Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines
Intensive Care Med
Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines
Annika Reintam Blaser 0 2 3
Joel Starkopf 0 1 3
Mette M. Berger
Michael P. Casaer
Adam M. Deane
Stephan M. Jakob
Cecilia I. Loudet
Manu L. N. G. Malbrain
Juan C. Montejo González
Arthur R.H. van Zanten
Jan De Waele
Heleen M. Oudemansv‑an Straaten
ESICM Working Group on Gastrointestinal Function
0 Department of Anaesthesiology and Intensive Care, University of Tartu, Tartu, Estonia Full author information is available at the end of the article
1 Department of Anaesthesiology and Intensive Care
2 Center of Intensive Care Medicine, Lucerne Cantonal Hospital , Lucerne , Switzerland
3 Department of Anaesthesiology and Intensive Care, University of Tartu , Tartu , Estonia
Purpose: To provide evidence‑ based guidelines for early enteral nutrition (EEN) during critical illness. Methods: We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined “early” EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta‑ analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds. Results: We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta‑ analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion. Conclusions: We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high‑ output fistula without distal feeding access.
Abdominal problems; Parenteral nutrition; Contraindications; GI symptoms; Early enteral nutrition; Delay of enteral nutrition
Take-home message: The administration of early EN appears to reduce
infections and should be used for the majority of critically ill patients.
However, there are certain situations when we recommend EN be
Existing guidelines recommend initiating enteral
nutrition (EN) within the first 24–48 h after intensive care
unit (ICU) admission if patients are unable to eat, not
clearly defining reasons to delay EN [
]. The present
guideline is issued by the Working Group on
Gastrointestinal Function within the Metabolism, Endocrinology
and Nutrition (MEN) Section of the European Society
of Intensive Care Medicine (ESICM) and is endorsed by
ESICM. Our objective was to provide evidence-based
guidelines for early enteral nutrition (EEN) in critically
ill patients, focusing on specific clinical conditions
frequently associated with delayed EN. Caloric and protein
requirements, time to reach targets, type and route of
EN, and timing of supplemental or full parenteral
nutrition (PN) were not addressed. A full version of the
introduction with references is available in Supplement 1.
A full version of methods with references is available in
We performed a systematic review of “early” EN (EEN)
vs. early parenteral nutrition (PN) and EEN vs. delayed
EN in adult critically ill patients. After critical appraisal
of identified studies and in accordance with current
], we defined EEN as EN started within
48 h of admission independent of the type or amount.
Thereafter, we predefined conditions in which EN is
frequently delayed and performed a systematic review for
each of these questions.
If randomised controlled trials (RCT) were available,
we gave an evidence-based recommendation; if not, our
recommendations were based on expert opinion (very
low quality evidence), as all observational studies
evaluating EEN are intrinsically biased, because patients who
Start EN at a slow rate (10–20 ml/h) while carefully monitoring abdominal/
Increase EN slowly once previous symptoms are resolving and no new
Do not increase EN in cases of intolerance or new symptoms, such as pain,
abdominal distension or increasing intra‑abdominal pressure. In these
circumstances EN should be either continued at a slow rate or ceased
depending on the severity of symptoms and suspected underlying
sinister pathology (e.g. mesenteric ischaemia)
Do not aim to cover full energy target with EEN. The optimal energy and
protein target in the early phase of acute critical illness is not known. EEN
that exceeds actual energy expenditure appears harmful and should be
], whereas hypocaloric EEN may be safe [
In case of gastric retention without other new abdominal symptoms use
prokinetics and/or postpyloric feeding in a protocolised way 
During introduction and increasing the rate of EN, measurement of intra‑
abdominal pressure (IAP) provides an additional numeric value to detect
negative dynamics of IAP during EN in patients with severe abdominal
pathology, hypoperfusion or fluid overload
For patients with diminished consciousness and inadequate swallowing,
precautions to prevent aspiration of gastric contents may be useful,
including considering postpyloric feeding
Premorbid health and course of the acute illness may differ between
patients with similar diagnose; therefore an individual approach should
always be applied
are less severely ill are more likely to receive and tolerate
We focussed on specific conditions in which EN is
frequently delayed and tolerance of EN might be impaired.
Therefore, all our recommendations are based on general
principles and precaution measures outlined in Table 1
]. All study questions and recommendations refer to
adult critically ill patients.
All recommendations with the final agreed results are
presented in Table 2.
A flow chart with evidence identification process
(Supplement 2), number of identified abstracts and assessed
full texts for each study question (Supplement 3),
Pubmed search formulas (Supplement 4), evidence tables for
each question with respective references (Supplement 5),
evidence profiles for questions with meta-analyses
(Table 3), evidence profiles for additional meta-analyses
for Question 1 and 11 (Supplement 6), Forest plots for
meta-analyses (Figs. 1, 2 and Supplement 7) are provided.
Question 1: Should we use EEN in critically ill adult patients?
