ACERTO guidelines of perioperative nutritional interventions in elective general surgery

Objective: to present recommendations based on the ACERTO Project (Acceleration of Total Post-Operative Recovery) and supported by evidence related to perioperative nutritional care in General Surgery elective procedures. Methods: review of relevant literature from 2006 to 2016, based on a search conducted in the main databases, with the purpose of answering guiding questions previously formulated by specialists, within each theme of this guideline. We preferably used randomized controlled trials, systematic reviews and meta-analyzes but also selected some cohort studies. We contextualized each recommendation-guiding question to determine the quality of the evidence and the strength of this recommendation (GRADE). This material was sent to authors using an open online questionnaire. After receiving the answers, we formalized the consensus for each recommendation of this guideline. Results: the level of evidence and the degree of recommendation for each item is presented in text form, followed by a summary of the evidence found. Conclusion: this guideline reflects the recommendations of the group of specialists of the Brazilian College of Surgeons, the Brazilian Society of Parenteral and Enteral Nutrition and the ACERTO Project for nutritional interventions in the perioperative period of Elective General Surgery. The prescription of these recommendations can accelerate the postoperative recovery of patients submitted to elective general surgery, with decrease in morbidity, length of stay and rehospitalization, and consequently, of costs.


INTRODUCTION
I n recent years there has been important technological developments in the fields of surgery and anesthesia.
Many perioperative conducts, usually employed and empirically passed over decades, are now obsolete in the light of evidence and should therefore be abandoned.New equipment and new access techniques to body cavities have been developed thanks to laparoscopic and robotic operations.Laparoscopy alone showed that traditional care, such as early postoperative feeding and discharge are safe and feasible.In parallel, several guidelines of multimodal protocols 3,4 based on randomized studies and meta-analyzes have also shown in recent years that even in large open operations it is possible to abbreviate preoperative fasting with liquids containing carbohydrates for two hours before anesthesia, to feed early in the postoperative period and to reduce the length of hospital stay safely.
In 2005, the ACERTO Project (Acceleration of Total Postoperative Recovery), based on a large bibliographical review on perioperative care, initiated a pioneering multimodal program in the Brazilian territory, which, from its conception, highlighted the importance of nutritional issues in the recovery of the surgical patient 5 .Evidence-based Medicine has widely shown that postoperative recovery-acceleration programs, similar to ACERTO, are safe, reduce postoperative com-plications and hospitalization time, without increasing readmission rates [6][7][8] .
Although the association between malnutrition and adverse postoperative outcomes is well known, the prescribing of perioperative nutritional therapy as recommended by these modern guidelines, supported by important medical societies, is still forgotten among surgeons 9 .With more than ten years of existence, the ACERTO Project has been increasingly widespread and used throughout the country, as well as in Latin American countries that have epidemiolo-

METHODS
The authors searched the main databases (Medline, Scopus, SciELO and Cochrane) between 2006 and 2016 on clinical studies involving perioperative nutritional care for elective operations in general surgery following the precepts of McKeever et al. 10 .
The Medical Subjects Headings used as keywords were "fasting", "preoperative care", "surgery", "nutritional therapy", "perioperative care" and "immune nutrition".The keywords were combined individually or together with other specific areas of general surgery such as "colon", "stomach", "esophagus", "pancreas", "gallbladder", "liver", "Biliary tract", etc.In addition, we also searched for terms not present in Medical Subjects Headings such as "fast track", "enhanced recovery after surgery", "ERAS", "ACERTO".Some routines and guidelines were cited in some contexts, but did not interfere in the evaluation of the recommendations.We excluded review articles (non-systematic) and consensuses.We selected randomized controlled trials, systematic reviews and meta-analyzes.In the absence of these studies, we also selected and analyzed cohort studies with appropriate methods.We defined "General surgery" in the context of this Guideline as those procedures performed on the digestive tract, abdominal wall and head and neck surgery.Excluded from this definition were surgery for abdominal organ transplantation, those performed on an emergency basis or in critical care, pregnant and pediatric patients.
The authors first elaborated recommendations on several topics, previously selected and grouped as answers to guiding questions, formulated in order to address the main issues inherent to the decision-making process of the surgical patient, in the context of the objectives proposed for this Guideline.Each recommendation was then put to the vote and suggestions, by means of an anonymous questionnaire for collecting information, specially constructed for the elaboration of this Guideline, using the online SurveyMonkey® tool (http://www.surveymonkey.com,SurveyMonkey Inc., Palo Alto, Calif., USA), and based on the adapted Delphi method 11 .A consensus was reached when at least 60% of the panel authors agreed with each recommendation.
The quality of the evidence and the strength of the recommendations were graded by the GRADE System (Grading of Recommendations, Assessment, Development and Evaluation) 12 .By this method, each information is assigned a degree of evidence and a strength of recommendation.The degree of evidence represents confidence in the information used and was classified into four levels: High, Moderate, Low or Very Low.In turn, the strength of recommendation expresses the emphasis on whether a particular conduct is adopted or rejected, considering potential advantages and disadvantages, such as effect size, quality of evidence and intervention costs, and was classified as Strong or Weak.To exemplify, a recommendation classified as Strong would be one in which the authors are confident that the desired effects on adherence to this recommendation outweigh possible undesirable effects.On the other hand, a Weak recommendation would be one in which the desired effects on adhe-rence to a particular conduct also outweighs undesirable effects, but the authors are not so confident for a Strong recommendation.It is necessary to clarify that the recommendation (Strong or Weak) is not only based on the quality of the studies that support it, but also on the balance between desirable and undesirable effects of the conduct applied In this way, a Strong recommendation, for example, may have a low quality of evidence.

