in traumatic brain injury models
comparing early EN to parenteral saline alone [
]. In a small
study by Hadfield et al., mucosal integrity was restored
following the administration of EN in 24 critically ill
(predominately post-cardiopulmonary bypass patients) patients as
measured by D-xylose and 3-O methyl glucose (absorption), and
lactulose and L-rhamnose (permeability) [
Recent Data on Timing
The 2004 EAST guidelines gave a level I recommendation to
the notion that enteral nutrition support should be initiated
within 72 h when feasible. Within this recommendation, the
authors noted no difference between 48 and 72 h. The one
caveat to this was a statement regarding the initiation of
enteral support as early as possible in the setting of severe burns
due to increased incidence of gastroparesis observed in
delayed groups [
]. Of note, distinction was given between
three injury types: burns, blunt/penetrating
abdominal/torso, and head injury again highlighting the heterogeneity of
the Btrauma patient.^ Due to the nature of the available
trials for examining this question, groups are more easily
broken down to involve early (<72 h) versus late (>72 h)
Unfortunately, the available trials examining this question
in a prospective fashion specifically among trauma patients
are few. Doig et al. performed meta-analysis in trauma
patients, which included only three studies comprised of 126
patients, which attempted to delineate appropriate timing of
enteral support. This study focused on trials where enteral
nutrition was provided within 24 h of insult. The
metaanalysis demonstrated a mortality improvement in patients
receiving early EN within the first 24 h [
]. However, as is
commonplace in the existing nutrition support literature, it
should be noted that confounders were readily apparent. To
illustrate this point, the most recent included trial in the
metaanalysis from 2004 by Kompan et al. examined 52 multiply
injured trauma patients (ISS > 20, mean 32) where one group
received early EN (mean 10 h) and another received late
(mean 38 h) EN with primary endpoints being pneumonia
and gastrointestinal intolerance. Of note, the late EN group
also received PN which confounds the results if the focus
remains on the timing question. There was a statistically
significant increase in pneumonia and intolerance in the late
(and PN) group [
]. Supplemental parenteral nutrition is
not widespread practice in the USA, somewhat limiting the
applicability of these data.
More recent studies by ASPEN and SCCM provided more
thorough, though less focused, evaluation of critically ill
patients. The ASPEN/SCCM guidelines examined 21 trials
(conducted between 1979 and 2012) that included 936
critically ill patients in a meta-analysis. This was a heterogeneous
group of critically ill patients. The authors found significant
reductions in mortality and infectious complications in the
early enteral group when compared to delayed groups
prompting the recommendation for early enteral support in
critically ill patients within 24-48 h of admission to the ICU.
Of note, authors noted that the quality of evidence was Bvery
2 , 3
]. However, recently, at least one post hoc
secondary analysis of a large recent RCT raised concerns for harm
associated with the delivery of any nutrient type (parenteral or
enteral) early in the setting of critical illness . The
EPANIC trial was designed to examine the role for early
supplemental PN in critical illness versus no supplemental PN.
This was a large trial comprised of 4640 critically ill patients
]. This post hoc analysis suggested that regardless of the
route of administration (PN or EN), any nutrient administered
early resulted in a delayed recovery.
Finally, the question arises regarding the Bdosing^ of
enteral nutrition. Several recent trials have suggested that
Btrophic^ feeding strategies (set volume of EN support with
caloric delivery far below traditional caloric requirement
calculations) are equivalent to full feeding strategies in critically
ill patients. Arabi et al. randomized 894 critically ill patients
(of which 20 % were non-operative trauma patients) to
permissive underfeeding (trophic targeting 40–60 % of goal) or
standard enteral feeding (70–100 % targeted goal) and found
no difference in outcomes between the feeding strategies [
Studies in acute lung injury patients and surgical ICU patients
have yielded similar results in demonstrating non-inferiority
of Btrophic^ feeding strategies with follow-up extending to
1 year after intervention [
]. This notion coincides with
the concept of non-nutritional EN benefits in maintaining GI
barrier function and microbiome composition, as the
provision of some substrate at the level of the gut early appears to
be of greater importance than the amount provided.
The Enteral Versus Parenteral Question
The 2004 EAST guideline recommendation supporting the
initiation of early EN was based largely on studies published
in the 1980s and 1990s [
]. The proposed superiority of EN
support appears to manifest clinically as a reduction in
infectious complications; however, mortality differences have not
been consistently demonstrated. In fact, one meta-analysis
demonstrated lower mortality in the PN group despite higher
infectious morbidity . The more recent ASPEN/SCCM
guidelines, both in 2009 and 2016, recommended EN over
PN in critically ill patients with a quality of evidence rated
as Blow to very low^ [
2 , 3
]. The authors performed
metaanalysis including nine studies comprised of 496 patients
comparing EN to PN which demonstrated a significant
reduction in infectious complications in the EN group [
]. Five of
these nine studies were conducted in trauma patients, one of
which was in the setting of traumatic brain injury [
They describe the use of EN as Bpractical and safe^ likely
highlighting the reduced cost and technical administration of
EN when compared to PN .