The methodology is described in Supplement 1.
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1. Although the randomization method was inappropriate or unclear in four RCTs out of ive, we did not downgrade for risk of bias because the overall results did not change after
excluding high risk of bias trials from the analysis, it is unlikely that risk of bias affected the mortality estimate.
2. We did not downgrade for inconsistency (I2 = 9%)
3. We downgraded for imprecision by one level because the CI included signi icant bene it and harms (076, 1.19)
4. We downgraded for risk of bias by one level, most RCTs were non-blinded and had unclear or inappropriate methods of randomization
5. We downgraded for inconsistency by one level due to significant statistical heterogeneity (I2 = 65%)
Question 1A: Should we use EEN rather than early
For infection, we included seven RCTs (2729 patients).
Eight trials fulfilled the criteria and were included in
meta-analyses (Supplement 5, Table 1A). Results are
presented in Fig. 1.
EEN reduced the risk of infections compared to early PN
(RR 0.55; 95% CI 0.35–0.86; P = 0.009; I = 65%). The
certainty of evidence was low. We rated down for risk of
bias and inconsistency (Table 3).
For mortality, we included seven RCTs (2686 patients).
Adding 11 additional studies identified during searches
EEN did not reduce mortality compared to early PN (RR
0.95; 95% CI 0.76–1.19; P = 0.64; I = 9%). The certainty
of evidence was moderate. We rated down for
imprecision (Table 3).
for questions in specified patient groups did not
significantly change our results (included studies are presented
in Supplement 5, Table 1C; evidence profiles in
Supplement 6 and Forest plots in Supplement 7, Fig. 3).
1. We downgraded the quality of evidence by two levels for serious imprecision, the CI included extreme bene it and harm
2. We downgraded the quality of evidence for risk of bias by one level
3. We downgraded the quality of evidence by two levels for imprecision, the CI is very wide
Question 1B: Should we use EEN rather than delay
For mortality, we included 12 RCTs (662 patients). EEN
Fourteen studies fulfilled the criteria and were included in
the meta-analysis (Supplement 5, Table 1B). Results of the
did not reduce mortality compared to delayed nutritional
intake (RR 0.76; 95% CI 0.52–1.11; P = 0.149; I = 0%).
For infection, we included 11 RCTs (597 patients). EEN
meta-analyses on EEN vs. delayed nutritional intake
(includreduced risk of infection compared to delayed EN (RR
ing delayed EN, oral diet or PN) are presented in Fig. 2.
Severe acute pancreatitis
SAP (as stated by the authors). Early (early as de ined by the authors) EN vs. PN
The certainty of evidence was low. We rated down for
risk of bias and imprecision (Table 3).
In one study it was not possible to determine whether
was also used in some patients in the EEN
]. Adding eight additional studies identified
via specific searches did not significantly change the
results (included studies are presented in Supplement 5,
plots in Supplement 7, Fig. 4).
Recommendation 1. We suggest using EEN in critically ill
adult patients rather than early PN (Grade 2C) or delaying
EN (Grade 2C).
Question 2: Should we delay EN in patients with shock receiving vasopressors or inotropes?
No RCTs were retrieved. We identified and analysed four
prospective cohort studies, four case series/retrospective
cohort studies and two reviews (Supplement 5, Table 2).
Emergency GI surgery. Early EN vs delayed EN.
Imprecision Other considerations
1. The CI is extremely wide and number of events is very low, therefore, we downgraded by two levels for imprecision
2. All studies were non-blinded, therefore, we downgraded by one level for risk of bias
3. I2=46% but we did not consider this as a substantial heterogeneity
4. The number of events is small and the CI included both substantial and small bene it
5. We downgraded the quality of evidence by two levels for serious imprecision
Elective GI surgery. Early EN vs early PN
1. both trials were non-blinded, we downgraded for risk of bias
2. We downgraded the quality of evidence for imprecision by one level, the CI included the unity line
4. We downgraded for imprecision, the number of events was very small and the results were sensitive to pooling method
There is concern that EN in shock further
jeopardassociated with reduced mortality compared to late EN
izes the already impaired splanchnic perfusion.
Non(>48 h) [
]. These results suggest that the use of
conocclusive bowel necrosis or non-occlusive
comitant vasopressors (especially with stable or
decreasischaemia (NOMI) has been reported in fewer than 1%
ing doses) should not preclude a trial of EN, despite
of patients [
], without evidence for causal
relaa high prevalence of feeding intolerance . In very
tionship between shock, vasopressors, EN and
unstable patients, EN
may not have priority and
]. In a large observational study, EEN (<48 h) in
tial positive effects of EN are unlikely to help improve
patients with ‘stable’ haemodynamics after fluid
resusinstability. Persisting lactic acidosis
may help identify
citation, whilst receiving at least one vasopressor, was
sumption and CO2 production. However, the process of
starving mobilises endogenous stores and is
]. Acidosis may represent persistent shock and
possibly contribute to gut dysfunction. Identifying and
treating the cause of shock has priority over the initiation
of EN. Similarly, in uncontrolled life-threatening
hypoxaemia and hypercapnia, EN should be delayed until the
symptoms are resolving.
