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86
Nutr Hosp. 2011;26(1):86-90
ISSN 0212-1611 • CODEN NUHOEQ
S.V.R. 318
Original
Safety of oral glutamine in the abbreviation of preoperative fasting;
a double-blind, controlled, randomized clinical trial
D. Borges Dock-Nascimento1, J. E. D Aguilar-Nascimento2, C. Caporossi2, M. Sepulveda Magalhães
Faria2, R. Bragagnolo3, F. Stephan Caporossi3and D. Linetzky Waitzberg4
1Department of Food and Nutrition. Federal University of Mato Grosso. Cuiabá. Brazil. 2Department of Surgery. Federal
University of Mato Grosso. Cuiabá. Brazil. 3Multidisciplinary Team. Julio Muller Hospital. Federal University of Mato
Grosso. Cuiabá. Brazil. 4Department of Gastroenterology. São Paulo University. São Paulo. Brazil.
SEGURIDAD DE LA GLUTAMINA ORAL EN LA
ABREVIACIÓN DEL AYUNO PREOPERATORIO;
UN ENSAYO CLÍNICO DOBLE CIEGO,
CONTROLADO, ALEATORIZADO
Resumen
Introducción: Ningún estudio hasta el momento ha
investigado una bebida que contiene glutamina 2 h antes
de la anestesia en pacientes sometidos a cirugía.
Objetivos: El objetivo del estudio fue investigar: 1) la
seguridad de la abreviación del ayuno preoperatorio para
2 h con una bebida conteniendo carbohidratos y L-gluta-
mina, y 2) el volumen gástrico residual (RGV), medido
después de la inducción de la anestesia en colecistecto-
mías laparoscópicas.
Métodos: Ensayo controlado aleatorizado con 56 muje-
res (42 (17-65) años) sometidas a colecistectomía laparoscó-
pica electiva. Las pacientes fueron aleatorizadas para reci-
bir ayuno preoperatorio convencional de 8 horas (grupo
ayuno, n = 12) o una de tres bebidas diferentes tomadas la
noche antes de la cirugía (400 ml) y también 2 horas antes
del inicio de la anestesia (200 ml). Las bebidas eran agua
(grupo placebo n = 12), 12,5% (240 mOsm/l) maltodextrina
(grupo carbohidrato, n = 12) o carbohidrato además de 50 g
(40 g la noche anterior y 10 g por la mañana) de L-gluta-
mina (grupo glutamina, n = 14). Una sonda nasogástrica 20
F fue insertada inmediatamente después de la inducción de
la anestesia general para aspirar y medir el RGV.
Resultados: Cincuenta pacientes completaron el estu-
dio. Ninguno de los pacientes han presentado regurgita-
ción durante la inducción de la anestesia ni complicacio-
nes postoperatorias. La mediana (variación) del RGV fue
de 6 (00-80) mL. El RGV fue similar (p = 0,29) entre el
grupo glutamina (4,5 [0-15] mL), el grupo carbohidrato
(7,0 [0,80] mL), grupo placebo (8,5 [0-50] mL), y grupo
ayuno (5,0 [0-50] mL).
Conclusión: La abreviación del ayuno preoperatorio
para 2 h con carbohidratos y L-glutamina es seguro y no
aumenta el RGV durante la inducción de la anestesia.
(Nutr Hosp. 2011;26:86-90)
DOI:10.3305/nh.2011.26.1.4993
Palabras clave: Colecistectomía. Ayuno preoperatorio.
Glutamina. Volumen gástrico residual. Estudio controlado
aleatorizado.
Abstract
Introduction: No study so far has tested a beverage con-
taining glutamine 2 h before anesthesia in patients under-
going surgery.
Objectives: The aim of the study was to investigate: 1)
the safety of the abbreviation of preoperative fasting to 2 h
with a carbohydrate-L-glutamine-rich drink; and 2) the
residual gastric volume (RGV) measured after the induc-
tion of anesthesia for laparoscopic cholecystectomies.
