Role of preoperative carbohydrate loading: A systematic review

Abstract

Surgical stress in the presence of fasting worsens the catabolic state, causes insulin resistance and may delay recovery. Carbohydrate rich drinks given preoperatively may ameliorate these deleterious effects. A systematic review was undertaken to analyse the effect of preoperative carbohydrate loading on insulin resistance, gastric emptying, gastric acidity, patient wellbeing, immunity and nutrition following surgery.
All studies identified through PubMed until September 2011 were included. References were cross-checked to ensure capture of cited pertinent articles.
Overall, 17 randomised controlled trials with a total of 1,445 patients who met the inclusion criteria were identified. Preoperative carbohydrate drinks significantly improved insulin resistance and indices of patient comfort following surgery, especially hunger, thirst, malaise, anxiety and nausea. No definite conclusions could be made regarding preservation of muscle mass. Following ingestion of carbohydrate drinks, no adverse events such as apparent or proven aspiration during or after surgery were reported.
Administration of oral carbohydrate drinks before surgery is probably safe and may have a positive influence on a wide range of perioperative markers of clinical outcome. Further studies are required to determine its cost effectiveness.

Full text

15Ann R Coll Surg Engl 2014; 96: 15–22 15
REVIEW
Ann R Coll Surg Engl 2014; 96: 15–22
doi 10.1308/003588414X13824511650614
KEYWORDS
Preoperative – Carbohydrate loading – Surgery
Accepted 30 April 2013
CORRESPONDENCE TO
Dilraj Bilku, Department of Surgery, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK
T: +44 (0)116 258 4683; E: dilrajbilku@yahoo.co.uk
Role of preoperative carbohydrate loading:
a systematic review
DK Bilku, AR Dennison, TC Hall, MS Metcalfe, G Garcea
University Hospitals of Leicester NHS Trust, UK
ABSTRACT
INTRODUCTION Surgical stress in the presence of fasting worsens the catabolic state, causes insulin resistance and may
delay recovery. Carbohydrate rich drinks given preoperatively may ameliorate these deleterious effects. A systematic review was
undertaken to analyse the effect of preoperative carbohydrate loading on insulin resistance, gastric emptying, gastric acidity,
patient wellbeing, immunity and nutrition following surgery.
METHODS All studies identifi ed through PubMed until September 2011 were included. References were cross-checked to
ensure capture of cited pertinent articles.
RESULTS Overall, 17 randomised controlled trials with a total of 1,445 patients who met the inclusion criteria were identifi ed.
Preoperative carbohydrate drinks signifi cantly improved insulin resistance and indices of patient comfort following surgery,
especially hunger, thirst, malaise, anxiety and nausea. No defi nite conclusions could be made regarding preservation of muscle
mass. Following ingestion of carbohydrate drinks, no adverse events such as apparent or proven aspiration during or after
surgery were reported.
CONCLUSIONS Administration of oral carbohydrate drinks before surgery is probably safe and may have a positive infl uence on
a wide range of perioperative markers of clinical outcome. Further studies are required to determine its cost effectiveness.
Insulin resistance is a central metabolic change during sur-
gical stress that is directly proportional to the magnitude of
the operation. It causes hyperglycaemia in non-diabetic pa-
tients. As a consequence, various endocrine and infl amma-
tory systems are stimulated. This results in an exacerbation
of the existing postoperative catabolic state with marked
loss of body fat and protein stores.1,2 Aggressive treatment
with insulin to maintain glycaemic control has resulted in
reduced organ dysfunction and mortality.3,4 Additionally, in-
sulin resistance has been shown to be an independent factor
infl uencing length of stay in hospital postoperatively.1
The aim of this review is to systematically appraise the
available data regarding the safety and benefi cial role of
preoperative carbohydrate loading in patients undergoing
surgery and, where possible, make comparison with pla-
cebo or traditional practice.
Methods
A PubMed literature search was undertaken using the
keywords ‘carbohydrate loading’, ‘preoperative’, ‘surgery’
and ‘insulin resistance’. Search limits consisted of any
Figure 1 Flow diagram of study selection
Volume 96 Issue 1.indb 15Volume 96 Issue 1.indb 15 06/12/13 3:39 pm06/12/13 3:39 pm

16 Ann R Coll Surg Engl 2014; 96: 15–22
BILKU DENNISON HALL METCALFE GARCEA ROLE OF PREOPERATIVE CARBOHYDRATE LOADING:
A SYSTEMATIC REVIEW
article published up until September 2011, studies involving
adults undergoing general surgical operations and English
language manuscripts. The references of all articles were
cross-checked to include all pertinent articles (Fig 1). The
primary outcome measure was effect of preoperative carbo-
hydrate loading on insulin resistance. Secondary outcome
measures were the effect of carbohydrate treatment on gas-
tric emptying, gastric acidity, wellbeing of patient (assessed
qualitatively), immunity, clinical outcome and nutrition.