In patients with acute lung injury, an RCT comparing
trophic to full EN for up to 6 days was associated with less
gastrointestinal intolerance when compared to full EN,
without affecting ventilator-free days, infectious
complications, physical function, or survival [
]. There are no data
suggesting EN in patients with chronic, subacute,
compensated or permissive hypercapnia is unsafe or not feasible.
Recommendation 3. We suggest delaying EN in case
of uncontrolled life‑threatening hypoxaemia, hypercapnia
or acidosis, but using EEN in patients with stable
hypoxaemia, and compensated or permissive hypercapnia
and acidosis (Grade 2D).
Question 4: Should we delay EN in patients receiving neuromuscular blocking agents?
One prospective study was identified (Supplement 5,
Table 4), reporting similar gastric emptying as measured
by gastric residual volume (GRV) in sedated patients
with or without concomitant use of neuromuscular
blocking agents [
]. The critical condition necessitating
the use of neuromuscular blocking agents always needs
to be considered, but these agents per se should not
preclude EN. Analgosedation is known to slow gastric
]. Increased rate of EN intolerance is expected in
deeply sedated patients with/without concomitant use of
neuromuscular blocking agents.
Recommendation 4. We suggest that EN should not
be delayed solely because of the concomitant use
of neuromuscular blocking agents (Grade 2D).
Question 5: Should we delay EN in patients receiving therapeutic hypothermia?
One case series study addressing EN during
therapeutic hypothermia was identified [
] (Supplement 5,
During therapeutic hypothermia, energy
metabolism might be markedly reduced [
shivering is prevented. The rationale to withhold EN during
therapeutic hypothermia is based on the presumed
decrease in gut motility due to hypothermia [
and required analgosedation [
]. It has been
suggested that EN could be successfully administered to
b Infec ons
these patients [
]. Tolerance to enteral feeding was
impaired during hypothermia, but improved during
Recommendation 5. We suggest starting low dose
EEN in patients receiving therapeutic hypothermia
and increase the dose after rewarming (Grade 2D).
Question 6: Should we delay EN in patients receiving extracorporeal membrane oxygenation (ECMO)?
No RCTs and no prospective cohort studies were
identified. Four case series in adult patients with ECMO were
assessed (Supplement 5, Table 6), suggesting that EN is
feasible during ECMO.
Recommendation 6. We suggest using EEN in patients
receiving ECMO (Grade 2D).
Question 7: Should we delay EN during prone position?
One prospective cross-over, one cohort and three case
series studies were identified (Supplement 5, Table 7).
Data on tolerance of EN in prone position are
controversial. Observational studies found similar GRVs in
prone and supine position [
], whereas poor feeding
tolerance was improved with semi-recumbent position
during supine periods and prokinetics [
]. Although no
RCTs on EN tolerance during prone position are
available, reported studies do not support withholding EN in
prone position. Gastric emptying seems not to be
significantly influenced by prone position and adverse events in
most studies not increased.
Recommendation 7. We suggest that EN should not be
delayed solely because of prone positioning (Grade 2D).
Remark: We suggest considering early use of
prokinetics followed by post-pyloric feeding in case of persisting
Question 8: Should we delay EN in patients with traumatic brain injury?
We identified a Cochrane review with two updates and
one recent meta-analysis, comparing early vs. late
feeding, independent on the route of nutrition (EN or PN)
(Supplement 5, Table 8C). We identified three RCTs
comparing EEN vs. early PN, three RCTs comparing EEN
vs. delayed EN (one with restricted randomisation), and
one RCT comparing early PN vs. delayed EN
(Supplement 5, Table 8A).
Question 8A: EEN vs. early PN
Three RCTs (116 patients) were included. EEN
compared to early PN in patients with traumatic brain injury
did not affect mortality (RR 1.91; 95% CI 0.59–6.18;
P = 0.279; I2 = 0%) or the risk of pneumonia (RR 1.23;
95% CI 0.79–1.90; P = 0.36; I2 = 0%). The certainty of
evidence for mortality outcome was low, for
pneumonia it was very low. We rated down for risk of bias and
imprecision (Table 3). Supplement 7, Fig. 5.
Question 8B: EEN vs. delayed EN
For mortality, two RCTs (86 patients) were included.
EEN did not affect mortality compared to delayed EN
(RR 0.66; 95% CI 0.18–2.45; P = 0.53; I2 = 0%). The
certainty of evidence was low. We rated down for
imprecision (Table 3).
For pneumonia, three RCTs (118 patients) were
included. EEN did not affect the risk of pneumonia
compared to delayed EN (RR 0.86; 95% CI 0.55–1.35;
P = 0.51; I2 = 0%). The certainty of evidence was very
low. We rated down for risk of bias and imprecision
(Table 3). Supplement 7, Fig. 6.