Methods: Randomized controlled trial with 56 women
(42 (17-65) years-old) submitted to elective laparoscopic
cholecystectomy. Patients were randomized to receive
either conventional preoperative fasting of 8 hours
(fasted group, n = 12) or one of three different beverages
drunk in the evening before surgery (400 mL) and 2 hours
before the initiation of anesthesia (200 mL). The beverages
were water (placebo group, n = 12), 12.5% (240 mOsm/L)
maltodextrine (carbohydrate group, n = 12) or the latter
in addition to 50 g (40 g in the evening drink and 10g in the
morning drink) of L-glutamine (glutamine group, n = 14).
A 20 F nasogastric tube was inserted immediately after
the induction of general anesthesia to aspirate and mea-
sure the RGV.
Results: Fifty patients completed the study. None of the
patients had either regurgitation during the induction of
anesthesia or postoperative complications. The median
(range) of RGV was 6 (0-80) mL. The RGV was similar
(p = 0.29) between glutamine group (4.5 [0-15] mL), car-
bohydrate group (7.0 [0-80] mL), placebo group (8.5 [0-
50] mL), and fasted group (5.0 [0-50] mL).
Conclusion: The abbreviation of preoperative fasting
to 2 h with carbohydrate and L-glutamine is safe and does
not increase the RGV during induction of anesthesia.
(Nutr Hosp. 2011;26:86-90)
DOI:10.3305/nh.2011.26.1.4993
Key words: Cholecystectomy. Preoperative fasting. Gluta-
mine. Residual gastric volume. Randomized controlled study.
Correspondence: Jose E. Aguilar-Nascimento.
Department of Surgery. Federal University of Mato Grosso.
Rua Estevao de Mendonça, 81, apto. 801.
78043-300 Cuiabá. Brazil.
E-mail: aguilar@terra.com.br
Recibido: 22-VII-2010.
1.ª Revisión: 15-IX-2010.
Aceptado: 22-IX-2010.
Introduction
The main reason for traditional 8 hours of preopera-
tive fasting is to reduce the volume and acidity of stom-
ach contents, thus decreasing the risk of regurgitation
and aspiration recognized as Mendelson’s syndrome.1
In the 1980s, it was already known that gastric empty-
ing of water and other noncaloric fluids followed an
extremely fast exponential curve in volunteers.2,3 Vari-
ous randomized controlled studies4-6 and a meta-
analyse7in adults scheduled for elective surgery have
consistently documented that oral intake of water and
other clear fluids up to 2 h before induction of anesthe-
sia does not increase gastric volume or acidity. The use
of carbohydrate-rich beverage in the immediate preop-
erative period is not only safe, but may also reduce the
catabolic stress response to surgery and thus enhance
postoperative recovery.8,9 The use of additional meta-
bolic conditioning agents such as glutamine may be of
potential benefit to patients undergoing surgery. Gluta-
mine is a conditionally essential amino acid, which
improves both gastrointestinal perfusion and immune
function,10 and possesses a multiple beneficial systemic
function.11 A beverage containing glutamine in addi-
tion to carbohydrate may, therefore, provide additional
benefits to surgical patients, beyond carbohydrate
loading alone. One study has shown that gastric empty-
ing time for beverages containing glutamine is approx-
imately 160 minutes in healthy volunteers.12 However
no study so far has tested this solution in patients
undergoing surgery offered two hours before anesthe-
sia. The aim of the study was to investigate: 1) the
safety of the abbreviation of preoperative fasting to 2 h
with a carbohy drate-L-glutamine-rich drink; and 2) the
residual gastric volume (RGV) measured after the
induction of anesthesia for laparoscopic cholecystec-
tomies.
Materials and methods
A group of 56 adult women (median age = 42 (17-
65) years-old) scheduled to undergoing elective
laparoscopic cholecystectomy at Santa Rosa Hospital,
Cuiabá, Brazil were eligible for inclusion in this trial.
Exclusion criteria were: American Society of Anesthe-
siologists (ASA) score above II, diabetes mellitus,
pregnancy, age above 65 years old, renal or hepatic
failure, gastroesophageal reflux, acute cholecystitis,
use of corticosteroids up to 6 months previously, and
any noncompliance or violation on the assigned proto-
col of preoperative fasting. The local ethics committee
approved the study, and all patients gave written
informed consent before randomization.