Results
Seventeen randomised controlled trials with a total of 1,445
patients who met the inclusion criteria were analysed.5–21
The size of the studies varied from 6 to 252 patients. All tri-
als excluded patients with metabolic disorders including
diabetes mellitus, ASA (American Society of Anesthesiolo-
gists) grade >2, gastro-oesophageal refl ux disease and those
associated with factors affecting gastric emptying (obesity,
pregnancy, sliding hernia of stomach, medications). The
protocol for provision of preoperative carbohydrate was
variable. Multiple combination of outcomes were analysed
by all the studies, making the data too heterogeneous for a
meta-analysis.
Effect of preoperative carbohydrate on insulin
resistance
In total, seven articles investigated the effect of preopera-
tive carbohydrate on insulin sensitivity.5–11 Various meth-
ods were used to analyse insulin resistance (Table 1). Four
studies used the hyperinsulinaemic normoglycaemic clamp
technique, which is considered to be the gold standard.8–11
One article assessed insulin resistance using the HOMA-IR
(homeostatic model assessment – insulin resistance) equa-
tion.7 One study used an artifi cial pancreas with a closed
loop system (STG-22).5 One study used the quantitative in-
sulin sensitivity check index.6 The time of assessment var-
ied from one week preoperatively to up until three days
after surgery. Frequency varied from being assessed once
postoperatively or on two separate occasions (preoperative
and after surgery).
Six trials demonstrated a signifi cant reduction in insulin
resistance following the use of preoperative carbohydrate
loading (Table 2).9–11 The maximum improvement in insulin
action observed was by a factor of 50% (p<0.01) after the
morning dose of carbohydrate on the day of surgery.12
In contrast, only one study demonstrated no effect of
carbohydrate on postoperative peripheral insulin sensitivity
(borderline signifi cance, p=0.049). This may be due to a type
II error, the small sample size (12 patients) or the timing of
surgery and diverse fasting durations.8
Effect of preoperative carbohydrate on gastric emptying
Five articles investigated the effect of carbohydrate admin-
istered preoperatively on gastric emptying (Table 3).6,12–15
The protocol used in the trials varied with comparisons
made between oral carbohydrate drinks and fasting from
midnight or water or oral nutritional supplement or mixture
of carbohydrate and soy protein or intravenous glucose and
electrolytes. The time and number of drinks administered
was also variable.
All the studies reported no difference in gastric empty-
ing times between the groups that received placebo or fast-
ing from midnight or intravenous glucose and carbohydrate
drinks.6,12–15 However, three patients in the study conducted
by Hausel et al had large residual gastric fl uid volumes.15 It
was noted that one of these patients had a history of previ-
ous intestinal obstruction, one had a short interval between
intake of drink and premedication, and the third patient had
abnormal fasting plasma glucose.
Effect of preoperative carbohydrate on gastric acidity
Three randomised trials examined the effect of carbohy-
drate drinks given preoperatively on gastric acidity in pa-
tients undergoing surgery.6,13,15 Modes of assessing gastric
Table 1 Methods used to measure insulin resistance
Technique Methodology
Hyperinsulinaemic normoglycaemic clamping This is the gold standard for measuring insulin sensitivity. Insulin is infused intravenously
at a rate of 0.8mu/kg/min for 120 minutes. Glucose (200mg/ml) is infused simultane-
ously, also intravenously, at a variable rate to maintain the blood glucose concentration
at 4.5mmol/l. Insulin sensitivity is expressed as the mean glucose infusion rate during a
steady-state period during the last 60 minutes.
HOMA-IR HOMA-IR = insulin (μu/ml) x blood glucose (mg/dl) / 405
Artifi cial pancreas with a closed loop system
(STG-22)
Blood is sampled continuously from a peripheral vein at a rate of 2ml/h and the glucose
concentration is monitored. Blood glucose levels are maintained in a target zone by regular,
automatic infusion of insulin or glucose into the blood circulation. In the study by Okaba-
yashi et al,5 the target blood glucose level was set between 80mg/dl and 110mg/dl, and
the requirements for insulin to maintain this glucose level for 16 hours following hepatic
resection were quantifi ed using the artifi cial pancreas STG-22.
QUICKI This is derived from the inverse of the sum of the decimal logarithms of the fasting insulin
and fasting glucose, and provides a crude estimation of insulin sensitivity.
HOMA-IR = homeostatic model assessment – insulin resistance; QUICKI = quantitative insulin sensitivity check index
Volume 96 Issue 1.indb 16Volume 96 Issue 1.indb 16 06/12/13 3:39 pm06/12/13 3:39 pm

17Ann R Coll Surg Engl 2014; 96: 15–22
BILKU DENNISON HALL METCALFE GARCEA ROLE OF PREOPERATIVE CARBOHYDRATE LOADING:
A SYSTEMATIC REVIEW
acidity varied between the studies (Table 4). The study by
Hausel et al assessed acidity by automatic back titration
with sodium hydroxide to pH 7.15 A study by Yagci et al used
a urine pH meter.13 The third trial used biochemical indica-
tor paper.6 All the studies demonstrated that there was no
difference in gastric acidity following a carbohydrate drink
compared with placebo or intravenous glucose or, more im-
portantly, fasting.
