Perioperative nutritional support in patients undergoing gastrointestinal surgery: Current views with an emphasis on prehabilitation efforts

Abstract

Continuously increasing reports in the international medical literature, along with current guidelines from international societies, support the view that perioperative enteral nutrition (EN) and immunonutrition offer significant benefits to patients with benign and/or malignant digestive disorders, including reduction of postoperative infections and hospital stay. A vital component of the rehabilitation of patients after major gastrointestinal surgery is a comprehensive nutritional rehabilitation program. It has been shown that implementing an integrated nutritional support program significantly improves patients’ immune responses, accelerates wound healing processes, reduces pain and accompanying anxiety, and decreases hospital length of stay. It appears that, in addition to the efforts of rehabilitation, prehabilitation, i.e. the return to the presurgery level of physical fitness, is or should be a vital objective of the team responsible for rehabilitating patients undergoing gastrointestinal surgery. The present review summarized the most up-to-date data on the role of perioperative nutritional support (EN and immune EN) in the rehabilitation and prehabilitation of patients undergoing major digestive surgery. Systematic and comprehensive perioperative nutritional support for these patients should become a daily clinical practice element of paramount importance.

Key Words: Immunonutrition; Nutrition; Perioperative care; Gastrointestinal surgery; Prehabilitation

Core Tip: Perioperative nutritional support [enteral nutrition and immune enteral nutrition] and prehabilitation, i.e. the return to the presurgery level of physical fitness of patients undergoing major digestive surgery, is of paramount importance for the outcome of patients treated for benign or malignant gastrointestinal disorders with surgery as it can reduce the rate of postoperative complications and hospital stay. This strategy is increasingly applied in daily clinical practice. The scientific interest in the various parameters of the method is constantly increasing since it is a field of intensive scientific research, especially in developed countries.

INTRODUCTION

The role of surgery in the treatment of a large number of benign or malignant digestive diseases is essential. It is becoming increasingly important with the improvement of surgical and anesthetic techniques. While the immediate surgical results are evident and effective in many cases, postoperative morbidity is still a concern as the duration of hospitalization is prolonged due to unsatisfactory healing of the surgical wound or subsequent immunosuppression, which favors postoperative infections and adversely affects the quality of life of patients. Furthermore, a factor that has not received sufficient attention in daily surgical clinical practice concerns assessing nutritional status and correcting nutritional deficiencies present in the perioperative period in a high proportion of patients with benign or malignant digestive diseases[1].

The role of perioperative nutritional support, particularly in cases of malignant digestive tumors, is supported by many clinical studies and laboratory data[2]. Nutritional support is achieved by administering enteral nutrition (EN) or immune EN (IEN) and/or parenteral nutrition in cases where enteral feeding is difficult or impossible. It is undoubtedly the case that EN is preferable to parenteral nutrition for many reasons, including the maintenance of satisfactory digestive function and intestinal barrier function, which are the most desirable consequences of EN. This integrated nutritional support is recognized as a significant supportive action in patients undergoing surgery for benign or malignant digestive disease. Integrated nutritional support can combine EN and parenteral nutrition. The patient’s nutritional status has long been known to negatively affect the immune system since several micronutrients are necessary to maintain satisfactory immune responses.

Malnutrition increases the likelihood of infection in the postoperative period. To a certain extent, comprehensive nutritional support restores impaired immune functions with favorable effects on postoperative morbidity. Finally, integrated nutritional support through several mechanisms can psychologically support the patient, relieving postoperative pain.

PERIOPERATIVE NUTRITIONAL SUPPORT

Perioperative nutritional support encompasses preoperative, intraoperative, and postoperative care for patients undergoing major surgery due to benign or malignant digestive system disease. EN, IEN, and prehabilitation are included. The most critical data on these actions are described below.