In addition to RCTs, five cohort studies addressing this
question were identified (Supplement 5, Table 8B).
Existing evidence did not allow determining or
excluding any benefit or harm of EEN, therefore our
recommendation is based on expert opinion.
Recommendation 8. We suggest using EEN in patients
with traumatic brain injury (Grade 2D).
Question 9: Should we delay EN in patients with stroke (haemorrhagic or ischaemic)?
We identified two RCTs in patients with ischaemic
stroke and one retrospective study in patients with
hypertensive intracerebral haemorrhage (Supplement 5,
Tables 9A, B).
One small RCT compared early vs. delayed EN and
reported amelioration of cell-mediated immunity [
however, both groups received PN to meet caloric targets
from day 1. A large RCT compared EEN (“as soon as
possible”) to no nutrition within 7 days and reported a trend
towards reduction of long-term mortality (6 months)
with EN, with an increased risk of poor neurologic
outcome in survivors [
]. An observational study reported
reduction in infectious complications with EEN vs.
delayed EN [
Recommendation 9. We suggest using EEN in patients
with stroke (ischaemic or haemorrhagic) (Grade 2D).
Question 10: Should we delay EN in patients with spinal cord injury?
One RCT addressed EEN (<72 h) vs. delayed EN in
cervical spinal injury [
]. No differences in outcome
variables were identified. One retrospective cohort study
addressed safety of EN early after spinal cord injury and
reported no major complications [
] (Supplement 5,
Tables 10A, B).
Recommendation 10. We suggest using EEN in patients
with spinal cord injury (Grade 2D).
Question 11: Should we delay EN in patients with severe acute pancreatitis (SAP)?
We identified five systematic reviews with
meta-analyses comparing EN to PN while not considering timing
(Supplement 5, Table 11B). All meta-analyses concluded
that EN was beneficial in reducing infections and three
reported reduced mortality [
3, 34, 35
We identified five RCTs addressing EEN (“early” as
defined by the authors) vs. early PN in SAP whereas
only two studies defined “early” as <48 h. Three further
RCTs addressed EEN vs. early PN and one RCT EEN vs.
delayed EN in “predicted SAP”. Two RCTs addressing
acute pancreatitis independent of severity and one RCT
studying mixed patients undergoing abdominal surgery
were not included. Supplement 5, Table 11A.
We performed three separate meta-analyses all
comparing EEN vs. early PN: (A) SAP and “early” as defined
by the authors of the original study; (B) predicted SAP
and “early” as defined by the authors of the original study;
(C) predicted SAP and early defined as <48 h.
Question 11A: SAP (as stated by the authors). Early (“early” as defined by the authors) EN vs. PN
For mortality we included five RCTs (283 patients).
EEN did not reduce the risk of death compared to PN
(RR 0.57; 95% CI 0.23–1.38; P = 0.21; I2 = 35.1%). The
certainty of evidence was low. We rated down for
imprecision (Table 3).
For any infections we included five RCTs (283 patients).
EEN reduced the risk of infections compared to PN (RR
0.48; 95% CI 0.23–0.98; P = 0.045; I2 = 76%). The
certainty of evidence was low. We rated down for
inconsistency and imprecision (Table 3).
For pancreatic infections we included four RCTs (233
patients). EEN reduced the risk of pancreatic infections
compared to PN (RR 0.33; 95% CI 0.21–0.52; P < 0.0001;
I2 = 0%) The certainty of evidence was low. We rated
down for risk of bias and imprecision (Table 3).
Supplement 7, Fig. 7.
Question 11B: Predicted SAP. Early (“early” as defined by the authors) EN vs. PN
For mortality we included eight RCTs (417 patients).
EEN did not reduce the risk of death compared to PN
(RR 0.50; 95% CI 0.22–1.13; P = 0.09; I2 = 38%). The
certainty of evidence was low. We rated down for
imprecision (Supplement 6).
For any infections we included eight RCTs (417
patients). EEN reduced the risk of infections compared to
PN (RR 0.53; 95% CI 0.30–0.91; P = 0.023; I2 = 63.5%).
The certainty of evidence was low. We rated down for
risk of bias and inconsistency (Supplement 6).
For pancreatic infections we included five RCTs (202
patients). The use of EEN reduced the risk of pancreatic
infections compared to PN (RR 0.35; 95% CI 0.24–0.52;
P < 0.0001; I2 = 0%). The certainty of evidence was low.
We rated down for risk of bias and imprecision
(Supplement 6). Supplement 7, Fig. 8.
Question 11C: Predicted SAP. Early (<48 h) EN vs. PN
For mortality we included five RCTs (232 patients).
EEN (<48 h) did not reduce the risk of death compared to
PN (RR 0.61; 95% CI 0.15–2.55; P = 0.50; I2 = 41%). The
certainty of evidence was low. We rated down for
imprecision (Supplement 6).
