562841

research-article2014
NCPXXX10.1177/0884533614562841<italic>Nutrition in Clinical Practice</italic> X(X)Elke et al

Invited Review
Nutrition in Clinical Practice
Volume XX Number X
Gastric Residual Volume in Critically Ill Patients: A Dead Month 201X 1­–13
© 2014 American Society
Marker or Still Alive? for Parenteral and Enteral Nutrition
DOI: 10.1177/0884533614562841
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Gunnar Elke, MD1; Thomas W. Felbinger, MD2; and Daren K. Heyland, MD3

Abstract
Early enteral nutrition (EN) is consistently recommended as first-line nutrition therapy in critically ill patients since it favorably alters
outcome, providing both nutrition and nonnutrition benefits. However, critically ill patients receiving mechanical ventilation are at risk
for regurgitation, pulmonary aspiration, and eventually ventilator-associated pneumonia (VAP). EN may increase these risks when
gastrointestinal (GI) dysfunction is present. Gastric residual volume (GRV) is considered a surrogate parameter of GI dysfunction during
the progression of enteral feeding in the early phase of critical illness and beyond. By monitoring GRV, clinicians may detect patients with
delayed gastric emptying earlier and intervene with strategies that minimize or prevent VAP as one of the major risks of EN. The value of
periodic GRV measurements with regard to risk reduction of VAP incidence has frequently been questioned in the past years. Increasing
the GRV threshold before interrupting gastric feeding results in marginal increases in EN delivery. More recently, a large randomized
clinical trial revealed that abandoning GRV monitoring did not negatively affect clinical outcomes (including VAP) in mechanically
ventilated patients. The results have revived the discussion on the role of GRV monitoring in critically ill, mechanically ventilated patients
receiving early EN. This review summarizes the most recent clinical evidence on the use of GRV monitoring in critically ill patients.
Based on the clinical evidence, it discusses the pros and cons and further addresses whether GRV is a dead marker or still alive for the
nutrition management of critically ill patients. (Nutr Clin Pract.XXXX;xx:xx-xx)

Keywords
gastric residual volume; pneumonia; critical illness; enteral nutrition; gastrointestinal transit; gastrointestinal motility; ventilator associated
pneumonia; respiratory aspiration

In critically ill patients who are unable to resume oral food
intake, artificial nutrition has evolved into a primary therapeu-
tic intervention with the aim to improve the outcome by attenu-
ating the stress-induced catabolic response and preventing
adverse outcomes related to nutrition deficits or preexisting
malnutrition. There is widespread agreement among interna-
tional nutrition guidelines that early enteral nutrition (EN)
should be preferentially used within the first 24–48 hours after
intensive care unit (ICU) admission in patients without an
absolute contraindication to EN.1–3 Apart from the nutrition
benefits, early EN is considered to maintain structural and
functional gut integrity, thus preventing increases in intestinal
permeability, and support the humoral immune system.4
However, the success of EN to favorably alter the outcome of
critically ill patients is inevitably dictated by the function of the
gastrointestinal (GI) tract.
Pathophysiology of GI Dysfunction During
Critical Illness
The GI tract has multiple functions, including digestion and
absorption of nutrients and fluids, mucosal barrier control to
modulate absorption of intraluminal microbes (and their prod-
ucts), and endocrine and immune functions.5 GI dysfunction,
including impaired gastric emptying and intestinal dysmotility,
is a common event during critical illness6,7 and can be both a
trigger and a consequence of the underlying disease or (multi)
organ failure, respectively. The pathophysiology of GI dys-
function is multifactorial and complex, involving inadequate
tissue perfusion and secretion, dysmotility,5,8–10 and a dysregu-
lated intestinal microbiota and host immune interaction.11
From the 1Department of Anesthesiology and Intensive Care Medicine,
University Medical Center Schleswig-Holstein, Campus Kiel, Kiel,
Germany; 2Department of Anesthesiology, Critical Care and Pain Medicine,
Neuperlach Medical Center, Munich, Germany; and 3Clinical Evaluation
Research Unit, Kingston General Hospital, Kingston, Ontario, Canada.
Financial disclosure: None declared.
Conflict of interest: GE has received speaker honoraria from Abbott, B
Braun, and Fresenius Kabi. TWF has received speaker honoraria from
Abbott, B Braun, Baxter, Fresenius Kabi, and Nutricia- Danone. DKH
has received research grants and speaker honoraria from Fresenius Kabi,
Baxter, and Biosyn.
Corresponding Author:
Gunnar Elke, MD, Department of Anesthesiology and Intensive Care
Medicine, University Medical Center Schleswig-Holstein, Campus Kiel,
Arnold-Heller-Str. 3 Haus 12, 24105 Kiel, Germany.
Email: gunnar.elke@uksh.de

