Thomson
Perioperative fasting in adults and children: guidelines fromthe European Society of AnaesthesiologyIan Smith, Peter Kranke, Isabelle Murat, Andrew Smith, Geraldine O'Sullivan, Eldar Søreide, Claudia Spiesand Bas in't Veld
This guideline aims to provide an overview of the present
surgery in adults and children, although patients should not
knowledge on aspects of perioperative fasting with assessment
have their operation cancelled or delayed just because they are
of the quality of the evidence. A systematic search was
chewing gum, sucking a boiled sweet or smoking immediately
conducted in electronic databases to identify trials published
prior to induction of anaesthesia. These recommendations also
between 1950 and late 2009 concerned with preoperative
apply to patients with obesity, gastro-oesophageal reflux and
fasting, early resumption of oral intake and the effects of oral
diabetes and pregnant women not in labour. There is insufficient
carbohydrate mixtures on gastric emptying and postoperative
evidence to recommend the routine use of antacids,
recovery. One study on preoperative fasting which had not been
metoclopramide or H2-receptor antagonists before elective
included in previous reviews and a further 13 studies
surgery in non-obstetric patients, but an H
published since the most recent review were identified.
2-receptor antagonist
should be given before elective caesarean section, with an
The searches also identified 20 potentially relevant studies
of oral carbohydrates and 53 on early resumption of oral
2-receptor antagonist given prior to emergency
intake. Publications were classified in terms of their
caesarean section, supplemented with 30 ml of 0.3 mol l1
evidence level, scientific validity and clinical relevance. The
sodium citrate if general anaesthesia is planned. Infants should
Scottish Intercollegiate Guidelines Network scoring system for
be fed before elective surgery. Breast milk is safe up to 4 h and
assessing level of evidence and grade of recommendations was
other milks up to 6 h. Thereafter, clear fluids should be given as in
used. The key recommendations are that adults and children
adults. The guidelines also consider the safety and possible
should be encouraged to drink clear fluids up to 2 h before
benefits of preoperative carbohydrates and offer advice on the
elective surgery (including caesarean section) and all but one
postoperative resumption of oral intake.
member of the guidelines group consider that tea or coffee with
Eur J Anaesthesiol 2011;28:556–569
milk added (up to about one fifth of the total volume) are still clearfluids. Solid food should be prohibited for 6 h before elective
Published online 28 June 2011
Why were these guidelines produced?
Widespread consultation suggested that guidelines on perioperative fasting would be useful to European Society ofAnaesthesiology (ESA) members.
Our guideline aims to provide an overview of the present knowledge on perioperative fasting with assessment of thequality of the evidence in order to allow anaesthesiologists all over Europe to integrate this knowledge in their dailycare of patients.
What is similar to previous guidelines?The ESA guidelines endorse a 2-h fasting interval for clear fluids and a 6-h interval for solids.
What is different from previous guidelines?The ESA guidelines:
are recent and include several studies published since previous guidelines; increase the emphasis on encouraging patients not to avoid fluids for any longer than is necessary; offer practical, pragmatic advice on chewing gum, smoking and drinks containing milk; consider the safety and possible benefits of preoperative carbohydrates; offer advice on the postoperative resumption of oral intake.
From the University Hospital of North Staffordshire, Stoke-on-Trent, UK (IS), University Hospitals of Wu¨rzburg, Wu¨rzburg, Germany (PK), Armand Trousseau Hospital, Paris,France (IM), Royal Lancaster Infirmary, School of Health and Medicine, Lancaster University, Lancaster (AS), Guy's and St Thomas' NHS Foundation Trust, London (GOS),UK, Department of Anaesthesia and Intensive Care, Stavanger University Hospital, Stavanger, Norway (ES), Department of Anaesthesiology and Intensive Care Medicine,Charite´ – Universita¨tsmedizin Berlin, Berlin, Germany (CS) and Department of Anesthesiology and Pain Medicine, Haaglanden Medical Centre, The Hague, TheNetherlands (BV)
Correspondence to Dr Ian Smith, Directorate of Anaesthesia, University Hospital of North Staffordshire, Newcastle Road, Stoke-on-Trent, Staffordshire ST4 6QG, UKTel: +44 1782 553054; e-mail:
0265-0215
ß 2011 Copyright European Society of Anaesthesiology
Copyright European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
Perioperative fasting in adults and children
1. Summary of recommendations
Fasting in adults and childrenAdults and children should be encouraged to drink clear fluids (including water,
pulp-free juice and tea or coffee without milk) up to 2 h before elective surgery(including caesarean section)All but one member of the guidelines group consider that tea or coffee with milk added
(up to about one fifth of the total volume) are still clear fluids
Solid food should be prohibited for 6 h before elective surgery in adults and children
Patients with obesity, gastro-oesophageal reflux and diabetes and pregnant women
not in labour can safely follow all of the above guidelinesHowever, these factors may alter their overall anaesthetic management
Patients should not have their operation cancelled or delayed just because they are
chewing gum, sucking a boiled sweet or smoking immediately prior to inductionof anaesthesiaThe above is based solely on effects on gastric emptying and nicotine intake (including smoking,
nicotine gum and patches) should be discouraged before elective surgery
Fasting in infantsInfants should be fed before elective surgery. Breast milk is safe up to 4 h and
other milks up to 6 h. Thereafter, clear fluids should be given as in adults
Prokinetic and other pharmacological interventionsThere is insufficient evidence of clinical benefit to recommend the routine use of
antacids, metoclopramide or H2-receptor antagonists before elective surgery innon-obstetric patients
An H2-receptor antagonist should be given the night before, and on the morning of,
elective caesarean sectionThe guidelines group recognises that most of the evidence relates to surrogate measures,
such as changes in gastric volume and pH, rather than a clear impact on mortality
An intravenous H2-receptor antagonist should be given prior to emergency caesarean
section; this should be supplemented with 30 ml of 0.3 mol l
S1 sodium citrateif general anaesthesia is plannedThe guidelines group recognises that most of the evidence relates to surrogate measures,
such as changes in gastric volume and pH, rather than a clear impact on mortality
Oral carbohydratesIt is safe for patients (including diabetics) to drink carbohydrate-rich drinks up to
2 h before elective surgeryThe evidence for safety is derived from studies of products specifically developed for perioperative
use (predominantly maltodextrins); not all carbohydrates are necessarily safe
Drinking carbohydrate-rich fluids before elective surgery improves subjective
well being, reduces thirst and hunger and reduces postoperative insulin resistanceTo date, there is little clear evidence to show reductions in length of postoperative stay and mortality
Fasting in obstetric patientsWomen should be allowed clear fluids (as defined above) as they desire in labour
Solid food should be discouraged during active labour
The guidelines group recognise that it may be impractical to stop all women from eating during labour,
especially low-risk women. Consideration should be given to easily digestible, low-residue foods
Postoperative resumption of fluidsAdults and children should be allowed to resume drinking as soon as they wish after
elective surgery. However, fluid intake should not be insisted upon before allowingdischarge from a day or ambulatory surgery facility
, recommended best practice based on the clinical experience of the guidelines development group.
