594013

research-article2015
NCPXXX10.1177/0884533615594013<italic>Nutrition in Clinical Practice</italic> X(X)Pogatschnik and Steiger

Invited Review
Nutrition in Clinical Practice
Volume XX Number X
Review of Preoperative Carbohydrate Loading Month 201X 1­–5
© 2015 American Society
for Parenteral and Enteral Nutrition
DOI: 10.1177/0884533615594013
ncp.sagepub.com
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Cassandra Pogatschnik, RD, LD, CNSC1, and Ezra Steiger, MD, FACS, FASPEN1 online.sagepub.com

Abstract
Preoperative carbohydrate-containing clear liquids (usually composed of approximately 12% carbohydrate predominantly in maltodextrin
form) have provided benefits for the surgical population and further have been included in the Enhanced Recovery After Surgery (ERAS)
Society’s recommendations as part of a multimodal approach to reduce surgical patients’ length of stay and complication rates. Carbohydrate
metabolism is greatly affected by the fed state, which is activated by preoperative carbohydrate fluids given up to 2 hours prior to surgery
in contrast to the traditional midnight preoperative fast. Carbohydrate-rich fluids have been proven to enhance patient comfort prior to
surgery and have been theorized to reduce insulin resistance, reducing patient catabolism, with a positive impact on perioperative glucose
control and muscle preservation. This practice is further hypothesized to support the ERAS goals of reducing both complication rate
and length of stay. Preoperative carbohydrate fluid loading is difficult to prove, as the degree of surgical procedure and postoperative
pathways are likely more reflective of patient outcome. The use of carbohydrate-loading protocols warrants further adequately blinded,
placebo-controlled studies, including the use of variable surgical techniques, reproduction of the hyperinsulinemic euglycemic technique
measurements, investigation of ideal carbohydrate fluid composition, and the use of similar surgeries in comparison. Preoperative
carbohydrate loading is just one of the many strategies linked to the success of ERAS protocols. (Nutr Clin Pract.XXXX;xx:xx-xx)

Keywords
nutrition therapy; surgical procedures; preoperative care; perioperative period; fasting; carbohydrate metabolism

Many studies have shown the value of a comprehensive
perioperative approach to managing surgical patients known
as Enhanced Recovery After Surgery (ERAS).1 One of the
main nutrition-related elements of the ERAS Society’s strong
recommendations is that carbohydrate (CHO)–containing clear
fluids should be allowed up to 2 hours prior to the induction of
anesthesia.1 We review the rationale for this recommendation
and outcome data reports in the literature.
Carbohydrate Metabolism
As nutrients are consumed and the body moves from the fasted
to fed state, insulin is released to accommodate nutrient stor-
age (see Table 1). In the fed state, blood glucose levels rise,
resulting in a myriad of metabolic changes. Gluconeogenesis
is stopped; the liver no longer releases glucose from glycogen
storage and returns to preservation mode, attempting to store
excess glucose in the form of glycogen. Activation of muscle
glucose transporters, such as glucose transporter type 4
(GLUT-4), allows for increased glucose uptake by the muscle
cells, in which some is stored as glycogen. Lipolysis and pro-
tein breakdown are both halted, with no further fat release
from fat cells or further muscle breakdown. This fed state con-
tinues for approximately 4 hours. With the release of insulin
and glycogen preservation, an individual achieves an anabolic
state, the desired state, for a patient about to endure a surgical
procedure.
Effect of Surgery on Carbohydrate
Metabolism
However, surgery itself causes heightened insulin resistance,
which is thought to be proportional to the intensity of tissue
trauma or injury.2,3 Open surgical techniques lead to increasing
severity of insulin resistance and hyperglycemia.1,4 This height-
ened stress response lasts 2 to 3 weeks, with hyperglycemia
being most prominent on postoperative day (POD) 1.3,4
Although debated, glycemic control is thought to be instrumen-
tal on reducing morbidity and mortality postoperatively.2,5
Postsurgical patients in intensive care units (ICU) who under-
went thoracic or abdominal surgery were studied using various
glucose control measures. When an intensive insulin therapy
protocol was used, morbidity and mortality among this thoracic
and abdominal surgery population were decreased by 40%.6 In
contrast, a well-known randomized controlled trial (RCT),
Normoglycemia in Intensive Care Evaluation–Survival Using
From the 1Center for Human Nutrition & Center for Gut Rehabilitation
and Transplantation, Department of General Surgery and Digestive
Disease Institute, Cleveland Clinic, Cleveland, Ohio.
Financial disclosure: None declared.
Corresponding Author:
Cassandra Pogatschnik, RD, LD, CNSC, Cleveland Clinic, 175 Millcreek
Lane, Moreland Hills, OH 44022, USA.
Email: pogatsc@ccf.org

