From the Departments of Surgical Sciences (Drs Pacelli, Bossola, Papa, Malerba, Bellantone, and Doglietto), Anesthesiology (Dr Modesti), and Internal Medicine and Geriatrics (Dr Sgadari), Catholic University of the Sacred Heart, Rome, Italy.
Immediate enteral feeding following major abdominal surgery reduces postoperative complications and mortality when compared with parenteral nutrition.
A prospective multicenter randomized trial.
A university hospital department of digestive surgery.
Patients and Interventions
Two hundred forty-one malnourished patients undergoing major elective abdominal surgery were randomly assigned to receive, after surgery, either enteral (enteral nutrition group: 119 patients) or parenteral nutrition (total parenteral nutrition group: 122 patients). The patients were monitored for postoperative complications and mortality.
The rate of major postoperative complications was similar in the enteral and parenteral groups (enteral nutrition group: 37.8%; total parenteral nutrition group: 39.3%; P was not significant), as were the overall postoperative mortality rates (5.9% and 2.5%, respectively; P was not significant).
The present study failed to demonstrate that enteral feeding following major abdominal surgery reduces postoperative complications and mortality when compared with parenteral nutrition.
ENTERAL NUTRITION (EN) is considered to be better than total parenteral nutrition (TPN) for providing feeding in various clinical settings because it is less expensive, safer, and maintains the nutritional, metabolic, immunological and barrier function of the intestines.1,2 Moreover, it has been recently shown that patients fed via EN after abdominal surgery for trauma developed fewer septic complications than patients who received TPN.3- 6
However, to our knowledge, no study demonstrates that postoperative EN is superior to TPN with respect to outcome in patients who underwent major elective abdominal surgery.7- 13
This article reports the results of a cooperative, multicenter randomized clinical trial designed to comppare the efficacy of postoperative EN and TPN in malnourished patients undergoing major elective abdominal surgery. The primary objective of this trial was to determine whether EN reduces major postoperative complications, mortality, or both in such patients.
The protocol of the study was approved by the ethical committees of the participating centers. Informed consent was obtained from the patients before entering the study.
All patients between the ages of 18 and 80 years who were admitted to surgical units of the participating centers from January 1996 to June 1998 and who were candidates for nonemergency abdominal surgery (excluding appendectomy, cholecystectomy, and viscerolysis) were screened for the presence of malnutrition according to the Nutritional Risk Index: [1.519 × serum albumin level (grams per deciliter)] + [0.417 × (actual weight/usual weight)] × 100.14,15 All patients with an index less than 90% were potentially eligible for the study. The patients who entered the study were assigned by computer-generated random numbers to the EN group or to the TPN group. All patients in the TPN group had a central venous catheter inserted at the time of surgery; by contrast, in the EN group, a central venous catheter was not required by protocol. However, if a central venous catheter had been positioned immediately before or during the operation for monitoring or fluid administration or both, it also was used during the postoperative course in the EN group. In patients randomized to receive EN, a needle-catheter jejunostomy or a nasojejunal tube was inserted intraoperatively in the proximal jejunum. Feeding was initiated at 9 AM on the first postoperative day in both groups. The parenteral formula contained 0.2 g/kg per day of nitrogen and 25 nonprotein kcal/kg per day (30% lipids), with supplemental vitamins and minerals.
The enteral feed used was Nutrison (Nutricia, Zoetermeer, the Netherlands), providing 1 kcal/mL, 40 g of proteins per liter, 123 g of carbohydrates per liter, 38.9 g of lipids per liter, plus supplemental vitamins and minerals. The enteral feed began with a full-strength formula introduced at 30 mL/h, and increased gradually, depending on tolerance, up to a goal of 25 kcal/kg per day, comparable with that of the TPN group. During the induction time of EN (up to 3 days), TPN was added to achieve the same caloric intake of the TPN group. According to protocol, all patients in both the TPN and EN groups continued their nutritional regimens until oral intake was resumed, with a target of 1000 mL of fluids per day. If oral intake was not resumed after 10 days or if a complication occurred portending prolonged restriction of oral intake, either EN or TPN could be instituted by the surgeons of the participating centers according to the availability of access and the type of complication.
All patients received short-term perioperative antibiotic prophylaxis and a subcutaneous injection of low-molecular-weight heparin sodium (3000 IU/d) as deep venous thrombosis prophylaxis.
The patients were monitored for postoperative complications and mortality by physicians not associated with the surgical teams. Complications were classified by objective criteria as major or minor, and as infectious or noninfectious (Table 1) according to a previously described classification.16
The primary objective for comparison was the incidence of major postoperative complications. Based on previous studies performed on our surgical population,17 we anticipated a 40% incidence rate of major postoperative complications in the TPN group. A reduction of this rate by half (to 20%) in the EN group would be considered clinically important.
Detecting a difference of this magnitude or greater, with a level of statistical significance of P = .05 and a power of 0.90 with a 2-tailed test of proportions, would require a total of 118 patients in each group. Thus, the goal total for the accrual of patients was 240 patients for the final outcome analysis.
Continuous variables were compared by analysis of variance and categorical variables by the Fisher exact test. Analysis of categorical covariates was performed using the Mantel-Haenzsel technique. All statistical analyses were 2-tailed and based on the intention-to-treat concept (ie, patients randomized to receive EN who crossed over to TPN were analyzed in the EN group).
During the 29-month patient accrual, 241 patients identified as potentially eligible for the study consented to participate in the study and were randomly assigned to the EN (n = 119) or to the TPN group (n = 122). The 2 groups were similar regarding demographic data, nutritional status, and diagnosis, as is presented in Table 2.