2. Purpose and development of the guideline
with expertise in their field to join the task force. Further
The European Society of Anaesthesiology (ESA) is
experts were co-opted onto the task force as required.
committed to the production of high-quality, evidence-
Several European national anaesthesiology societies have
based clinical guidelines. After the formation of the
already produced recommendations for aspects of perio-
Guidelines Committee in 2008, a prioritisation exercise
perative fasting. Our guideline aims to provide an over-
suggested that guidelines on perioperative fasting
view of the present knowledge on the subject with
would be useful to ESA members and a task force was
assessment of the quality of the evidence in order to
established in June 2009 to produce this guideline. The
allow anaesthesiologists all over Europe to integrate –
chairpersons of the relevant subcommittees (Evidence-
wherever possible – this knowledge in their daily care
based Practice and Quality Improvement, Ambulatory
of patients.
Anaesthesia, Obstetric Anaesthesia, Paediatric Anaesthe-sia and Anaesthesia for the Elderly) of the ESA Scientific
Evidence to support the recommendations was obtained
Committee were asked to nominate an ESA member
as follows. A systematic search was conducted by
European Journal of Anaesthesiology
2011, Vol 28 No 8
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members of Cochrane Anaesthesia Review Group of
European nation. Although national societies and
the electronic databases Ovid, MEDLINE and Embase
individuals are free to use the guidelines, modified as
to identify trials published between 1950 and late 2009
necessary for local and national practice contexts, they are
concerned with preoperative fasting, early resumption of
under no obligation to do so. Further, the potential legal
oral intake and the effects of oral carbohydrate mixtures
implications may be a point of concern.It cannot be
on gastric emptying and postoperative recovery. A total
emphasised enough that guidelines may not be appro-
of 3714 abstracts from MEDLINE and 3660 from Embase
priate for all clinical situations. The decision whether or
were identified from the search. After elimination
not to follow a recommendation from a guideline must be
of duplicates, irrelevant studies, non-clinical trials and
made by the responsible physician on an individual basis,
studies with a non-clinical outcome, one study on
taking into account the specific conditions of the patient
preoperative fasting which had not been included in
and the available resources. Therefore, deviations from
previous reviewand a further 13 studies published
guidelines for specific reasons should remain possible and
since the most recent reviewwere identified. The
can certainly not be interpreted as a base for negligence
searches also identified 20 potentially relevant studies
claims. However, we hope that these guidelines will
of oral carbohydrates and 53 on early resumption of oral
both assist anaesthesiologists throughout Europe to
bring research evidence to bear on their clinical practiceand also provide support to colleagues and healthcare
These publications were classified in terms of their
funders in making changes and improvements necessary
evidence level, scientific validity and clinical relevance.
to enhance patient care.
We used the Scottish Intercollegiate Guidelines Network(SIGN) scoring system for assessing level of evidence and
Differences from existing guidelines
grade of recommendations Highest priority
Although there is little new evidence relating to fasting
was given to meta-analyses of randomised, controlled
for fluids and solids, the current guidelines review more
clinical trials. In reaching consensus, particular emphasis
recent literature than any of the existing guidelines.
was placed on the level of evidence, ethical aspects,
In addition, the American Society of Anesthesiology
patient preferences, clinical relevance, risk/benefit ratios
(ASA) guidelines on the subjectwere published in
and degree of applicability. For example, a pragmatic
1999 and contain little on preoperative carbohydrate,
solution to an acceptable amount of milk in tea or
whereas the UK Royal College of Nursing guidelines
coffee was agreed based on the unpublished experience
deal with the safety aspect of preoperative carbohydrate,
accumulated by several members of the group over
but not possible benefits. In these current guidelines,
we have also tried to address practical problems such as
These guidelines have undergone the following review
chewing gum.
process. The final draft was reviewed by members ofthe relevant Subcommittees of the ESA's Scientific
Committee who were not involved in the initial pre-
paration of the guideline. It was posted on the on ESA
website for 4 weeks and all ESA members, individual andnational, were contacted by electronic mail to invite them
Adults and children should be encouraged to drink clear
to comment on the draft. It was also sent to the Inter-
fluids (including water, pulp-free juice and tea or coffee
national Association for Ambulatory Surgery (IAAS) for
without milk) up to 2 h before elective surgery (including
information and comment. All those who commented
caesarean section) (evidence level 1þþ, recommen-
are listed in the ‘Acknowledgements' section below.
dation grade A).
Comments were collated by the chair of the guideline
All but one member of the guidelines group consider that tea or
task force and the guideline amended as appropriate.
coffee with milk added (up to about one fifth of the total volume)
The final manuscript was approved by the Guidelines
are still clear fluids.
Committee and Board of the ESA before submission forpublication in the European Journal of Anaesthesiology.
Since the landmark work of Maltby et al.in 1986, a large
These guidelines are produced as a service to ESA
body of evidence has been accumulated to show that
members and other anaesthesiologists and healthcare
the oral intake of clear fluids up to 2 h before an elective
staff in Europe. The ESA recognises that practice and
operation is Many countries have, therefore,
opinion varies in different European countries. Despite
changed their fasting guidelines, allowing most patients
the availability of the same scientific information, the way
take clear fluids (water, clear juices and coffee or tea
in which healthcare services are organised may result in
without milk) up to 2 h before elective surgery.
different practices in the various European countries.
Thus, it is not always possible to produce guidelines
In addition to the liberalising of fasting guidelines, the
which will be both appropriate and relevant for every
emphasis is now changing, with the realisation that
European Journal of Anaesthesiology
2011, Vol 28 No 8
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Perioperative fasting in adults and children
Key to evidence statements and grades of recommendations
High-quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias
Well conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias
Meta-analyses, systematic reviews, or RCTs with a high risk of bias
High-quality systematic reviews of case–control or cohort studies
Well conducted case–control or cohort studies with a low risk of confounding or bias and a moderate
probability that the relationship is causal
Case–control or cohort studies with a high risk of confounding or bias and a significant risk that the
relationship is not causal
Non-analytic studies, e.g. case reports, case series
Grades of recommendation
Note: the grade of recommendation relates to the strength of the evidence on which the recommendation isbased. It does not refect the clinical importance of the recommendation.