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2 Nutrition in Clinical Practice XX(X)
Table 1. Fasting vs Fed State, Carbohydrate Metabolism.
Constituents of Metabolism Fasting State Fed State
Glucose Normal Elevated
Insulin Normal Elevated
Muscle uptake of glucose Reduced Increased
Protein catabolism Increased Halted
Glycogen Broken down Restored
Metabolism Catabolic Anabolic
Glucose Algorithm Regulation (NICE-SUGAR), demonstrated
that morbidity and mortality were increased when using an
intensive insulin protocol targeting glucose control of 81–100
mg/dL vs a target glucose of ≤180 mg/dL in surgical and medi-
cal ICU patients. However, the authors concluded that the cause
of insult was inconclusive, possibly related to reduced blood
glucose level, hypoglycemic episodes, increased insulin admin-
istration, and/or study methods. Further study may be warranted
to determine target insulin levels in postsurgical patients.7
Traditional Surgical Fast and Its
Complications
Traditionally, patients have fasted overnight, instructed to be nil
per os (NPO) after midnight; these instructions were developed
due to concerns of pulmonary aspiration.3,5 In 1848, the first
anesthesia death was recorded after a patient aspirated.3,5
Anesthesiologists and surgeons wanted to ensure an empty
stomach preoperatively to protect the laryngeal reflux and to
avoid aspiration pneumonitis.8 To avoid these complications, it
is estimated that the maximum volume of gastric contents
should be no more than 200 mL prior to a surgical procedure.9
Several studies have detected mean gastric contents ranging
from 10–30 mL, with a rare 120-mL maximum after a clear
liquid diet is given up to 2 hours prior to an operation.9 However,
these studies would not apply to patients with gastric stasis or
peritonitis.9 It is also pertinent to note that smoking, functional
dyspepsia, psychological stress, and female hormones may all
delay gastric emptying to some extent.9 A meta-analysis of 7
studies by Bilku et al2 showed that volume and pH of gastric
contents were nearly identical between a standard fast and a
shortened 2-hour fast. Both clear liquids and CHO solutions
emptied in about 90 minutes. The authors concluded that there
was no increased risk for aspiration or regurgitation in patients
who did not traditionally fast.2 Awad et al10 completed a meta-
analysis of 21 RCTs and also noted no reported pulmonary
complications in the CHO-consuming group. An RCT by Yagci
et al11 including 70 patients undergoing cholecystectomies or
thyroidectomies also concluded that CHO drinks did not alter
gastric pH or content volume. The European Society of
Anesthesiology (ESA) guidelines note that patients who are
obese, have gastroesophageal reflux or diabetes, and/or are
pregnant who are not in labor can safely consume fluids 2 hours
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prior to anesthesia.12 After careful study by the Cochrane
Review, it was concluded that there were no reports of any
cases of aspiration pneumonia using the 2-hour clear liquid
limit.13 As a result, many anesthesia societies recommend short-
ened preoperative fasting times, with clear liquid fluids given
up to 2 hours prior to anesthesia (see Table 2).3,5,12–15
Ramifications of Traditional Fasting and
Potential Benefits of CHO Beverages
Insulin Resistance and Immune Response
Traditional fasting places a patient in a catabolic state, intensi-
fying a patient’s response to trauma. Surgical delay may
increase this effect.3 Fluids containing enough complex CHO
(usually containing approximately 12% carbohydrate, predom-
inately in maltodextrin form to limit osmolality and prevent
delayed gastric emptying)16 to act as a meal 2–3 hours prepro-
cedure may generate a more anabolic state, stimulating post-
prandial glycemia, reducing glycogen loss, and controlling
hyperglycemia with increased glucose uptake by the skeletal
muscle (see Table 1). Clear liquids alone will not have the
same effect on metabolism, nor will sports drinks have enough
CHO for adequate effect (sports drinks contain 6%–7%
CHO).12 A total of 50 g of complex CHO in 400 mL of fluid
has demonstrated the ability to decrease insulin sensitivity by
50% and has an appropriate osmolality for sufficient gastric
emptying.12 (See Table 3 for CHO-containing beverages rec-
ommended globally.) Similarly, increased insulin resistance
may lead to increased inflammation markers. Zelic et al4 dem-
onstrated that CHO-rich beverages prior to colon cancer resec-
tion vs fast showed a smaller increase in serum levels of
interleukin-6 (IL-6), although there was no difference in length
of stay (LOS). In a cohort study of 38 patients, Vigano et al17
found that preoperative CHO was associated with lower insu-
lin resistance, glucose levels, and IL-6 levels, although they
also found no association with decreased LOS. IL-6 may be a
stronger than C-reactive protein (CRP) as an inflammation
indicator as CRP peaks later, up to 24 hours after surgery.
A few studies have detected increased insulin resistance in
the surgical patient when using the normoglycemic clamp
and homeostasis model assessment of insulin resistance
(HOMA-IR) equation. The hyperinsulinemic normoglycemic
clamp is the gold standard as it measures insulin resistance in
the carbohydrate fed state. The HOMA-IR equation measures
the basal rate and fasted state, which makes it less sensitive and
less accurate. This may imply less insulin resistance than
actual.5 Twenty patients who underwent hip replacement sur-
gery were randomized between CHO and tap water flavored
with lemon, and both groups had a similar but significant
decrease in insulin sensitivity; therefore, the CHO-containing
fluid did not reverse the insulin resistance induced by
surgery.18 The systematic review by Bilku et al2 resulted in 6 of
7 RCTs (totaling 1445 patients, in which 4 studies used the
Pogatschnik and Steiger 3

