Preoperative oral carbohydrate nutrition: an update
Jonas Nygren, Anders Thorell and Olle Ljungqvist
Insulin resistance is a central feature of the metabolic response
after elective surgery as well as other trauma, and has been
shown to be a predictor of the length of stay after surgery.
Carbohydrate treatment instead of overnight fasting before
surgery has been shown to reduce postoperative insulin
resistance and to reduce hospital stay approximately 20% after
elective surgery. For potential use as a clinical routine before
surgery, a carbohydrate-rich drink was developed. Gastric
emptying of a 50 g oral carbohydrate load using this drink is
complete within 90 min after intake. Oral carbohydrate loading
before surgery has confirmed previous data, using glucose and
insulin infusions, that postoperative insulin resistance is reduced
compared with overnight fasted patients before surgery, and
this is associated with improved well-being before and after
surgery. Curr Opin Clin Nutr Metab Care 4:255±259. # 2001 Lippincott Williams
& Wilkins.
Centre of Gastrointestinal Disease, Karolinska Institutet at Ersta Hospital and
Huddinge University Hospital, Stockholm, Sweden
Correspondence to Olle Ljungqvist, MD, PhD, Centre of Gastrointestinal Disease,
Ersta Hospital, PO Box 4622, SE-116 91 Stockholm, Sweden
Tel: +46 8 714 6100; fax: +46 8 714 6665; e-mail: olle.ljungqvist@ersta.se
Current Opinion in Clinical Nutrition and Metabolic Care 2001, 4:255±259
Abbreviations
IGF-1
LOS
insulin-like growth factor type 1
length of stay
# 2001 Lippincott Williams & Wilkins
1363-1950
Introduction
Surgery is a common treatment for medical disorders. In
Sweden, with 8 million inhabitants, over 400 000 surgical
treatments are performed annually, excluding outpatients. Approximately 5% of the population thus
undergo surgery every year. Surgical trauma, as well as
other causes of injury, induce a catabolic response
characterized by the release of stress hormones (glucagon, cortisol and catecholamines) and in¯ammatory
mediators such as cytokines. In addition, there is a
reduction in the effects of insulin (insulin resistance) and
usually a compensatory increase in insulin release.
Despite increased insulin release, insulin action is
reduced, resulting in increased blood glucose levels
and a state of metabolism similar to non-insulindependent diabetes mellitus [1]. Using stable isotopes
of glucose (6,6,[2H2]-glucose) and the hyperinsulinaemic, normoglycaemic clamp technique, it has been
shown that the splanchnic tissues play only a minor
role, and that the main sites of postoperative insulin
resistance are in the periphery [2]. Further studies [3]
have revealed that a defect in speci®c intracellular
glucose transporting proteins, GLUT 4, seem to be
involved in the development of postoperative insulin
resistance. Intracellularly, glucose oxidation seems to be
better maintained, whereas non-oxidative glucose metabolism (glycogen synthesis) is unresponsive to insulin
[2]. Despite initially increased levels of growth hormone,
there is a reduction in the circulating levels of insulinlike growth factor type 1 (IGF-1), another important
anabolic hormone with several insulin-like effects, and
the development of `growth hormone resistance' [4].
Post-surgical catabolism also results in a loss of protein
and fat stores, and the catabolic changes are likely to be
important for the outcome of surgery. A recent statistical
analysis of postoperative insulin resistance [1] showed
that this metabolic change was an independent factor
predicting the variation in length of hospital stay. A
lower degree of postoperative insulin resistance therefore seems to be associated with improved recovery from
surgery.
Efforts to reduce surgical stress
Considerable efforts have been made to reduce the
stress during surgery, such as the development of epidural and other regional anaesthesiological techniques
[5], the maintenance of body temperature during the
operation [6], minimally invasive surgical techniques,
and techniques aiming at reducing blood loss and tissue
damage [7]. Also, after the operation, acute pain control,
with the minimal use of opioids, using epidural
255
256 Carbohydrates
anaesthesia and non-steroidal anti-in¯ammatory drug
therapy may facilitate early enteral nutrition and
mobilization, and this multimodal approach has been
demonstrated to accelerate recovery after major abdominal surgery [5].