For any infections we included five RCT (232 patients),
EEN (<48 h) reduced the risk of infections compared to
PN (RR 0.49; 95% CI 0.28–0.83; P = 0.008, I2 = 9%). The
certainty of evidence was low. We rated down for risk of
bias, inconsistency and imprecision (Supplement 6).
For pancreatic infections we included three RCTs (167
patients). EEN (<48 h) reduced the risk of pancreatic
infections compared to PN (RR 0.40; 95% CI 0.22–0.73;
P = 0.003; I2 = 0%). The certainty of evidence was low.
We rated down for risk of bias and imprecision
(Supplement 6). Supplement 7, Fig. 9.
Taken together, the studies in different subpopulations
have demonstrated a reduction of infections but no
convincing effect of EEN on mortality.
Recommendation 11. We suggest using EEN in patients
with severe acute pancreatitis (Grade 2C).
Question 12: Should we delay EN in patients after GI surgery?
Out of three published meta-analyses [
addressing early postoperative feeding including early oral diet,
the two more recent papers [
] reached different
conclusions: reduced mortality and length of stay (LOS)
but increased risk of vomiting analysing 15 RCTs  vs.
no difference in mortality and LOS, but reduced
complications in early group from 13 RCTs [
We identified three RCTs comparing early vs. delayed
EN after emergency GI surgery and six RCTs in elective GI
surgery. Two RCTs compared EEN vs. early PN in patients
after elective GI surgery (Supplement 5, Table 12).
Question 12A: Emergency GI surgery. EEN vs delayed EN
Three RCTs (343 patients) were included. EEN did not
affect mortality compared to delayed EN (RR 0.80; 95%
CI 0.46–1.40; P = 0.44; I2 = 0%). EEN reduced the risk
of infections compared to delayed EN (RR 0.61; 95% CI
0.40–0.93; P = 0.02; I2 = 0%). The certainty of evidence
was low. We rated down for risk of bias and imprecision
(Table 3). Supplement 7, Fig. 10.
Question 12B: Elective GI surgery. EEN vs. delayed EN
For mortality three RCTs (346 patients) were included.
EEN did not affect mortality compared to delayed EN in
patients after elective GI surgery (RR 0.83; 95% CI 0.25–
2.81; P = 0.77; I2 = 17%). The certainty of evidence was
low. We rated down for imprecision (Table 3).
For any infections six RCTs (432 patients) were
included. EEN reduced the risk of infections compared
to delayed EN (RR 0.43; 95% CI 0.23–0.82; P = 0.01;
I2 = 46%). The certainty of evidence was low. We rated
down for risk of bias and imprecision (Table 3).
Five RCTs (404 patients) reported anastomotic
leak. EEN reduced the risk of surgical leak compared
to delayed EN (RR 0.43; 95% CI 0.20–0.93; P = 0.03;
I2 = 0%). The certainty of evidence was low. We rated
down for imprecision (Table 3). Supplement 7, Fig. 11.
Question 12C: Elective GI surgery. EEN vs early PN
Two RCTs (440 patients) were included. EEN did not
reduce the risk of pneumonia compared to early PN (RR
0.59; 95% CI 0.31–1.14; P = 0.12, I2 = 0%), but reduced the
risk of anastomotic leak compared to early PN (RR 0.42;
95% CI 0.19–0.95; P = 0.04; I2 = 63%). The certainty of
evidence was low. We rated down for risk of bias,
inconsistency and imprecision (Table 3). Supplement 7, Fig. 12.
Recommendation 12. We suggest using EEN in patients
after GI surgery (Grade 2C).
Question 13: Should we delay EN in patients after abdominal aortic surgery?
No RCTs but two cohort studies were identified
(Supplement 5, Table 13). Cohort studies both in elective [
and emergency repair [
] did not compare EEN with
any of our comparators, but showed that EEN was
successful in a minority of patients. A multimodal approach
has been proposed [
], including early removal of
nasogastric tubes, immediate postoperative mobilisation
early oral or enteral feeding, accepting GRV up to 500 ml
and use of prokinetics. Although these patients are at risk
of bowel ischaemia with prevalence reported between 7
and 17% [
], the risk itself should not lead to
withholding EN, unless bowel ischaemia is suspected (see also
Recommendation 13. We suggest using EEN in patients
after abdominal aortic surgery (Grade 2D).
Question 14: Should we delay EN in patients with abdominal trauma?
Ten RCTs and ten cohort studies addressing EEN in
trauma patients (RCTs: within 6–48 h; cohort studies:
within 12–96 h) were identified, but abdominal trauma
specifically was addressed in six RCTs, four of them
compared EEN to early PN and two EEN to delayed EN
(Supplement 5, Table 14A).
Question 14A: EEN vs early PN
For mortality two RCTs (142 patients) were included.