Table 2. International Recommendations for Intake of Solids and Liquids Preoperatively.12,14,15

Anesthesia Society

Recommendation Canada (2015) Europe (2011) United States (2011)

Fast for liquids, h ≤2 ≤2 ≤2
Fast for solids, h ≤6 light meal; ≤8 meat or fatty food ≤6 solid food ≤6 light meal; ≤8 fatty food
CHO fluids No comment Consider preoperative CHO drinks No comment

CHO, carbohydrate.

Table 3. Carbohydrate-Containing Fluids Recommended to Be Given Preoperatively.31

Product Location Available Volume, mL Osmolality, mOsm/kg Maltodextrin, g % CHO

preOp Europe, United Kingdom, Canada 400 285 40 12.0
Clearfast United States 355 270 44 12.0
ONS 300 Germany 300 266 50 16.6
ONS 400 Germany 400 266 50 12.5
Preload United Kingdom 400 135 47.5 13.0
Arginaid H2O Japan 250 200 52 18.0
Maxjul United Kingdom, Europe 420 420 43.25 32.0

CHO, carbohydrate.

hyperinsulinemic normoglycemic clamp technique, 1 used
HOMA-IR, 1 used an artificial pancreas with a closed-loop
system, and 1 used a quantitative insulin sensitivity check
index) showed significant reduction of insulin resistance.2 An
RCT of 48 colorectal patients by Wang et al19 demonstrated
that insulin resistance was greater in fasting patients. They also
reported that immediate postoperation muscle protein tyrosine
kinase (PTK) activity, phosphatidylinositol 3-kinase (PI3K)
level, and protein kinase B (PKB) level were significantly
increased in the CHO group, while GLUT-4 was unaffected.
The Cochrane Review supports the hypothesis that CHO-
containing fluids decrease insulin resistance with high-quality
evidence. In the 3 trials reviewed of 41 patients, mean glucose
was reduced by 0.76 mg/kg/min determined by the hyperinsu-
linemic euglycemic clamp method.13 Surgical complications of
insulin resistance are similar to complications that occur in
diagnosed diabetic patients; however, surgical patients have a
more rapid onset of complications induced by acute postopera-
tive hyperglycemia.1 Immune, endothelial, and neural cells are
affected with the potential to cause increased risk of infection,
neuropathy, renal failure, and mechanical ventilation.1 These
cells are forced to take up glucose on heightened plasma glu-
cose levels; however, there is a lack of intracellular capacity
for glucose storage, therefore stimulating glycolysis and the
production of free radicals, causing more inflammation.1
Nutrition in Relationship to Intake of
Preoperative CHO Intake
With the understanding of CHO metabolism and its effect on
halting protein lysis, some authors have studied the impact of
CHO-rich fluids on muscle preservation. The meta-analysis by
Bilku et al2 explored a number of these studies that reviewed
this. Yuill et al20 showed preservation of muscle mass in the
CHO drinking group, while Mathur et al21 noticed no preserva-
tion of muscle mass. As a result, Bilku et al2 could make no
conclusion but had no reason to believe that postoperative
nitrogen loss could be attenuated. Lidder et al22 demonstrated
that handgrip strength deteriorated in all groups after surgery
(placebo, preoperative CHO with postoperative placebo, pre-
operative placebo with postoperative CHO, and preoperative
CHO with postoperative CHO) but significantly improved in
the preoperative placebo with postoperative CHO and the pre-
operative CHO with postoperative CHO groups. Noblett et al23
showed a significant (P < .05) decrease in manual muscle test-
ing in fasted patients in comparison with their preoperative
values.2 Further studies are needed to prove that preoperative
CHO fluids are able to preserve muscle mass and function.
Postoperative Well-Being
Perioperative thirst, hunger, malaise, fatigue, and anxiety have
been reported to improve with a decrease in length of fasting
and the use of CHO-containing fluids. Hausel et al24 conducted
an RCT involving 252 patients undergoing abdominal surgery
randomized into 3 groups: overnight fast, placebo, and CHO
beverage. Preoperatively, the CHO group was less hungry and
anxious than the placebo and fasting groups. However, both
the CHO beverage and placebo groups had diminished thirst.
The CHO group also experienced less discomfort in trends of
malaise and unfitness. The fasted group had a notable inability
to concentrate and an increase in weakness, hunger, and thirst.