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2 Nutrition in Clinical Practice XX(X)
The GI tract is one of the first organs to be affected by shock
and the last to be resuscitated if circulatory failure arises.12,13
Cytokine release during sepsis directly impedes intestinal
myocyte function and inhibits enteric neuromuscular transmis-
sion.14 Intestinal edema resulting from capillary leakage syn-
drome is another factor that influences GI function during
systemic inflammation. Dysregulation of important GI hor-
mones, including cholecystokinin, peptide YY, ghrelin, and
motilin, is also described as a contributor to GI dysfunction
during critical illness.15–18 Apart from these “intrinsic” mecha-
nisms, several “extrinsic” risk factors for GI dysfunction and
slow gastric emptying in particular are present in the ICU set-
ting, including the use of sedatives, opioids, and vasopressors;
hyperglycemia; and electrolyte abnormalities.6,8,19,20 The com-
position of the enteral formula and the method of administra-
tion (bolus vs continuous feeding) may also affect gastric
emptying patterns or intestinal transit time.21–25
Terminology and Epidemiology of GI
Dysfunction
Terminology
GI dysfunction comprises motility disorders that include a
delayed passage with slow gastric emptying and constipation
as well as an accelerated passage with impaired small intestinal
nutrient absorption or nutrition-related diarrhea, respec-
tively.8,26 The term feeding intolerance is frequently being used
as a synonym for GI dysfunction that generally indicates an
insufficient EN intake resulting from impaired gastroduodenal
motility and absorption.6,8,27 However, a clear definition of
either term is missing. The Working Group on Abdominal
Problems of the European Society of Intensive Care Medicine
(ESICM) has therefore developed consensus definitions and a
grading system of GI dysfunction (acute GI injury grades I–IV)
to provide a better clinical communication and comparison for
future clinical research.5
Epidemiology
In this respect, a recent systematic review of 33 studies high-
lighted the great variability of definitions used for feeding
intolerance.27 Three main categories were identified that were
most commonly used to describe feeding intolerance: (1)
“large” gastric residual volumes (GRVs), (2) the presence of
GI symptoms, or (3) inadequate delivery of EN. GI symptoms
included the presence of increased abdominal girth or disten-
sion, vomiting, diarrhea, or subjective discomfort.
Depending on what definition was being used, the preva-
lence of feeding intolerance varied markedly (range, 2%–75%;
pooled proportion of 38.3% [95% confidence interval (CI),
30.7%–46.2%]) among studies.27 Feeding intolerance was also
associated with increased length of ICU stay and mortality.
GRV (either alone or in combination with vomiting, diarrhea,
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and/or abdominal distension) was the main determinant for the
definition of feed intolerance in most studies. The median vol-
ume used to define a “large” GRV was reported to be 250 mL,
with a range from 75–500 mL. Interestingly, large GRVs were
defined most frequently based on only a single
measurement.27
A recent large observational cohort study in 1888 ICU
patients revealed that the incidence of feeding intolerance was
30.5% and already occurred, on average, within the first 3 days
from initiation of EN.28 Intolerance was defined by the inter-
ruption of EN due to a composite of large GRVs and GI symp-
toms, including abdominal distension, emesis, diarrhea, or
subjective discomfort. The presence of feeding intolerance was
associated with poorer nutrition adequacy, increased duration
of mechanical ventilation and length of ICU stay, and a trend
toward increased mortality. The highest rates of feeding intol-
erance were observed among patients with cardiovascular, GI,
and sepsis admission categories. This is in accordance with
previous reports,29–31 in which delayed gastric emptying was
found in almost 50% of mechanically ventilated patients and
up to 85% in certain diagnostic groups, including patients with
polytrauma, traumatic brain injury, and sepsis.
A close relationship between feeding intolerance (defined
solely on the presence of large GRV) and severity of illness
was also reported in a study of 61 ICU patients.32 GRVs were
generally higher in more severely ill patients and proportion-
ally correlated to an increase in the mean daily Sequential
Organ Failure Assessment (SOFA) score. Patients with
decreasing GRV had a lower ICU mortality compared with
patients without decreasing GRV.
Clinical Consequences of GI Dysfunction
Based on its nature and severity, GI dysfunction leads to a mul-
titude of subsequent clinical symptoms and complications.5
For the purpose of this review, main complications pertaining
to impaired GI motility involve regurgitation or vomiting of
gastric contents and consecutive risk of aspiration and ventila-
tor-associated pneumonia (VAP). Aspiration is also regarded
as the most serious side effect of EN. In this respect, the pres-
ence of a nasogastric tube (large size or diameter) and use of
noncontinuous feeding are among various risk factors for aspi-
ration that are summarized below.20,33–35
Major factors for macro- and microaspiration are as
follows:
•• Previous episode of aspiration
•• Neurologic deficit/decreased level of consciousness
(sedation, increased intracranial pressure)
•• Neuromuscular disease
•• Structural abnormalities of the aerodigestive tract/
endotracheal intubation
•• Vomiting
•• (Persistently) high GRV
Elke et al 3
•• Posture of patient (no head of bed elevation)
•• Impossible closure of vocal cords
•• Longitudinal folds in high-volume, low-pressure poly-
vinyl chloride cuffs
•• Underinflation of tracheal cuff
Additional risk factors are as follows:
•• Presence of a nasoenteric tube (large size and/or
diameter)
•• Malpositioned feeding tube
•• Noncontinuous or intermittent feeding
•• Abdominal/thoracic surgery or trauma
•• Delayed gastric emptying (diabetes, hyperglycemia
independent of diabetes, electrolyte abnormalities,
comedication known to reduce gastric emptying)
•• Age
•• Inadequate nursing staff
•• Patient transport
•• Zero positive end expiratory pressure
•• Low peak inspiratory pressure
•• Tracheal suctioning
•• Nasogastric tube
•• EN
Aspiration can be either silent or symptomatic depending
on the volume and type of material aspirated (micro- or [mul-
tiple] macroaspiration) and lead to a variety of pulmonary con-
ditions that can range from (noninfectious) pneumonitis to
pneumonia and acute respiratory distress syndrome in its most
severe form.20 Besides micro- and macroaspiration, risk factors
for VAP can be divided into patient-related variables, including
age (<1 or >65 years), impairment of the immune system (spe-
cific [ie, immunosuppression] or unspecific), severe neuro-
logic deficits, and preexisting pulmonary disease,34,36,37 as well
as intervention-related variables such as long-term intubation
and mechanical ventilation, reintubation, surgical procedures,
and the use of sedatives.34,35,38
Similar to the incidence of feeding intolerance, reports on
aspiration and VAP incidence are variable owing to the under-
lying definition and diagnostic test or criteria used. Thus, stud-
ies that look at VAP as a clinical end point are likely to have
considerable measurement error. However, aspiration and par-
ticularly microaspiration appear to be a common event in intu-
bated patients, with a range of 50%–75%.20 In mechanically
ventilated patients, the mean incidence density of VAP is
reported to be 5.44 cases per 1000 ventilator days,39 with an
absolute attributable mortality of 16% (range, 10%–47%).40–42
To reduce VAP rates and improve patient outcomes, a number
of preventative strategies that pertain to the gastropulmonary
route of infection are recommended. These include subglottic
secretion drainage tubes, head of the bed elevation, and small
bowel feeding tubes.43–45
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Monitoring GI Function
Given the reported frequencies of GI motility disorders and
evidence that development of GI problems is related to worse
outcome in critically ill patients, there is widespread agree-
ment that an evaluation of GI function and clinical examina-
tion of the abdomen should be performed on a regular
basis.2,46,47 This appears all the more important in the presence
of early EN.
Regular monitoring of GI function or tolerance respectively
pursues the following aims:
1. Early detection and treatment of GI dysfunction
2. Risk reduction and/or prevention of pulmonary com-
plications from aspiration
3. “Improved” management of EN
GRV
An elevated GRV is considered a surrogate parameter indicat-
ing GI motility disorders in general and slow gastric emptying
in particular.6,48 Monitoring GRV and holding or interrupting
EN for large or elevated GRV has had a firm place in the rec-
ommendations of critical care or nutrition guidelines within the
past years.2,47,49 It is also probably one of the most traditional
and widely accepted nursing practices in the ICU. A national
survey among the American Association of Critical Care
Nurses showed that more than 97% of the nurses reported mea-
suring GRV.50 The most frequently used threshold levels for
interrupting EN in this survey were 200 mL and 250 mL, while
about 25% used thresholds of 150 mL or less and only 12.6%
GRVs of up to 500 mL.
Methods of GRV Measurement
Two main approaches to measure GRV are principally used in
the ICU, either aspiration of the gastric content using a syringe
or gravity drainage into a reservoir. There is supposed to be a
high variability in the practice of measuring GRV since it has
rarely been standardized or validated.51,52 Table 1 summarizes
reasons that may influence the GRV measurement, including
investigator-related variables as well as tube-related factors.
A study by Metheny et al53 of 75 critically ill patients
showed that GRVs obtained from large-diameter sump tubes
are about 1.5 times greater than those obtained from 10-French
(Fr) tubes. In a recent simulated laboratory study, the accuracy
of GRV assessment via tube aspirations made from known vol-
umes was evaluated by controlling the syringe pull technique,
feeding tube properties (different size and material), fluid vis-
cosity, and placement of tubes in the fluid.54 Of 108 GRVs ana-
lyzed, the actual content was underestimated 19% on average
and varied across tube size and viscosity. Intermittent and slow
syringe pull techniques yielded greater aspirate quantities,
although neither technique aspirated the full amount of volume
4 Nutrition in Clinical Practice XX(X)

