Outcome and cost-effectiveness of perioperative enteral immunonutrition in patients undergoing elective upper gastrointestinal tract surgery: a prospective randomized study.

HYPOTHESIS: Perioperatively administered enteral immunonutrition will improve early postoperative morbidity and cost-effectiveness after gastrointestinal tract surgery. DESIGN: A prospective, randomized, double-blind, multicenter clinical trial. SETTING: Surgical departments in German university and teaching hospitals. PATIENTS: One hundred fifty-four patients with upper gastrointestinal tract malignant neoplasms who were eligible for analysis. INTERVENTION: Preoperatively, patients received 5 days of oral immunonutrition (an arginine-, RNA-, and omega3 fatty acid-supplemented diet) or an isoenergetic control diet (1 L/d). Early postoperative enteral feeding with immunonutrition or an isoenergetic, isonitrogenous control diet using a catheter jejunostomy was performed for 10 days. MAIN OUTCOME MEASURES: Postoperative infectious complications, their treatment costs, and cost-effectiveness of immunonutrition were analyzed. Plasma levels of the fatty acids eicosapentaenoic acid and docosahexaenoic acid were measured. RESULTS: In the immunonutrition group, significantly fewer infectious complication events occurred (14 vs 27; P = .05). The number of patients with complications was significantly lower in the supplemented diet group after postoperative day 3 (7 vs 16; P = .04). The treatment costs of complications in the supplemented diet group were suggestively lower than in the control diet group (DM 75172 vs DM 204273). Cost-effectiveness was DM 1503 in the experimental group vs DM 3587 in the control group, where DM denotes deutsche mark (German currency). CONCLUSION: The perioperative administration of an enteral immunonutrition significantly (P = .05) decreased the early occurrence of postoperative infections and reduced substantially the treatment costs of the complications after major upper gastrointestinal tract surgery.

Early postoperative enteral immunonutrition: clinical outcome and cost-comparison analysis in surgical patients.

OBJECTIVE: To determine if early postoperative feeding of patients with upper gastrointestinal malignancy, using an enteral diet supplemented with arginine, dietary nucleotides, and omega-3 fatty acids (IMPACT, Sandoz Nutrition, Bern, Switzerland) results in an improved clinical outcome, i.e., reduced infectious and wound complications and decreased treatment costs when compared with an isocaloric, isonitrogenous control diet. DESIGN: A prospective, randomized, placebo-controlled, double-blind, multicenter trial of the clinical outcome and a retrospective cost-comparison analysis. SETTING: Surgical intensive care units in three different German university hospitals. PATIENTS: Of 164 patients enrolled in the study, 154 patients were eligible for analysis. They were admitted to the intensive care unit after upper gastrointestinal surgery for cancer and they received an enteral diet via needle catheter jejunostomy. Infectious complications were defined as sepsis or systemic inflammatory response syndrome, pneumonia, urinary tract infection, central venous catheter sepsis, wound infection, and anastomotic leakage. The complication events were prospectively divided into two groups: early (postoperative days 1 to 5) and late (after the fifth postoperative day) postoperative complications. The treatment costs of each complication were analyzed and compared in both groups. INTERVENTIONS: Patients were randomized to receive either the immunonutritional diet (n = 77) or an isocaloric and isonitrogenous placebo diet (n = 77). Enteral feeding was initiated 12 to 24 hrs after surgery, starting with 20 mL/hr and advanced to a target volume of 80 mL/hr by postoperative day 5. MEASUREMENTS AND MAIN RESULTS: Clinical examination and adverse gastrointestinal symptoms were recorded on a daily basis. Both groups tolerated early enteral feeding well, and the rate of tube feeding-related complications was low. Postoperative complications occurred in 17 patients in the immunonutrition group vs. 24 patients in the control group (NS). Further, in the early phase (postoperative day 1 to 5), complications occurred to a similar extent in both groups (12 patients in the immunonutritional group vs. 11 patients in the control group). However, in the late phase (after postoperative day 5), considerably fewer patients in the experimental diet group experienced complications compared with the control group (5 vs. 13, p < .05). In addition, the frequency rate of complicating events were recorded in each group. In the experimental diet group, a total of 22 complicating events were recorded vs. a total of 32 events in the placebo diet group (NS). However, the occurrence of late complicating events, i.e., complicating events after the fifth postoperative day, was significantly reduced in the immunonutrition group when compared with the control group (8 vs. 17 events, p < .05). The total costs for the treatment of the complications were 83,563 German marks in the experimental diet group vs. 122,430 German marks in the control group, resulting in a cost-reduction of 38,867 German marks. (At the end of December 1995, the conversion rate from German marks to U.S. dollars was 1.4365 German marks to $1.00.) CONCLUSIONS: Early enteral feeding with an arginine, dietary nucleotides, and omega-3 fatty acids supplemented diet, as well as an isonitrogenous, isocaloric control diet (placebo) were well tolerated in patients who underwent upper gastrointestinal surgery. In patients who received the supplemented diet, a significant reduction in the frequency rate of late postoperative infectious and wound complications was observed. Thereby, the treatment costs were substantially reduced in the immunonutrition group as compared with the control group.