At least one meta-analysis, systematic review, or RCT rated as 1
and directly applicable to the target population; or
a body of evidence consisting principally of studies rated as 1directly applicable to the target population, and demonstrating overall consistency of results
A body of evidence including studies rated as 2
directly applicable to the target population, and demonstrating overall consistency of results;
or
extrapolated evidence from studies rated as 1
A body of evidence including studies rated as 2
directly applicable to the target population, and demonstrating overall consistency of results;
or
extrapolated evidence from studies rated as 2
Evidence level 3 or 4; or
extrapolated evidence from studies rated as 2
Good practice points
Recommended best practice based on the clinical experience of the guideline development group
Scottish Intercollegiate Guidelines Network (SIGN) grading system. RCT, randomised controlled
prolonged fasting is an inappropriate way to prepare
drinking up until 2 h before surgery in order to reduce
for the stress of surgery. Abstaining from fluids for
their discomfort and improve their well being.
a prolonged period prior to surgery is detrimental forpatients, especially the elderly and small children. Rather
3.1.1. Milk in tea or coffee
than ensuring a minimal fasting interval has been
Milk in large quantities curdles in the stomach and acts
achieved, it is important to encourage patients to keep
like a solid, but smaller quantities are handled like other
European Journal of Anaesthesiology
2011, Vol 28 No 8
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liquids and are safe. There is anecdotal evidence
boiled sweet or smoking immediately prior to induction
(including from some members of this group) that when
milk is allowed to be added to tea or coffee consumed
The above is based solely on effects on gastric emptying and
before elective surgery, regurgitation and aspiration are
nicotine intake (including smoking, nicotine gum and patches)
no more likely to occur, but no randomised studies
should be discouraged before elective surgery.
have looked specifically at the safety of this practice.
Some studies of preoperative tea and coffeedid
allow milk to be added if desired (R. Maltby, personal
There is ongoing debate on how to deal with patients
communication), but this is not recorded in the published
chewing gum in the immediate preoperative period and
text and the number of such patients was small. Unpub-
what constitutes a safe fasting interval. There are only
lished work has shown that adding small quantities of
three (partly) randomised controlled studies concerning
milk (from a 12 ml single-portion pot) to a model stomach
the intake of chewing gum during the perioperative
caused no restriction in emptying, but that adding three
fasting period.
or more measures caused clumping (R. Maltby, personalcommunication). However, the model comprised a glass
In one comparison of 77 patients16 did not chew
vessel with a fixed burette tap as an outlet and, therefore,
any kind of gum, 15 patients were allowed to chew
did not mimic either a sphincter which can relax or the
gum until transfer to the operating room and 46 were
effects of churning from muscle contractions.
allowed to chew gum as long as they wished, even untilthe time of anaesthesia induction. The last group was not
The lack of evidence from human studies and the
allocated by means of randomisation. Both gastric fluid
uncertainty in defining and controlling a safe amount
volume as well as pH did not differ significantly among
of milk, means that most guidelines only advocate black
the three groups.
tea or coffee. Although this may appear a safe approach,some patients would rather have nothing at all if they are
Another study compared 46 children between 5 and
denied milk in their morning cup of tea or coffee. With
17 years old who were allowed to chew either sugar-free
one exception, the guidelines group considered that tea
or sugared gum up to 30 min before transfer to the
or coffee with a modest amount of milk added (up to
operating room. Both the sugar-free and sugared gum
about one fifth of the total volume) should still be
chewers had significantly higher gastric fluid volume and
considered as clear fluids and, therefore, safe up to
pH than the control group who did not chew any
2 h before the induction of anaesthesia. Drinks made
Søreide et al.compared 106 female patients scheduled
predominantly from milk, however, should be treated
for elective gynaecologic surgery. They were either
smokers or non-smokers and were allowed to chewnicotine-containing chewing gum or nothing (smokers)
or sugar-free gum or nothing (non-smokers), respectively.
Up to one chewing gum per hour was given until
Solid food should be prohibited for 6 h before elective
transportation to the operating room. The non-smoking
surgery in adults and children (evidence level 1þ, recom-
chewers as well as the smokers (chewing or not) had
mendation grade A).
significantly higher gastric fluid volume than the non-smokers who did not chew gum. As far as gastric pH
values are concerned, the levels were higher in both
No recent studies have attempted to define a minimal safe
non-smoking groups than in both smoking groups.
period for preoperative fasting for solid food. One previous
No case of aspiration or other complication during anaes-
study found no increase in gastric volume after a light
thesia induction was reported. Although the differences
breakfast of tea and buttered toast consumed 2–4 h before
in pH and gastric volumes were statistically significant,
elective surgery,but the presence of residual solids in the
the authors did not believe the difference (30 versus
stomach at induction of anaesthesia could not be ruled out
20 ml) was clinically significant (E. Søreide, personal
by the methodology used. It remains common practice to
avoid solid food for at least 6 h before elective surgery.
Most patients will accept this if they are permitted to
3.4. Patients with delayed gastric emptying
drink until closer to their surgery. There is no clear benefit
to reducing the fasting time for solids below 6 h.
Patients with obesity, gastro-oesophageal reflux anddiabetes and pregnant women not in labour can safely
3.3. Chewing gum, sweets and smoking
follow all of the above guidelines (evidence level 2,
recommendation grade D).
Patients should not have their operation cancelled or
These factors may, however, alter their overall anaesthetic
delayed just because they are chewing gum, sucking a
European Journal of Anaesthesiology
2011, Vol 28 No 8
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Perioperative fasting in adults and children
metoclopramide 10 mg orally 60–90 min before inductionof anaesthesia. There was no significant difference in
A great number of factors can potentially delay gastric
either gastric pH or fluid volume.
emptying. These include obesity, gastro-oesophagealreflux and diabetes. Studies of preoperative fasting have
So far, valid studies that investigate the effect of
not evaluated these groups of patients adequately enough
preoperatively administered metoclopramide alone on
to provide definitive evidence. However, the evidence
gastric pH and gastric fluid volume are lacking, although
which does exist suggests that limitation of gastric
metoclopramide significantly improves gastric emptying
emptying is, at most, mild and that these patients can
in cardiac surgery patients 18 h postoperatively compared
follow the same guidelines as healthy adults. This advice
also applies to pregnant women who are not in labour.