Less attention has been given to treatments in the
preoperative period that may affect the outcome. It has
been demonstrated that improving the nutritional status
of the patient using total parenteral nutrition over several
days before surgery is only bene®cial in patients with
severe malnutrition (410% weight loss) [8]. Preoperative enteral nutrition, although studies are limited, has
not been shown to reduce postoperative morbidity in
otherwise well-nourished patients [9]. Even if all agree
that a medical treatment should be scienti®cally proved
to be ef®cient in order to be recommended, there are
still many common medical treatments that depend
more on tradition and clinical experience than scienti®c
evaluation. Such examples are the frequent use of
nasogastric tubes, abdominal drains and restrictions in
oral intake after surgery, some of which are still in use
despite evidence against them [10].
Another old tradition is the practice of overnight fasting
before elective surgery. This has been recommended
ever since the early days of anaesthesia, to avoid
pulmonary aspiration of gastric contents during anaesthesia and surgery. Patients may be fasted for 12±16 h
from their last meal in the evening before the operation
until the initiation of surgery. After this period of fasting,
liver glycogen stores are largely depleted and body
metabolism is in the fasted state, with a net breakdown
of fat and protein, glycogenolysis and increased gluconeogenesis at hand [11]. Along with this, anabolic
activity in the fasted patient is low in response to the
caloric restriction. Whether the metabolic state before
surgery has any impact on postoperative metabolism and
clinical outcome has thus been tested in a number of
recent studies.
Carbohydrate treatment before surgery
Earlier studies have shown that glucose infusion before
surgery reduced nitrogen losses immediately after
surgery compared with patients fasted before surgery
[12]. In addition, the infusion of glucose, insulin and
potassium before cardiac surgery has repeatedly been
shown to reduce cardiac morbidity and hospital stays
[13,14]. As reviewed elsewhere, a series of animal studies
demonstrated that rats fed before haemorrhagic or
endotoxaemic stress had an attenuated stress response
and a better outcome than rats starved before the same
stress [15]. As a result of such animal studies, which all
showed a clear bene®t from being in the fed as opposed
to the fasted state at the onset of stress, surgical patients
were studied. This hypothesis was ®rst tested in a
randomized study using a high-dose intravenous infusion
of glucose (5 mg/kg/min) overnight before surgery in
patients undergoing elective open cholecystectomy [16].
This glucose infusion rate increased endogenous insulin
release to serum insulin levels seen after a normal meal
[17]. Studies using the hyperinsulinaemic, normoglycaemic clamp technique [16] showed that these patients
displayed 42% less insulin resistance on the ®rst postoperative day compared with patients fasted overnight
before the same surgical procedure. In a follow-up study
[18], a slightly different mode of changing metabolism
was used. This time, patients undergoing hip replacement were given both insulin and glucose infusion for a
couple of hours before and during surgery. Again, using
the hyperinsulinaemic, normoglycaemic clamp technique and (6,6,[2H2]-glucose), these patients were found
to have unchanged insulin sensitivity (+ 18%), whole
body glucose disposal (+ 23%), and substrate utilization
in the ®rst few hours after the completion of surgery,
compared with measurements in the same subjects
before surgery. This maintenance of insulin sensitivity
and substrate utilization after surgery in insulin and
glucose infused subjects was in contrast to the reduction
in insulin sensitivity and glucose disposal (740 and
729%) found in patients who were fasted overnight
before the same surgical procedure [18].
In clinical practice, the use of intravenous glucose (10±
20% glucose in order to avoid ¯uid overloading of the
patient) and insulin infusions require access to large
veins, frequent controls of blood glucose levels, and
adjustment of the glucose infusion rates to maintain
blood glucose at a preferred level by trained staff. Many
of these problems would be overcome if carbohydrates
could be provided enterally. However, gastric emptying
rates of glucose beverages are slower than for water and
other low-caloric clear ¯uids, and increased volumes in
the stomach at the start of anaesthesia might increase the
risk of aspiration.
Preoperative oral carbohydrate treatment
During the past few years, the rationale for the old
preoperative fasting routine has been questioned. A
strong body of evidence shows that the free intake of
clear ¯uids, such as water, light apple juice, tea and
coffee can be allowed up until 2±3 h before anaesthesia
and surgery without increased risk for the patients [19].