EN

EN means direct oral or nasogastric tube feeding or tube feeding, e.g., percutaneous gastrostomy and endoscopic jejunostomy. Patients’ energy requirements do not differ from those of healthy individuals (25-30 kcal/kg/d). It has been estimated that 1.2-1.5 or 2 g/kg/d of protein should be provided; however, this amount should be lower (1 g/kg/d) in patients with coexisting renal failure. Finally, the lipid/carbohydrate ratio should be determined according to the patient’s clinical condition.

EN and IEN are safer, cheaper, and more physiological than parenteral nutrition. ΕΝ has the significant advantage of maintaining the structural and functional integrity of the gastrointestinal tract. However, compared to EN, parenteral nutrition should be considered in patients with impaired gastrointestinal function despite the increased risk of infections. In general, severely ill patients, especially those suffering from end-stage malignant disorders, are not expected to significantly benefit from nutritional support since the rate of complications is expected to increase. Therefore, it is generally accepted that EN should be applied in those cases where the benefit is expected to significantly outweigh the side effects likely to occur[3].

Preoperative early administration of EN and assessment of nutritional status is expected to exert a favorable effect on early postoperative outcomes. All international scientific societies’ guidelines recommend the use of EN. Existing data support the idea that perioperative EN reduces the postoperative rate of complications and hospitalization without affecting survival. Furthermore, EN in the postoperative period helps to reduce weight loss, particularly in patients undergoing gastrectomy, and offers significant help to those patients receiving neoadjuvant or adjuvant antineoplastic therapy[4].

IEN

IEN allows the regulation and modification of the function of the immune system through the administration of specific nutrients or nutritional preparations that promote or beneficially regulate the immune system. Certain nutrients have become known as immune nutrients, of which glutamine, arginine, ornithine ex-ketoglutarate, and omega-3 fatty acids have been studied extensively. Still, the list could also include nucleotides, trace elements such as selenium, and probiotics.

Arginine promotes nitric oxide synthesis and growth hormone production and increases the number of T helper cells. Omega-3 fatty acids have proven anti-inflammatory actions, which help to reduce immune suppression by reducing the production of eicosanoids. Glutamine is considered to be a very significant element in immunocytes. Nucleotides have a less well-defined role but appear to affect T cell function significantly. They also enhance glutathione production, thus improving the antioxidant status. In conclusion, the individual components of IEN are the amino acids glutamine and arginine, polyunsaturated omega-3 fatty acids, nucleotides, and antioxidants[5].

It has been proven that major surgical procedures performed on patients with both benign and malignant digestive diseases result in a decrease in immune responses. This leads to an increase in mortality and morbidity, mainly associated with postoperative infections and a decrease in healing of the surgical wound. Therefore, restoring immune responses through artificial nutrition products and solutions enriched with nutrients that can restore nitrogen balance and increase protein synthesis is expected to reduce the incidence of these complications[6].

IEN is only beneficial if administered promptly. Furthermore, it does not benefit patients with a preoperatively normal level of nutrition, patients in whom IEN is contraindicated, or patients who cannot be nutritionally assisted. Recent studies supporting the above are presented below.

Yu et al[7] randomized 112 patients with gastric cancer and concomitant cachexia to receive either IEN (n = 56) or standard EN support (SEN, n = 56) preoperatively. They noticed that the rate of all complications was lower in the IEN group than in the SEN group. Moreover, patients in the IEN group had lower peripheral blood white blood cell count, C-reactive protein, and interleukin-6, higher lymphocyte count, and higher IgA levels than the SEN group, received fewer antibiotics, had a shorter hospital stay, and had lower hospitalization costs than the SEN group.

Martínez González et al[8] separated 134 patients with gastric cancer who underwent total gastrectomy into a group (79 patients) who received a standard diet and a second group (55 patients) who received IEN high in arginine, nucleotides, omega-3 fatty acids, and extra virgin olive oil, preoperatively and postoperatively for 10 days. They noticed that less weight loss, a smaller decrease in postoperative albumin and serum cholesterol, shorter hospital stay, lower risk of infectious complications, and less duration of parenteral nutrition administration were found in the IEN group. This demonstrated that IEN reduced postoperative complications and hospital length of stay while optimizing nutritional outcomes.