EN has been evaluated in multiple scenarios common in
the trauma population, including the open abdomen.
Multiinstitutional retrospective analysis of 597 patients with open
abdomen as a result of damage control surgery demonstrated
safety in patients with bowel injury as well as improved fascial
closure, decreased complications, and decreased mortality in
those receiving EN without bowel injury. . EN has been
evaluated prospectively in the setting of prone positioning
(comparing nasogastric to post-pyloric placement)  and
gastrointestinal anastomosis  all demonstrating safety.
Absolute contraindications to EN are few, but include
proximal gastrointestinal discontinuity, bowel obstruction, and
concern for mesenteric ischemia. Most experts would avoid EN in
the setting of active ongoing resuscitation or increasing
vasopressor requirements [
2 , 3
Understandably, given the above evidence, enteral support
has become the standard approach to nutrition support in the
trauma patient and viewed as the superior option. However,
recent trials have resulted in controversy regarding the true
risk associated with PN administration. Co-interventions in
the ICU have changed dramatically over the last two decades
and, as can be seen, most of these trials predate many of these
improvements. As an example, glycemic control has become
a standard throughout ICUs in the USA and many of these
trials were conducted prior to this realization which could
directly impact studies regarding efficacy of PN. The
advances in critical care have led physicians and surgeons to
question if the administration of parenteral nutrition
currently is as Brisky^ as shown in the earlier studies from the
1980s and 1990s.
In an attempt to examine this question, Doig et al.
examined 1372 patients with relative contraindications to
EN and these patients were randomized to receive either
PN or standard care. The PN was given immediately upon
admission to the ICU in the PN group and the standard
group was supported at the discretion of the treating
physician (average 2.8 days to EN or PN support). The
authors found no difference in infectious complications or
mortality between the groups, but did demonstrate a
reduction in ventilator days (0.5 days) and less muscle
wasting (as per subjective global assessment) in the early
PN group . This trial hinted at the potentially
improved safety profile associated with current PN
administration when compared to historical populations but
translatability was limited by the contraindications to EN in the
study population. A second study, the CALORIES trial by
Harvey et al. examined the outcomes of critically ill
patients receiving EN versus PN in a multi-institutional
pragmatic design. The study population consisted of
2400 critically ill adult patients expected to be admitted
to the ICU for greater than 72 h. Nutrition support was
initiated within 36 h and continued for a period of five
days. The enteral group was fed with a nasogastric or
nasojejunal tube with expectation to reach goal (25 kcal/
kg adjusted body weight) within 48 to 72 h. The
parenteral group was given 25 kcal/kg PN through a dedicated
central venous access lumen. Moderate glycemic control
was maintained in both groups (<180 mg/dL). The
primary endpoint was all cause mortality at 30 days and
secondary endpoints included duration of organ support,
infectious complications, length of stay, and mortality at
ICU discharge, 90 days, and 1 year. Interestingly, both
groups received equivalent calories and protein. They
found no outcome difference with regard to mortality.
Among secondary outcomes, vomiting and hypoglycemic
episodes were found to be significantly increased in the
EN group . Thus, two large recent trials contradict
the majority of the findings of the earlier trials possibly
indicating that due to changes in critical care, PN may
now carry substantially less risk than once believed.
These findings thus need to be evaluated critically in the
publication of future guidelines.
Conclusion and Recommendations
Recent trials examining fundamental concepts relevant to
nutrition support in the critically ill patient have altered clinical
practice. While there are substantial inherent limitations in the
available literature, a current reasonable recommendation in the setting
of severe trauma is the provision of early EN when feasible.
However, findings from the CALORIES trial certainly lower
the threshold for earlier initiation of PN in patients where EN is
not feasible and long-term nutrition support is indicated.
Additionally, dosing strategies based on several recent trials imply
that trophic feeding during the first week will likely yield similar
outcome benefits to full feeding strategies. Finally, regardless of
the route of administration, most of the available evidence
supports ongoing nutritional support of critically ill/injured patients
over the withholding of nutrition support during critical illness.
Compliance with Ethical Standards
Conflict of Interest Dr. Miller has recieved honoraria from Abbott and
Nestle Nutrition. The additional authors declare they have no conflicts of
Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
of the authors.
Papers of particular interest, published recently, have been
Of major importance
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