The intake of these drinks improves the subjective wellbeing of the patient by reducing thirst before the
operation. However, such ¯uids contain only limited
amounts of calories, and the fasting state before surgery
is not affected by these new guidelines.
To be able to give patients a large carbohydrate load
before surgery, the risks associated with this treatment
had to be assessed, and had to be proved to be minimal.
Preoperative oral carbohydrate nutrition Nygren et al. 257
For this purpose, a carbohydrate-rich beverage was
developed (12.5% carbohydrate, 285 mOsm) for preoperative use. The carbohydrates were mixed primarily
in the form of polymers (maltodextrins) to reduce the
osmolarity of the ¯uid given and thereby accelerate
gastric emptying of the beverage [20]. A dose of 400 ml
of this beverage, given to healthy volunteers or patients
about to undergo surgery, increased serum insulin to
levels seen after a standard mixed meal (60 mU/ml),
thereby providing enough energy to switch the patient
from the fasted to the fed state before the onset of
surgery [20]. Gastric emptying, measured by gamma
camera, of 400 ml of this beverage was found to be
complete within 90 min after intake in both healthy
individuals and in patients about to undergo surgery.
Moreover, gastric emptying was found not to be affected
in preoperative patients [20]. These data allowed further
clinical testing of the safety of this beverage. In a
preliminary report on approximately 120 patients undergoing elective surgery after an overnight fast [21], the
intake of 400 ml of the carbohydrate beverage or the
intake of placebo showed no difference in residual
volumes (approximately 35 ml) or the pH of the gastric
contents at the time of anaesthesia. These experiences
were later extended in clinical trials to involve approximately 600 patients, still with no adverse events
recorded (data on ®le). In addition, no adverse events
have been recorded in approximately 2000 patients
taking this regimen in clinical practice.
Patients with a probable delay in gastric emptying have
been excluded from the new fasting guidelines and the
studies of this treatment, including patients with
dyspepsia and gastroesophageal re¯ux. Safety issues
arising from oral carbohydrate treatment in any of these
groups with a suspected increased risk of aspiration have
to be dealt with in separate studies. So far, only patients
undergoing gastroscopy have been studied with regard to
the gastric emptying of this carbohydrate drink [22].
These patients all have some problems that are likely to
be located in the upper gastrointestinal tract, and they
are not routinely allowed to take any beverage before the
investigation. However, when these patients prepared
for gastroscopy with an overnight fast, or the above
regimens with carbohydrate or placebo beverages
(n = 3660), the average gastric volume was again the
same in all three groups. However, using 400 ml given as
a single dose 2 h before the gastroscopy, ®ve of these
patients had gastric volumes of more than 100 ml, and all
of these had taken a beverage. In a follow-up study [22],
the beverage was given as 200 ml twice, the ®rst dose
3 h before and the second dose 2 h before the
gastroscopy. Using this regimen, no patient had a gastric
volume greater than 140 ml. Even though there was no
evidence that gastric emptying was delayed in the study,
patients with gastroesophageal re¯ux may still have an
increased risk of aspiration. The emptying patterns of
this carbohydrate drink, and the risks and bene®ts
associated with preoperative carbohydrate loading in
these patients still need to be determined. The same is
also true for other subgroups of patients, such as those
with diabetes, and severely obese individuals.
Preoperative oral carbohydrate treatment to
reduce postoperative insulin resistance
The metabolic effects of preoperative carbohydrate
treatment have also been tested. An intake of 800 ml
(100 g carbohydrate) the evening before the operation
and another 400 ml approximately 2±3 h before the
operation was shown to reduce postoperative insulin
resistance by 29% 24 h after major abdominal surgery,
compared with patients fasted overnight before the same
surgical procedures [23]. The drink was thus as effective
as intravenous glucose infusions. Whole-body glucose
disposal was 47% less reduced (see Fig. 1), whereas no
effect from treatment was found in non-oxidative
glucose disposal. Although basal endogenous glucose
production increased in both groups after surgery, insulin
inhibition of endogenous glucose production was not
affected by surgery in any group. The endocrine
response to surgery may add some explanation for the
less reduced insulin sensitivity after preoperative carbohydrate loading. Although no differences were found
regarding the stress hormones cortisol, glucagon or the
catecholamines, levels of free IGF-1 were increased in
carbohydrate-loaded patients. This was associated with
an increased proteolysis of insulin-like growth factor
binding protein-protein-3, the main carrier protein of
circulating IGF-1 [24]. However, levels of insulin-like
growth factor binding protein-protein-1, another important regulator of IGF-1 activity, were no different
between the groups [25]. As IGF-1 have insulin-like
effects on glucose uptake, increased IGF-1 activity may
add to the improved insulin sensitivity after surgery in
carbohydrate-loaded patients.
