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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 lS1 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 Copyright European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
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 Copyright European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
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 Copyright European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
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 Copyright European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
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 European Journal of Anaesthesiology 2011, Vol 28 No 8 Copyright European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
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 Copyright European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
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 Copyright European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
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 European Journal of Anaesthesiology 2011, Vol 28 No 8 Copyright European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
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 Copyright European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
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 Copyright European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
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 be considered prior to both elective and emergency Systematic Rev 2009:CD005285.
Søreide E, Eriksson LI, Hirlekar G, et al. Preoperative fasting guidelines: an 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, patients undergoing elective procedures. Anesthesiology 1999; 90: 896–905.
Germany) and SonoSite GmbH (Erlangen, Germany). I.M. declares Maltby JR, Sutherland AD, Sale JP, Shaffer EA. Preoperative oral fluids: is a no conflict of interest.
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related to the content of this guideline.
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Edwards, Fresenius, GSK, Ko¨hler Chemie, Lilly, MSD, Novalung, Miller M, Wishart HY, Nimmo WS. Gastric contents at induction of Orion Pharma, Pfizer, Pfrimmer Nutricia and Wyeth. B.V. declares anaesthesia. Is a 4-h fast necessary? Br J Anaesth 1983; 55:1185–1188.
no competing interests in the last 5 years.
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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)

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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.