So far, there is insufficient evidence that preoperatively
Opioid analgesia can also delay gastric emptying, but
administered metoclopramide alone improves clinical
again there is insufficient evidence to make any
outcome, reduces gastric fluid volume or increases
recommendation. However, patients who have recently
taken sufficient opioids to have a significant effect ongastric emptying are unlikely to be undergoing elective
surgery often.
2-antagonists and proton pump
inhibitorsThe mechanisms of action of H
proton pump inhibitors (PPIs) differ. The former block
H2-receptors on the stomach's parietal cells, thereby
There is insufficient evidence of clinical benefit to
inhibiting the stimulatory effects of histamine on gastric
recommend the routine use of antacids, metoclopramide
acid secretion; the latter block the enzyme system
or H2-receptor antagonists before elective surgery in non-
of hydrogen/potassium ATPase (Hþ/Kþ ATPase), the
obstetric patients (evidence level 1þþ, recommendation
‘proton pump' of the gastric parietal cell, such that the
stimulatory actions of histamine, gastrin and acetyl-choline are inhibited. Both have been applied with the
aim of decreasing the risk of deleterious effects resultingfrom a potential acid aspiration syndrome.
4.1. Prokinetic medicationsIn contrast to the prevalence of the perioperative use
A recent meta-analysiscomparing these medications
of prokinetics, there is limited evidence to support
to therapeutic targets suggests that pre-medication
the prophylactic use of these agents to reduce the risk
with ranitidine is more effective than PPIs in reducing
of perioperative aspiration of gastric contents.
the volume of gastric secretions (by an average of0.22 ml kg1, 95% confidence interval 0.04–0.41) and
There are single studies that investigate the effect of
increasing gastric pH (by an average of 0.85 pH units,
prokinetics on gastric pH and gastric fluid volume during
95% confidence interval 1.14–0.28). These conclusions
anaesthesia induction. Iqbal et al.compared 75 women
could be drawn based on nine randomised controlled
undergoing caesarean section under general anaesthesia.
trials, of which seven were suitable for meta-analysis. In
these trials a total of 223 patients received ranitidine,
H2-antagonist (ranitidine) with a prokinetic drug (meto-
which was the sole H
clopramide), whereas 25 women served as a placebo
2-blocker used in the included trials,
and 222 patients received different PPIs (omeprazole,
control group (another 25 patients received only raniti-
lansoprazole, pantoprazole and rabeprazole). Overall, the
dine). The combination of the two drugs was significantly
size of the trials is rather small. Further, heterogeneity
more effective in increasing the pH and reducing the
could also be detected with respect to preoperative fast-
gastric fluid volume than placeb
ing time, route of administration, repeat administration
investigated the effect of ranitidine and meto-
and the specific PPIs used. It is interesting to note
clopramide versus placebo. Forty patients scheduled for
that patients in the trials received ranitidine at doses
laparoscopic gynaecological surgery were administered
equivalent to, or less than, the daily recommended dose
either 50 mg ranitidine with 10 mg metoclopramide
for the maintenance of peptic ulcer disease, whereas
intravenously (n ¼ 20) or the same volume of isotonic
patients received PPIs at doses higher than those recom-
saline in the control group. Gastric fluid volume was
mended for this purpose.
significantly higher in the placebo group, as was the
It is not clear how long the potential protective effect
gastric pH in the treatment
on gastric volume or pH lasts. It is also unclear whether
Bala et al.compared the combination of ranitidine–
these observed effects can be extrapolated to patient
erythromycin with ranitidine–metoclopramide. Forty
populations with a higher risk of aspiration, as all the
ASA I or II patients were given either erythromycin
included trials appeared to be in patients at very low
250 mg and ranitidine 150 mg or ranitidine 150 mg and
risk of aspiration and the observed parameters were used
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as a surrogate for the ‘true outcome', that is, mortality or
5.1. Carbohydrates versus clear liquids or intravenous
adult respiratory distress syndrome following gastric
aspiration, which could not be evaluated.
Taniguchi et al.investigated the safety and effective-ness of oral rehydration as compared with intravenous
5. Preoperative carbohydrates: gastric
rehydration prior to general anaesthesia. Fifty patients
emptying and potential benefits
were randomised to either 1000 ml of oral rehydration
solution or 1000 ml of an intravenous electrolyte solution.
Volume of gastric contents, as measured directly after
It is safe for patients (including diabetics) to drink carbo-
induction, was significantly lower in the oral rehydration
hydrate-rich drinks up to 2 h before elective surgery
(evidence level 1þþ, recommendation grade A).
Kaska et performed a randomised controlled trial
The evidence for safety is derived from studies of
products specifically developed for perioperative use
preparation with either oral or intravenous intake of
(predominantly maltodextrins); not all carbohydrates
carbohydrates, minerals and water.Oral intake shortly
are necessarily safe.
before surgery did not increase gastric residual volume
and was not associated with any risk.
Studies in animal models of severe stress, such as haemor-
In the study by Nygren et al.,gastric emptying of a
rhage and endotoxaemia, showed that several key systems
carbohydrate-rich drink was investigated before elective
involved in the stress responses were markedly impaired
surgery and in a control situation. Patients served as
even if the animal had been fasted for a brief period before
their own control pre and postoperatively. Despite the
the onset of a given stress. These key systems included
increased anxiety experienced by patients before surgery,
fluid homeostasis, stress hormone release, aspects of
gastric emptying did not differ between the experimental
metabolism, muscle function and gut integrity.If these
and control situations.
models were fasted for as long as 24 h, there was also a
Jarvela et investigated the effect of a preoperative
difference in survival. This indicates that the metabolic
oral carbohydrate drink versus overnight fasting on peri-
change caused by a recent meal (as opposed to fasting)
operative insulin requirements in 101 non-diabetic
and the loss of glycogen occurring even after a brief fast is
patients undergoing elective coronary artery bypass graft-
sufficient to alter the stress response.
ing. According to their findings, it is safe to allow cardiac
Allowing patients to drink clear fluids up to 2 h prior to
surgery patients to drink clear fluids up to 2 h before
surgery is not likely to produce any major change in
induction of anaesthesia, because gastric emptying of the
metabolism, as these drinks usually do not contain suffi-
drink was almost total and no aspiration occurred.
cient energy. The best known method for changing
Breuer et al.studied the effects of preoperative oral
metabolism from the overnight fasted state to that of a
carbohydrate administration on gastric fluid volume.
fed state is the use of carbohydrates. The key change
Before surgery, 188 ASA physical status III–IV patients
required to be achieved is a prompt insulin response,
undergoing elective cardiac surgery were randomised to
preferably to an extent similar to that observed after
receive a clear 12.5% carbohydrate drink, flavoured water
intake of a meal.