Three patients were excluded before randomization
due to refusal to participate (1) or age above 65 years-
old (2). Patients were randomized to receive either con-
ventional preoperative fasting of 8 hours (fasted group,
n =12) or one of three different beverages to be drunk
in the evening before surgery (400 mL) and 2 hours
before the initiation of anesthesia (200 mL). The bever-
ages were water (placebo group, n = 14), 12.5% (240
mOsm/L) maltodextrine (Nidéx®, Nestlé, São Paulo,
Brazil) (carbohydrate group, n = 12) or the latter in
addition to 50 grams (40 g in the evening drink and 10 g
in the morning drink 2 hours before the induction of
anesthesia) of L-glutamine (Resource Glutamine®,
Nestlé, São Paulo Brazil (glutamine group, n = 15).
Osmolarity of the beverage containing L-glutamine
was either 639.2 mOsm/L (evening drink, 400 mL) or
219.8 mOsm/L (morning drink, 200 mL).
Preoperative protocol
All patients received both oral and written informa-
tion about the protocol at the outpatient clinic. The
assignment was done by randomized numbers arranged
by a computer. Operations were scheduled to begin at
7:00 AM The evening before operation patients were
free to ingest solid food until 11:00 PM. The patients
belonging to the three groups of abbreviation of fasting
were told to ingest the beverage at 11:00 PM (400 mL)
and at 5:00 AM (200 mL), and be at the hospital admis-
sion unit at 6:00 AM.
Intraoperative protocol
A 20 F nasogastric tube was inserted immediately
after the induction of anesthesia to aspirate and mea-
sure the gastric contents. Placement of the nasogastric
tube was checked by a stethoscope positioned over the
epigastric region followed by a bolus injection of 10-20
cc of air. Patients were submitted to general anesthesia
without epidural blockage and received a single dose of
1 g of intravenous cefazolin.
Outcome variable and statistical analysis
Sample size was calculated supposing a mean differ-
ence of 3 mL (based on a pilot study) in the RGV and
with a standard deviation of 2 mL. Therefore a number of
11 cases per group were estimated to attain 80% power.
The main endpoint of the study was the RGV. Gastric
contents regurgitation during induction of anesthesia was
a secondary endpoint. Comparison of RGV among
groups was done by Kruskal-Wallis test. A 5% level was
adopted for significance. Data were presented as either
median (range) or mean ± SD as appropriate. All analysis
were done by SPSS statistical software v 10.0.
Results
The flowchart of the randomized trial is presented
in figure 1. Three patients were excluded due to either
Glutamine in preoperative fasting 87Nutr Hosp. 2011;26(1):86-90
88 D. Borges Dock-Nascimento et al.Nutr Hosp. 2011;26(1):86-90
being aged (2) or refused to participate (1). After ran-
domization three others were ruled out due to either
have not correctly ingested the beverage (one in glut-
amine group and one in placebo group) or cancella-
tion of the surgery (one case in placebo group). There-
fore, 50 patients completed the study. There was no
difference in demographic and biochemical data
between groups (table I). None of the patients had
regurgitation during the induction of anesthesia.
There were neither deaths nor postoperative compli-
cations.
The median (range) of RGV was 6 (0-80) (mean =
10.6) mL. Comparisons showed that the RGV was simi-
lar (p = 0.29) between glutamine group (median = 4.5 [0-
15], mean = 4.9) mL), carbohydrate group (median = 7.0
[0-80], mean = 12.6 mL), placebo group (media = 8.5 [0-
50], mean = 12.9 mL), and fasted group (median 5.0 [0-
50], mean = 12.1 mL). This can be seen in figure 2.
Discussion
The findings showed that the abbreviation of preop-
erative fasting for 2 hours with carbohydrate and L-
glutamine-rich drink was safe and was not associated
with complications during the induction of anesthesia.
Furthermore the RGV was similar in either fasted
patients or in groups treated with abbreviation of pre-
operative fasting to 2 h. This is most relevant since this
is the first study in the surgical setting that compared
RGV with a group drinking a beverage containing glut-
amine 2 h before anesthesia. The data suggest that this
new ingredient to abbreviate preoperative fasting is
safe thus encouraging further studies.
After an overnight fast, the stomach is almost never
completely empty and the RGV in healthy volunteers
can range from 0 to 95ml with a mean of 27 mL.12 Vari-
ous techniques are available to study gastric emptying,
Fig. 1.—Flowchart of
the randomization.