EEN did not affect mortality compared to early PN (RR
0.49; 95% CI 0.09–2.69; P = 0.41; I2 = 0%). The certainty
of evidence was very low. We rated down for risk of bias
and imprecision (Table 3).
For any infection four RCTs (219 patients) were
included. EEN did not affect the risk of infections
compared to early PN (RR 0.59; 95% CI 0.24–1.42; P = 0.24;
I2 = 59%). The certainty of evidence was very low. We
rated down for risk of bias, inconsistency and
imprecision (Table 3). Supplement 7, Fig. 13.
Question 14B: EEN vs delayed EN
Two RCTs (101 patients) were included. EEN did not
affect mortality compared to delayed EN (RR 0.74; 95%
CI 0.18–3.11; P = 0.708). The certainty of evidence was
very low. We rated down for risk of bias and imprecision
EEN did not affect the risk of infections compared to
delayed EN (RR 0.83; 95% CI 0.41–1.70; P = 0.837). The
certainty of evidence was very low. We rated down for
risk of bias, inconsistency and imprecision (Table 3). See
Supplement 7, Fig. 14.
Of note, earlier studies in this patient group almost
exclusively used surgical jejunostomy for EN.
Existing evidence did not allow verifying or excluding
any benefit or harm of EEN; therefore our
recommendation is based on expert opinion. In addition to RCTs,
nine observational studies were identified (Supplement 5,
An earlier meta-analysis in adult trauma patients in
ICU (not specifically abdominal trauma) showed survival
benefit in EEN commenced within 24 h after trauma [
Recommendation 14. We suggest using EEN in patients
with abdominal trauma when the continuity of the GI tract
is confirmed/restored (Grade 2D).
Question 15: Should we delay EN in patients with bowel ischaemia?
We identified no clinical studies, but physiological
knowledge and common sense support withholding
EN in patients with overt bowel ischaemia. However,
patients with endoscopic evidence of mild to moderate
large bowel mucosal ischaemia, without signs of
transmural ischaemia or bowel distension, might profit from
low dose EN. In this case we support considering EN. In a
recent retrospective study, survivors were more often fed
enterally before the diagnosis of acute mesenteric
ischaemia, but no independent association between EN and
mortality was demonstrated [
Recommendation 15. We suggest delaying EN in patients
with overt bowel ischaemia (Grade 2D).
Question 16: Should we delay EN in critically ill adult patients with intestinal fistula?
We identified one retrospective cohort study and two
case series, all showing outcome benefit of “early” EN
(Supplement 5, Table 16). However, “early” was defined
as EN started within 7 days or 14 days of admission.
Retrospective design further diminishes the importance of
Intolerance of EN or increasing fistula output causing
skin breakdown or fluid/electrolyte imbalance are
evident reasons to decrease or discontinue EN [
Recommendation 16. We suggest delaying EN in patients
with high‑output intestinal fistula if reliable feeding access
distal to the fistula is not achievable (Grade 2D).
Question 17: Should we delay EN in patients with an open abdomen?
Seven observational studies (one prospective cohort
study, three retrospective cohort studies and four case
series) were identified; two studies compared EEN
(different definitions) vs delayed EN and reported higher
rate of early abdominal closure, less fistula formation and
lower incidence of ventilator-associated pneumonia in
the “early” EN group (Supplement 5, Table 17). The
largest study comparing EN to no EN in patients with open
abdomen after abdominal trauma reported independent
associations between EN and ultimate fascial closure and
decreased mortality rate in patients without bowel injury,
but no difference in a subgroup of patients with bowel
Recommendation 17. We suggest using EEN in patients
with open abdomen (Grade 2D).
Question 18: Should we delay EN in patients with intra-abdominal hypertension?
Four observational studies were identified
(Supplement 5, Table 18), only one addressed early vs. delayed
]. All studies reported high incidence of feeding
intolerance associated with intra-abdominal
hypertension, but data are not conclusive regarding causality. A
recently published study demonstrated that EEN did not
increase intra-abdominal pressure, but values exceeding
15 mmHg were associated with higher rates of feeding
intolerance in patients with severe acute pancreatitis [
No prospective study addressing EN in patients with
abdominal compartment syndrome [
] was identified.
As abdominal compartment syndrome is an immediately
life-threatening condition with jeopardized splanchnic
perfusion, we suggest to withhold or stop EN and try to
lower intra-abdominal pressure.
Recommendation 18a. We suggest using EEN in patients
with intra‑abdominal hypertension without abdominal
compartment syndrome, but consider temporary
reduction or discontinuation of EN when intra‑abdominal
pressure values further increase under EN (Grade 2D).
Recommendation 18b. We suggest delaying EN in patients
with abdominal compartment syndrome (Grade 2D).
Question 19: Should we delay EN in patients with upper GI bleeding?