Table 1.  Factors That Influence Gastric Residual Volume Measurement.

Category Type
Tube related Type
length
Diameter
Side ports (number and size)
Position in the stomach
Collapse
Gastric access: transnasal or percutaneous
Methodology (gravity drainage/ Viscosity of residual content
syringe aspiration) Size and connection of syringe
Duration and time of procedure
Patient related Position of the patient
Intra-abdominal pressure
Comorbidities/comedications/exogenous fluids/“physiologic” gastrointestinal
secretions
Investigator related Individual performance (time and effort spent) of aspiration method
Time period enteral nutrition was stopped before measurement (fasting period)

available. Interestingly, the 10 Fr feeding tubes yielded larger
GRVs in more viscous fluid, while the 18 Fr tubes performed
better with fluids of lower viscosity.
Furthermore, physiologic fluid secretions of the GI tract
that may amount up to 5 L/d as well as exogenous contribu-
tions, including nutrition and water flushes for oral medica-
tions, for example, must be taken into account as constituents
to the quantity but also quality of GRV.55
Alternative Measurement Techniques
Other methods to detect delayed gastric emptying and assess
feeding intolerance include scintigraphy (as the “gold-stan-
dard” technique), paracetamol absorption test, breath tests,
refractometry, ultrasound, and gastric impedance monitoring
and were reviewed by Moreira and McQuiggan.56 Although
the authors concluded that refractometry may be the most
appropriate tool, the value of this method for clinical routine
remains questionable.57
Main disadvantages of these techniques in the ICU setting
are the unavailability at the bedside as well as the difficulty,
invasiveness, and time of the method to be performed. Soulsby
et al58 tested the validity of electrical impedance tomography
as a noninvasive and bedside-available tool for measuring gas-
tric emptying by changes in epigastric impedance. Their pre-
liminary study in healthy volunteers revealed that this method
showed patterns of gastric emptying over time but may not
provide an accurate estimate of gastric volume during continu-
ous enteral feeding. Ultrasound is probably the most attractive,
noninvasive, and clinically readily available technique that
probably outweighs some of the limitations described for GRV
measurement (eg, tube-related factors). In a study in healthy
volunteers, ultrasound assessment of the gastric antrum and
body provided qualitative information about gastric content
(empty or not empty) and its nature (gas, fluid, or solid).59
Perlas and coworkers60 further conducted a prospective quali-
tative and quantitative analysis of the gastric antrum in 200
fasted patients undergoing elective surgery. The authors pro-
posed a 3-point grading system based exclusively on qualita-
tive sonographic assessment of the gastric antrum that
correlated well with predicted gastric volume. They concluded
that this practice may be used for aspiration risk assessment but
yet requires validation in the ICU setting.
Notwithstanding these alternative strategies, the main
advantage of measuring GRV is the general simplicity of this
technique as a clinical indicator of gastric emptying.
Clinical Evidence on the Use of GRV
Monitoring
Observational Studies
In a prospective cohort study of 25 critically ill patients, gastric
emptying was measured using the very sensitive method of
scintigraphy as well as the 14C-breath test.48 Gastric emptying
of the liquid test nutrient was delayed in approximately 50% of
the patients and markedly delayed in about 20%. A cumulative
GRV already as low as 150 mL measured over 24 hours was
indicative of slow gastric emptying, with a reported sensitivity
of 0.636 (95% CI, 0.346–0.870) and specificity of 0.818 (95%
CI, 0.537–0.967). The positive predictive value was 0.778
(95% CI, 0.458–0.959), and negative predictive value was
0.692 (95% CI, 0.423–0.893).
Landzinski and coworkers61 evaluated gastric emptying in
30 ICU patients during gastric EN with limited GRV (tolerant
group, n = 10) vs patients with GRV ≥150 mL (intolerant

