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MCC 220208
REVIEW
URRENT
C
OPINION
Purpose of review
The current review summarizes different aspects of assessment of gastrointestinal function and provides a
practical approach to management of adult patients with gastrointestinal dysfunction in the ICU.
Recent findings
Different ways to define gastrointestinal failure have been used in the past. Recently, the term acute
gastrointestinal injury (AGI) has been proposed to specifically describe gastrointestinal dysfunction as a
part of multiple organ dysfunction syndrome. Possible pathophysiological mechanisms and different aspects
in assessment of gastrointestinal function in adult ICU patients are presented. Currently, there is no single
marker that could reliably describe gastrointestinal dysfunction. Therefore, monitoring and management is
still based on complex assessment of different gastrointestinal symptoms and feeding intolerance, even
though this approach includes a large amount of subjectivity. The possible role of biomarkers (citrulline,
enterohormones, etc.) and additional parameters like intra-abdominal pressure remains to be clarified.
Summary
Defining gastrointestinal failure remains challenging but broad consensus needs to be reached and
disseminated soon to allow conduct of interventional studies. A systematic approach to management of
gastrointestinal problems is recommended.
Keywords
acute gastrointestinal injury, dysfunction, failure, gastrointestinal, intensive care
INTRODUCTION
Gastrointestinal function in ICU patients is difficult
to evaluate and there is no unique and easily
applicable practical definition of gastrointestinal
failure. Various functions of the gastrointestinal
system (digestive, endocrinologic, immunologic,
and barrier) make its normal function fairly
indefinable in ICU patients. As a result, none of
the available scoring systems for multiple organ
dysfunction syndrome (MODS) does appraise the
gastrointestinal system, even though the importance of gastrointestinal failure in MODS has been
recognized for years [13].
The current review aims to summarize different
aspects of assessment of gastrointestinal function
and provides a practical approach to the management of adult patients with gastrointestinal
dysfunction in the ICU.
a
Department of Intensive Care Medicine, Lucerne Cantonal Hospital,
Lucerne, Switzerland, bDepartment of Anaesthesiology and Intensive
Care, University of Tartu, Tartu, Estonia, cDepartment of Intensive Care
Medicine, University Hospital of Bern, University of Bern, Bern,
Switzerland and dDepartment of Anaesthesiology and Intensive Care,
Tartu University Hospital, Tartu, Estonia
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MCC 220208
Gastrointestinal system
KEY POINTS
AGI could be used to describe gastrointestinal
dysfunction as a part of MODS.
Single symptoms describing different gastrointestinal
motility disorders cannot be equalized with
gastrointestinal organ failure.
A scoring system/grading of severity is needed to
allow conduct of interventional studies.
Diagnosis of feeding intolerance should not be based
only on gastric residual volumes but rather comprise an
algorithmic stepwise approach, possibly also including
defined management/treatment options.
Assessment of gastrointestinal function is still limited
today to clinical and radiological assessment; a few
promising biomarkers need to be further studied.
EPIDEMIOLOGY
Problems of the European Society of Intensive Care
Medicine, and resulted in definitions for acute
gastrointestinal injury (AGI) with four grades of
severity (Table 2) [16]. However, none of the existing
definitions is well validated providing grading with
readily applicable clinical severity scores. Moreover,
it needs to be underlined that none of these
approaches considers other than digestive function
(like endocrine, immunological, and barrier) of the
gastrointestinal system.