Comparison of EN and IEN results

Several clinical trial data and meta-analyses compared the results of EN and IEN use. The recent meta-analysis by Li et al[9], which included 12 studies with 1124 patients (565 patients in the IEN group and 559 in the EN group), found that CD4+ levels, lymphocyte counts, transferrin concentrations, and systemic inflammatory response syndrome did not differ significantly between the two groups. However, CD8+, CD4+/CD8+ ratio, IgG, IgM, proalbumin concentrations, and infectious complication rates were lower in the IEN group, suggesting that IEN is a highly effective nutritional intervention that can improve the immune function of patients undergoing surgery for gastric cancer.

Prehabilitation

The term prehabilitation refers to preoperative interventions that are carried out by a specialized multidisciplinary team. These interventions include physical exercises, nutrition optimization, and psychological support to improve postoperative parameters. Rehabilitation and recovery programs aim to improve patients’ perioperative physical fitness and mental well-being[10]. During the last few years, many clinical research studies, reviews, and meta-analyses have demonstrated the effectiveness of the application of the method in patients undergoing major digestive surgery. Several variations of the technique have been applied in clinical practice, ranging from short-term preparation lasting 7-14 days to more extended periods included in comprehensive multimodal prehabilitation programs[11]. An essential drawback of the studies is the heterogeneity of the nutritional interventions, which ultimately leads to a need for clearer evidence to formulate specific nutritional recommendations.

Recent studies have shown that postoperative physical activity in patients with major digestive diseases undergoing surgery is deficient. While it is right that patients should be encouraged to demonstrate an average level of physical activity postoperatively, certain patient-related factors seem to help in the early identification of high-risk patients[12]. Ultimately, prehabilitation can be seen as an attempt to improve the preoperative status of patients who are about to undergo any surgery. It is expected to improve the patient’s general condition, functionality, and function of various organs. This is particularly relevant for elderly and ill patients as well as patients with cancer of numerous organs. It is aimed at shortening the hospital stay, reducing perioperative morbidity, and enhancing recovery after surgery. Prehabilitation is an integral part of the preparation for elective surgery. In other words, it should be made a mandatory part of the preparation for planned surgery, contributing to a better final clinical outcome[13]. The most recent of these studies are analyzed below.

Systematic reviews and meta-analyses: Several systematic reviews and meta-analyses of existing research studies have addressed the role of prehabilitation in patients with severe gastrointestinal disease undergoing surgery. Skořepa et al[14] analyzed 16 studies (6 randomized clinical trials and 10 observational studies) that included 3339 patients (1468 in the prehabilitation group and 1871 in the control group). Meta-analysis of nine studies showed a reduction in hospital length of stay. A meta-analysis of ten studies showed a decline in severe complications by 44% in the prehabilitation group. Meta-analysis of four studies showed a pooled weighted mean difference of 40.1 min in the 6-min walk test, favoring prehabilitation.

In their meta-analysis of multimodal prehabilitation in patients undergoing upper gastrointestinal surgery, Amirkhosravi et al[15] included ten studies with 1503 patients. They found lower postoperative complication rates in the prehabilitation group compared to the control group. Of interest was the observation that prehabilitation reduced the length of hospitalization only in the group of patients in which the prehabilitation strategy included physical exercise.

Ricci et al[16] analyzed the results of physical prehabilitation in patients who underwent major abdominal surgery using a random-effects network meta-analysis. The results showed that aerobic exercise and the combination of aerobic exercise and inspiratory muscle training were the most effective methods of reducing overall morbidity. To minimize the occurrence of pneumonia, the most effective combination was aerobic exercise and inspiratory muscle training. Finally, aerobic exercise alone was the most effective combination for reducing hospitalization days. The most important conclusion of the study was that the most favorable result of prehabilitation was achieved with the simultaneous use of aerobic exercise and inspiratory muscle training.