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Elke et al 5
group, n = 20) using the paracetamol absorption test. The intol-
erant group with elevated GRV during gastric EN had signifi-
cantly delayed gastric motility compared with the patients who
were deemed to be tolerating EN.
The frequency of risk factors for increased GRV and upper
digestive intolerance was evaluated in a prospective, observa-
tional study of 153 mechanically ventilated ICU patients (58%
surgical).62 GI intolerance was defined as a GRV between 150
and 500 mL on 2 occasions at 2 consecutive measurements, a
GRV >500 mL, or the presence of vomiting. 14-Fr nasogastric
tubes were used and GRV was measured by aspiration using a
50-mL syringe. Forty-nine patients (32%) presented increased
GRV after a median EN duration of 2 days, and 70 patients
(46%) presented upper digestive intolerance. High GRV was
identified as an early marker of upper digestive intolerance and
occurred significantly more often in patients on vasopressors
or sedatives. Patients with high GRV received a lower caloric
intake and vomited significantly more than patients with nor-
mal GRV. The incidence of nosocomial pneumonia was non-
significantly increased in patients with high GRV alone (40%
vs 28% in patients with normal GRV), whereas sedation, vom-
iting, and upper digestive intolerance could be identified as
independent risk factors. Upper digestive intolerance was also
independently associated with a longer ICU stay and a higher
ICU mortality.62
A small observational study by Umbrello et al63 examined
78 patients (26% surgical) and found no significant difference
in the VAP rate when using either vomiting plus GRV 150–500
mL (2 episodes) or GRV >500 mL (1 episode) as a definition
for feeding intolerance. However, the authors alluded to nei-
ther the definition of VAP nor the type/size of nasogastric tube
used in this study. All patients were placed in a semirecumbent
position.
In a single-center study, Metheny et al64 evaluated the effect
of pepsin-positive tracheal secretions as a proxy for the aspira-
tion of gastric contents on clinical outcomes in 360 critically ill
tube-fed patients (76% surgical). At least 1 aspiration event
was identified in 88.9% (n = 320) of the patients, and the inci-
dence of pneumonia (as determined by the Clinical Pulmonary
Infection Score) increased from 24% on day 1 to 48% on day
4. Patients with pneumonia on day 4 had a significantly higher
percentage of pepsin-positive tracheal secretions than did those
without pneumonia (42.2% vs 21.1%, respectively; P < .001).
A low backrest elevation, vomiting, and gastric feedings were
identified as independent risk factors for aspiration and pneu-
monia. Only 182 patients who were consistently fed in the
stomach were included in the analysis to determine the effect
of GRV on aspiration. No significant difference was found
between mean GRVs in the high- and low-aspiration groups.
However, the presence of 2 or more GRVs ≥200 mL was
observed more frequently in the high-aspiration group than in
the low-aspiration group (n = 15 vs n = 5). The high GRVs
were usually identified in patients with a large-bore feeding
tube.
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The same study group investigated 206 critically ill,
mechanically ventilated patients (73% surgical; Acute
Physiology and Chronic Health Evaluation II [APACHE II]
score of 23.3) receiving EN ≥3 days to describe the association
between GRV and aspiration of gastric contents in another pro-
spective study.65 Of the patients, 93% had aspirated at least
once during the study period. Although aspiration also occurred
in the absence of high GRV, it happened significantly more
often when GRV was high. Using an adjusted logistic regres-
sion model including multiple other risk factors for aspiration,
2 or more GRVs ≥200 mL or 1 or more GRV ≥250 mL were
still significantly predictive for aspiration. In this study, GRV
was measured with 60-mL syringes every 4 hours, and aspira-
tion was defined as pepsin-positive tracheal secretions. Of
note, nearly 60% of the GRV measurements were obtained
with larger bore feeding tubes in the range of 14–20 Fr.
Poulard et al66 conducted a 7-day prospective “before-after”
comparative single-center study over a 2-year period. In total,
205 ICU patients receiving nasogastric feeding within 48 hours
after intubation were included. GRV monitoring was per-
formed during the first study period (n = 102) but not during
the subsequent intervention period (n = 103). For both groups,
the same protocol for advancement toward EN target was used,
starting with continuous administration of EN at 25 mL/h and
increasing by 25 mL/h every 6 hours to the goal of 85 mL/h. In
the event of EN intolerance, defined as GRV >250 mL and/or
vomiting (control group) or only vomiting (intervention
group), EN was decreased to the previously well-tolerated rate
and erythromycin initiated. If no further intolerance occurred
over the next 6 hours, the rate was again increased by 25 mL/h.
All patients were put in a semirecumbent position (45°). No
differences in VAP (19.6% vs 18.4%, P = .86 in the control and
intervention groups, respectively) or in the rate of vomiting
(24.5% vs 26.2%, P = .87) were found. EN intolerance was
significantly less frequent in the intervention group (26.2%)
compared with the control group (46.1%). Of note, in the inter-
vention group, only 1 parameter (ie, vomiting) specifically
defined EN intolerance. Patients without GRV measurement
received only approximately 100 mL/d of EN more (1489
mL/d [1349–1647] vs 1381 mL/d [1151–1591]). Interestingly,
ICU mortality was 24.5% in the control (“before”) group and
35% in the intervention (“after”) group (P = .13), and hospital
mortality was 35.3% vs 42.7% (P = .32). This may be related
to differences in illness severity between the 2 groups but may
also indicate that the absence of GRV assessment increased
mortality independent of an effect on VAP. However, the study
duration was too short and the sample size too small to further
explore this potential signal of harm.
Main Limitations of the Observational Trials
The inherent limitation of these trials is the observational
design that cannot distinguish association from causation.
However, the large observational studies62,64,65 used robust
6 Nutrition in Clinical Practice XX(X)

Table 2.  Randomized Controlled Trials on the Use of Monitoring GRV.

Surgical
Study N Patients, % GRV Type/Size of Tube Methoda Primary End Pointb Main Result

GRV higher vs lower thresholds

Pinilla et al, 200168 96 (80 in final 50 >150 mL vs >250 NG: Aspiration every 4 h Frequency of GI No statistical
analysis) mLc 14–18 Fr: n = 41 intolerance: high difference, trend of
10 Fr: n = 25 GRV, emesis, or improved EN, and
n = 14: alternations diarrhea reduced time to reach
of the 2 sizes goal rate with GRV
>250 mLd
McClave et al, 200569  40 62.5 >200 mL vs >400 mL NG: n = 21 NA Frequency of No statistical difference
12 Fr: n = 19 regurgitation/
8 Fr: n = 2 aspiration
PEG: n = 19
Montejo et al, 201070 329 (322 17.2 >200 mL vs >500 NG: Gravity drainage Diet volume ratiog First week of ICU stay:
in final mLe <8 Fr: 3% for 10 min or mean EN volume
analysis) 8 Fr: 6% aspiration (50-mL ratio
10 Fr: 14.8% syringe)f 200 mL: 84.5%
12 Fr: 34% 500 mL: 88.2% (P =
>12 Fr: 42% .0002)
No between-group
difference after
second week
Monitoring vs not monitoring GRV
Reignier et al, 201371 449 NA (93% >250 mL vs no GRV NG: no size reported Aspiration (50-mL VAP No difference
medical) measurement syringe)
Regular vs variable time interval of monitoring GRV
Williams et al, 201472 357 NA (28% GRV aspiration 4 NG: 12–14 Fri Aspiration Number of gastric More tube aspirations
trauma) hourly (control) vs tube aspirations per day in the control
variable regimen per day group (5.4 vs 3.4
(up to 8 hourly, in the intervention
intervention)h group, P < .001)