Should the patient receive preoperative information?
"The patient should receive, preferably in writing (booklet, pamphlet) guidelines and advice that help him/her have a fast recovery in the perioperative period."

Degree of recommendation: STRONG Evidence Strength: LOW
Transmitting some information about the operation to the patient may decrease anxiety, as well as "help one help oneself" postoperatively 13 .For example, knowing that one can shorten preoperative fasting time for certain types of liquids, that one can feed and ambulate early postoperatively, etc., may increase the patient's adherence to these behaviors, especially at times when the surgeon or other members of the multiprofessional team are not present.
Likewise, preoperative information enables preconceived or ingrained ideas about the perioperative period, such as the prohibition of walking or the need for an excessively long period of fasting, to be clarified and no longer affect or interfere with the conduct of accelerated recovery through the multimodal program.This information should be preferably available in the form of a pamphlet or small booklet that should be given to the patient.Aguilar-Nascimento et al. 15 observed a lower risk of nausea and postoperative pain in the group that received preoperative information in a systematized manner.The information should include, in addition to estimated discharge time, nutritional guidelines of abbreviated preoperative fasting (six hours for solids and two hours for carbohydrate containing liquids), early feedback and ambulation, among others.Li et al. 18 carried out a study in patients submitted to resection of colorectal cancer in two periods, before and after the intervention with pre-habilitation.The results showed benefits in functional capacity only in patients in the intervention group.There was no difference in morbimortality or hospitalization time.However, Valkenet et al. 19 , in a systematic review, showed that preoperative physical exercises are effective in decreasing the time of postoperative hospitalization and reducing complications in patients undergoing cardiac and abdominal surgery.In another study, 77 patients who were candidates for colorectal cancer surgery were randomized to receive preoperative exercises for four weeks at home (n=38) or not (n=39).Again, there was improvement in physical capacity tests, but there was no difference in terms of postoperative complication rates and hospitalization time 20 .Bruns et al. 21recently published a systematic review involving five studies in the elderly undergoing colorectal surgery.None of the studies showed improvement in complication rates and length of hospital stay.Four studies showed improvement in functional capacity with pre-habilitation.

Is there a benefit in prescribing preoperative nutritional therapy?
"Oral, enteral or parenteral preoperative nutritional therapy should be instituted for patients who are candidates to moderate to major operations and have moderate to high nutritional risk, accessed by any of the available methods."

Degree of recommendation: STRONG Evidence Strength: HIGH
The nutritional status interferes with the postoperative results.The more compromised the nutritional status, the higher the risks of morbidity and mortality, and therefore the higher hospital costs 22,23 .This is much more evident among the elderly 24 .The preoperative evaluation of nutritional status and, even better, nutritional risk for postoperative morbidity and mortality should be established preferentially by the use of the NRS-2002 25 tool.In this context, the prescription of 5-10 days of preoperative nutritional therapy, preferably by the oral use of protein supplements or, if not possible, enterally or parenterally, improves the aforementioned outcomes [26][27][28][29][30] .The positive results of this nutritional intervention were demonstrated mainly in studies involving patients operated on for cancer of the digestive tract or of the head and neck region 31,32 4. Are immunonutrient-containing formulations indicated in the perioperative period?
"The nutritional formula used in the perioperative period may contain immunonutrients or not.
However, in patients at greater risk and undergoing major surgery, nutritional therapy should include immunonutrients, both by the oral and enteral routes."

