Year : 2009 | Volume
: 5 | Issue : 4 | Page : 232--239
Is early feeding after major gastrointestinal surgery a fashion or an advance? evidence-based review of literature
Shailesh V Shrikhande, Guruprasad S Shetty, Kailash Singh, Sachin Ingle
Department of Gastrointestinal and Hepato-Pancreato-Biliary Surgery, Tata Memorial Hospital, Mumbai, India
Shailesh V Shrikhande
Gastrointestinal and Hepato-Pancreato-Biliary Surgery, Ernest Borges Marg, Tata Memorial Hospital, Mumbai 400 012
Early enteral nutrition (EN) after major digestive surgery has been receiving increasing attention. Supporting evidence has not been clear. This evidence-based review traces the development of early EN and analyses whether it is indeed an advance. We performed a PubMed search in October 2009 with the key words enteral nutrition, early feeding, and gastrointestinal surgery. Our emphasis was on earliest studies documenting the benefits or adverse effects of EN, comparative studies, documenting the benefits or adverse effects of EN, comparative studies, and randomized controlled trials. Thirty-one results were returned from which 17 were included for evaluation (1979-2009). Fifteen papers concluded that early EN was beneficial. In general, patients put on early EN and immunonutrition postoperatively seemed to have decreased hospital stay, decreased complication rates, decreased treatment and hospital costs, and even decreased morbidity and mortality; however, judicious use has been suggested. One study did not recommend early enteral feeding in well-nourished patients at low risk of nutrition-related complications and another suggested that immunonutrition is not beneficial and should not be used routinely. Early EN has been safely given after major digestive surgery since 1979. It benefits patients undergoing major gastrointestinal (GI) surgeries, with reduction in perioperative infection, better maintainance of nitrogen balance, and shorter hospital stay. Early EN may be superior to total parenteral nutrition (TPN). However, TPN is perhaps better tolerated in the immediate postoperative period. Early enteral immunonutrition should be used only in malnourished and in transfused patients. Early EN after major digestive surgery is an old advance that is now in fashion.
|How to cite this article:|
Shrikhande SV, Shetty GS, Singh K, Ingle S. Is early feeding after major gastrointestinal surgery a fashion or an advance? evidence-based review of literature.J Can Res Ther 2009;5:232-239
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Shrikhande SV, Shetty GS, Singh K, Ingle S. Is early feeding after major gastrointestinal surgery a fashion or an advance? evidence-based review of literature. J Can Res Ther [serial online] 2009 [cited 2021 Oct 19 ];5:232-239
Available from: https://www.cancerjournal.net/text.asp?2009/5/4/232/59892
A 'nil by mouth' (NBM) approach after major gastrointestinal (GI) surgery has been well known for many years. Early enteral nutrition (EN), as opposed to the conventional NBM and intravenous fluids (IVF) approach, has received increasing attention in recent years. Several advantages have been propounded, though the evidence has not always been clear. Through an evidence-based review, this paper attempts to evaluate whether early EN is merely a fashion or genuinely an advance.
Materials and Methods
We performed a PubMed search in October 2009 with the key words enteral nutrition, early feeding, and gastrointestinal surgery. The definition of enteral feeding was 'a mode of feeding that uses the GI tract, e.g., oral or tube feeding.' Early feeding was defined as resumption of feeds within 24-72 h of surgery. Major GI surgeries were resections of esophagus, stomach, and pancreas, and extensive colonic resections and other procedures dealing with liver transplantation, severe acute pancreatitis, and perforative peritonitis. Other GI surgeries were considered as minor and studies involving them were excluded.
The search was restricted to studies involving humans. The types of studies considered were limited to clinical trials, meta-analysis, practice guidelines, randomized clincal trials (RCTs), and reviews. Publications in English, French, German, and Japanese were included and only core clinical journals were evaluated. Studies that received emphasis included earliest studies documenting the benefits or adverse effects of EN, objective comparative studies, and RCTs.