All studies were performed in mechanically ventilated patients; no blinding was performed. EN, enteral nutrition; Fr, French; GI, gastrointestinal; GRV, gastric residual
volume; ICU, intensive care unit; NA, not available; NG, nasogastric; VAP, ventilator-associated pneumonia.
a
No information on how long EN was stopped before GRV measurement in all studies.
b
Only in the 2 latest studies (Montejo et al70 and Reignier et al71) was a true primary end point defined.
c
Patients in the higher GRV group mandatorily received prokinetic therapy.
d
Neither VAP nor mortality data analyzed.
e
All patients mandatorily received metoclopramide (10 mg every 8 hours) intravenously as a prophylactic prokinetic therapy during the first 3 days of EN.
f
No significant between-group difference was detected in the method used.
g
Diet volume ratio (%) calculated as (administered volume of diet/prescribed volume) × 100.
h
GRV was returned if the volume was ≤300 mL.
i
Small bowel feeding was allowed in GI-intolerant patients, but a gastric tube was also inserted for gastric decompression and aspiration.

statistical methodology to adjust for important confounding
variables.
With respect to the study by Poulard et al,66 the unblinded
before-and-after study design had a high likelihood that the study
team in the single center tended to perform differently throughout
the second study period (“Hawthorne effect”).67 So, for example,
both vomiting and VAP could have been unconsciously (or even
consciously) underreported in the intervention group.
Randomized Controlled Trials: Higher vs
Lower GRV Threshold
Table 2 gives an overview on important study characteristics of
the available 5 randomized controlled trials (RCTs) to date
comparing higher vs lower GRV thresholds (n = 3), not moni-
toring vs routine monitoring GRV (n = 1), or comparing regu-
lar vs variable time interval of monitoring GRV (n = 1).
In the “first” prospective study by Pinilla and coworkers,68
96 ICU patients were randomized to 2 feeding protocols with a
GRV threshold of 150 mL or 250 mL and mandatory prokinetic
therapy. The incidence of feeding intolerance, defined as epi-
sodes of high GRV, emesis, or diarrhea, was significantly lower
in the latter group, but the amount of EN and the time to reach
the target EN rate were not significantly different between the
2 groups. Clinical outcome measures, including VAP rate, were
not measured in this early study.
The prospective RCT by McClave and colleagues69 included
40 critically ill patients receiving mechanical ventilation and
EN. The validity of GRV as a marker of aspiration was evaluated
by using colored microspheres and food coloring added to the
nutrition formula. Patients were randomized to 2 management
strategies using a GRV threshold of either >200 mL or >400 mL.
Both regurgitation (mean frequency 31%) and aspiration (mean
frequency 22%) occurred frequently, which was likely due to the