Table 3 lists the operative procedures undergone by the patients of the 2 groups, as well as the main operative factors.
Enteral feeding was infused through a jejunostomy in 81 patients (68.1%) and through a nasojejunal tube in 38 patients (31.9%). The parenteral supplementation during the first 3 days of treatment in the EN group was infused through a peripheral vein or a central venous catheter in 37 patients and 82 patients, respectively. In the TPN group, parenteral nutrition was infused in all cases through a central venous catheter. Mean ± SD durations of EN and TPN infusion were 8.7 ± 5.9 and 9.6 ± 4.5 days, respectively. Patients in the EN group received a mean ± SD quantity of 1650.6 ± 87 kcal/d, while those in the TPN group received 1665 ± 72.8 kcal/d. The mean ± SD amount of nitrogen infused per day was 10.3 ± 0.2 g and 12.8 ± 0.1 g for the EN and TPN groups, respectively.
Seven (5.9%) of the 119 patients assigned to the EN group and 3 (2.5%) of the 122 patients assigned to the TPN group died during the postoperative period. The difference was not statistically significant.
The rates of major postoperative complications were similar in the 2 groups: 45 (37.8%) of the 119 patients receiving EN and 48 (39.3%) of the 122 patients of the TPN group had such complications.
The rates of major infectious complications were similar in the 2 groups: 17 (14.3%) of the 119 patients receiving EN and 14 (10.7%) of the 122 receiving TPN had such complications. Similarly, there were no differences between the EN and TPN groups considering noninfectious complications; the rates being 23.5% and 27.9%, respectively.
The rates of minor postoperative infectious complications and noninfectious complications were comparable in the EN and TPN groups. The rates of individual complications and the relative risk and confidence intervals are presented in Table 4.
Duration of postoperative hospital stay was 15.2 ± 3.6 days in the EN group and 16.1 ± 4.5 days in the TPN group. The most common treatment-related complications in the EN group were abdominal bloating (3 cases), diarrhea (4 cases), and occlusion or displacement of the enteral tube (4 cases). Chylous fistula (2 cases) and hemorrhage from jejunostomy (1 case) were also observed. Among patients in the TPN group, 5 experienced mild metabolic complications (transient hypoglycemia in all cases), and 2 had central venous catheter sepsis.
No patients from TPN group required interruption of parenteral feeding due to nutrition-related complications, whereas EN was stopped in 14 patients (11.8%). These 14 patients were crossed over to TPN by a peripheral or central route in 9 and 5 cases, respectively; however, for the analysis of postoperative complications, they were included in the EN group.
Although it has been demonstrated for many years18 that the interruption of the natural nutrition mechanism (as observed after surgery of the digestive tract) quickly exhausts the carbohydrate store, leading to use of the protein compartment as an alternative source of energy, the role of postoperative nutritional support has not yet been completely investigated.19
As far as the efficacy of postoperative nutritional support is concerned, no study to date clearly shows that this procedure reduces postoperative complications when compared with controls (this includes not only controls in normonourished patients, as we have previously demonstrated,16 but also in the malnourished ones19).
As far as the route of feeding is concerned, many arguments are still open for debate.1
First, the role of the enteral route in modifying the intestinal barrier function, and therefore the clinical outcome in patients undergoing major digestive surgery, has been questioned.13- 20 Second, the efficacy of immune-enhanced EN, although suggested by many recent studies,21 has not yet been confirmed from either the statistical or clinical points of view.21,22 Third, the majority of the studies concerning this topic are characterized by inadequate patient selection in consequence of the inclusion of normonourished patients,23,24 small size,7,25- 27 and insufficient definition of complications.19 The present study was therefore designed with the aim of overcoming all these problems through adequate statistical power, a clear definition of patient population, and precise outcome measures. The results showed no significant reduction of morbidity and mortality when postoperative EN was compared with postoperative TPN. Even when subdividing postoperative complications into different types (minor and major, infectious and noninfectious), we observed no statistically significant differences between the 2 groups.
Moreover, although the study population was composed of high-risk malnourished patients affected by cancer in the majority of cases (91.7%), the high incidence of postoperative complications in both groups brings to question the efficacy of postoperative support in itself. In fact, patients in the present study seemed not to benefit from postoperative artificial feeding, confirming that, as millions of years of evolution have shown, in injured mammals, food is not a top priority.
However, because it is difficult from an ethical point of view to defend starvation as a standard management of malnourished surgical patients, more well-designed studies comparing standard EN or TPN with immune enhancing formulas are now urgently required. In conclusion, the present study, according to recently published figures,1 failed to demonstrate that immediate EN with standard diet following major abdominal surgery reduces postoperative complications and mortality when compared with TPN.
The following members participated in patient randomization and data collection: Messina, Italy: M. L. Terranova, MD. Naples, Italy: M. De Siena, MD. Rome, Italy: G. Capuano, MD. Siena, Italy: N. Calomino, MD. Torino, Italy: P. Cotogni, MD. Velletri, Italy: M. Gravani, MD. Verona, Italy: A. Fontana, MD; G. Motton, MD. Viterbo, Italy: A. Goglia, MD; G. Delle Monache, MD; M. Piciollo, MD.
Corresponding author and reprints: Fabio Pacelli, MD, Department of Digestive Surgery, Istituto di Clinica Chirurgica, Catholic University School of Medicine, Largo A. Gemelli, 8, 00168 Rome, Italy (e-mail: firstname.lastname@example.org).
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