Thirty-one potential articles were available from the primary search (1979.2009). Fourteen papers were excluded due to various reasons and 17 papers were selected for detailed evaluation [Flow chart 1]. Fifteen papers were prospective studies, while two [SUPPORTING:1] were papers with a systematic review and meta-analysis in each. Of the 15 prospective studies, 13 were randomized and two were non-randomized. The number of patients included in these studies ranged from 24 to 1173. The type of surgeries included were elective GI surgeries in six studies, upper GI surgeries in three studies, traumatic intestinal perforation and peritonitis in one study, colorectal and intraabdominal vascular surgeries in one study, pancreatic and gastric cancer surgeries in three studies, liver transplantation in one study, both esophagectomies and pancreatectomies in one single study, and severe acute pancreatitis in one study. Fifteen papers concluded that early EN was beneficial. Four of these 15 papers recommended enteral immunonutrition (one perioperatively and three postoperatively). One paper demonstrated that early EN did not influence postoperative ileus but neverthelesss recommended early EN.
One study showed the superiority of elemental diet over conventional treatment when it was started in the immediate postoperative period.  Another study revealed the safety of starting solid foods immediately after removing the nasogastric tube after major GI operations.  In a study related to liver transplantation, the effects of early EN was comparable with that of TPN at maintaining the nutritional status, with additional potential benefits of reduced costs and complications.  A randomized study comparing early EN with placebo revealed decreased infectious complications and postoperative complications.  Another randomized study comparing early EN with conventional treatment showed improved protein kinetics and decreased morbidity and mortality in the early EN group.  In a study comparing early enteral immunonutrition to placebo, the immunonutrition group showed similar immediate and fewer delayed postoperative complications, and decreased costs of treatment of complications.  Another study comparing EN, immunonutrition, and TPN showed that immunonutrition enhanced the host response, induced a switch from acute-phase to constitutive proteins, and perhaps improved outcomes.  However, another prospective, randomized study comparing early enteral immunonutrition to controls showed that immunonutrition was not beneficial and was not recommended as a routine after surgery for upper GI malignancies.  One study comparing EN, enteral immunonutrition, and TPN revealed that an immunonutrition diet was of benefit, especially in malnourished and transfused patients.  In another study, the results showed that immediate postoperative EN should not be a routine in well-nourished patients who are at low risk of nutrition-related complications.  A systematic review and meta-analysis done in 2001, comparing EN with starvation postoperatively, revealed no statistical significance of the benefits of early EN.  However, another meta-analysis concluded that early commencement of EN was beneficial as compared to delayed EN with respect to postoperative complications, mortality, and hospital stay.  An RCT comparing EN to TPN clearly documented that EN resulted in decreased postoperative complications and hospital stay but that TPN was better tolerated.  Another randomized study evaluating the functional recovery of the gut postoperatively, concluded that as there is no reason to withhold oral intake following open colorectal or abdominal vascular surgery, postoperative management should include early resumption of diet.  A comparison of early EN and TPN, post gastrectomy, showed that EN could decrease treatment cost and length of hospital stay and, besides, was an efficient way to provide nutrition and possibly prevent intestinal atrophy.  In patients with predicted severe acute pancreatitis (SAP), a comparison of early nasogastric feeding and TPN revealed that although the former was feasible there was no documented benefit of early feeding.  In cases of perforative peritonitis, a study revealed that immediate postoperative feeding was feasible and even decreased septic morbidity. 
Thus, patients on EN were doing better metabolically in one study, had decreased hospital stay in three studies, decreased complication rates in three studies, decreased hospital costs in two studies, decreased morbidity and mortality in one study, and even seemed feasible in cases of perforative peritonitis, decreasing septic morbidity in one study. In predicted SAP, EN seemed feasible and showed better control of sugars, although the complication rates were higher.
Studies that evaluated enteral immunonurition also showed decreased complication rates in two studies, decreased hospital costs in two studies, and increased host response with improved outcomes in one study. One study recommended enteral immunonutrition in malnourished and transfused patients. One study did not recommend early enteral feeding in well-nourished patients at low risk of nutrition-related complications and another suggested that immunonutrition is not beneficial and should not be used routinely.
Details of all studies evaluated are in shown in [Table 1] .
Our results revealed many interesting aspects related to early EN after major GI surgery.