Influence of a total parenteral nutrition enriched with omega-3 fatty acids on leukotriene synthesis of peripheral leukocytes and systemic cytokine levels in patients with major surgery.

OBJECTIVE: Nutritive immunomodulation of patients after major surgery. DESIGN: Prospective, randomized controlled double-blind study. PATIENTS: Forty patients undergoing major intestinal surgery. Patients were divided into two groups: one received a total parenteral nutrition enriched with omega-3 fatty acids for 5 days postoperatively, the other an isocaloric, control nutrition. MATERIALS AND METHODS: We analyzed the leukocyte ability to release leukotrienes from whole blood leukocytes stimulated with the calcium ionophore A23187 (5 micromol/L) by reverse phase high-performance liquid chromatography and circulating cytokines by enzyme-linked immunosorbent assay. RESULTS: Leukocytes from patients of the omega-3 fatty acids group generated significantly higher amounts of less biologically active leukotriene B5 as compared to the control group (p < or = 0.001). This was accompanied by a significant decrease in the generation of proinflammatory leukotriene B4 (p < or = 0.006) in the study group. In contrast to interleukin-1beta, interleukin-6, and interleukin-10 systemic levels of tumor necrosis factor-alpha (p < or = 0.05) were postoperatively decreased in the study group. CONCLUSION: Our data provide evidence that a total parenteral nutrition enriched with omega-3 fatty acids modulates the lipid mediator pattern and systemic tumor necrosis factor-alpha levels.

[A new model for economic studies of therapies exemplified by postoperative parenteral nutrition]. / Ein neues Modell zur Wirtschaftlichkeitsuntersuchung von Therapien am Beispiel der postoperativen parenteralen Ernährung.

In this economic evaluation we compared the costs of a new therapeutic system (two-chamber bag) in total parenteral nutrition (TPN) with the comparative standard therapeutic systems (multiple-bottle system in intensive care patients followed by a combination solution (glass bottles) on the ward). In the model, standard treatment algorithms of a 10-day course TPN for patients after major gastric surgery were specified for both application systems, the two-chamber bag and the comparative system. Based on the standard treatment pattern, the resource utilisation (manpower services, medical needs, material) was assessed. In a base case analysis the types and amounts of resources were valued using salaries, prices and tariffs to assess the costs. The costs per day and per case of the therapeutic systems were compared. Sensitivity analyses were carried out to validate the cost-estimates. The total costs per patient of the two-chamber bag amounted to DM 2324.41, which was substantially less than the DM 2728.99 cost of the comparative system. The average daily costs for the two-chamber bag system were 12% to 23% lower than for the comparative system. The results were shown to be valid for the whole range of tested parameters. This model makes it possible to obtain an economic evaluation of various therapeutic modalities without undertaking a prospective randomized study with the attendant high time and cost requirements.

Early postoperative enteral nutrition with arginine-omega-3 fatty acids and ribonucleic acid-supplemented diet versus placebo in cancer patients: an immunologic evaluation of Impact.

OBJECTIVE: To evaluate the effect of early postoperative feeding with a nutritionally complete enteral diet supplemented with the nutrients arginine, ribonucleic acid (RNA), and omega-3 fatty acids on the immune function in patients undergoing surgery for upper gastrointestinal (GI) malignancies. DESIGN: Prospective, randomized, placebo-controlled, double-blind study. SETTING: Surgical intensive care unit (ICU) in a German university hospital. PATIENTS: Forty-two consecutive patients receiving an enteral diet via needle catheter jejunostomy after GI surgery for cancer. INTERVENTIONS: Patients were randomized to receive either the arginine, RNA, and omega-3 fatty acids supplemented diet or an isocaloric and isonitrogenous placebo diet. Early enteral nutrition was started on postoperative day 1 in the surgical ICU with 20 mL/hr and progressed to the optimal goal of 80 mL/hr by postoperative day 5. MEASUREMENTS AND MAIN RESULTS: Clinical examination and adverse GI symptoms were recorded on a daily basis. Body weight was determined twice weekly. Immunoglobulin concentrations were determined by laser nephelometry. Interferon-gamma concentrations were measured with a modified enzyme-linked immunosorbent assay method. Fluorescence-activated cell scan flow cytometry was performed to analyze B cells, T lymphocytes and their subsets. Clinical patient characteristics and mean caloric intake were similar between the two groups and both formulas were well tolerated. The number of T lymphocytes and their subsets, helper T cells (CD4) and activated T cells (CD3, HLA-DR), were significantly higher in the supplemented diet group on postoperative days 10 and 16 (p < .05). Mean interferon-gamma concentration after phytohemagglutinin stimulation was higher in the supplemented diet group on postoperative day 16. In the supplemented diet group, mean immunoglobulin M concentrations were significantly higher on postoperative day 10 and mean immunoglobulin G concentrations were higher on postoperative day 16 (p < .05) compared with the results in the placebo group. B-lymphocyte indices were significantly higher in the supplemented vs. the placebo diet group on postoperative days 7 and 10 (p < .05). CONCLUSIONS: Supplementation of enteral diet with arginine, RNA, and omega-3 fatty acids in the early postoperative time period improves postoperative immunologic responses and helps to overcome more rapidly the immunologic depression after surgical trauma.