Effect of preoperative carbohydrate on patient wellbeing
Eight studies examined the impact of preoperative carbo-
hydrate drinks on patient wellbeing (Table 5).6,12,14–19 Six
Table 2 Randomised clinical trials investigating the effect of preoperative carbohydrate on insulin resistance
Study nType of surgery Intervention groups Technique Conclusions p-value
Okabayashi,
20105
26 Hepatic resection 1. Control – no additional
dietary supplement
2. Aminoleban® EN (mixture
of carbohydrate and BCAAs)
– 50g given orally twice a
day started 2 weeks prior to
surgery
Artifi cial pancreas
with a closed loop
system (STG-22)
IS better in Aminoleban® EN
group
0.039
Kaska,
20106
221 Colorectal resec-
tion
1. Control – overnight fasting
2. IV 500ml 10% glucose with
10ml 7.45% KCl and 10ml
20% MgSO4 – pm and am
3. Oral 400ml potion containing
maltodextrin and electrolytes
– pm and am
Quantitative
insulin sensitivity
check index
IS reduced in control group 0.05
Faria,
20097
21 Laparoscopic
cholecystectomy
1. Overnight fasting
2. CHO 200ml – am
HOMA-IR IS higher in CHO group than
fasted group
0.03
Svanfeldt,
20078
12 Colorectal resec-
tion
1. High CHO group – 125mg/
ml CHO
2. Low CHO group – 25mg/ml
CHO 800ml – pm, during
the waiting period on the day
of surgery: 200ml portion
given every hour. In total, 3
or 4 portions (600–800ml)
ingested, with last portion
no later than 2 hours before
premedication.
HN clamp –
measured before
and on the fi rst
postoperative day
No effect seen on postopera-
tive peripheral IS
0.049
Svanfeldt,
20059
6 Simulated preop-
erative setting; no
surgery
1. Overnight fasting
2. CHO 800ml – pm
3. CHO 400ml – am
4. CHO 800ml – pm, 400ml
– am
HN clamp – meas-
ured 120 minutes
after the morning
drink
IS increased by 50% 3 hours
after morning drink
<0.01
Nygren,
199910
30 Colorectal surgery
(n=14), THR
(n=16)
1. CHO 800ml – pm, 400ml
– am
2. Placebo – similar protocol
HN clamp
THR –1 week
before surgery and
immediately after
completion of
surgery
Colorectal surgery
– day before sur-
gery and 24 hours
postoperatively
THR: 37% reduction in IS in
placebo group immediately
after surgery. No signifi cant
reduction in IS found in CHO
group.
Colorectal surgery: 24%
greater reduction in IS in
fasted group than in CHO
group at 24 hours after
surgery
<0.05
Ljungqvist,
199411
12 Laparoscopic
cholecystectomy
1. Control – overnight fasting
2. Overnight glucose infusion
5mg/kg/min
HN clamp –
measured 3 days
preoperatively
and on fi rst day
postoperatively
IS reduced in control patients
compared with treatment
group
<0.01
BCAAs = branched chain amino acids; IS = insulin sensitivity; pm = evening before surgery; am = morning of surgery; CHO = carbohydrate
drink; HOMA-IR = homeostatic model assessment – insulin resistance; HN = hyperinsulinaemic normoglycaemic; THR = total hip replacement
Volume 96 Issue 1.indb 17Volume 96 Issue 1.indb 17 06/12/13 3:39 pm06/12/13 3:39 pm

18 Ann R Coll Surg Engl 2014; 96: 15–22
BILKU DENNISON HALL METCALFE GARCEA ROLE OF PREOPERATIVE CARBOHYDRATE LOADING:
A SYSTEMATIC REVIEW
trials used a visual analogue scale (VAS) to assess patient
comfort.12,14–17,19 The variables measured by the VAS were
thirst, hunger, anxiety, depression, pain, tiredness, weak-
ness, inability to concentrate, mouth dryness and nausea.
The numbers of variables studied in each trial were differ-
ent. In the study by Kaska et al, the psychosomatic status of
patients was assessed by the modifi ed Beck questionnaire,6
which consists of 21 questions addressing symptoms such as
fatigue and irritability. Hausel et al used two methods: VAS
and objective analysis by nursing staff.18
Preparation with carbohydrate led to a signifi cant reduc-
tion in thirst, hunger, anxiety and malaise in two trials com-
Table 3 Randomised clinical trials investigating the effect of preoperative carbohydrate on gastric emptying
Study nType of surgery Intervention groups Analysis Gastric
emptying
p-value
Kaska,
20106
221 Colorectal resection 1. Overnight fasting
2. IV 500ml 10% glucose with
10ml 7.45% KCl and 10ml
20% MgSO4 – pm and am
3. Oral 400ml potion containing
maltodextrin and electrolytes –
pm and am
NG tube GFV lower in
group 3 than in
group 1
Not stated
Nygren,
199512
12 Laparoscopic
cholecystectomy,
parathyroid surgery
1. CHO – 400ml
2. Water – 400ml
3. Control – protocol repeated
among the same patients 53
±7 days after operation
4. The same protocol was
performed among healthy
volunteers after ingestion of
CHO or water.