Early evidence supporting EN after major GI surgery
The earliest study to address the issue of elemental diet (ED) in the early post-operative period was in 1979, when 30 patients who had undergone major GI operations were given either ED or conventional treatment postoperatively.  The ED group did significantly better than controls clinically and metabolically and lost less weight. Energy intake was higher in the ED group and negative nitrogen balance was more in the control group throughout the initial seven postoperative days. The authors concluded that ED could be given from the first postoperative day, with patients faring better metabolically and requiring shorter hospitalization.
Safety of solid diet after major GI surgery
While the 1980s saw more studies addressing this concept, the first randomized study was reported in 1992.  This study evaluated 171 patients who had undergone an intervention affecting the integrity of the GI tract (gastroenterostomy, cystogastrostomy, Billroth II anastomosis, suture of perforation, small bowel anastomosis, colocolostomy, enterobiliary anastomosis, Whipple resection, etc.), The study subjects were randomized into two groups. The first group began liquid oral intake 4 h after nasogastric tube removal, while the second group began regular solid intake soon after tube removal. The criterion to remove the tube was based on the finding of normal bowel sounds (confirmed by a minimum of two senior surgeons). There was no significant difference between the two groups with regard to occurrence of GI disturbances. Most disturbances (i.e., vomiting, abdominal distension, acute gastric dilatation, etc.) were observed after lower intestinal tract operations. Nine patients in the first group and seven in the second required reinsertion of the nasogastric tube. This study became the first RCT to suggest that early EN, comprising solid food, immediately after nasogastric tube removal could be safely advised after major GI operations. 
Is early EN superior to TPN? The liver transplant experience
Until 1994, TPN was routinely used in patients undergoing orthotopic liver transplantation. However, TPN was associated with complications such as central catheter infections, thromboembolism, severe metabolic fluctuations, electrolyte disturbances, and increased bacterial gut translocation. Wicks et al.  compared the efficacy and tolerability of early EN with TPN after liver transplantation. Twenty-four patients were studied of whom 14 received EN and 10 received TPN. EN was started within 18 h of surgery, was well tolerated, and the efficacy was reported to be comparable to that of TPN. Mid-arm circumference, triceps skin-fold thickness, and biceps skin-fold thickness were, in comparison with preoperative values, maintained on the 10 th postoperative day in both groups. Early postoperative absorptive capacity, as assessed by a combined carbohydrate test, was reduced significantly in both groups but not sufficiently enough to be of nutritional concern. Intestinal mucosal integrity, as assessed by an intestinal permeability test, was maintained throughout. The median number of days for patients to start eating and to achieve 70% intake of estimated requirements orally did not differ significantly. This study concluded that the practical aspects of EN after liver transplantation were surmountable and that it was as effective at maintaining nutritional status as TPN. It was also perceived that EN had potential benefits in terms of reduced complications and costs. 
Does early EN influence incidence of postoperative infections?
This question was addressed in 1996 by an RCT where 30 patients received Nutri-drink (a brand of a nutritional orange flavoured supplement for early postoperative enteral nutrition) and 30 received placebo through a naso-duodenal feeding tube  starting from the day of surgery itself. Only two of 30 patients in the EN group developed infectious complications compared to 14 of 30 patients in the control (placebo) group and these differences were obviously significant. More pertinently, the two groups were similar with regard to preoperative nutritional status and the type of surgeries performed (esophagectomies, gastrectomies, and major colorectal resections with anastomosis) and a single investigator was involved in the study. Furthermore, the total postoperative complications were significantly more in the placebo group than in the EN group (19 vs 8). It was concluded that early EN in patients after major abdominal surgery resulted in an important reduction in infectious complications. 
Influence of early EN on whole-body protein kinetics in upper GI cancers
Patients with upper GI cancers are at increased risk for malnutrition and associated morbidity and even mortality. Hochwald et al. evaluated the protein kinetic effects of early EN, comparing them with standard postoperative care of NBM and IVF.  Twelve patients were randomized to receive early EN and 17 received conventional treatment. It was observed that early EN decreased fat oxidation and whole-body protein catabolism while improving net nitrogen balance. By significantly improving protein metabolism, it was suggested that early EN could decrease postoperative morbidity and mortality in upper GI cancer patients.