PATHOPHYSIOLOGICAL MECHANISMS
Gastrointestinal failure develops as a direct consequence of organ injury or secondary to hypoperfusion. In both situations, depending on the type
and severity of the insult, an inflammatory response
may amplify the vicious circle of hypoperfusion and
gastrointestinal injury (Fig. 1) [15,20,21]. Hormonal
mediators of gastrointestinal motility may be
relevant in pathophysiology of gastrointestinal dysfunction, clinically often expressed as delayed gastric emptying [22]. However, the gastrointestinal
failure associated with MODS is most likely caused
by hypoperfusion and ischaemia/reperfusion injury
leading to altered mucosal barrier and immunoinflammatory reaction via release of biologically
active factors into the blood as well as mesenteric
lymphatics [21] (Fig. 1). Some recent studies have
tried to address these pathophysiological events. In
acute aortic dissection, serum levels of diamine
oxidase, an enzyme mostly located in intestinal
mucosa, are increased and correlated with inflammatory markers [23]. Translocation of bacterial
products has also been shown in patients with heart
failure and chronically impaired gastrointestinal
2
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GI dysfunction [6]
GI failure [7]
GI failure [9]
GI failure [11]
Gastrointestinal failure
Definition
GI dysfunction [5]
Gastrointestinal dysfunction
Term
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None
0 normal GI function;
1 enteral feeding <50% of
calculated needs or no feeding
3 days after abdominal
surgery; 2 FI (enteral feeding
not applicable because of high
gastric aspirate volume,
vomiting, bowel distension, or
severe diarrhoea) or IAH;
3 FI and IAH; 4 abdominal
compartment syndrome
None
0 normal functioning;
1 (moderate) acalculous
cholecystitis or stress ulcer;
2 (severe) bleeding from
stress ulcer necessitating
transfusion of more than 2 units
RBC per 24 h, necrotizing
enterocolitis and/or
pancreatitis, and/or
spontaneous perforation of
gallbladder
None
Grading
Comment
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Rapid reduction of small-bowel enterocytic function
because of acute reduction of enterocyte mass and/
or acute dysfunction of enterocytes responsible for
decreased absorptive capacity and reduced
citrulline synthesis
None
None
Grading
AGI, acute GI injury; FI, feeding intolerance; GI, gastrointestinal; IAH, intra-abdominal hypertension; MODS, multiple organ dysfunction syndrome.
AGI [16]
Other
Definition
Intestinal failure
Term
Table 1 (Continued)
Comment
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Gastrointestinal system
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MCC 220208
Grade
Definition
No AGI
No malfunctioning of GI system
AGI grade I
AGI grade II
AGI grade IV
AGI, acute GI injury; GI, gastrointestinal; GRV, gastric residual volume; IAH, intra-abdominal hypertension; IAP, intra-abdominal pressure; MODS, multiple organ
dysfunction syndrome.
assessment of gastrointestinal symptoms is important in detecting the tip of the iceberg in the complex
mechanism of gastrointestinal failure.
Clinical assessment
Evaluation of the gastrointestinal tract is greatly
interfered by therapies applied in critically ill
patients. There is no consensus whether dysphagy
should be seen as a part of gastrointestinal dysfunction or not. We feel that this serious problem in
critically ill patients leading to aspiration of gastric
contents needs special attention, but should be
addressed separately from gastrointestinal dysfunction. Therefore, this issue is not further addressed in
the current review. Abdominal signs and symptoms
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Gastrointestinal system
Abdominal pathology
(e.g. trauma, surgery)
Inflammatory response 1
Recovery
distension, emesis, diarrhoea, or subjective discomfort) [51 ]. Using this definition, feeding intolerance
was observed in 30.5% of mechanically ventilated
patients staying in ICU for at least 72 h and its
development was associated with impaired outcomes [51 ]. However, the likelihood of resulting
in discontinuation of enteral nutrition is probably
very different between vomiting, diarrhoea, and
discomfort.
In the future, a consensus on definition of
feeding intolerance should be reached. The issue
is complicated as completely different approaches
are needed to address intolerance to feeding in
upper and lower parts of the gastrointestinal tract.
Therefore, we suggest to base this future definition
on the algorithm, possibly including stepwise application of theraputic measures (e.g. prokinetics and
postpyloric feeding).
Of note, feeding intolerance cannot be considered as the only equivalent of gastrointestinal
failure as its diagnosis requires a challenge of enteral
feeding, whereas gastrointestinal failure should
be possible to be diagnosed also independent of
feeding.