Zhang et al[17] in their systematic meta-analysis included a total of 28 randomized clinical trials. They found that compared with conventional preoperative care, rehabilitation or preoperative lifestyle management enhanced the postoperative 6-min walk test and reduced the complication rate. No significant differences were observed in the quality of life or the aggregate and postoperative duration of hospitalization between the groups. Further analysis revealed that rehabilitation lifestyle management reduced complication rates and length of hospital stay[17]. However, the combined approach of physical, nutritional, and psychological intervention emerged as the most effective, reassuring us of the robustness of these findings. This suggests that in patients with colorectal cancer, prehabilitation offers clear benefits as far as postoperative functional recovery and reduction of complications are concerned. While a challenge, the heterogeneity in pooled results also presents an opportunity for future studies to be more uniform in design, making future meta-analyses more valid.

In conclusion, these recent (2024) meta-analyses demonstrated the beneficial effects of implementing rehabilitation programs that should be adopted in daily clinical practice.

Clinical trials: Single randomized clinical studies also demonstrated the value of prehabilitation programs in many benign or malignant digestive conditions. In a recent survey, Powell et al[18] attempted to document the impact of a prehabilitation program on emotional well-being in people with cancer who underwent surgery. The program included physical activity, wellness, and nutritional support. The results showed that patients showed less anxiety and were more confident about the successful outcome of treatment efforts. The ongoing, implicit psychological support provided by Exercise Specialists is also valued. Some patients positively evaluated the opportunities to talk about their problems with other sufferers but not with others outside the program. Therefore, participation in a prehabilitation and recovery program yields valuable emotional well-being benefits without needing specialized psychological support. The method was also applied to other chronic digestive diseases, such as ulcerative colitis and Crohn’s disease, for which a multidisciplinary approach is paramount[19,20].

The results in elderly patients undergoing major gastrointestinal surgery are interesting. It appears that applying a nutritional prehabilitation model results in better physical and mental status while reducing infection rates and shortening hospital stays[21]. Bausys et al[22] randomized 122 patients who underwent elective surgery or surgery after neoadjuvant chemotherapy to prehabilitation or standard care. Prehabilitation included exercises emphasizing endurance, respiratory muscle strength, stretching, and nutritional and psychological support. The prehabilitation group showed increased physical capacity preoperatively compared to the baseline value. Even the prehabilitation group had a lower rate of non-adherence to neo-operative treatment, a 60% reduction in patients with postoperative complications and an improved quality of life compared to the control group. Prehabilitation reduces morbidity in gastric cancer patients undergoing surgical treatment.

Through nutritional support, surgeons can positively influence the degree of postoperative healing of wounds and pressure ulcers. Other elements of improvement relate to the characteristics of the inflammatory process (swelling, redness, pain) and other parameters such as stress and reduction of recovery time[23].

Discussion

The results of published studies, a collaborative effort of healthcare professionals, researchers, and policymakers, safely and adequately demonstrate that a comprehensive nutritional support program significantly improves many vital parameters, such as immune function, through an effect on white blood cells and the CD4+/CD8+ and CD4+/T cell ratio. These are indicators of an immunological improvement that reduces the number of postoperative infections. In addition, the integrated nutritional support program maintains the function of the intestinal barrier and reduces the displacement of the intestinal flora, thus contributing to the reduction of postoperative infections[24].