(placebo), or to fast overnight (control). Carbohydrates
In the first instance, intravenous glucose has been
and placebo were treated in double-blind format and
proposed and used for this purpose. The insulin response
patients received 800 ml of the corresponding beverage
to glucose infusions is determined by the rate of delivery
in the evening and 400 ml 2 h before surgery. Ingested
of glucose in a dose-dependent manner. Infusion of
liquids did not cause increased gastric fluid volume or
glucose (and insulin) has been shown to induce an
other adverse events.
insulin response to levels of about 60 mU ml1,reduce
In these five randomised studies, there was no evidence
postoperative insulin resistand retain substrate
of an increased gastric volume after ingesting carbo-
oxidation. This is important because postoperative
hydrates. Care should be taken in extrapolating this
insulin resistance and hyperglycaemia are associated with
evidence beyond those specific carbohydrates which
an impaired outcome after surgery.Preoperative oral
have been studied; not all oral carbohydrates will necess-
carbohydrate loading in humans also reduces postopera-
arily behave similarly.
tive insulin resistance. Dietary interventions, therefore,represent a promising and attractive therapeutic strategyto optimise postprandial glycaemia. Thus far, inter-
5.2. Diabetic patients versus healthy individuals
ventions with respect to the preoperative addition of
Investigators have been reluctant to give diabetic
carbohydrates have focused on safety, metabolic effects,
patients oral carbohydrates because of the unknown
personal perioperative well being and postoperative
effects on preoperative glycaemia and gastric emptying.
length of stay.
Gustafsson et al.investigated the effect of preoperative
European Journal of Anaesthesiology
2011, Vol 28 No 8
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Perioperative fasting in adults and children
oral carbohydrate loading in type 2 diabetic patients.
study of 14 patients displayed less reduced insulin
Twenty-five patients with type 2 diabetes and 10 healthy
sensitivity after colorectal surgery following preoperative
controls were studied. A carbohydrate-rich drink (400 ml,
oral carbohydrate administration as compared with
12.5%) was given with paracetamol 1.5 g for deter-
patients who were operated on after an overnight fast.
mination of gastric emptying. Patients with type
A recently published study in patients undergoing open
2 diabetes showed no signs of delayed gastric emptying,
colorectal surgery also showed reduced postoperative
suggesting that a carbohydrate-rich drink may be safely
insulin resistance after preoperative oral carbohydrates,
administrated 180 min before anaesthesia without risk of
as well as reduced thirst and hungHowever, a pre-
hyperglycaemia or aspiration preoperatively.
operative oral carbohydrate drink did not reduce post-operative insulin resistance or postoperative nausea and
On the basis of this limited evidence, diabetes (of
vomiting in an investigation of 101 non-diabetic patients
either type) should not be seen as a contraindication to
undergoing elective coronary artery bypass
preoperative oral carbohydrates.
In a randomised study in 65 patients undergoing
5.3. New formulas for preoperative drinks
major abdominal surgery, carbohydrates contributed to
Beverages containing either amino acids (glutamine)
the maintenance of muscle In two randomised
or peptides (soy peptides) have been studied with regard
trials in 86and 172 patientsundergoing laparoscopic
to their Glutamine (15 g) with carbohydrate
cholecystectomy, there was either no or only a
in 300–400 ml of water seems to be safe to give 3 h
reduction in postoperative nausea and vFaria
preoperatively in healthy volunteers based on stomach
et showed improved glucose metabolism and
emptying time. A drink containing soy peptide given to
organic response in 21 female patients participating in
patients admitted for elective bowel resections has been
a randomised controlled trial and undergoing laparo-
shown to be safe. There was no difference in gastric
emptying time between the carbohydrate group (12.5 g
Helminen et studied 210 patients, undergoing
per 100 ml carbohydrate drink) and carbohydrate/peptide
gastrointestinal surgery, randomly assigned to fasting,
group (12.5 g per 100 ml carbohydrate and 3.5 g per 100 ml
intravenous or oral carbohydrates. Intravenous glucose
of hydrolysed soy protein)More research is necessary
infusion did not decrease the sense of thirst and hunger as
to determine the effects of clear liquids with amino acid
effectively as in the oral intake group, but it did alleviate
or hydrolysed protein in metabolic response and insulin
the feelings of weakness and tiredness.
sensitivity after surgery.
Taniguchi et al.investigated 50 patients randomised toeither 1000 ml of oral rehydration solution or 1000 ml of
5.4. Carbohydrates, metabolic response and
an intravenous electrolyte solution. Patients' satisfaction
postoperative discomfort
favoured oral rehydration as they experienced less
feelings of hunger, less occurrence of dry mouth and less
Drinking carbohydrate-rich fluids before elective surgery
restriction of movement. Similar subjective benefits were
improves subjective well being, reduces thirst and hunger
observed in a recent small study of gynaecological
and reduces postoperative insulin resistance (evidence
level 1þþ, recommendation grade A).
Kaska et al.performed a randomised controlled trial
comparing preoperative fasting with preoperative pre-
In postoperative patients in need of intensive care,
paration with either oral or intravenous intake of carbo-
studies have shown that, when glucose is controlled by
hydrates, minerals and water. Consumption of the mix of
intensive insulin therapy, mortality and morbidity can be
water, minerals and carbohydrates offered some protec-
reduced.In addition, data suggest that postoperative
tion against surgical trauma in terms of metabolic status,
discomfort can be reduced when patients are given a
cardiac function and psychosomatic status.
carbohydrate-rich beverage preoperatively.