Impact of early EN (immunonutrition) on clinical outcomes and cost after major upper GI cancer surgery
To assess the impact of early enteral immunonutrition (compared to an isocaloric, isonitrogenous diet) on clinical outcomes and cost after major upper GI cancer surgery, a randomized, prospective, multicenter trial was conducted in the mid-90s and results were reported in 1997 and updated again in 1999.  The EN diet was supplemented by arginine, dietary nucleotides, and omega-3 fatty acids and administered to 77 patients, while another 77 received an isocaloric, isonitrogenous diet (placebo). Thus a total of 154 patients were evaluated after EN was started 12-24 h after surgery and the amount gradually increased up to 80 ml/h by the 5 th postoperative day. The complications were divided into early (postoperative days 1-5) and late (after the fifth postoperative day) postoperative complications. Both groups tolerated early EN, and the rate of tube feeding−related complications was low. Postoperative complications occurred in 17 patients in the immunonutrition group compared to 24 patients in the control group and this difference was insignificant. Also, in the early period, complications occurred to a similar extent in both groups. However, in the late period (after postoperative day 5), significantly fewer patients in the immunonutrition group developed complications than in the placebo group (5 vs 13). Furthermore, there was a significant reduction in the frequency of development of late complications and wound infections in the immunonutrition group. Since a retrospective cost-comparison analysis was also performed, the above findings ensured that patients in the immunonutrition group incurred substantially lesser costs compared to those in the placebo group. Evaluating outcomes and cost-effectiveness of perioperative EN (immunonutrition) in patients undergoing elective major upper GI surgery, the same group  reported significantly decreased early occurrence of postoperative infections and reduced treatment costs of the complications in those who were administered perioperative EN.
Around the same period, another prospective RCT (involving 260 patients undergoing pancreaticoduodenectomy or gastrectomy for cancer) evaluated the route of delivery and formulation of postoperative nutritional support on host defense, protein metabolism, infectious complications, and outcomes after these major resections.  While one group received standard EN, another received an immunonutrition, and the third received TPN. All the three regimes were isocaloric and isonitrogenous. This trial reported that the immunonutrition group fared better then the other two groups (better recovery of immune parameters on postoperative day 8). Postoperative infection rate was 14.9% in the immunonutrition group, 22.9% in the standard group, and 27.9% in the parenteral group (P = 0.06). Mean (± SD) length of hospital stay was 16.1 ± 6.2, 19.2 ± 7.9, and 21.6 ± 8.9 days in the immunonutrition, standard, and parenteral groups, respectively (P = 0.01 vs standard group; P = 0.004 vs parenteral group). It thus became evident that early EN was a valid alternative to TPN in patients undergoing major surgery. Furthermore, the study concluded that immunonutrition enhanced the host response, induced a switch from acute-phase to constitutive proteins, and perhaps improved outcomes. 
The several advantages of immunonutrition reported by the above studies, were not corroborated by data from the Memorial Sloan Kettering Cancer Center.  In their RCT of 195 patients (undergoing surgery for esophageal, gastric, peripancreatic, and bile duct cancers) they evaluated early EN (immune-enhancing formula, i.e., IEF) after resection of upper GI malignancy vs controls; they reported no significant differences in the number of minor, major, or infectious wound complications between the groups. There was one bowel necrosis associated with IEF requiring re-operation. The hospital mortality was 2.5% and median length of hospital stay was 11 days, which was not different between the groups. This study concluded that early EN (immunonutrition) was not beneficial and could not be recommended as a routine after surgery for upper GI malignancies. 