&
&
Severe illness
Non-abdominal
pathology
Hypoperfusion
Resuscitation
Vasopressors
Fluids
Secondary injury to
GI system
Inflammatory response 2
Loss of barrier
Sepsis
Ischaemia/reperfusion
edema
Recovery
Inflammatory response 3
MODS
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Intra-abdominal pressure
Intra-abdominal pressure (IAP) is not a direct reflection of gastrointestinal function. On the other hand,
increased IAP may reduce blood flow to intraabdominal organs, including the gastrointestinal
tract, with consequent functional impairment
[52]. Simplicity and relatively well validated
measurement technique of IAP via the bladder fosters its application [40]. Gastrointestinal symptoms
occur more frequently in patients with increased
IAP, whereas the direction of this relationship is
unclear [53]. Few attempts have been made to
incorporate IAP values in scoring systems for gastrointestinal dysfunction/failure [10,54]. The role of
IAP in routine assessment/monitoring of gastrointestinal failure remains to be clarified in large-scale
prospective studies.
Radiological imaging
Static radiological imaging (ultrasound, abdominal x-ray, computed tomography, or magnetic
resonance imaging) allows detecting structural
changes, which could be linked with functional
disturbances. Dynamic studies require specific
complex investigations, but may give valuable
information on motility. There are no clear recommendations when which specific imaging technique should be used, but some suggestions are
provided in Table 3.
Volume 22 Number 00 Month 2016
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Occurrence of any visible
regurgitation of gastric content
irrespective of the amount [16]
Absence of stool for three or more
consecutive days without
mechanical obstruction [16].
No consensus
Lower GI paralysis
Bowel dilatation
848% [31,32]
Not known
Vomiting/regurgitation
Hyperperistalis
Not known
3841% [11,30]
Not known
5963% [29,30]
Abdominal discoloration
521% [11,2931]
Tympany on percussion
suggesting increased content of
air in the abdomen. Observerdependent
Tympany on percussion
Not known
Prevalence in ICU
Abdominal distension
Application/importance
Gastrointestinal symptoms
Abdominal pain
Clinical assessment
Definition/s
Table 3. Recommendations for assessment of gastrointestinal function in clinical practice and management suggestions in ICU patients
If concomitant abdominal
distension and pain >
consider imaging and measure
IAP
Management
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IAP >20 mmHg together with new
or worsening organ failure [40]
Abdominal compartment
syndrome
Free air/fluid
Intra-abdominal hypertension
IAP
Feeding intolerance
Large GRV
Diarrhoea
Measurement of GRV
Definition/s
GI bleeding
Table 3 (Continued)
Application/importance
14% [4244]
2040% [4144]
275% [39]
9% with proposed definition [32]
1421% [37,38]
Prevalence in ICU
Management according to
specific GI symptom
Gastroparesis: prokinetics
(metoclopramid and
erythromycin) and postpyloric
feeding
Lower GI paralysis bowel
dilatation: see above
200500 ml at single
measurement -> continue
regular measurements
>500 ml -> reduce/stop EN [16]
Management
MCC 220208
Gastrointestinal system
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None unless bowel distension
ACS, abdominal compartment syndrome; EN, enteral nutrition; GI, gastrointestinal; GRV, gastric residual volume; IAP, intra-abdominal pressure; PPI, proton pump inhibitor; WSACS, the Abdominal Compartment
Society.
Individual interpretation
Individual interpretation
Intestinal pneumatosis
Management
Prevalence in ICU
Application/importance
Warrants immediate caution
Definition/s
Decreased/interrupted
mesenteric blood flow
Table 3 (Continued)
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Gastrointestinal system
Yes
GI symptoms ?
No
AGI I
Yes
AGI II
No
Diarrhoea
GI symptoms ?
Metoclopramid
Erythromycin
No
No AGI
Persisting feeding
intolerance
Consider postpyloric EN
EN tolerated ?
Condition improving?