Breuer et studied the effects of preoperative oral
In a placebo-controlled randomised trial of 252 patients
carbohydrate administration on postoperative insulin
undergoing elective gastrointestinal surgery, it was shown
resistance, preoperative discomfort and variables of organ
that the intake of carbohydrate-rich clear fluid until
dysfunction in 188 ASA physical status III–IV patients
2 h before the operation led to less thirst, restlessness,
undergoing elective cardiac surgery, including those
weakness and concentration problems as compared
with non-insulin-dependent type-2 diabetes mellitus.
to placebo.Two small placebo-controlled double-blind
Carbohydrates and placebo were administered in double-
studies in 15and patients, respectively, under-
blind format and patients received 800 ml of the corres-
going hip surgery, showed that the intake of a carbo-
ponding beverage in the evening and 400 ml 2 h before
hydrate-rich clear fluid until 2 h before the operation
surgery. Blood glucose levels and insulin requirements
reduced insulin resistance on days 1 and 3.Another
did not differ between the groups. Patients receiving
European Journal of Anaesthesiology
2011, Vol 28 No 8
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carbohydrate and placebo were less thirsty compared with
preoperative period does not appear to impact on the
controls. The carbohydrate group, however, required
intragastric volume or pH of children.This also applies
less intraoperative inotropic support after initiation of
to overweight and obese children.
cardiopulmonary bypass weaning (P
<
6.1. Breast milk and infant formula
One study of 36 patients undergoing colorectal surgery
Fasting time for breast milk and infant formula is slightly
has demonstrated a reduction in median length of stay
more controversial. It was demonstrated more than
associated with oral carbohydrate A retrospec-
25 years ago that the gastric emptying of 110–200 ml
tive analysis of three small prospective randomised
of human milk was 82 11% after 2 h in neonates
trials (one matched-control study), primarily investi-
and infants of less than 1 year of age, 84 21% after
gating postoperative insulin resistance,showed that
whey-hydrosylated formula, 74 19% after whey-predo-
although the studies were too small to show a significant
minant formula, 61 17% after casein-predominant
reduction in length of stay individually, the combined
formula and 45 19% after cow's milk.Thus, human
effect was a significant reduction of about 20%.This
milk and whey-predominant formula emptied faster than
was confirmed in the randomised trial of Yuill et alin
casein-predominant formula and cow's milk. Two other
2005 in 72 patients undergoing elective abdominal
studies performed before anaesthesia also demonstrated
surgery. However, the recently published randomised
that breast milk empties from the stomach faster than
trial of Mathur et al.in 142 patients undergoing
most formulas in infants and both require more than 2 h
colorectal surgery or liver resection did not confirm these
to ensure complete gastric emptAccording
to these data, the American guidelines recommended4 h fasting time for breast milk and 6 h for infant formula
6. Perioperative fasting in children and
and non-human milk.These recommendations were
also endorsed by the Royal College of Nursing that
considered there was insufficient evidence to changecontemporary best practice (i.e. breast milk up to 4 h
Children should be encouraged to drink clear fluids
and formula and cows' milk up to 6 Scandinavian
(including water, pulp-free juice and tea or coffee without
guidelines recommended 4 h fasting for breast milk but
milk) up to 2 h before elective surgery (evidence level
also for formula milk in infants of less than 6 months
1þþ, recommendation grade A).
of Thus, it is recommended to finish breast feeding
All but one member of the guidelines group consider that tea or
4 h before anaesthesia and to stop infant formula 4–6 h
coffee with milk added (up to about one fifth of the total volume)
prior to anaesthesia depending on the age and on local
are still clear fluids.
considerations. Both cow's milk and powdered milk areconsidered as solid food.
Infants should be fed before elective surgery. Breast milkis safe up to 4 h and other milks up to 6 h. Thereafter,
clear fluids should be given as in adults (evidence level
Recommendations for fasting of solid food in children do
1þþ, recommendation grade A).
not differ from those proposed for healthy adults. There
is no evidence against these recommendations.
The recommendations are based on reviews and
guidelines published in the late 1990s and more
Data on fasting in injured children are minimal. One
recently.Fasting is aimed at decreasing the
study suggested that the volume of gastric contents may
risk of pulmonary aspiration, but the incidence of this
depend on the nature of the trauma, but gastric content
complication is very low in recent series and, although the
was not related to the length of Gastric volume
risk of aspiration appears to be slightly greater in children
was better linked to the interval between the last
than in adults,the difference is less than that previously
meal and the trauma. Thus, the injured child should
reported. All recent surveys indicate the relatively
be considered as a patient with a full stomach. However,
good outcome of this event in the paediatric population
an increasing number of minor surgical procedures are
compared with previous series.
done under sedation in the emergency department. The
There is a lot of evidence that clear fluids can be given
available literature does not provide sufficient evidence
up to 2 h prior to surgery in neonates, infants and
to conclude that pre-procedure fasting results in a
children. In neonates and infants, gastric emptying of
decreased incidence of adverse outcomes in children
clear fluids follows first-order kinetics as in older children
undergoing either moderate or deep
and adults.Allowing clear fluids prior to surgeryimproves comfort of the child and the parents, decreases
6.4. Postoperative fluids
thirst and decreases the risk of preoperative dehydration
Oral fluid intake is usually allowed within the first 3
in young infanThe volume of fluids permitted in the
postoperative hours in most paediatric patients. Early
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2011, Vol 28 No 8
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Perioperative fasting in adults and children
oral fluid intake was previously required in most
Low-risk nulliparous women in labour (n ¼ 2443) were
institutions before discharging the patient from hospital.
randomised to either an ‘eating' or a ‘water only' group.
This view was challenged, as it has been reported that
The results were analysed by intention to treat. No
withholding oral fluids postoperatively from children
significant difference was found in the normal vaginal
undergoing day surgery reduces the incidence of vomit-
delivery rate; the instrumental vaginal delivery rate;
However, the most recent study did not find that
the caesarean section rate; the duration of labour; or
postoperative fasting reduces the incidence of vomiting
the incidence of vomiti
after general anaesthesia in children when compared
Maternal death from aspiration of regurgitated gastric
with a liberal regimen.Thus, it seems reasonable to
content is now extremely rare, and its decline probably
let children eat and drink according to their own desires,
owes more to the widespread use of regional anaesthesia
but not to insist on oral intake before discharge.
for operative obstetrics than to fasting policies. In view ofthe predominant use of regional techniques on most
7. Fasting in obstetric patients
delivery units, rigid fasting policies are arguably no longer
appropriate during labour and mothers should, therefore,
Women in labour should be allowed clear fluids (as
be allowed to alleviate thirst during labour by consuming
defined above) as they desire. (evidence level 1þþ,
ice chips and clear fluids (isotonic sports drinks, fruit
recommendation grade A).
juices, tea and coffee, etc).