Early EN (immunonutrition) is useful in malnourished and transfused patients
The above observation about early immunonutrition  was answered by another trial in 1998.  This RCT, involving 166 patients undergoing curative resections for gastric or pancreatic cancer, evaluated the impact of the route of administration of artificial nutrition and the composition of the diet on outcomes. At operation, the patients were randomized into three groups to receive: a) a standard enteral formula (control group; n = 55); b) the same enteral formula enriched with arginine, RNA, and omega-3 fatty acids (enriched group; n = 55); and c) total parenteral nutrition (TPN group; n = 56). The three regimens were isocaloric and isonitrogenous. EN was started within 12 h following surgery. The infusion rate was progressively increased to reach the nutritional goal of 25 kcal/kg/day on postoperative day 4. Early enteral infusion was well tolerated. Side effects were recorded in 22.7% of the patients, but only 6.3% failed to reach the nutritional goal. The enriched group had a significantly lower severity of infection than the parenteral group (4.0 vs 8.6). In subgroups of malnourished (n = 78) and homologous transfused patients (n = 42), the administration of the enriched formula significantly reduced both severity of infection and length of stay compared with the parenteral group. Moreover, in transfused patients, the rate of septic complications was 20.0% in the enriched group, 38.4% in the controls, and 42.8% in the TPN group. This trial was different from the previous trials since it not only suggested that early EN is a suitable alternative to TPN after major abdominal surgery, but also demonstrated that an enriched diet was of benefit in malnourished and transfused patients. 
Can early EN delay postoperative recovery?
A small RCT reported negative outcomes after early EN.  This trial attempted to determine whether immediate EN minimized early postoperative decreases in handgrip and respiratory muscle strength. While 13 patients received early EN, 15 were treated by conventional NBM and IVF management. It was observed that immediate postoperative feeding was associated with impaired respiratory mechanics and postoperative mobility and did not influence the loss of muscle strength or the increase in fatigue. This study suggested that immediate postoperative EN should not be a routine in well-nourished patients who are at low risk of nutrition-related complications.
Outcomes of systematic review and meta-analyses
It was only in 2001 that a systematic review and meta-analysis was done to determine whether a period of starvation (nil by mouth) after GI surgery is beneficial in terms of specific outcomes.  Three electronic databases (PubMed, EMBASE, and the Cochrane controlled trials register) were used for this study. Eleven studies with 837 patients were evaluated. In six studies, patients in the intervention groups were fed directly into the small bowel and in five studies patients were fed orally. Early feeding reduced the risk of any type of infection and the mean length of hospitalization. Also, risk reductions were seen for anastomotic dehiscence, wound infection, pneumonia, intra-abdominal abscess, and mortality, though these failed to reach statistical significance. However, the risk of vomiting was increased among patients fed early. It was concluded that there seemed to be no clear advantage in keeping patients NBM after elective GI resection and early feeding could be of benefit. It was also concluded that an adequately powered trial was required to confirm or refute the benefits seen in small trials.  In 2009, a systematic review and meta-analysis evaluating whether EN within 24 h of intestinal surgery is beneficial as compared to late commencement of feeding in patients was published by the same authors.  Thirteen RCTs fulfilled their inclusion criteria and a total of 1,173 patients were included. Mortality was reduced with early postoperative feeding but increased vomiting was noted. There was a suggestion of reduced postsurgical complications and hospital stay. The study concluded supporting the notion that early feeding may be of benefit.
EN is superior to TPN
The questions raised by the meta-analysis  appear to have been answered by a RCT that was published soon after.  This study aimed to test the hypothesis that postoperative EN is better (i.e., there were fewer postoperative complications) than parenteral nutrition containing similar energy and nitrogen amounts [112 kJ/kg/day and 1.4 g aminoacid/kg/day ]. Malnourished patients undergoing major GI surgery (317) were assigned to EN or TPN. Analysis was by intention to treat. Postoperative complications occurred in 54 (34%) patients fed enterally vs 78 (49%) fed parenterally. Length of postoperative stay was 13.4 days and 15.0 days in the EN and TPN groups, respectively. Both the differences were significant. Adverse effects occurred in 56 (35%) patients fed enterally vs 22 (14%) patients fed parenterally. Fourteen (9%) patients on EN had to switch to TPN, whereas none with TPN crossed over to EN. This trial clearly concluded that early EN significantly reduced the complication rate and duration of postoperative stay compared with TPN, although TPN was perhaps better tolerated than EN. 