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Elke et al 7
use of the sensitive techniques. Definitive pneumonia, as defined
quantitatively by an endotracheal, bronchoalveolar lavage or
protected specimen brushing culture, occurred in 50% of the
study patients. Neither was there a difference in regurgitation/
aspiration and pneumonia between the 2 GRV cutoff levels nor a
relationship between GRV and aspiration/regurgitation and
pneumonia, respectively. The positive predictive value of a high
GRV and aspiration was in the range of 18%–25%, whereas the
negative predictive value (low GRV and no aspiration occurred)
was around 77%. Notably, the frequency of regurgitation and
aspiration was less with percutaneous endoscopic gastrostomy
compared with nasogastric tube (size 8–12 Fr).
The REGANE (Gastric Residual Volume During Enteral
Nutrition in ICU Patients) study by Montejo et al70 was an open,
prospective RCT in 28 ICUs in Spain and compared the effects
of 200 mL (control group) vs 500 mL GRV (study group) on the
adequacy of EN (primary end point). Secondary end points
were the frequency of GI complications (macroaspiration, vom-
iting, abdominal distension, diarrhea) and outcome measures,
including pulmonary aspiration, pneumonia, days on mechani-
cal ventilation, length of ICU stay, day 5 and final SOFA score,
and ICU and hospital mortality. No study-specific EN protocol
was established, but investigators were requested to follow
national nutrition guideline recommendations. However, the
choice of nutrition requirements and type of enteral formula
diet were left at the discretion of each investigator, and EN was
established via a nasogastric tube in all patients.
Of 329 intubated and mechanically ventilated adult ICU
patients who were randomized, 322 patients (n = 165 in the con-
trol group and n = 157 in the study group) could be finally ana-
lyzed. Most patients were medical (83%). Patients in the study
group received significantly more EN during the first week of the
ICU stay and also at day 12. The frequency of GI complications
was higher in the control group (63.6% vs 47.8%, P = .004), but
the difference appeared to be due only to the frequency of high
GRV. The rate of other predefined GI complications, including
abdominal distension, vomiting, diet regurgitation, or diarrhea,
was not significantly different between groups. Also, the methods
used for GRV measurement (gravity drainage or aspiration) were
similar. The incidence of “ICU-acquired pneumonia”’ (defined as
the presence of a new or progressive radiographic infiltrate and at
least 2 of the 3 following clinical features: temperature higher
than 38°C, leukocytosis or leukopenia, and purulent secretions)
was 45 (27.3%) in the control group and 44 (28.0%, P = .88) in
the study group. However, adjudication of pneumonia was not
blinded, and no microbiological confirmation was required.
There were also no significant between-group differences in any
of the other outcome variables.
Not Monitoring vs Routine Monitoring GRV
The NUTRIREA1 (Study of Impact of Not Measuring Gastric
Residual Volume on Nosocomial Pneumonia Rates) trial by the
French Clinical Research in Intensive Care and Sepsis (CRICS)
group is the largest and so far the only RCT that has tested the
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hypothesis that the risk of VAP is not increased when GRV is not
monitored compared with routine GRV monitoring.71 This study
was a noninferiority, open-label, multicenter RCT conducted in 9
ICUs in France. In total, 449 patients receiving invasive mechan-
ical ventilation (>48 hours) and early EN (started via a nasogas-
tric tube within 36 hours) were included. In the intervention
group (no GRV monitoring), EN was adjusted only in the case of
vomiting, defined as gastric contents in the oropharynx or outside
the mouth, including regurgitation. In the control group (GRV
monitoring), EN intolerance was diagnosed by vomiting, a GRV
>250 mL measured every 6 hours by aspiration, or both with sub-
sequent adjustment of EN. In both groups, an aggressive feeding
protocol was used, whereby EN was started at goal rates and
titrated down when predefined EN intolerances occurred. All
patients were placed in a semirecumbent position (30°–45°) and
received oral care every 6–8 hours with chlorhexidine solution.
The primary outcome was the proportion of patients with at
least 1 VAP episode within 90 days after randomization (VAP
defined as progressive infiltrates on the chest radiograph with at
least 2 of the following criteria: leukocytosis, leukocytopenia,
body temperature ≥38.5°C or ≤35.5°C, and purulent tracheal aspi-
rates plus positive microbiological data). In contrast to the Poulard
et al study,66 VAP was now adjudicated by a committee blinded to
patient group assignment. In the intention-to-treat (ITT) analysis,
no significant differences in the VAP rate were detected (16.7% in
the intervention group vs 15.8% in the control group; difference,
0.9%; 90% CI, –4.8% to 6.7%). There were also no significant
between-group differences with regard to secondary end points,
including other ICU-acquired infections, diarrhea, duration of
mechanical ventilation, ICU stay length, or mortality rates.
The proportion of patients receiving 100% of their calorie
goal was higher in the intervention group (odds ratio [OR],
1.77; 90% CI, 1.25–2.51; P = .008), leading to a lower cumula-
tive energy deficit within the first week of ICU stay (median
319 kcal in the control group vs 509 kcal in the intervention
group). However, the clinical significance of a median differ-
ence of 111 kcal within the first week (around 15 kcal/d) is
questionable. Significantly more patients vomited in the inter-
vention group than in the control group (39.6% vs 27.0% in the
modified ITT analysis and 41.8% vs 26.5% in the per-protocol
analysis, respectively), and the total number of vomiting epi-
sodes was also higher in the intervention group (modified ITT:
OR, 1.86 [90% CI, 1.32–2.61], P = 0.003; per protocol: OR,
1.93 [90% CI, 1.36–2.75], P = .002). Not surprisingly, the
number of patients meeting the group-specific definition of EN
intolerance was higher in the control group (GRV plus vomit-
ing vs only vomiting in the intervention group), and thus more
patients received prokinetic therapy (65.3% in the control vs
41.4% in the intervention group, modified ITT analysis).
Regular vs Variable Time Interval of
Monitoring GRV
Williams et al72 recently conducted the first prospective, mono-
center RCT in 357 ICU patients comparing a regime of regular
8 Nutrition in Clinical Practice XX(X)
tube aspirations (every 4 hours, control group) with variable
aspirations of up to 8 hours (intervention group). The number
of tube aspirations performed per day (primary outcome) was
significantly higher in the control group (5.4 vs 3.4 in the inter-
vention group). With respect to secondary outcomes, the rate
of vomiting/regurgitation was increased in the intervention
group (3.6% vs 2.1%, P = .02). No significant differences were
found in the VAP rate (14.1% vs 13.2% in the control and inter-
vention groups, respectively), which were defined as tempera-
ture >38.5°C or <35°C or leukocytosis or leukocytopenia plus
changes in sputum, clinical worsening of respiration patterns
or gas exchange, isolation of pathogenic bacteria from endotra-
cheal aspirate (2 criteria), and a new radiographic infiltrate on
1 x-ray (reviewed by an intensivist). Despite the higher fre-
quency of aspirations in the control group, the nutrition intake
was similar between the groups.
Main Limitations of the RCTs
A clear limitation of the early RCT by McClave et al69 and the
RCT by Pinilla et al68 is the small sample size. Moreover,
McClave and coworkers were unable to evaluate the quantity
(ie, volume) of aspirate, which may have better correlated with
pneumonia.69
The main limitation of the REGANE70 and NUTRIREA1
trials71 is that patients at high risk for feeding intolerance,
including surgical patients and patients with shock, were not
truly represented. In the REGANE study, only 12 patients
(8.1%) had a surgical admission diagnosis, whereas 32 patients