As bed-rest and hypocaloric nutrition may contribute to
reduced insulin sensitivity after surgery [2], the effect of
preoperative oral carbohydrate loading was also studied
in patients undergoing total hip replacement immediately after the completion of surgery in a randomized
placebo-controlled study [26 . .] (see Fig. 1). Also
immediately after surgery, carbohydrate-loaded patients
displayed 58% less insulin resistance and 49% less
reduced insulin stimulated glucose disposal compared
with those given placebo. As in previous studies, insulin
did not increase non-oxidative glucose disposal in any
group after surgery, whereas insulin suppression of
endogenous glucose production was unaffected by
surgery in both groups [2,23]. In addition, glucose
oxidation rates were less affected (+42% versus 76%,
carbohydrate and placebo), whereas fat oxidation rates
258 Carbohydrates
Figure 1. The relative change in whole-body glucose disposal after
elective abdominal surgery or hip replacement compared with the
preoperative situation in ' patients given a carbohydrate-rich drink
before surgery filled bar or being fasted overnight (abdominal
surgery, control open bar) or given placebo (hip replacement,
control open bar)
Abdominal
surgery
0
% Change vs.
preoperatively –10
– 20
– 30
– 40
– 50
– 60
Hip replacement
*
*
Mean+SEM, *P50.05 versus control. Data adapted from Nygren et al.
[23] and Soop et al. [26 . .].
were lower in carbohydrate-loaded individuals during
and after surgery. This may also be an additional
explanation for the improved insulin sensitivity in
carbohydrate-loaded individuals, because it is well
known that the increased availability of free fatty acids
by the infusion of lipids and the subsequent increase in
fat oxidation reduce insulin sensitivity [27].
Preoperative oral carbohydrates improve
well-being before and after surgery
In addition, although still preliminary, data have been
produced to suggest reduced preoperative discomfort (as
determined using visual analogue scales) in patients
given a carbohydrate-rich beverage preoperatively. This
treatment had a positive effect with regard to thirst,
hunger, and anxiety [21]. In another preliminary study of
patients undergoing elective colorectal surgery [28],
postoperative discomfort was also reduced by this
preoperative preparation. Moreover, a preliminary report
from a Danish group [29], using a very similar beverage,
reported that preoperative oral carbohydrates showed a
strong trend towards improving muscle strength for one
month after colorectal surgery. The underlying mechanisms of this somewhat surprising effect are not known.
Preoperative carbohydrate treatment
reduces hospital stay after surgery
To investigate if the change in metabolic state from the
overnight fasted state to that of a carbohydrate fed state
has any impact on length of stay (LOS) in hospital after
surgery, data from three studies of patients loaded with
carbohydrates before surgery either intravenously or
orally, were analysed [30]. The hospital records from
those studies [16,18,23] were retrieved, and LOS and
complications (none) were recorded retrospectively. All
studies can be referred to as randomized controlled trials,
albeit not double blinded. However, because the
physicians taking care of the patients were not aware
of which patient had received which treatment, and as
LOS was not under investigation at the time of the
studies, the risk of bias is very low. A multiple regression
analysis was performed on the entire material (a total of
52 patients) to reveal what factors might in¯uence the
variation in LOS. These were the type of surgery, body
mass index, age, and preoperative carbohydrate treatment. Using these four variables, 71% of the variation in
LOS could be explained. In this analysis it was shown
that after open cholecystectomy, LOS was reduced by
0.7 days, after hip replacement by 1.4 days, and after
colorectal surgery by 2.1 days [30]. Although all three
studies showed the same trend towards shorter LOS
after preoperative carbohydrate treatment, this was not
statistically signi®cant in the individual studies. However, when these values were used in a meta-analysis
[30], the average effect of preoperative carbohydrate
treatment was signi®cant (P50.02), with an average
reduction in LOS of 1.2 days, corresponding to
approximately 20%.