Degree of recommendation: STRONG Evidence Strength: HIGH
In recent years, much emphasis has been placed on the use of immunonutrition as a complement to the protein formula of oral supplements or enteral nutrition.Most of the studies used nutritional formulas containing arginine, omega-3 fatty acids and nucleotides.This interaction of immunonutrients can favorably modulate the inflammatory response, improve the immune response and promote healing 33 .
Although there are studies that have not shown differences in postoperative outcomes 34 , in the great majority of them the use of diet with immunonutrients was related to the reduction of complications, mainly infectious, and decreased hospitalization time [35][36][37] .The addition of arginine, omega-3 fatty acids and nucleotides to conventional nutritional supplements confer these additional perioperative nutritional advantages.There are more than 50 prospective, randomized studies on the subject in the literature today, which were the subject of five meta-analyzes.Braga et al. 38 recently reviewed the five meta-analyzes and consistently confirmed that in severe or moderate malnutrition, pre-operative nutritional therapy for seven to 14 days with diets enriched with immunonutrients is associated with reduction of postoperative infections and length of hospital stay.In addition, these benefits may be associated with a reduction in hospital costs, considering the reduction of length of stay in the ICU, antibiotic use, length of mechanical ventilation time, risk of rehospitalization etc 39 .In head and neck surgery, a meta-analysis showed a decrease in length of hospital stay, though with no significant difference in the incidence of postoperative complications with the use of an immunomodulatory diet 40 .Regarding the most appropriate period of administration, a recent meta-analysis suggested that administering diets enriched with immunonutrients is more beneficial throughout the perioperative period (pre and postoperative) or only postoperatively than only preoperatively 37 .

How should preoperative fasting be prescribed to ensure patient safety and benefit?
"Pre-operative fasting should not be prolonged.For most patients who are candidates for elective procedures, it is recommended they fast six to eight hours before anesthetic induction.Carbohydrate-containing liquids (maltodextrin) should be ingested up until two hours of anesthesia, except for cases of delayed esophageal or gastric emptying or emergency procedures."

Degree of recommendation: STRONG Evidence Strength: HIGH
There is extensive documentation in the literature showing safety in the abbreviation of fasting for two hours prior to anesthetic induction 41,42 .The volume of gastric residue with 12, eight, or six hours of complete fasting is similar to that found in fasting of six hours for solids and two hours for clear liquids, with or without carbohydrates 43,44 .The meta-analysis results involving 27 studies and 1976 participants did not show any case of aspiration or pneumonia with the abbreviation of preoperative fasting for 2h to 3h 45 .
For this reason, a recent systematic review of 19 different preoperative fasting guidelines showed that there is agreement in recommending avoiding prolonged fasting and safety in the prescription of clear liquids containing or not carbohydrates up to two hours prior to anesthetic induction 46 .Although fasting after midnight is a difficult dogma to be modified, some studies show an increasing adherence of surgeons and anesthetists in adopting these new recommendations 47 .

Can carbohydrate and protein-contai-
ning beverages be used to shorten preoperative fasting?
"Beverages containing carbohydrates associated with protein source (glutamine or whey protein) can safely be ingested up until three hours before the anesthetic procedure." Degree of Recommendation: WEAK

Strength of Evidence: MODERATE
The addition of nitrogen source containing glutamine, protein hydrolyzate or whey protein to the carbohydrate-containing beverage, besides being safe 64,65 , seems to increase the benefits associated with improved insulin sensitivity, functional capacity, higher glutathione production and lower acute Inflammatory reaction 42,43,66,67 .Although all randomized studies to date indicate safety, they are still few in comparison to those who used only maltodextrin and, in addition, they included few patients 42,43,66,67 .
Some old limitations of the abbreviation of preoperative fasting are being modified, such as for the diabetic patient or for the patient undergoing obesity surgery.There have been at least three randomized studies that have shown safety in abbreviating fasting in obese patients undergoing bariatric surgery [68][69][70] .
Patients with controlled diabetes mellitus, not using without insulin and without gastroparesis can undergo abbreviated fasting 71 .However, due to the lack of studies in these groups of patients, it should be considered that more data are needed for a better understanding of the abbreviation of fasting in morbidly obese and diabetic patients.

When should feeding be restarted in
1][82] .The oral route should be the first option for early feedback, even after large procedures 83 .The current trend in the postoperative period is to avoid prolonged fasting and to abandon the classic oral diet from liquid to pasty and finally solid and to allow an oral precocious diet at will 81,84 .
According to the reviewed studies, although the tolerance of the patient to the resumption of the diet is not universal, it is generally high 85-87 (above 70%), and may be even greater with the association of the prescription of other perioperative routines present in multimodal acceleration protocols of postoperative recovery.These include preoperative information (as discussed above), use of chewing gum from the immediate postoperative period on 88 , early mobilization 89 , use of prokinetic drugs such as alvimopan 90 (not yet marketed in Brazil), non-use of opioid medication 91 , and avoiding overload of perioperative intravenous fluids through the use of more rigorous therapy strategies (target-directed therapy) 92,93 or even restrictive ones 94 , especially with regard to the use of crystalloid solutions and with high sodium content.
Still in this respect, careful management of intravenous crystalloid liquids on the day of operation is warranted.The greater the volume infused, the longer the postoperative ileus period, the greater the intolerance to the early diet and the longer the hospitalization 90,95 ..