(7%) were not medical in the NUTRIREA1 study, and abdomi-
nal surgery was defined as an exclusion criterion. In addition,
the sample sizes were underpowered for mortality and length
of stay measures, which also applies to the monocenter RCT
by Williams and coworkers.72 Thus, the external validity and
generalizability of the results to surgical and also to sicker,
multiorgan failure patients are compromised.73,74 Due to the
unblinded design, an inherent risk of the aforementioned
Hawthorne effect cannot be ruled out in all RCTs as well. All
patients in the REGANE study received metoclopramide for
prophylactic prokinetic therapy, which is not consistent with
practice patterns worldwide, as recently reported.28 In addition
to the aforementioned limitation regarding VAP as a clinical
end point, not using motility prokinetic agents prophylactically
may not achieve the same risk/benefit from increasing the
GRV and further limits the generalizability of the results.
Systematic Reviews
A first systematic review by McClave and Snider75 more than
a decade ago concluded that GRV appears not to be a clinically
reliable marker to protect patients against aspiration pneumo-
nia since no strong correlations could be found between GRV
and gastric emptying, volume of gastric contents, or regurgita-
tion/aspiration.
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Another systematic review was recently published by
Kuppinger and coworkers.76 A total of 12 prospective studies,
of which 6 were RCTs and 6 were observational studies exam-
ining specific end points related to either GI complications or
aspiration/pneumonia, were identified, most of which were
described above. Only the REGANE70 and NUTRIREA171
RCTs were rated as high-quality studies. The authors of this
review pointed out that a meta-analysis of the existing RCTs
was not feasible due to the heterogeneity in outcome measures
(VAP diagnosis), target population, and differences in GRV
measurement methods. However, they concluded that monitor-
ing of GRV appears unnecessary to guide nutrition in mechani-
cally ventilated patients with a medical ICU admission
diagnosis, while surgical patients might still benefit from a low
GRV threshold set at 200 mL.
Pros and Cons of Monitoring GRV
Based on the cumulative evidence from both observational
studies and RCTs, the significance and clinical relevancy of
routine GRV monitoring in critically ill patients have been
questioned frequently.67,77,78 In light of the findings from the
NUTRIREA1 trial,71 the “end of an era” was even heralded for
GRV monitoring.79 In the following, the pros and cons of GRV
monitoring are highlighted to summarize the main findings of
the available clinical data.
Pros: Advantages of GRV Monitoring
•• GRV provides a simple method of monitoring GI
dysfunction.
○ Apart from just the volume, the color and consis-
tency of the gastric residual content may add value
to the clinical significance of monitoring GRV (eg,
bilious or green color in the presence of duodeno-
gastric reflux or blood-stained/hemorrhagic reflux
as an early sign of GI bleeding). The detection of
undigested tube feed via GRV during small intesti-
nal feeding is often indicative of tube dislocation
in clinical practice. However, studies are not avail-
able that specifically looked at the quality of GRV,
and none of the aforementioned RCTs alluded to
this additional aspect.
•• Clinicians may detect patients with delayed gastric
emptying earlier and intervene with strategies that
minimize the clinical consequences of GI
dysfunction.
•• The high prevalence and reported adverse outcomes of
GI dysfunction and delayed gastric emptying per se jus-
tify measurement of GRV, particularly in high-risk
patients (surgery, sepsis, trauma category).
•• Based on observational studies,
Elke et al 9
○ GRV >150 mL is already indicative of slow gastric
emptying and vomiting.
○ 2 or more GRVs ≥200 mL or 1 or more GRV ≥250
mL are independent risk factors for aspiration.
○ the combination of GRV, vomiting, and/or clinical
GI symptoms increases the predictability of pul-
monary complications.
•• The 2 available RCTs showing no benefit of higher vs
lower GRV threshold or not monitoring at all provided
evidence only for medical patients and underrepre-
sented those high-risk patients who have the highest
prevalence for GI dysfunction. Furthermore, these
RCTs used experienced nursing staff and standardized
protocols that implemented concepts to minimize the
risk of pulmonary complications, including head of bed
elevation and regular oral decontamination. Instead, in
the “GRV-positive” observational studies, most patients
were surgical, and no strict protocols were used, reflect-
ing more “real-life” data.
•• To abandon GRV may take a lot of effort to see that
nurses consistently do the right thing (use appropriately
in select patients). The least path of resistance that will
guarantee safety in all patients is to keep doing it in all
patients. Protocols, particularly feeding protocols, are
designed to be applied to a broad group of heteroge-
neous patients. From an implementation point of view,
designing a feeding protocol to have GRV assessments
performed in some but not all patients may not be ideal
except for an exclusively medical unit with low inci-
dence of GI disorders.
Cons: Disadvantages of GRV Monitoring
•• The practice of measuring GRV is neither standardized
nor validated, and GRV alone does not correlate with
radiologic abdominal findings or was shown only to be
indicative of slow gastric emptying in observational
studies of small sample size.
•• The method itself is invalidated and lacks reproducibil-
ity by several determinants, including patient-, tube-,
and technique-related variables.
•• Available large RCTs consistently showed no beneficial
effect of GRV monitoring.
○ The fact that even a higher rate of vomiting was not
associated with higher rates of VAP supports uncer-
tainties related to the pathomechanisms and sug-
gests that the oropharyngeal route is more important
than the gastropulmonary route for aspiration and
subsequent pulmonary complications.43,80
•• GRV monitoring
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○ has been frequently considered one of the main
reasons for EN discontinuation,81 impeding ade-
quate EN and thereby promoting underfeeding.
However, the aforementioned RCTs revealed that
the gains in nutrition adequacy are rather trivial
and under conditions of mandatory prokinetic
therapy.70,71 Moreover, more recent data support
the notion that interruptions for diagnostic or ther-
apeutic procedures are the leading cause for EN
interruptions, not a high GRV.82
○ may consume valuable nursing time and allocation
of healthcare costs.83
○ is associated with higher incidence of tube
clogging.84
Current Guideline Recommendations
So how do current (inter)national guidelines interpret the avail-
able evidence on the role of GRV? Table 3 provides an over-
view on the currently available recommendations on the use of
GRV. Among these, the Canadian Practice Guidelines1 and the
guidelines from the German Nutrition Society85 are the most
up to date and already have considered the results from the
NUTRIREA1 trial. The Canadian guidelines committee stated
that a recommendation to abandon the practice of GRVs and
use a 500-mL or higher threshold was premature, based on lim-
ited external validity of the existing trials. A GRV threshold
range of 250–500 mL was recommended.
In contrast, the German nutrition society recommends in
their latest S3 guideline update that a concept of not monitor-
ing GRV should be applied to patients with a medical diagno-
sis, provided that the ICU team can safely handle such a
strategy (grade A, strong consensus).85 In these patients, EN
delivery rate should be modified if vomiting occurs. The posi-
tive concomitant effect would be the reduction on nurses’
workload. Given the fact that surgical patients were underrep-
resented in the aforementioned RCTs, the German society still
recommends that in (abdomino)surgical patients, GRV should
be measured regularly, and a threshold of 200 mL should be
considered to adjust the EN delivery rate.