Conclusion
Carbohydrate treatment shortly before elective surgery
reduces postoperative insulin resistance. This metabolic
change is an independent factor predicting the variation
in LOS, and is likely to be an important determinant for
the recovery of the patient. In addition, preliminary data
suggest that well-being is improved pre- and postoperatively when carbohydrates are given as a beverage
2±3 h before the operation. This method has been
tested in a total of approximately 600 patients in various
studies and in approximately 2000 patients in regular
clinical practice without any adverse events being
reported, suggesting that it is safe to use. Finally, a
meta-analysis of three prospectively controlled trials [30]
indicated that LOS is reduced by approximately 20% by
preoperative carbohydrate compared with surgery in the
overnight fasted state, suggesting that this simple
treatment may have a positive effect on outcome after
elective surgery.
Acknowledgements
This paper summarizes work that was partly supported by the Swedish
Medical Research Council (09101), with funding from the Karolinska
Institutet, Sweden and from Numico Research, Holland.
References and recommended reading
Papers of particular interest, published within the annual period of review, have
been highlighted as:
.
of special interest
..
of outstanding interest
1
Thorell A, Nygren J, Ljungqvist O. Insulin resistance: a marker of surgical
stress. Curr Opin Clin Nutr Metab Care 1999; 2:69±78.
Preoperative oral carbohydrate nutrition Nygren et al. 259
2
Nygren J, Thorell A, Efendic S, et al. Site of insulin resistance after surgery:
the contribution of hypocaloric nutrition and bed rest. Clin Sci (Colch) 1997;
93:137±146.
3
Thorell A, Hirshman MF, Nygren J, et al. Exercise and insulin cause GLUT-4
translocation in human skeletal muscle. Am J Physiol 1999; 277:E733±E741.
4
Timmins AC, Cotterill AM, Hughes SC, et al. Critical illness is associated
with low circulating concentrations of insulin-like growth factors-I and -II,
alterations in insulin-like growth factor binding proteins, and induction of an
insulin-like growth factor binding protein 3 protease. Crit Care Med 1996;
24:1460±1466.
17 Gutniak M, Grill V, Efendic S. Effect of composition of mixed meals ± lowversus high-carbohydrate content ± on insulin, glucagon, and somatostatin
release in healthy humans and in patients with NIDDM. Diabetes Care 1986;
9:244±249.
18 Nygren JO, Thorell A, Soop M, et al. Perioperative insulin and glucose
infusion maintains normal insulin sensitivity after surgery. Am J Physiol 1998;
275:E140±E148.
19 Fasting S, Soreide E, Raeder JC. Changing preoperative fasting policies.
Impact of a national consensus. Acta Anaesthesiol Scand 1998; 42:1188±
1191.
20 Nygren J, Thorell A, Jacobsson H, et al. Preoperative gastric emptying.
Effects of anxiety and oral carbohydrate administration. Ann Surg 1995;
222:728±734.
5
Kehlet H. Multimodal approach to control postoperative pathophysiology and
rehabilitation. Br J Anaesth 1997; 78:606±617.
6
Sellden E, Lindahl SG. Amino acid-induced thermogenesis reduces
hypothermia during anesthesia and shortens hospital stay. Anesth Analg
1999; 89:1551±1556.
7
Bardram L, Funch-Jensen P, Jensen P, et al. Recovery after laparoscopic
colonic surgery with epidural analgesia, and early oral nutrition and
mobilisation. Lancet 1995; 345:763±764.
22 Hausel J, Thorell A, Nygren J, et al. Preoperative beverages in patients with
upper GI symptoms. Clin Nutr 2000; 19 (Suppl. 1):132.
8
The Veterans Affairs Total Parenteral Nutrition Cooperative Study Group.
Perioperative total parenteral nutrition in surgical patients. N Engl J Med
1991; 325:525±532.