No studies addressing EEN were identified. One RCT
in bleeding due to gastric or duodenal ulcer reported
shorter hospital stay (4.2 ± 1.2 vs. 5.9 ± 1.4 days,
P < 0.001) in the early oral feeding group [
EN as protection against stress ulceration and GI
bleeding is suggested in one meta-analysis [
retrospective study in burns [
] and several reviews
]. An RCT comparing ranitidine and sucralfate
reported EN as an independently protective factor
against GI bleeding [
]. The main rationale to
prohibit eating/EN is based on fear for disturbed visibility
in a further endoscopy/intervention due to rebleeding.
Therefore, delaying EN for 48–72 h in patients with a
high risk of rebleeding has been suggested [
Considering the absence of evidence to support this time
frame, we suggest starting EN during the first 24–48 h
after bleeding has been stopped; prolonged
postponement of EN is unnecessary or even harmful because of
increased risk of stress ulceration. Importantly, there
is no evidence that fine-bore nasogastric tubes cause
variceal bleeding [
Recommendation 19. We suggest delaying EN in patients
with active upper GI bleeding, and starting EN when the
bleeding has stopped and no signs of rebleeding are
observed (Grade 2D).
Question 20: Should we delay EN in patients with acute liver failure?
We could not identify any study in acute or
acute-onchronic liver failure patients. Some benefits of EN have
been shown in patients with alcoholic hepatitis,
malnourished patients with cirrhosis and patients with liver
], where glycogen stores may be
depleted after an overnight fast and metabolic conditions
resemble prolonged starvation in healthy individuals
]. EN in fulminant acute liver failure has never been
studied. These patients often present with
hypoglycaemia, which should be corrected with intravenous glucose,
sometimes together with insulin. Fulminant liver failure
is associated with increased serum amino acid
concentrations, especially glutamine [
]. It seems likely
that a failing liver is unable to provide effective metabolic
support required for nutrition. The pathophysiological
rationale to delay EN in fulminant hepatic failure would
be to “spare” the severely injured liver from the duties
of metabolising and storing nutrition during a period of
stress and also to avoid additional increases in ammonia.
Intravenous provision of nutrients except correction of
hypoglycemia and appropriate provision of vitamins and
trace elements may be futile or harmful early in the
clinical course .
Recommendation 20. We suggest starting low dose EN
when acute, immediately life‑threatening metabolic
derangements are controlled with or without liver support
strategies, independent on grade of encephalopathy
Remark: Arterial ammonia levels should be monitored.
Question 21: Should we delay EN in patients with large gastric aspirate volumes (GAV)?
We identified no study addressing this question. Based
on existing evidence from two RCTs comparing the
threshold volumes to stop already started EN [
a clear threshold volume (in ranges up to 500 ml) that
increased the risk of ventilator-associated pneumonia
was not identified. Measurements of GAV/GRV are not
a gold standard and alternative methods (like ultrasound)
can be applied to diagnose overfilling of the stomach.
Gross distension of the stomach is likely to be
undesirable and therefore we suggest that EN should be delayed
when GAV/GRV is >500 ml/6 h , either for a
limited time period or until administration of prokinetics.
For patients with persistently large GAV/GRVs the use
of postpyloric feeding should be considered rather than
withholding EN, unless bowel ischaemia or obstruction is
suspected (see also Recommendation 15).
Recommendation 21. We suggest delaying EN if gastric
aspirate volume is above 500 ml/6 h (Grade 2D).
Question 22: Should we delay EN in patients with absent bowel sounds?
One cohort study was identified [
] (Supplement 5,
Table 22). Bowel sounds are frequently absent in
mechanically ventilated patients and this is associated with
impaired outcome [
]. The concept that bowel sounds
must be present before initiation of enteral feeding is
not based on evidence and should be abandoned [
After laparotomy small intestinal motility is frequently
preserved despite gastric and colonic paresis. The small
intestine may contract silently (absence of gas), while
feeding is well tolerated [
]. Gastric and colonic paresis
may effectively be treated with prokinetics [
of EN in absence of bowel sounds might be associated
with earlier return of bowel sounds, fewer episodes of
vomiting, and shorter ICU and hospital stay [
Recommendation 22. We suggest using EEN regardless
of the presence of bowel sounds unless bowel ischaemia or
obstruction is suspected (Grade 2D).
Question 23: Should we delay EN in patients with diarrhoea?
There were no studies testing delay of EN in case of
diarrhoea, but diarrhoea is often considered as a reason
to delay EN [
]. Prevalence of diarrhoea in unselected
ICU population is between 14 and 21% [
include impaired digestion/absorption, bacterial
overgrowth or infection such as Clostridium difficile.
Observational studies [
] suggest that diarrhoea can be
effectively managed with protocolised measures other
than immediate cessation in EN. We recommend
analysing the causes of diarrhoea and treat appropriately (e.g.
C. difficile colitis). We also suggest considering treating
bacterial overgrowth by selective decontamination,
fibreenriched or semi-elementary diet or digestive enzymes to
Recommendation 23. We suggest using EEN in patients
with diarrhoea (Grade 2D).