Asessed for elegibility
(n = 56)
Allocation
(n = 53)
Follow-up
(n = 50)
Analysis
(n = 50)
Placebo group
(n = 12)
Placebo group
(n = 12)
Fasted group
(n = 12)
Fasted group
(n = 12)
Carbohydrate group
(n = 12)
Carbohydrate group
(n = 12)
Glutamine group
(n = 14)
Glutamine group
(n = 14)
Fasted group
(n = 12)
Carbohydrate group
(n = 12)
Glutamine group (n = 15)
1 excluded - non compliance
with the protocol
Placebo group
(n = 14)
2 excluded due to
cancellation of surgery;
or non-compliance with
the protocol
Randomized (n = 53)
Excluded (n = 3):
2 were over 65 years old
1 refused to participate
Glutamine in preoperative fasting 89Nutr Hosp. 2011;26(1):86-90
all of them having specific advantages and disadvan-
tages. Since the introduction of radionuclide gastric
emptying tests, considerable improvement has been
achieved in both methodology and operational equip-
ment, and scintigraphy has become the “gold standard”
for measurements of gastric emptying in research and
in the clinical setting.13 Recently magnetic resonance
image has been also used.12 While room to criticism
may exist in connection with the accuracy of this
method, other studies have also reported its useful
application at the surgical unit.14,15 Moreover, the data
showed that all groups including glutamine group had
similar RGV at induction of anesthesia.
Another importance of these findings is that it keeps
opened the gate for testing other nutrients for abbrevia-
tion of preoperative fasting in addition of carbohy-
drate-rich beverages. The use of L-glutamine associ-
ated with carbohydrate beverage may theoretically
accelerate postoperative recovery by improving glu-
cose metabolism and insulin requirements,16 reduce
anti-oxidative and anti-inflammatory response,17 and as
a result reduce postoperative complications11,18 and
mortality.11 Insulin resistance as a result of prolonged
fasting may be also reduced. Insulin resistance is a
mark of metabolic response to both prolonged fasting
and trauma.9Further studies are necessary to confirm
all these benefits associated to the abbreviation of pre-
operative fasting with beverages containing L-gluta-
mine.
The present findings allow us to conclude that the
abbreviation of preoperative fasting to 2 h with carbo-
hydrate and L-glutamine is safe and does not increase
the RGV during induction of anesthesia.
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Table I
Demographic and biochemical data of the study population
Group
Variable Fasted Placebo Carbohydrate Glutamine p
Age (years)†42 (19-65) 44 (17-63) 34 (17-62) 45 (22-65) 0.46
BMI (kg/m2)†26.5 (20.4-31.2) 27 (20.4-33.3) 24.7 (23.3-29.1) 22.8 (19.2-29.1) 0.10
Serum glucose (mg/dl)* 88.1 ± 4.9 82.6 ± 8.4 83.8 ± 10.8 85.5 ± 11.5 0.75
Hemoglobin (g/dl)* 13.6 ± 1.1 12.4 ± 0.9 12.4 ± 1.0 13.2 ± 1.3 0.10
Creatinine (mg/dl)* 0.64 ± 0.84 0.69 ± 0.21 0.73 ± 0.23 0.67 ± 0.98 0.72
SGOT (u/l)* 17.3 ± 5.0 23.8 ± 9.6 20.8 ± 4.1 17.5 ± 3.6 0.31
SGPT (u/l)* 19 ± 55 23.6 ± 9.3 22.8 ± 12.2 16.3 ± 4.3 0.27
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I 8 (66.6) 7 (58.3) 8 (72.7) 8 (57.1) 0.84
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* = Mean ± SD.
†= Median (range).
SGOT: serum glutamic-oxalacetic transaminase.
SGPT: serum glutamic-pyruvate transaminase.
ASA: American Society of Anesthesiologists score.
Fig. 2.—Gastric residual volume in the four groups. Data ex-
press the median, variation, and interquartile range (p = 0.29).
Black dots are outliers.
90
80
70
60
50
40
30
20
10
0
-10
MF
N = 12 12 12 14
Placebo Fasted Carbohydrate Glutamine
Group
Gastric Residual Volume (mL)
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