23 Nygren J, Soop M, Thorell A, et al. Preoperative oral carbohydrate
administration reduces postoperative insulin resistance. Clin Nutr 1998;
17:65±71.
9
Meijerink WJ, von Meyenfeldt MF, Rouflart MM, Soeters PB. Efficacy of
perioperative nutritional support. Lancet 1992; 340:187±188.
24 Bang P, Nygren J, Carlsson-Skwirut C, et al. Postoperative induction of
insulin-like growth factor binding protein-3 proteolytic activity: relation to
insulin and insulin sensitivity. J Clin Endocrinol Metab 1998; 83:2509±2515.
10 Holte K, Kehlet H. Postoperative ileus: a preventable event. Br J Surg 2000;
87:1480±1493.
11 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.
12 Crowe PJ, Dennison A, Royle GT. The effect of pre-operative glucose
loading on postoperative nitrogen metabolism. Br J Surg 1984; 71:635±637.
13 Lazar HL, Philippides G, Fitzgerald C, et al. Glucose±insulin±potassium
solutions enhance recovery after urgent coronary artery bypass grafting. J
Thorac Cardiovasc Surg 1997; 113:354±360; discussion 360±362.
14 Quinones-Galvan A, Ferrannini E. Metabolic effects of glucose-insulin
infusions: myocardium and whole body. Curr Opin Clin Nutr Metab Care
2001; 4:157±163.
15 Ljungqvist O, Nygren J, Hausel J, Thorell A. Preoperative nutrition therapy ±
novel developments. Scand J Nutr/NaÈringsforskning 2000; 44:3±7.
16 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.
21 Nygren J, Thorell A, Lagercranser M, et al. Safety and patient well-being after
preoperative oral intake of carbohydrate rich beverage. Clin Nutr 1996; 16
(Suppl. 1):28.
25 Nygren J, Carlsson-Skwirut C, Brismar K, et al. Insulin infusion increases
levels of free IGF-1 and IGFBP-3 proteolytic activity in patients after surgery.
Am J Physiol 2001; in press.
26 Soop M, Nygren J, Myrenfors P, et al. Preoperative oral carbohydrate treatment
. . attenuates immediate postoperative insulin resistance. Am J Physiol Endocrinol
Metab 2001; 280:E576±E583.
This reference shows that preoperative oral carbohydrates reduce postoperative
insulin resistance in the absence of confounding factors such as immobilisation
and semi-starvation.
27 Groop LC, Saloranta C, Shank M, et al. The role of free fatty acid metabolism
in the pathogenesis of insulin resistance in obesity and noninsulin-dependent
diabetes mellitus. J Clin Endocrinol Metab 1991; 72:96±107.
28 Hausel J, Nygren J, AlmstroÈm C, et al. Preoperative oral carbohydrates
improve well being after elective colorectal surgery. Clin Nutr 1999; 18
(Suppl. 1):80.
29 Henriksen M, Hansen H, Dela F, et al. Preoperative feeding might improve
postoperative voluntary muscle function. Clin Nutr 1999; 18 (Suppl. 1):82.
30 Ljungqvist O, Nygren J, Thorell A, et al. Preoperative nutrition ± elective
surgery in the fed or the overnight-fasted state. Clin Nutr 2001, in press.
MCO (CN)
Manuscript No.
040408
Clinical Nutrition and
Metabolic Care
Typeset by Elite Typesetting for
Lippincott Williams & Wilkins
www.elitetypesetting.com
QUERIES: to be answered by AUTHOR
AUTHOR: The following queries have arisen during the editing of your manuscript.
Please answer the queries by marking the requisite corrections at the appropriate positions
in the text.
QUERY DETAILS
QUERY NO.
Reference bullet(s) do not correspond with each
other in reference section and text.
References are bulleted but have no annotations.
26
References have annotations but are not bulleted.
30
References which have more than 3 authors
need et al. If only 4 authors, leave as 4 authors.
Incorrect page spans in references.
Page spans need to be in full.
References missing.
The following references are missing
their volume number.
The following references are missing
their initials.
The following references are missing
their journal title.
Additional queries:
1
60 mU/ml in text - is this correct?
21