No
AGI III
Intervention is needed
Consult surgeons, gastroenterologist, radiologists
Stop EN, insert/open nasogastric tube
Consider
Endoscopy (to stop bleeding or decompress)
Interventional radiology to stop bleeding or
drain fluid collections
Laparotomy
Stop laxatives
and prokinetics
Find trigger37
Exclude or treat
C. difficlle
Check
anamnesis
medications
Consider
malassimilation
Lower GI paralysis
Consider laxatives
Measure IAP
Bowel distension
Consider
Neostigmine
Supportive therapy
Specific after diagnosis
Continue EN
AGI IV
Yes
FIGURE 2. Assessment and management of different grades of acute gastrointestinal injury (AGI). AGI I, increased risk
of developing gastrointestinal dysfunction or failure; AGI II, gastrointestinal dysfunction; AGI III, gastrointestinal failure; AGI IV,
manifesting gastrointestinal failure, life-threatening. ACS, abdominal compartment syndrome; CT, computed tomography; EN,
enteral nutrition; FI, feeding intolerance; GRV, gastric residual volume; IAP, intra-abdominal pressure; PPI, proton pump
inhibitor; WSACS, The Abdominal Compartment Society.
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&
Laboratory markers
Diamine oxidase has been proposed as a specific
marker for gut mucosal damage because the enzyme
seems to be preferentially located in intestinal
mucosa. However, values in patients with and without suspected damage overlap widely [23].
Similarly, intestinal fatty acid-binding protein
(I-FABP) is supposed to be expressed exclusively in
the epithelium of the gastrointestinal tract. Recent
studies demonstrated significantly higher I-FABP
concentrations in patients with mesenteric ischaemia compared to patients with acute abdomen and
preserved gut perfusion [65,66]. Although specificity was 100% and sensitivity 90% for the proposed
cut-off value, both D-dimer and leukocyte reached
the same percentages as I-FABP. In patients with
acute abdomen without mesenteric ischaemia, both
specificity and sensitivity for I-FABP were below 80%
when compared with control study participants and
worse than the percentages for D-dimer and leukocyte counts [65].
Management
Management of gastrointestinal failure is based on a
complex clinical assessment, optimizing organ perfusion, and treatment of specific gastrointestinal
symptoms.
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FUTURE RESEARCH
Missing description of normal gastrointestinal function in ICU patients and subjectivity in clinical
assessment results in difficulties to define study
endpoints and outcome measures. International
collaboration is warranted to reach consensus on
how to plan the future research in this field.
CONCLUSION
Defining gastrointestinal failure in ICU patients
remains challenging. A validated scoring system
describing a continuum of this organ dysfunction
still needs to be developed to allow proper conduction of interventional studies. Until then, daily
clinical assessment of gastrointestinal symptoms
and syndromes should be applied. For this, we
recommend using terminology, definitions and
grading of acute gastrointestinal injury. The care
of these patients should be based on a systematic
management approach.
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Acknowledgements
None.
Financial support and sponsorship
This work was supported by the Ministry of Education
and Research of Estonia (IUT3424).
Conflicts of interest
A.R.B. has received honoraria for advisory board
participation from Fresenius Kabi, Nestle and Nutricia.
S.M.J.: The Department of Intensive Care Medicine,
Inselspital Bern, has, or has had in the past, research
contracts with Abbott Nutrition International, B. Braun
Medical AG, CSEM SA, Edwards Lifesciences Services
GmbH, Kenta Biotech Ltd, Maquet Critical Care AB, and
Omnicare Clinical Research AG; and research & development/consulting contracts with Edwards Lifesciences SA,
Maquet Critical Care AB, Nestle and Orion Pharma. The
money is/was paid into a departmental fund; S.M.J. does
not/did not receive any personal financial gain. The
department has received unrestricted educational grants
from the following organizations for organizing a quarterly postgraduate educational symposium, the Berner
Forum for Intensive Care: Fresenius Kabi; GSK; MSD;
Lilly; Baxter; Astellas; AstraZeneca; BjBraun; CSL Behring; Maquet; Novartis; Covidien; Mycomed; RobaPharma; Orion Pharma. J.S. has received honoraria for
advisory board participation from B. Braun Melsungen
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