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4 Nutrition in Clinical Practice XX(X)
The authors concluded that preoperative CHO fluids affected a
patient’s well-being. In the meta-analysis by Bilku et al,2 CHO
beverage led to vast improvement in thirst, hunger, anxiety,
and malaise in 2 RCTs. In contrast, the Cochrane Review found
no difference in patient well-being during hospital stay post-
surgery among CHO vs fasting groups.13 The ESA found fast-
ing to be detrimental in the elderly and children12; preoperative
fluid has been found to result in less pediatric irritability.24
Interestingly, intravenous (IV) dextrose and oral CHO
improved tiredness and weakness in comparison with fasting,
but IV dextrose did not improve hunger and thirst as oral CHO
did in 210 post–gastrointestinal (GI) surgery patients in
Helminen et al.25 The Cochrane Review commented that
administration route needs to be fully investigated since only 2
studies were conducted that examined IV dextrose infusion.13
There have been mixed reviews on CHO fluids’ effect on post-
operative nausea and vomiting. The RTC by Hausel et al24
showed a lower rate of postoperative nausea and vomiting in
the CHO beverage vs fasting group in lap cholecystectomy
patients. In contrast, Bisgaard et al26 and Lidder et al22 found
no difference between preoperative CHO fluid consumption
and patients who had fasted.
Surgical Complications and LOS
It has been hypothesized that because of the positive effects that
presurgical oral CHO has on insulin resistance and GI symptoms,
LOS may be reduced. The meta-analysis by Awad et al10 investi-
gated clinical end points in 1685 randomized patients. CHO flu-
ids had no overall effect on in-hospital complications and no
overall impact on LOS; however, among the 762 patients under-
going major abdominal surgery, LOS was significantly reduced.
The letters to the editor regarding the Jones article8 commented
that caution should be used regarding the relationship between
surgical site infections and high blood sugars since there was
weak evidence to support the proof for oral CHO fluid use.29 It
was noted by Thorell et al28 that insulin resistance was an inde-
pendent factor of LOS and that blood loss during surgery and
surgical type affected the variation of LOS by 7%.1 No difference
in postoperative infections or LOS was found in Mathur et al,21
but it was noted that there was an earlier return of gut function in
the CHO group, although with no statistical significance, which
may have affected LOS. The RCT by Noblett et al23 of 36 patients
divided in fasting, placebo, and CHO groups found reduced LOS
and hastened return of GI function. The Cochrane Review ana-
lyzed 19 trials, containing 1351 participants, comparing fasting,
placebo, and CHO groups. Patients in the CHO group had a 0.3-
day shorter LOS than the fasting group, but no difference (mean
difference of –0.13 days) was detected in comparing placebo vs
CHO.13 In 2 trials that reviewed 86 patients, CHO fluid intake
was associated with shortened postoperative return of flatus;
however, no difference was detected when looking at actual time
to first bowel movement.13
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ERAS