Gamma cameras and a
radiotracer mixed with
the drink
No difference.
For CHO group:
90 minutes.
<0.05
Yagci,
200813
70 Laparoscopic
cholecystectomy,
thyroidectomy
1. CHO – 800ml pm, 400ml am
2. Control – overnight fasting
NG tube No difference 0.61
Henriksen,
200314
29 Bowel resection 1. CHO – 400ml pm, 400ml am
2. CHO + peptide (drink made of
12.5g/100ml carbohydrate and
3.5g/100ml hydrolysed soy
protein) – same protocol
3. Control – water until 3 hours
before induction
Dye dilution technique No difference.
For CHO group:
<90 minutes.
Not stated
Hausel,
200115
252 Laparoscopic
cholecystectomy,
colorectal resection
1. CHO – 800ml pm, 400ml am
2. Placebo – same protocol
3. Overnight fasting
In 245 patients: NG tube
In 142 patients: single
marker dilution technique
No difference.
7 of 245
patients had
GFV of >100ml.
Not stated
IV = intravenous; pm = evening before surgery; am = morning of surgery; NG = nasogastric; GFV = gastric fl uid volume;
CHO = carbohydrate drink
Table 4 Randomised clinical trials investigating the effect of preoperative carbohydrate on gastric acidity
Study nType of surgery Intervention groups Technique Conclusions
Kaska,
20106
221 Colorectal resection 1. Overnight fasting
2. IV 500ml 10% glucose with 10ml 7.45% KCl
and 10ml 20% MgSO4 twice – pm and am
3. Oral 400ml potion containing maltodextrin
and electrolytes – pm and am
Biochemical
indicator paper
Gastric pH was com-
parable for all three
groups
Yagci,
200813
70 Laparoscopic
cholecystectomy,
thyroidectomy
1. CHO – 800ml pm, 400ml am
2. Control – overnight fasting
Urine pH meter Gastric pH was
comparable for both
groups
Hausel,
200115
252 Laparoscopic
cholecystectomy,
colorectal resection
1. CHO – 800ml pm, 400ml am
2. Placebo – same protocol
3. Overnight fasting
Automatic back ti-
tration with sodium
hydroxide to pH 7
Gastric pH was com-
parable for all three
groups
IV = intravenous; pm = evening before surgery; am = morning of surgery; CHO = carbohydrate drink;
Volume 96 Issue 1.indb 18Volume 96 Issue 1.indb 18 06/12/13 3:39 pm06/12/13 3:39 pm

19Ann R Coll Surg Engl 2014; 96: 15–22
BILKU DENNISON HALL METCALFE GARCEA ROLE OF PREOPERATIVE CARBOHYDRATE LOADING:
A SYSTEMATIC REVIEW
Table 5 Randomised clinical trials investigating the effect of preoperative carbohydrate on wellbeing of the patient
Study nType of surgery Intervention groups Technique Conclusions
Kaska,
201011
221 Colorectal surgery 1. Overnight fasting
2. IV 500ml 10% glucose with
10ml 7.45% KCl and 10ml
20% MgSO4 – pm and am
3. CHO 400ml – pm and am
Modifi ed Beck
questionnaire
Group 3: Reduced thirst, hunger,
anxiety and pain
Nygren,
199512
12 Laparoscopic
cholecystec-
tomy, parathyroid
surgery
1. CHO 400ml – am
2. Water 400ml – until 4 hours
before induction of anaes-
thesia
3. Control – protocol repeated
among the same patients 53
±7 days after operation
The same protocol was also per-
formed among healthy volunteers
after ingestion of CHO or water.
VAS Thirst was reduced during the fi rst
60 minutes after CHO and 40
minutes after water. Thereafter, no
signifi cant changes observed.
Hunger was reduced after 20 min-
utes of water but not after CHO.
Anxiety was reduced after water but
not after CHO.
Henriksen,
200314
48 Bowel resections 1. CHO 400ml – pm, 400ml
– am
2. CHO + peptide (drink made
of 12.5g/100ml carbohydrate
and 3.5g/100ml hydrolysed
soy protein – same protocol
3. Control – water until 3 hours
before induction of anaes-
thesia
VAS No difference found between the
groups in thirst, hunger, anxiety,
wellbeing, fatigue, pain (pain at rest,
with cough and mobilisation) and
nausea
Hausel,
200115
252 Laparoscopic
cholecystectomy,
colorectal surgery
1. CHO 800ml – pm, 400ml
– am
2. Placebo – similar protocol
3. Overnight fasting
VAS Group 1: Reduced hunger, thirst,
anxiety, malaise and unfi tness
Group 2: Increased nausea, tired-
ness, inability to concentrate. No
consistent trend for hunger or thirst.