When
Formulas containing omega-3 fatty acids determine a minor postoperative acute-phase inflammatory reaction [119][120][121] , although this has not been confirmed in some studies.The use of intravenous glutamine in the postoperative period of patients receiving parenteral nutrition was safe in a recent multicenter study 122 .However, it did not modify the postoperative clinical results 123 .

9.
In what patients should specialized nutritional therapy be maintained after discharge?
"Oral nutritional therapy (with oral supplements) or enteral nutrition should be maintained after discharge in patients who have used nutritional therapy in the perioperative period and still cannot maintain protein-calorie needs only by mouth."

Degree of recommendation: STRONG Evidence Strength: LOW
The risk of postoperative infectious complications in malnourished patients, especially in large operations, is quite high.In recent years, special attention has been devoted to the risk of rehospitalization in surgical patients 124 .In addition to being an indicator of morbidity, readmissions are strongly correlated with increased hospital costs 125 .The main risk factors associated with rehospitalization in this group are malnutrition and inadequate functional status (high ASA score, for example) [126][127][128] .As previously discussed, perioperative nutritional therapy is recommended in these cases, as there is sufficient evidence that this can positively influence this outcome and reduce the need for rehospitalization.However, many patients on perioperative nutritional therapy are discharged after a few days without guidance to maintain adequate nutrient supply.This leads to a greater risk of rehospitalization and of high late morbidity and mortality 129 .
The use of nutritional strategies, including the prescription of oral supplements in the postoperative period and after discharge from patients undergoing major operations, can prevent complications and reduce the chances of readmission 130,131 .This is especially important in elderly patients 132 .Maintenance of enteral nutrition in home care (with home-based nutritional therapy) may contribute to increase nutritional intake after major operations 133 and prevent post-operative nutritional deterioration 134,135 .

Areas for future research
Few studies have investigated the effects of preoperative education on elective general elective surgery patients, although there is a strong recommendation for this practice.There is also a lack of studies on the effects of pre-habilitation on postoperative results.
Further knowledge of the deleterious effects of preoperative sarcopenia and ways to reverse it before surgery can bring valuable information to improve recommendations in the future.Further studies on the use of nitrogen sources in preoperative oral supplements are also awaited, although there is enough literature to recommend them.Likewise, more studies on early feeding after esophagectomies and total gastrectomy are expected so as to enable the elaboration of specific recommendations on early oral route feeding for these operations.
There is also a lack of studies on formulas with intact or hydrolyzed nutrients in the postoperative period.In the same way, there is a lack of studies to clarify

REFERENCES
gical realities and similar conducts to those we have in Brazil.Being a model for dynamic decision-making, throughout this period the program has been constantly updated, including new scientific information from the publication of methodologically well-designed studies.The purpose of this Guideline is to present recommendations from specialists of the Brazilian College of Surgeons and the Brazilian Society of Parenteral and Enteral Nutrition on various nutritional prescriptions applied to the perioperative period of elective procedures in general surgery based on the latest evidence proposed by the ACERTO Multimodal Project.

2 .
Should a pre-habilitation program be recommended prior to surgery?"A pre-habilitation program should be performed before surgery in patients at higher risk (less functional reserve) by combining physical exercises with other measures, such as adequate nutritional care.Most studies show improvement in postoperative functional capacity, but without reducing the rate of complications and without reducing length of hospital stay."Degree of Recommendation: WEAK Evidence Strength: LOW Malnutrition is an important cause for decreased muscle mass.However, currently other situations in which loss of muscle mass may have occurred have been well studied, among them sarcopenia.Primary sarcopenia is related to the aging process, but other causes have also been associated 16 .Because sarcopenia is amenable to reversal through nutritional interventions and progressive resistance training, it becomes a potentially modifiable risk factor in elective surgical patients.In the postoperative period, several factors can alter body composition, especially at the expense of muscle mass consumption.The operation must be analyzed from the metabolic point of view as a planned trauma.The purpose of the surgical pre-habilitation is to prepare the patient to support the surgical stress with the least possible physical and functional repercussion, with the improvement of the parameters of physical conditioning before the operation, in order to optimize postoperative recovery and to maintain the muscular physical function.The ideal pre-habilitation program should be done for a period of four weeks, intercalating aerobic and resistance exercises 17 .In addition to nutritional care and physical conditioning, other care should be part of the preoperative optimization, such as cessation or reduction of smoking and alcohol use, optimization of doses of medications used, and compensating diabetes mellitus, hypertension and cardiopulmonary function whenever indicated.
the best time to initiate parenteral nutrition therapy in non-critical patients postoperatively.In this article, we synthesized the possible recommendations in light of the evidence.The prescription of these recommendations can accelerate the postoperative recovery of patients submitted to elective general surgery, with decrease in morbidity, length of stay and rehospitalization, and consequently, of costs.