Effect of early EN on functional GI recovery
Postoperative convalescence is mainly determined by the extent and duration of postoperative ileus. A recent study conducted in 2007  evaluated the effects of early EN on functional GI recovery and quality of life. One hundred and twenty-eight patients undergoing elective open colorectal or abdominal vascular surgery were enrolled. Of these, 67 were randomized to a conventional return to diet and 61 to a regimen allowing resumption of an oral diet as soon as tolerated ('free diet' group). It was observed, that reinsertion of a nasogastric tube was necessary in 20% of the free diet group and in 10% of the conventional group; the difference was not statistically significant. The complication rate was similar for both groups, as was return of GI function. A normal diet was tolerated after a median of 2 days in the free diet group compared with 5 days in the conventional group and this difference was significant. Quality of life scores were similar in both groups. This trial thus proved that early resumption of oral intake did not diminish the duration of postoperative ileus or lead to a significantly increased rate of nasogastric tube reinsertion. Tolerance of oral diet was thus not influenced by gastrointestinal functional recovery. The inference was that postoperative management should include early resumption of diet. 
Recent Advances in Major GI Conditions/Resections
Surgical advances have increased the certainty of a successful esophago-enteric anastomosis, making early oral enteral feeding after surgery feasible. A recent study  compared the benefits of EN and TPN in patients undergoing total gastrectomy for gastric cancer. Nutrition and intestinal permeability were assessed. Complications were similar in both groups. Treatment cost was less and length of hospital stay was shorter in the EN group. We thus have evidence that EN is an efficient way to provide nutrition to patients and possibly prevent intestinal atrophy in patients who traditionally have had to endure prolonged postoperative fasting. 
Severe acute pancreatitis (SAP)
SAP results in multiple organ dysfunction and one of the suggested means to prevent further worsening of inflammatory response of SAP is to initiate early EN. There is a solitary RCT that has compared the efficacy and safety of early EN with TPN in patients with predicted SAP.  Fifty patients were randomized to TPN or EN groups. Total complications (25 vs 52; P = 0.04) and pulmonary complications (10 vs 21; P = 0.04) were significantly more frequent in EN patients, though the complications were diagnosed predominantly within the first 3 days. Thus, in predicted SAP, nasogastric early EN was feasible and even resulted in better control of blood glucose levels, although the overall early complication rate was higher in the EN group. No beneficial effects on intestinal permeability or the inflammatory response were seen by EN treatment. Thus, this trial demonstrated feasibility but did not document any benefit in predicted SAP.
Non-traumatic intestinal perforation and peritonitis
A study on the role of early EN in the setting of perforative peritonitis was published in 1998.  Immediate postoperative EN was shown to be effective in reducing septic morbidity in patients with abdominal trauma. This study was designed to investigate the feasibility and efficacy of immediate EN in patients with non-traumatic intestinal perforation and peritonitis. Forty-three patients (21 in the study group and 22 in the control group) were included. Patients in the study group achieved a positive nitrogen balance by the third postoperative day; patients in the control group remained in negative nitrogen balance throughout the study. The mortality rate was similar in both groups (18.2% vs 19.1%). The control group had a total of 22 septic complications vs eight in the study group, and this difference was significant. The authors concluded that immediate postoperative feeding was feasible in patients with perforative peritonitis and that it reduced septic morbidity.
This evidence-based review reveals that early EN (irrespective of route of administration) can be safely given in the immediate postoperative period after major digestive surgery. It benefits patients undergoing major surgery like pancreatectomy, esophagectomy, gastrectomy, and colonic resections. There is reduction in perioperative infection, better maintainance of nitrogen balance, and shorter hospital stay. Early EN should be considered superior to TPN, barring exceptional clinical scenarios. Early enteral immunonutrition should be used judiciously since it benefits only malnourished and transfused patients. Although there is evidence in the literature to prove the benefits of early EN, there is a lot of resistance to its implementation. Advances in intensive care and pain management, along with rapid development of modern nutritional supplementation via alternative routes, have greatly aided early patient recovery; consequently, early EN and enhanced recovery programs have gained ground in recent years. This review highlights a number of studies that are convincingly in favor of early EN. It can be objectively said that early EN after major digestive surgery is an old advance that is now in fashion.
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