Role of the EN Strategy
The decision to use GRV as a (complementary) indicator of GI
dysfunction and EN intolerance may depend not only on the
patient characteristics but also on the nutrition strategy pur-
sued. Two strategies for “targeted or goal-directed” EN,
respectively, exist: (1) the traditional rate-based feeding
(“ramp-up”), in which the total 24-hour goal volume is divided
into an appropriate hourly rate delivered throughout the day
and interruptions in delivery result in lost volume, or (2) a
more aggressive approach in which patients are started right on
the maximal hourly rate (“top-down” approach). In this latter
10 Nutrition in Clinical Practice XX(X)
Table 3.  Current Guideline Recommendations on the Use of GRV Monitoring.
Guidelinesa DGEM 201385
GRV For patients, especially those who are
admitted with a medical diagnosis, units
that can safely handle a concept of not
monitoring GRV should do so, thereby
reducing nurses’ workload. EN delivery rate
should be modified in the event of vomiting
(A; strong consensus).
In (abdomino)surgical patients, GRV should
be measured regularly (every 4–6 hours),
and a threshold of 200 mL should be
considered to adjust the EN delivery rate.
If threshold is reached, the EN delivery rate
should be modified (strong consensus).
The use of lower GRV thresholds is
unnecessary.
A.S.P.E.N., American Society for Parenteral and Enteral Nutrition; CCPG, Canadian Clinical Practice Guidelines; DGEM, German Society for
Nutritional Medicine; EN, enteral nutrition; GRV, gastric residual volume.
a
No specific information on the use of GRV monitoring in the currently available ESPEN (European Society for Clinical Nutrition and Metabolism)
guidelines on EN in intensive care medicine.3,47
approach, several strategies have been bundled together to
maximize the likelihood of success with early EN, such as
24-hour volume-based feeds and prophylactic motility agents
and protein supplements, and is known as the PEPuP (Enhanced
protein-energy provision via the enteral route feeding)
protocol.86–88
In the RCT by Reignier et al,71 an aggressive “top-down”
EN protocol was used, starting directly at goal rate and decreas-
ing gradually in the event of predefined intolerances. The
absence of GRV monitoring was associated with improved EN,
although differences in caloric deficit within the first week
were moderate. As the protocol was not volume based, any EN
solution lost by vomiting, being discarded, or both was neither
measured nor could be returned, thus even resulting in poten-
tial overestimation of delivered calories. These factors may
have attenuated any mortality difference related to differences
in delivered EN volume.
Desachy et al89 randomized 100 mechanically ventilated
ICU patients to either a “top-down” or “ramp-up” strategy of
early EN, starting within 24 hours following intubation. Flow
rates of the nutrition solution (25-mL/h increments or decre-
ments) were adjusted according to GRV (threshold of 300 mL),
measured every 8 hours. The “top-down” strategy led to a sig-
nificant improvement in actual calorie supply (95% vs 76% of
optimal calorie intake). High GRV (>300 mL) was signifi-
cantly more frequent in the “top-down” group, with no differ-
ences in the frequency of defined adverse events, including
colectasia, vomiting, regurgitation, or aspiration. A limitation
was that aspiration was only clinically suspected, and occur-
rence of aspiration pneumonia was not studied. Here, GRV suf-
ficiently guided the aggressive EN strategy and did not impede
delivery, as was the case in the recent multicenter cluster RCT
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CCPG 20131 A.S.P.E.N. 20092
There are insufficient data to Holding EN for gastric residual
make a recommendation for volumes <500 mL in the
not checking GRVs and for absence of other signs of
establishing a specific gastric intolerance should be avoided
residual volume threshold. (grade B).
Based on 1 level 2 study, a gastric
residual volume of either 250
or 500 mL (or somewhere in
between) is acceptable as a
strategy to optimize delivery of
EN in critically ill patients.
in 1059 critically ill patients in whom the effect of the PEPuP
protocol, combined with a nursing educational intervention on
nutrition intake, was compared with standard care.82
While current nutrition guidelines widely agree that early
EN is beneficial,1–3 the fundamental question on the optimal
dose of EN and corresponding nutrition strategy to be used,
particularly in the acute phase of illness, remains
controversial.90–96
The recent large EDEN (Early vs Delayed Enteral Feeding to
Treat People With Acute Lung Injury or Acute Respiratory
Distress Syndrome) RCT randomized 1000 patients with acute
lung injury to an initial strategy of trophic feeding within the first
6 days of ICU stay or full enteral feeding.97 No significant differ-
ence in clinical outcomes was found, including duration of
mechanical ventilation, infectious morbidity, and mortality,
between the 2 strategies. However, the full-feeding group experi-
enced more vomiting (2.2% vs 1.7% of patient feeding days; P =
.05), more elevated GRV defined by a threshold of >400 mL
(4.9% vs 2.2% of feeding days; P < .001), and constipation (3.1%
vs 2.1% of feeding days; P = .003), despite receiving more proki-
netic agents. No between-group differences were observed in the
rates for diarrhea, aspiration, or abdominal distension or cramp-
ing. In the full-feeding group, EN was initiated at 25 mL/h and
advanced to goal rates as timely as possible according to the
GRV, which was checked every 6 hours while EN was increased.
In summary, if the individual nutrition strategy consists of ini-
tial trophic feeding or slow advancement of EN for whatever rea-
son, GRV monitoring may be disclaimed more confidently, or at
least the time interval of measurement can be extended. In the
setting of goal-directed EN using a volume-based feeding strat-
egy, for example, GRV should still be considered, especially in
the initial phase and in patients at high risk for EN intolerance.
Elke et al 11
Conclusions
We have learned from recent large RCTs on ICU nutrition97–99
that not all ICU patients are the same and that a global nutrition
strategy is not applicable according to the “one size fits all”
principle.100 This also holds true for metabolic and GI monitor-
ing as an integral part of nutrition management. The emerging
concept of “personalized” nutrition therapy implies stratifica-
tion of the patient based on the individual risk profile and
inherent intraindividual and interindividual alterations in GI
function and metabolic changes throughout the disease
process.
So is GRV a dead marker for GI dysfunction or still alive?
It is dead probably in a medical ICU setting that fulfills criteria
of (1) an experienced nursing team and (2) an established stan-
dardized nutrition protocol including other safety criteria, such
as semirecumbent position and oropharyngeal hygiene mea-
sures, as was the case in the aforementioned RCTs, as well as
proactive risk reduction strategies (prophylactic prokinetic
therapy, jejunal feeding).
We submit that GRV is still alive, however, in a patient
population at high risk for GI dysfunction (ie, in particular sur-
gical ICU and most severely ill patients), given the main limi-
tations of the available RCTs and signals from robust
observational studies. To improve the validity of the measure-
ment, one may consider standardization of the (aspiration)
technique and use larger bore feeding tubes. Finally, in light of
the reported high incidence of GI dysfunction and associated
adverse outcomes in these patient categories and the lack of
alternative clinically useful measures, GRV should still be
regarded as one piece in the puzzle of monitoring GI function.
Given that feeding protocols should be designed to be as safe
as possible in the widest range of patients, we would err on the
side of retaining GRV measurements in a feeding protocol
operational in multidisciplinary ICUs where such measure-
ments are the current standard of care.
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