Group 3: Increased hunger, thirst,
tiredness, weakness and inability to
concentrate
Mathur,
201016
142 Colorectal
surgery, hepatic
resection
1. CHO 800ml – pm, 400ml
– am
2. Placebo – similar protocol
VAS No benefi t of CHO demonstrated on
anxiety, depression, hunger, thirst,
inability to concentrate, malaise,
nausea, pain at rest, pain with
cough, unfi tness or irritability
Helminen,
200917
210 Abdominal sur-
gery, thyroidec-
tomy, parathyroid
surgery
1. IV 1,000ml 5% dextrose
between midnight and 6am
2. CHO 400ml – am
3. Overnight fasting
VAS Group 1: Increased thirst, mouth dry-
ness and anxiety. No consistent trend
for hunger, weakness or tiredness.
Group 2: Reduced thirst. Hunger
better than IV glucose group.
Group 3: Increased thirst, hunger,
tiredness, anxiety, weakness and
mouth dryness
Hausel,
200518
172 Laparoscopic
cholecystectomy
1. CHO 800m – pm, 400ml –
am
2. Placebo – similar protocol
3. Overnight fasting
Two methods:
1) Objective analysis
of nausea and vomit-
ing by nursing staff
2) VAS
Incidence of nausea and vomiting
was similar in the three groups dur-
ing the fi rst 12 hours. Between 12
and 24 hours, more patients in the
fasted group experienced nausea and
vomiting than in the CHO group.
Bisgaard,
200419
94 Laparoscopic
cholecystectomy
1. CHO 800ml – pm, 400ml
– am
2. Placebo – similar protocol
VAS Preoperative CHO had no infl uence
on postoperative discomfort in terms
of general wellbeing, fatigue, ap-
petite, pain, nausea, vomiting, sleep
and physical activity compared with
placebo.
IV = intravenous; pm = evening before surgery; am = morning of surgery; CHO = carbohydrate drink; VAS = visual analogue scale
Volume 96 Issue 1.indb 19Volume 96 Issue 1.indb 19 06/12/13 3:39 pm06/12/13 3:39 pm

20 Ann R Coll Surg Engl 2014; 96: 15–22
BILKU DENNISON HALL METCALFE GARCEA ROLE OF PREOPERATIVE CARBOHYDRATE LOADING:
A SYSTEMATIC REVIEW
pared with fasting and placebo (fl avoured water).15,18 The
improvement in thirst was similar for the placebo and car-
bohydrate groups. Two trials compared intravenous glucose
with fasting from midnight and oral carbohydrate drinks.6,17
These studies demonstrated that the fasted patients had
increased thirst, hunger, tiredness, anxiety and mouth dry-
ness scores. On the contrary, both intravenous and oral car-
bohydrates alleviated feelings of tiredness and weakness
compared with fasting. However, intravenous glucose infu-
sion did not decrease the sense of thirst and hunger as ef-
fectively as oral carbohydrates.
Hausel et al investigated the effect of carbohydrate on
postoperative nausea and vomiting in 172 patients undergo-
ing an elective laparoscopic cholecystectomy.18 Between 12
and 24 hours after surgery, there was a signifi cantly low-
er incidence of nausea and vomiting in the carbohydrate
group than in the fasted group. Three studies demonstrated
no benefi cial effect of carbohydrate drinks on similar vari-
ables measuring general wellbeing of the patient prior to
surgery.14,16,19
Effect of preoperative carbohydrate on immunity and
clinical outcome
Two trials examined the impact of carbohydrate drinks on
postoperative immunity and clinical outcomes.16,20 Mathur
et al conducted the largest double blind placebo controlled
trial in 2009 to study the effect of preoperative carbohydrate
drinks on a number of clinical outcomes after colorectal sur-
gery and hepatic resection.16 There was no difference in the
incidence of postoperative infections in the carbohydrate
group compared with the placebo group. Furthermore, no
signifi cant benefi t was observed in the carbohydrate group
with regard to length of stay and time to intake of oral diet.
In contrast to this, Noblett et al demonstrated that
preoperative treatment with carbohydrate drinks reduced
the length of hospital stay compared with placebo or water.20
Earlier return of gut function was also noticed in the carbo-
hydrate group although this was not statistically signifi cant.
The early return of gut function could be a contributory fac-
tor for reduced postoperative hospital stay.
Effect of preoperative carbohydrate on nutrition
Five studies examined the effect of preoperative carbo-
hydrate on the postoperative nutritional status of the pa-
tient.6,14,16,20,21 Varied methods were employed for meas-
urement of nutrition. Four trials used anthropometric
measurements.14,16,20,21 A dynamometer measured grip
strength in the dominant hand. Other measurements in-
cluded triceps skinfold thickness and mid-arm circumfer-
ence. One study measured muscle power in hand grip with
a digital tension meter.6
In the study conducted by Henriksen et al, no signifi cant
difference was observed between the groups when analysed
per se.14 However, when the results of the two intervention
groups (carbohydrate only, and carbohydrate and peptide)
were pooled together, they had a signifi cantly better muscle
strength in the quadriceps muscles than the control (water)
group after one month (p<0.05). Despite this, no difference
was observed between the three groups in voluntary iso-
metric hand grip strength. Noblett et al demonstrated a sig-
nifi cant reduction in grip strength on discharge in the fasted
patients compared with their preoperative values (p<0.05).20
In contrast, both the carbohydrate and placebo groups did
not show a signifi cant reduction in their postoperative grip
strength. Similar results were noted by Kaska et al but the
values were not signifi cant.6
Yuill et al found no signifi cant difference in the body
mass index between the carbohydrate and control groups or
loss of fat mass from baseline to discharge.21 Nevertheless,
preoperative oral glucose improved preservation of mus-
cle mass compared with placebo. In contrast to the above
fi ndings, Mathur et al did not notice greater preservation
of muscle mass in the carbohydrate group.16 Furthermore,
carbohydrate treatment did not ameliorate postoperative ni-
trogen loss although it did increase the levels of insulin-like
growth factor 1 postoperatively.