Solid food should be discouraged during active labour
As eating confers no benefit to obstetric outcome, women
(evidence level 1þ, recommendation grade A).
should be discouraged from eating solid food duringlabour. However, in view of the almost negligible inci-
Pregnant women, including obese individuals, can
dence of deaths from aspiration, low-risk women could
consume clear liquids until up to 2 h prior to surgery
consume low-residue foods (such as biscuits, toast or
(under regional or general anaesthesia) (evidence level
cereals) during labour. In addition, when deciding
2, recommendation grade D).
whether or not women should eat during labour, the
An H2-receptor antagonist should be given the night
use of parenteral opioids should also be considered
before, and on the morning of, elective caesarean section
because of their profound delay on the rate of gastric
(evidence level 1þþ, recommendation grade A).
emptying. Units who perform a significant volume oftheir emergency obstetric surgery under general anaes-
An intravenous H2-receptor antagonist should be given
thesia should probably not allow women in labour to eat.
prior to emergency caesarean section; this should besupplemented with 30 ml of 0.3 mol l1 sodium citrate
In high-risk pregnancies, it remains appropriate to not eat
if general anaesthesia is planned (evidence level 1þþ,
during labour and to achieve hydration by limited
recommendation grade A).
volumes of oral clear fluids or by the intravenous route.
The guidelines group recognises that most of the evidencerelates to surrogate measures, such as changes in gastric
7.2. Preparation for caesarean section
volume and pH, rather than a clear impact on mortality.
7.2.1. Preoperative fasting in elective obstetric surgeryEvidence suggests that pregnant women, including obese
individuals, can consume clear liquids until up to 2 h priorto surgery (under regional or general anaesthesia)
7.1. Oral intake during labour
(evidence level 1þ, recommendation A).
Surgery during labour is usually unplanned, and when itoccurs the degree of emergency can range from minimal to
7.2.2. Recommended drug regimens in detail
surgery that is life saving for either mother or baby. Againstthis background, logic dictates that all mothers should be
7.2.2.1. Elective obstetric surgery
All mothers should
starved during labour. However, it is often argued that
be actively encouraged to have regional anaesthesia for
allowing mothers to eat and drink during labour will
an elective caesarean section.
prevent ketosis and dehydration and, thereby, improve
An H2-receptor antagonist (e.g. 150 mg ranitidine) or a
obstetric outcome. There is currently wide variation in
PPI (e.g. omeprazole 40 mg) should be given at bedtime
practice with respect to eating during labour in Europe.
and again 60–90 min before the induction of anaesthesia.
However, it has now been shown that although eating a
The administration of oral metoclopramide 10 mg at the
light diet during labour will prevent ketosis, it will also
same time as the H2-receptor antagonist or PPI should
increase gastric volume,whereas when isotonic ‘sport
also be considered.
drinks' are consumed during labour,ketosis can beeliminated without an increase in intragastric volume.
7.2.2.2. Emergency obstetric surgery under regional
A recent randomised controlled study evaluated the
Intravenous H2-antagonist (e.g. ranitidine
effect of food intake during labour on obstetric outcome.
50 mg) at time of decision for surgery. In high-risk women
European Journal of Anaesthesiology
2011, Vol 28 No 8
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the use of oral H2-antagonists (ranitidine 150 mg), at
an overnight Lewis and Crawfordnoted that
regular intervals during labour, should be considered.
in patients undergoing elective caesarean section, a mealof both tea (volume unknown) and toast 2–4 h pre-
7.2.2.3. Emergency obstetric surgery under general
operatively resulted in an increased gastric volume and
a decreased gastric pH when compared with a control
2-antagonist and oral antacid
(e.g. 30 ml sodium citrate 0.3 mol l1) prior to induction
group of patients. Particulate material was aspirated from
of anaesthesia.
the stomachs of two of the 11 patients who consumedboth tea and toast. Consumption of tea without toast
7.3. Eating and drinking after caesarean section
resulted in an increase in gastric volume, but it did not
The beneficial effects of early postoperative feeding
alter gastric pH.
have been clearly demonstrated in colorectal surgery.
Traditionally, eating and drinking after caesarean section
7.5. Pharmacological prophylaxis against acid
was not encouraged, food and fluid were usually withheld
pulmonary aspiration in obstetrics
for the first 12–24 h after surgery, after which fluids were
The risk of failed intubation is three to 11 times greater
slowly introduced, with food being allowed once bowel
in pregnant patients than in non-pregnant pati
sounds had been heard or flatus was passed. A Cochrane
Airway oedema, breast enlargement, obesity and the
review published in 2002 (the review included six articles
high rate of emergency surgery, all contribute to the risk
published between 1993 and 2001) concluded that there
of failed intubation in pregnant women. Aspiration
was no evidence to justify restricting oral fluids or food
pneumonitis is often associated with difficult or failed
following uncomplicated caesarean section.
intubation during the induction of general anaesthesia.
Pregnant women undergoing caesarean section or other
More recent studies have indicated that clear fluids,
surgical procedures (both elective and emergency)
commenced between 30 min and 2 h after caesarean
should, therefore, receive antacid prophylaxis.
section, are well tolerated and result in women requiringless intravenous fluids, earlier ambulation and earlier
7.5.1. H2-receptor antagonists
breast-feeding. Earlier solid intake appears to cause
H2-receptor antagonists block histamine receptors on the
more nausea which tends to be self-lCurrent
oxyntic cell and, thus, decrease gastric acid production.
evidence, therefore, suggests that early oral hydration
This results in a slight reduction in gastric volume in the
following caesarean section is well tolerated and should
fasting patient. When given intravenously, an H2-recep-
perhaps be encouraged. Solid foods should be introduced
tor antagonist begins to take effect in as little as 30 min,
more cautiously.
but 60–90 min are required for maximal effect. After oraladministration, gastric pH is greater than 2.5 in approxi-
7.4. Effects of pregnancy on gastric function
mately 60% of patients at 60 min and in 90% at 90 min.
Gastro-oesophageal reflux, resulting in heartburn, is a
Most studies have evaluated the administration of 50–
common complication of late pregnancy. Pregnancy
100 mg of ranitidine administered intravenously or intra-
compromises the integrity of the lower oesophageal
muscularly or 150 mg administered orally.These
sphincter as a result of an alteration in the anatomical
studies have noted that the administration of ranitidine
relationship of the oesophagus to the diaphragm and
results in a gastric pH greater than 2.5 within 1 h.
stomach, an increase in intragastric pressure and the
Therapeutic concentrations of ranitidine are sustained
relaxing effect of progesterone on smooth muscle. A
for approximately 8 h.
pregnant woman at term, requiring anaesthesia, should,therefore, be regarded as having an incompetent lower
7.5.2. Proton pump inhibitors
oesophageal sphincter. These physiological changes are
Omeprazole (20–40 mg orally) and lansoprazole (15–
less 48 h after delivery.