Modulation of postoperative immune response by enteral nutrition with a diet enriched with arginine, RNA, and omega-3 fatty acids in patients with upper gastrointestinal cancer.

OBJECTIVE: To find out whether an enteral diet supplemented with arginine, RNA, and omega-3 fatty acids modulated the production of interleukin-1 (IL-1), interleukin-2 (IL-2), IL-2 receptor, interleukin-6 (IL-6), and tumour necrosis factor alpha (TNF-alpha) after operations for upper gastrointestinal cancer. DESIGN: Prospective double blind clinical study. SETTING: University hospital, Germany. SUBJECTS: 42 patients randomised into two groups (n = 21 each), one of which was given an isocaloric and isonitrogenous placebo diet and one of which was fed the same diet supplemented with arginine, RNA, and omega-3 fatty acids. INTERVENTIONS: The cytokines were measured before operation and on postoperative days 1, 3, 7, 10, and 16. MAIN OUTCOME MEASURES: Comparison of concentrations of cytokines in the two groups. RESULTS: Among those receiving the placebo diet (after spontaneous stimulation) IL-6 concentrations were significantly higher on days 3 and 7 (p < 0.05) and TNF-alpha concentrations on day 7. In contrast (after stimulation with phytohaemagglutinin) mean concentrations of IL-2 receptor were significantly higher on days 3 and 7, and of IL-1 beta and IL-2 on day 16 (p < 0.05) in the group receiving the supplemented diet. CONCLUSION: Supplementation of an enteral diet with arginine, RNA and omega-3 fatty acids can modulate the acute phase reaction as indicated by the reduction in concentrations of TNF-alpha and IL-6 in the group fed the supplemented diet. Patients receiving the supplemented diet also showed accelerated recovery in the concentrations of IL-1 beta and IL-2 receptor.

[Regional hyperthermic fibrinolytic perfusion in postoperative deep venous thrombosis of the leg]. / Regionale hypertherme Fibrinolytika-Perfusion bei postoperativer tiefer Beinvenenthrombose.

Four days after an operation for fusion of lumbar and sacral vertebrae a 30-year-old man developed bilateral deep-vein thrombosis in the legs, extending on the left from the fibular group of veins to the popliteal vein. On the right all deep veins of the lower leg were occluded, including the confluence of the popliteal vein. As systemic fibrinolysis was contraindicated, surgical thrombectomy was undertaken. After incomplete removal of the thrombi, regional hyperthermic perfusion with streptokinase was performed using a heart-lung machine. After a compression bandage had been applied to the right leg above the veins the leg was perfused via the common femoral vein at 40 degrees C from the heart-lung machine, at a flow rate of 600-800 ml/min, for 60 min with a solution containing 1 million IU streptokinase. Measurement of various components in the perfusate indicated marked fibrinolysis (fibrinogen: not measurable; fibrinogen breakdown products: > 80 micrograms; streptokinase: 100 FU/ml after 30 min, 62 FU/ml after 60 min). At the same time there was no demonstrable fibrinolytic activity in the systemic circulation. Fibrinogen concentration fell from 340 mg/dl 30 min before the onset of perfusion to 245 mg/dl 90 min after it. After 60 min of perfusion the blood from the right leg was discarded and the leg flushed through with 1.5 l of an electrolyte solution and then filled up with previously obtained and stored patient's own blood concentrate. Subsequent phlebography and venous occlusion plethysmography demonstrated complete recanalization of the deep-vein system with normal venous valve function.

[Locoregional ultrahigh dosage fibrinolysis of deep leg vein thrombosis]. / Lokoregionäre ultrahochdosierte Fibrinolyse tiefer Beinvenen-Thrombosen.

The ultrahigh locoregional fibrinolysis in extracorporal circulation with the Heart-lung-machine allows fibrinolysis in cases of contraindicated systemic fibrinolysis. The early results are promising.

Lyophilized hyperimmune equine serum as a source of antibodies for neonatal foals.

In a study with 15 neonatal foals (5 per treatment group), foals were fed within 4 hours of birth as follows: 250 ml of colostrum, 250 ml of lyophilized serum reconstituted at 5 times the original concentration, or 250 ml of a mixture (1:1) of colostrum and lyophilized serum. Foal serum samples were tested for immunoglobulin (Ig)G concentration and titrated for anti-equine rhinovirus 1 and anti-equine influenza A1 and A2 antibodies at 0 and 24 hours after foals were born. Except in a foal which had suckled the dam before treatment, there was no evidence of IgG or specific viral antibodies in the samples taken at birth. There were no significant differences found in the serum IgG concentrations and antibody titers among the 3 treatment groups. Seemingly, IgG was absorbed efficiently from both serum and colostrum, so that the use of reconstituted lyophilized serum as a prophylactic measure of conferring passive immunity to a newborn foal deserves serious consideration.