Effect of preoperative carbohydrate in diabetic patients
Only one trial investigated the effect of carbohydrate drink
in diabetic patients.22 The effect of carbohydrate drink was
compared in 25 type 2 diabetic patients with 10 healthy con-
Table 6 Costs of oral drinks used in various trials
Type of drink Cost
preOp® (Nutricia, Trowbridge, UK) £3.50 per 200ml
(£21.00 per pa-
tient per surgery)
Roosvicee Vruchtenmix (Heinz, Zeist, Netherlands) – syrup of rosehip and other fruits diluted in water, 70ml syrup :
330ml water
£3.99 per 200ml
(£1.39 per pa-
tient per surgery)
100g Vitajoule® (Vitafl o, Liverpool, UK) dissolved in 800ml of water – pm, 50g Vitajoule® dissolved in 400ml of water
– am
£3.77 per 500g
(£1.13 per pa-
tient per surgery)
Aminoleban® EN (Otsuka Pharmaceutical, Tokyo, Japan) – mixture of carbohydrate and BCAAs, 100g per day given
orally for 2 weeks
£13.00 per 450g
(£40.00 per pa-
tient per surgery)
pm = evening before surgery; am = morning of surgery; BCAAs = branched chain amino acids
Volume 96 Issue 1.indb 20Volume 96 Issue 1.indb 20 06/12/13 3:39 pm06/12/13 3:39 pm

21Ann R Coll Surg Engl 2014; 96: 15–22
BILKU DENNISON HALL METCALFE GARCEA ROLE OF PREOPERATIVE CARBOHYDRATE LOADING:
A SYSTEMATIC REVIEW
trols. The gastric emptying rate was assessed using intesti-
nal paracetamol absorption as a marker. Administration of
carbohydrate drink 180 minutes before anaesthesia in un-
complicated diabetes patients is safe. It does not delay gas-
tric emptying or cause hyperglycaemia.
Discussion
The traditional practice of fasting patients before surgery
results in depletion of hepatic glycogen, enhanced gluco-
neogenesis and insulin resistance.23,24 This is further ag-
gravated by the insulin resistance caused by surgery.25 The
practice of overnight fasting was fi rst challenged in 1994 by
Ljungqvist et al in patients undergoing an open cholecys-
tectomy.11 Postoperative insulin resistance was reduced by
50% in patients receiving overnight intravenous glucose
infusion. Moreover, in patients receiving glucose infusion,
hepatic glycogen content was increased by 65% during sur-
gery compared with fasting patients.26
Preoperative thirst has been suggested to be the main
contributory factor of patient discomfort, followed by hun-
ger and anxiety.27 Clear drinks alleviate thirst but their ef-
fect on hunger is inconclusive.28,29 Use of high carbohydrate
drinks preoperatively was pioneered by Nygren et al in
1995.12 It was specially designed, consisting mainly of pol-
ymers to reduce the osmotic effect of the drink on gastric
emptying. They demonstrated that the carbohydrate drink
left the stomach in 90 minutes in patients undergoing a
laparoscopic cholecystectomy after ingestion on the morn-
ing of surgery. None of the studies analysed in this review
reported any adverse events following ingestion of carbohy-
drate drinks such as apparent or proven aspiration during
or after surgery.
Preoperative carbohydrate drinks improved patient
wellbeing after surgery signifi cantly, especially hunger,
thirst, malaise, anxiety and nausea. However, no benefi t
was noted by Bisgaard et al although the values were not
statistically signifi cant.19 A combination of heterogeneous
surgical procedures, surgical access and anaesthetic proto-
cols introduces a number of variables that could diminish
the possibility of detecting any clinical benefi t of carbohy-
drate drinks.16 A longer fasting time due to delay in the start
of surgery and lower carbohydrate dose can also alleviate
the effects of carbohydrate.
The review of trials examining the effect of carbohy-
drate on preservation of muscle mass presents a mixed pic-
ture and no conclusion could be drawn regarding the role of
preoperative carbohydrate treatment. The varied method-
ology and outcome measures used could be a contributory
factor. Future studies need to be carried out to investigate
this further.
Factors that increase the risk of gastric aspiration are
pregnancy, obesity, history of metabolic disorders including
diabetes, ASA grade >2 and gastrointestinal disorders. They
were excluded from all the trials owing to fear of gastric as-
piration resulting in pulmonary complications. No evidence
was available with regard to the safety of use of carbohy-
drate drinks in these patients.