30 mg orally) inhibit the hydrogen ion pump on the gastric
Gastric acid secretion is essentially unchanged during
surface of the oxyntic ceFor elective surgery, the
pregnancy.Pregnancy does not significantly alter the
efficacy of prophylaxis when using a PPI is similar to that
rate of gastric emptying.Gastric emptying is normal in
achieved with an H2-receptor antagonist. For emergency
early labour, but becomes delayed as labour advances.
caesarean section, studies have shown that H2-receptor
Parenteral opioids significantly delay gastric emptying
antagonists and PPIs, administered intravenously, are
during labour, as do bolus doses of epidural and intrathe-
equally effective adjuncts to 0.3 mol l1 sodium citrate
cal opioids.Continuous epidural infusion of low-
for reducing gastric acidity and volume.
dose local anaesthetic with fentanyl does not appear to
A recent meta-analysis on the effect of PPIs and
delay gastric emptying until the total dose of fentanyl
exceeds 100 mg.
(studies included both obstetric and
non-obstetric patients) concluded that H2-antagonists
Gastric emptying is not delayed in either obese or non-
were more efficacious than PPIs for both reducing gastric
obese parturients at term who ingest 300 ml water after
volume and increasing gastric pH.
European Journal of Anaesthesiology
2011, Vol 28 No 8
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Perioperative fasting in adults and children
As antacids such as 0.3 mol l1 sodium citrate can
Daniel Smole, Susanne Sujatta, Franc¸ois Sztark, Claudia Teipelke,
cause nausea and even vomiting, they need not be
the Dutch Society of Anesthesiology and Bernhard Walder.
administered prior to elective surgery under regional
Statements of interest of reviewers: Markus Hollmann has received
anaesthesia if the parturient has already received an
Lecture fees from Eurocept (The Netherlands), BBraun, Pfizer
H2-antagonist or a PPI. However, in the event of emer-
Germany, Schering-Plough and Merck, but all are unrelated to
gency obstetric surgery under general anaesthesia, an
this subject. Franc¸ois Sztark received fees for lectures and
antacid should be administered shortly before induction
consulting from Fresenius Kabi France and Abbott France and is
of general anaesthesia (e.g. within 20 min) with an H2-
co-investigator for Danone Research (study EUDRACT 2009-
antagonist, as time constraints may mean that the efficacy
of H2-antagonists cannot be guaranteed at the timeof induction.
Brady M, Kinn S, Stuart P. Preoperative fasting for adults to prevent
Metoclopramide 10 mg can further decrease gastric
perioperative complications. Cochrane Database Syst Rev
volume when used in conjunction with an H
Brady M, Kinn S, Ness V, et al. Preoperative fasting for preventing
prior to elective caesarean sectionand its use should
perioperative complications in children [review]. Cochrane Database
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caesarean section.
update [review]. Acta Anaesthesiol Scand 2005; 49:1041–1047.
Royal College of Nursing. Perioperative fasting in adults and children: anRCN guideline for the multidisciplinary team. London: Royal College ofNursing; 2005.
Scottish Intercollegiate Guidelines Network, Elliott House, 8-10 Hillside
I.S. has received research funding from Abbott and Anaxsys for
Crescent, Edinburgh EH7 5EA. 2010.
studies unrelated to these guidelines and declares no conflicts of
Schwartz PJ, Breithardt G, Howard AJ, et al. Task force report: the legal
interest. P.K. has received fees for lectures/consulting and/or study
implications of medical guidelines – a task force of the European Society ofCardiology. Eur Heart J 1999; 20:1152–1157.
material from Fresenius Kabi Deutschland GmbH (Bad Homburg,
American Society of Anesthesiologists Task Force on Preoperative Fasting.
Practice guidelines for preoperative fasting and the use of pharmacologic
Merck Sharp & Dohme Corp. (New Jersey, USA), Nutricia
agents to reduce the risk of pulmonary aspiration: application to healthy
Deutschland (Erlangen, Germany), Essex Pharma (Munich,
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Germany) and SonoSite GmbH (Erlangen, Germany). I.M. declares
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no conflict of interest.
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G.O.S. is part of a £3 million multi-centre trial investigating the
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has received gifts of equipment from Schering-Plough but not
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related to the content of this guideline.
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2005 fasting guidelines.
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Spam Detection Using Web Page Content: a New Battleground Marco Túlio Ribeiro, Pedro H. Calais Guerra, Leonardo Vilela, Adriano Veloso, Dorgival Guedes∗, Wagner Meira Jr. Universidade Federal de Minas Gerais (UFMG) Belo Horizonte, Brazil Marcelo H.P.C Chaves, Klaus Steding-Jessen, Cristine Hoepers Brazilian Network Information Center (NIC.br)
Meta-Analysis of Multiple Primary Prevention Trials of Cardiovascular Events Using Aspirin Alfred A. Bartolucci, PhD,a,* Michal Tendera, MDb, and George Howard, DrPHa Several meta-analyses have focused on determination of the effectiveness of aspirin (ace-tylsalicylic acid) in primary prevention of cardiovascular (CV) events. Despite these data,the role of aspirin in primary prevention continues to be investigated. Nine randomizedtrials have evaluated the benefits of aspirin for the primary prevention of CV events: theBritish Doctors' Trial (BMD), the Physicians' Health Study (PHS), the Thrombosis Pre-vention Trial (TPT), the Hypertension Optimal Treatment (HOT) study, the PrimaryPrevention Project (PPP), the Women's Health Study (WHS), the Aspirin for Asymptom-atic Atherosclerosis Trial (AAAT), the Prevention of Progression of Arterial Disease andDiabetes (POPADAD) trial, and the Japanese Primary Prevention of Atherosclerosis WithAspirin for Diabetes (JPAD) trial. The combined sample consists of about 90,000 subjectsdivided approximately evenly between those taking aspirin and subjects not taking aspirinor taking placebo. A meta-analysis of these 9 trials assessed 6 CV end points: total coronaryheart disease, nonfatal myocardial infarction (MI), total CV events, stroke, CV mortality,and all-cause mortality. No covariate adjustment was performed, and appropriate tests fortreatment effect, heterogeneity, and study size bias were applied. The meta-analysis suggestedsuperiority of aspirin for total CV events and nonfatal MI, (p <0.05 for each), with nonsignif-icant results for decreased risk for stroke, CV mortality, and all-cause mortality. There was noevidence of a statistical bias (p >0.05). In conclusion, aspirin decreased the risk for CV eventsand nonfatal MI in this large sample. Thus, primary prevention with aspirin decreased the riskfor total CV events and nonfatal MI, but there were no significant differences in the incidencesof stroke, CV mortality, all-cause mortality and total coronary heart disease.