Henrik Kehlet, a surgeon from Denmark, developed the con-
cept of “fast-track surgery” in the late 1990s.1 He documented
that his 17 colorectal patients were discharged in a median
time of 2 days after open colonic resections vs a standard
10-day LOS. The “fast-track surgery” title was removed and
was replaced with “enhanced recovery after surgery” (ERAS)
to focus on outcome rather than speed. The goal of ERAS is to
use a multimodal approach in reducing perioperative stress
and enhancing surgical recovery. With this approach, there is
the potential to affect the care and outcome of every surgical
patient. Currently, preoperative ERAS recommendations
include preoperative CHO fluid with clear fluids up to 2 hours
prior to surgery. Other ERAS recommendations include con-
tinuous epidural anesthesia, adequate postoperative pain con-
trol, early enteral feeding, and mobilization. Preoperative
CHO loading combined with epidural anesthesia is thought to
the reduce stress hormones epinephrine and cortisol, which, in
combination, have been thought to decrease insulin resistance
by approximately 50%.1 Bed rest was found to increase pro-
tein loss, and poor nutrition postoperatively only heightened
this response. This serves as a reminder that the earlier studies
on CHO-containing fluid and protein loss previously dis-
cussed may have had several confounding factors. A meta-
analysis in 2010 complied studies from 4 countries in which
the ERAS group included at least 4 ERAS elements in their
patient care protocol and concluded that LOS was reduced by
a mean of 2.5 days, as well as a 50% decrease in the complica-
tion rate. ERAS has been shown to reduce surgical complica-
tions and has demonstrated financial benefits due to its ability
to decrease LOS and complications.1 Gustaffson et al29 dem-
onstrated that compliance <50% produced an LOS of 9.4
days, a 45% complication rate, and an 11% readmission rate,
whereas compliance >90% resulted in an LOS of 6 days, a
19% complication rate, and a 2% readmission rate.
Preoperative CHO loading is just one of many factors involved
in the success of ERAS protocols.
Conclusions
Carbohydrate containing clear liquids have been demon-
strated to be safe when given up to 2 hours before surgery and
enhance patient comfort prior to surgery. The demonstrated
metabolic effects of lowering insulin resistance of surgery
have theoretical benefits; however, favorable outcome results
solely attributable to preoperative CHO loading are difficult
to prove. The magnitude of the surgical procedure and post-
operative care pathways are probably more important deter-
minants of outcomes. However, nutrition preparation of the
preoperative surgical patient combining proven approaches,30
along with CHO loading, is worth considering to ensure
better surgical outcomes.
Pogatschnik and Steiger
Statement of Authorship
C. Pogatschnik and E. Steiger equally contributed to the concepts
and content presented in this of the manuscript; C. Pogatschnik
drafted the manuscript; E. Steiger critically revised the manu-
script; and both authors agree to be fully accountable for ensuring
the integrity and accuracy of the work. Both authors read and
approved the final manuscript.
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