Diabetic patients are particularly at risk of poor gly-
caemic control after surgery.30 These patients have been
excluded from the majority of the studies because of fear
of delayed gastric emptying.31,32 In order to use preopera-
tive carbohydrate loading in diabetic patients, it would be
helpful to recognise patients with delayed gastric emptying.
Since the correlation between gastric emptying rate and au-
tonomic neuropathy and upper gastrointestinal symptoms
is weak, physical examination and indirect tests are of little
signifi cance.33–35 The only study that examined the effects
of carbohydrate drinks in diabetic patients was small (35
patients).22 The results cannot therefore be generalised to
all diabetic patients. Furthermore, it needs to be explored
whether carbohydrate loading has a similar benefi cial effect
on the metabolism as in non-diabetic patients.
Various oral carbohydrate preparations have been ana-
lysed and compared with placebo or overnight fasting (Table
6). The most commonly used oral formula for preoperative
carbohydrate loading in the trials was a 12.5% carbohydrate
drink (preOp®, Nutricia, Trowbridge, UK) in quantities of
400ml or 800ml. It has been shown to be iso-osmolar and
found to leave the stomach in 90 minutes with no reported
adverse effects. The commercial preparation is available in
a 200ml carton. The cost of one carton is £3.50 so it will cost
£21 per patient (4 x 200ml in the evening before surgery and
2 x 200ml on the morning of the surgery) per procedure.
One should evaluate whether this additional cost is worth
the advantageous effects of the carbohydrate drink on clini-
cal outcome.
Conclusions
Administration of oral carbohydrate drinks before surgery
is probably safe as it leaves the stomach in 90 minutes and
does not affect gastric acidity. It may have a positive infl u-
ence on a wide range of perioperative markers of clinical
outcome. There has been considerable focus in improving
the recovery times and therefore shortening postopera-
tive stay after both major and minor elective surgical pro-
cedures. This ethos has formed the basis of the enhanced
recovery programme. Preoperative carbohydrate loading
may be a useful adjunct in improving postoperative recov-
ery. Further studies are required, however, to assess its cost
effectiveness.
References
1. Thorell A, Nygren J, Ljungqvist O. Insulin resistance: a marker of surgical
stress. Curr Opin Clin Nutr Metab Care 1999; 2: 69–78.
2. Thorell A, Efendic S, Gutniak M et al. Insulin resistance after abdominal
surgery. Br J Surg 1994; 81: 59–66.
3. Krinsley JS. Effect of an intensive glucose management protocol on the
mortality of critically ill adult patients. Mayo Clin Proc 2004; 79: 992–1,000.
4. van den Berghe G, Wouters P, Weekers F et al. Intensive insulin therapy in
critically ill patients. New Engl J Med 2001; 345: 1,359–1,367.
5. Okabayashi T, Nishimori I, Yamashita K et al. Preoperative oral supplementation
with carbohydrate and branched-chain amino acid-enriched nutrient improves
insulin resistance in patients undergoing a hepatectomy: a randomized clinical
trial using an artifi cial pancreas. Amino Acids 2010; 38: 901–907.
6. Kaska M, Grosmanová T, Havel E et al. The impact and safety of preoperative
oral or intravenous carbohydrate administration versus fasting in colorectal
Volume 96 Issue 1.indb 21Volume 96 Issue 1.indb 21 06/12/13 3:39 pm06/12/13 3:39 pm

22 Ann R Coll Surg Engl 2014; 96: 15–22
BILKU DENNISON HALL METCALFE GARCEA ROLE OF PREOPERATIVE CARBOHYDRATE LOADING:
A SYSTEMATIC REVIEW
surgery – a randomized controlled trial. Wien Klin Wochenschr 2010; 122:
23–30.
7. Faria MS, de Aguilar-Nascimento JE, Pimenta OS et al. Preoperative fasting
of 2 hours minimizes insulin resistance and organic response to trauma after
video-cholecystectomy: a randomized, controlled, clinical trial. World J Surg
2009; 33: 1,158–1,164.
8. Svanfeldt M, Thorell A, Hausel J et al. Randomized clinical trial of the effect of
preoperative oral carbohydrate treatment on postoperative whole-body protein
and glucose kinetics. Br J Surg 2007; 94: 1,342–1,350.
9. Svanfeldt M, Thorell A, Hausel J et al. Effect of ‘preoperative’ oral carbohydrate
treatment on insulin action – a randomised cross-over unblinded study in
healthy subjects. Clin Nutr 2005; 24: 815–821.
10. Nygren J, Soop M, Thorell A et al. Preoperative oral carbohydrates and
postoperative insulin resistance. Clin Nutr 1999; 18: 117–120.
11. Ljungqvist O, Thorell A, Gutniak M et al. Glucose infusion instead of
preoperative fasting reduces postoperative insulin resistance. J Am Coll Surg
1994; 178: 329–336.
12. Nygren J, Thorell A, Jacobsson H et al. Preoperative gastric emptying. Ann Surg
1995; 222: 728–734.