We suggest using EEN, initiated at a low rate, in the
majority of critically ill patients; however, the evidence
is weak. Beneficial effects in terms of infection
prevention have been demonstrated in unselected critically ill
patients, as well as in patients with severe acute
pancreatitis and after GI surgery. However, we suggest delaying
EN in patients with uncontrolled shock (haemodynamic
and tissue perfusion goals are not met despite of fluids
and vasopressors), uncontrolled hypoxaemia and
acidosis, uncontrolled GI bleeding, overt bowel ischaemia
(occlusive or non-occlusive), bowel obstruction
(mechanical ileus), abdominal compartment syndrome, gastric
aspirate volume >500 ml/6 h or high-output fistula if
reliable distal feeding access is not achievable.
Electronic supplementary material
The online version of this article (doi:10.1007/s00134‑016‑4665‑0) contains
supplementary material, which is available to authorized users.
Tartu University Hospital, Tartu, Estonia. 4 Department of Medicine, Division
of Critical Care, McMaster University, Hamilton, Canada. 5 Department of Clini‑
cal Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.
6 Services of Adult Intensive Care Medicine and Burns, Lausanne University
Hospital, Lausanne, Switzerland. 7 Department of Intensive Care Medicine, Uni‑
versity Hospital Leuven, Louvain, Belgium. 8 Discipline of Acute Care Medicine,
University of Adelaide, Adelaide, Australia. 9 Department of Anaesthesiology
and Intensive Care Medicine, Medical University of Graz, Graz, Austria. 10 Kli‑
nische Abteilung für HerzT‑horax‑Gefäßchirurgische Anästhesie & Intensiv‑
medizin, Medizinische Universität Wien, Vienna, Austria. 11 Intensive Care Unit,
Hôpital Pasteur 2, University of Nice, Nice, France. 12 Department of Intensive
Care Medicine, University Hospital, University of Bern, Bern, Switzerland.
13 Intensive Care Unit, Hospital Interzonal General de Agudos General San
Martín de La Plata, Buenos Aires, Argentina. 14 Intensive Care Unit, Ziekenhuis
Netwerk Antwerpen, ZNA Stuivenberg, Antwerp, Belgium. 15 Department
of Intensive Care Medicine, Hospital Universitario 12 de Octubre, Madrid,
Spain. 16 Anesthesiology and Perioperative Care Medicine Department,
Hôpital Beaujon APHP, Clichy, France. 17 Department of Surgery/IntensiveCare
Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
18 Department of Intensive Care, Erasme University Hospital, Université Libre
de Bruxelles, Brussels, Belgium. 19 Intensive Care Department, Rabin Medical
Center, Beilinson Campus, Petah Tikva, Israel. 20 Anesthesia and Intensive
Care Division, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
21 Department of Intensive Care Medicine, Gelderse Vallei Hospital, Ede,
The Netherlands. 22 Department of Critical Care Medicine, Ghent University
Hospital, Ghent, Belgium. 23 Department of Intensive Care Medicine, Division
of Immunobiology and Transplantation, King’s College London, King’s College
Hospital, London, UK. 24 Department of Anaesthesiology and Intensive Care
Medicine, Karolinska University Hospital Huddinge and Karolinska Institutet,
Stockholm, Sweden. 25 Department of Critical Care and Anaesthesia, Queen
Elizabeth Hospital, Birmingham, UK. 26 Medical Intensive Care Unit, University
Hospital Leuven, Leuven, Belgium. 27 Department of Intensive Care Medicine,
VU University Medical Center, Amsterdam, The Netherlands.
Collaborators in ESICM Working Group on Gastrointestinal Function: Claudia
Spies, Klinik für Anästhesiologie mit Schwerpunkt operative Intensivmedizin
der Charité‑Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin; Pietro
Vecchiarelli, Intensive Care Unit, Ospedale Belcolle, Strada Sammartinese, Bel‑
colle Hospital, Viterbo, Italy; Anne Berit Guttormsen, Department of Anesthesia
and Intensive Care, Haukeland University Hospital, Bergen, Norway. The costs
covering the open access publication of this article were covered by the Inter‑
national Fluid Academy (IFA). The IFA is integrated within the not‑for ‑profit
charitable organization iMERiT (International Medical Education and Research
Initiative) under Belgian Law, and IFA website (http://www.fluidacademy.
org) is an official SMACC (Social Media and Critical Care) affiliated site, based
on the philosophy of FOAM (Free Open Access Medical Education).
Compliance with ethical standards
Conflicts of interest
See Supplement 8.
Open Access This article is distributed under the terms of the Creative
Commons Attribution‑NonCommercial 4.0 International License (http://
creativecommons.org/licenses/by‑nc/4.0/), which permits any noncommer ‑
cial use, distribution, and reproduction in any medium, provided you give
appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made.
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