Other improved parameters concern the more effective and faster healing of surgical wounds and the reduction of hospital stays for patients who underwent major gastrointestinal surgery. These results are related to the fact that comprehensive nutritional support provides the necessary amounts of proteins (including amino acids such as glutamine), trace elements (mainly zinc), and vitamins (especially vitamin C) that are necessary for tissue recovery. Omega-3 fatty acids are associated with improved healing of surgical wounds and enhanced immune function. Even vitamins A, B, and C positively affect the healing stages, while polyphenolic compounds favor tissue restoration with their anti-inflammatory effect[25]. The study under comment demonstrated that pain improvement is achieved in many ways, mainly related to reducing the inflammatory process. Furthermore, the degree of anxiety and depression was significantly reduced, proving that integrated nutritional support effectively improves patients’ psychological state. Finally, the length of stay of the patients in the hospital was significantly reduced compared to the control group, thus reducing hospitalization costs.

Some other important issues related to applying prehabilitation in daily clinical practice are the following. Because poor patient fitness increases the risk of postoperative complications and hospitalization, it is necessary to adopt preoperative measures to reduce postoperative complications. A significant additional element concerns integrating physical exercise into daily clinical practice, implementing specialist psychological support program and providing nutritional support to improve patients’ preoperative functional status[26]. Especially for the role of psychological parameters, it should be emphasized that various psychological factors, such as preoperative anxiety, depression, and low self-esteem, affect surgical outcomes and postoperative quality of life. The enhanced recovery after surgery strategy improves patients’ ability to have an uneventful postoperative return to normality. Incorporating prehabilitation into enhanced recovery after surgery protocols is expected to improve postoperative outcomes further. However, implementing these programs in clinical practice is problematic because it requires good organization and additional financial resources[27].

The ethical issues in implementing these programs primarily concern the patients and secondarily the treating physicians. As is apparent, patients should be fully informed about the procedures, benefits, and any side effects that may arise and should give their written consent. It is also understandable that any unexpected modifications should be communicated to patients and that such changes should be previously approved by the hospital’s bioethics committee[28].

CONCLUSION

Early feeding and effective nutritional intervention through the help of an appropriate nutritional screening tool can improve clinical outcomes and reduce potential complications[29]. Both surgeons and oncologists should be familiar with patient nutritional assessment methods. Interventions should be adapted preoperatively to improve postoperative clinical parameters. It is essential that the nutritional monitoring of cancer patients be multidisciplinary and tailored to each center. Compared with traditional nutrition management, nutrition support team intervention might benefit immune function recovery and nutritional status. Still, there is no evidence that nutrition support team intervention could improve the prognosis of elderly gastric cancer patients[30].

Based on the results of the available studies and meta-analyses, comprehensive nutritional support programs should be adopted and used regularly in patients undergoing gastrointestinal surgery, especially those who are seriously ill or suffering from malignant digestive diseases, especially during the postoperative period. Monitoring the nutritional status of patients is of great clinical importance. The dietary interventions should be adapted preoperatively to improve postoperative clinical parameters. Moreover, the prehabilitation strategy should be applied to all elderly, high-risk patients who will undergo surgery since its application reduces hospital stays and serious complications.

In the future, the number of patients included in carefully designed prospective studies should be sufficient to obtain results that will lead to confidence in the recommendations. All available nutritional support programs for patients undergoing gastrointestinal surgery should be re-evaluated. Moreover, the specific dietary components, the ideal combination of nutritional elements, and the quantity required for the best results should be determined. It should not be forgotten that the mechanisms of action of nutritional components in terms of surgical wound healing and patients’ immune responses are not fully understood. This should be an area of research. Integrated nutritional support should be fully adopted in daily clinical practice since its results are proven to benefit patient outcomes.

According to recently published bibliometric analysis data[31], current research tailors rehabilitation programs for specific groups. It was demonstrated that the number of relevant studies, including gastroenterological disorders, lung cancer, and aortic valve replacement, is increasing. It was also noticed that preoperative exercise is an essential part of prehabilitation, with growing interest in multimodal prehabilitation. Finally, North America and Western Europe are the most important countries in terms of contribution to research in rehabilitation. The authors also suggest that broadening the geographical scope would enhance the studies, contribute valuable insights for medical practitioners, and shape future research efforts.