13. Yagci G, Can MF, Ozturk E et al. Effects of preoperative carbohydrate loading
on glucose metabolism and gastric contents in patients undergoing moderate
surgery: a randomized, controlled trial. Nutrition 2008; 24: 212–216.
14. Henriksen MG, Hessov I, Dela F et al. Effects of preoperative oral carbohydrates
and peptides on postoperative endocrine response, mobilization, nutrition and
muscle function in abdominal surgery. Acta Anaesthesiol Scand 2003; 47:
191–199.
15. Hausel J, Nygren J, Lagerkranser M et al. A carbohydrate-rich drink reduces
preoperative discomfort in elective surgery patients. Anesth Analg 2001; 93:
1,344–1,350.
16. Mathur S, Plank LD, McCall JL et al. Randomized controlled trial of
preoperative oral carbohydrate treatment in major abdominal surgery. Br J Surg
2010; 97: 485–494.
17. Helminen H, Viitanen H, Sajanti J. Effect of preoperative intravenous
carbohydrate loading on preoperative discomfort in elective surgery patients.
Eur J Anaesthesiol 2009; 26: 123–127.
18. Hausel J, Nygren J, Thorell A et al. Randomized clinical trial of the effects of
oral preoperative carbohydrates on postoperative nausea and vomiting after
laparoscopic cholecystectomy. Br J Surg 2005; 92: 415–421.
19. Bisgaard T, Kristiansen VB, Hjortsø NC et al. Randomized clinical trial
comparing an oral carbohydrate beverage with placebo before laparoscopic
cholecystectomy. Br J Surg 2004; 91: 151–158.
20. Noblett SE, Watson DS, Huong H et al. Pre-operative oral carbohydrate loading
in colorectal surgery: a randomized controlled trial. Colorectal Dis 2006; 8:
563–569.
21. Yuill KA, Richardson RA, Davidson HI et al. The administration of an oral
carbohydrate-containing fl uid prior to major elective upper-gastrointestinal
surgery preserves skeletal muscle mass postoperatively – a randomised clinical
trial. Clin Nutr 2005; 24: 32–37.
22. Gustafsson UO, Nygren J, Thorell A et al. Pre-operative carbohydrate loading
may be used in type 2 diabetes patients. Acta Anaesthesiol Scand 2008; 52:
946–951.
23. Rothman D, Magnusson I, Katz LD et al. Quantifi cation of hepatic
glycogenolysis and gluconeogenesis in fasting humans with 13C NMR. Science
1991; 254: 573–576.
24. Sunzel H. Effects of surgical trauma on the liver glycogen in fasting and in
glucose-fed patients. Acta Chir Scand 1963; 125: 118–128.
25. Nygren J. The metabolic effects of fasting and surgery. Best Pract Res Clin
Anaesthesiol 2006; 20: 429–438.
26. Thorell A, Alston-Smith J, Ljungqvist O. The effect of preoperative carbohydrate
loading on hormonal changes, hepatic glycogen, and glucoregulatory enzymes
during abdominal surgery. Nutrition 1996; 12: 690–695.
27. Madsen M, Brosnan J, Nagy VT. Perioperative thirst: a patient perspective.
J Perianesth Nurs 1998; 13: 225–228.
28. Splinter WM, Stewart JA, Muir JG. Large volumes of apple juice preoperatively
do not affect gastric pH and volume in children. Can J Anaesth 1990; 37:
36–39.
29. Splinter WM, Stewart JA, Muir JG. The effect of preoperative apple juice on
gastric contents, thirst, and hunger in children. Can J Anaesth 1989; 36:
55–58.
30. Furnary AP, Zerr KJ, Grunkemeier GL, Starr AJ. Continuous intravenous insulin
infusion reduces the incidence of deep sternal wound infection in diabetic
patients after cardiac surgical procedures. Ann Thorac Surg 1999; 67:
352–360.
31. Park MI, Camilleri M. Gastroparesis: clinical update. Am J Gastroenterol 2006;
101: 1,129–1,139.
32. Horowitz M, O’Donovan D, Jones KL et al. Gastric emptying in diabetes: clinical
signifi cance and treatment. Diabet Med 2002; 19: 177–194.
33. Stacher G, Lenglinger J, Bergmann H et al. Impaired gastric emptying and
altered intragastric meal distribution in diabetes mellitus related to autonomic
neuropathy? Dig Dis Sci 2003; 48: 1,027–1,034.
34. Ziegler D, Schadewaldt P, Pour Mirza A et al. [13C]octanoic acid breath test
for non-invasive assessment of gastric emptying in diabetic patients: validation
and relationship to gastric symptoms and cardiovascular autonomic function.
Diabetologia 1996; 39: 823–830.
35. Jebbink HJ, Bravenboer B, Akkermans LM et al. Relationships between
dyspeptic symptoms and gastrointestinal motility in patients with type 1
(insulin-dependent) diabetes mellitus. Diabetologia 1993; 36: 948–954.
Volume 96 Issue 1.indb 22Volume 96 Issue 1.indb 22 06/12/13 3:39 pm06/12/13 3:39 pm