Preoperative Immunonutrition: Cost-Benefit Analysis
From the * Department of Surgery, Vita-Salute San
Raffaele University, Milan, Italy; and the Correspondence: Marco Braga, MD, Department of Surgery, San Raffaele Hospital Via Olgettina 60, 20132 Milan, Italy. Electronic mail may be sent to braga.marco{at}hsr.it.
Background: To evaluate whether preoperative immunonutrition might
lead to a savings in patient care. Data on resources consumed to treat
postoperative complications are scanty, but morbidity costs continue to be a
major burden for any health care system. A recent randomized clinical trial
carried out in well-nourished patients with gastrointestinal cancer showed
that a 5-day preoperative oral immunonutrition reduced postoperative morbidity
compared with conventional treatment (no supplementation). Methods:
The abovementioned trial was the basis for the economic evaluation.
In-hospital related costs of routine surgical care and costs of nutrition were
calculated. Estimates of complication costs were based on both resources used
for treatment and additional length of hospital stay. Cost comparison and
cost-effectiveness analysis were then carried out. Results: Total
cost of nutrition was Despite improved surgical techniques, postoperative morbidity and related medical-treatment costs continue to be a major burden for any health care system. In recent years, increased attention to prevent surgery-related complications and continuous research for new cost-effective treatments has been strongly recommended.1–3 Among the potential new strategies to improve outcome, the modulation of postoperative immunoinflammatory response by means of key nutrients may play an important role.4–9
Two prospective, randomized, double-blind, clinical trials demonstrated
that cancer patients fed before and after surgery with a diet supplemented
with arginine, A recent randomized clinical trial carried out in well-nourished patients with gastrointestinal cancer showed that oral administration of immunonutrition for 5 days before surgery was as effective as the perioperative treatment in reducing postoperative morbidity.13 Furthermore, both approaches were significantly superior when compared with conventional treatment (no supplementation). The aim of the present study is to evaluate whether preoperative immunonutrition might lead to cost savings in patient care.
Clinical Trial A prospective, randomized, controlled, clinical trial was the basis for the economic evaluation.13 A total of 305 well-nourished patients with neoplasm of the gastrointestinal (GI) tract and candidates to major elective surgery were included into the study. They were randomized into (1) a preoperative group (n = 102) who received Oral Impact (Novartis Consumer Health, Nyon, Switzerland) for 5 days before surgery; (2) a perioperative group (n = 101) who received the same preoperative treatment plus jejunal infusion of Impact (Novartis Consumer Health) for 7 days after surgery; and (3) a conventional group (n = 102; no supplementation). The 3 study groups were well balanced for age, gender, primary diagnosis, comorbidities, weight loss, body mass index, albumin, prealbumin, arginine plasma levels, type and duration of operation, blood loss, and transfusion rate.13 Trained members of the surgical staff who were not directly involved in the study were required to register postoperative complications, as previously a priori defined.14 These staff members also independently decided the day of hospital discharge. Follow-up for complications was performed for a 30-day period after hospital discharge.
Economic Analysis The following costs were calculated: the mean in-hospital-related costs of routine surgical care per patient, the costs of treating postoperative infectious and noninfectious complications, the costs of nutrition, and the overall costs for all patients. Depending on the type of surgical intervention, patients without complication had a certain mean length of stay (LOS). Multiplying these LOS days by the daily costs covering routine hospital care for GI surgical intervention results in the mean in-hospital-related costs of routine surgical care per patient.
To obtain the costs for patients with complications, complication costs
have to be added to the above costs. These complication costs were calculated
separately for the 2 groups, as complication cost may vary under the influence
of immunonutrition. A specific electronic record form was created to enable a
detailed assessment of the amount of health care goods and resources that each
patient with postoperative complication received for the treatment of these
complications. The following items were assessed: general patient information
(primary diagnosis, comorbidities, study group, surgical intervention);
complication type and duration in days; laboratory and microbiology analysis;
medical, technical, and diagnostic services; surgical and therapeutic
interventions; medications; and ambulatory follow-up consultations. For
patients who developed more than 1 complication, resource use was separately
recorded for each complication. For all resources used to treat complications,
their costs per unit (per day, per service, per analysis, etc) were gathered.
Diagnostic and therapeutic services, pharmaceuticals, and devices were valued
according to the National List of Sanitary Costs by the Italian Ministry of
Health. ICU stay was valued at a flat rate per day ( The additional LOS was likewise valued at a daily rate, which covers the cost of board, lodging, routine medical supervision, and nursing. Indirect costs (eg, loss of productivity by the patient) were not taken into account. To get the costs of treatment with the supplemented diet, the average administered volume was multiplied by the current price in Italy. Effectiveness was defined as the percentage of complication-free patients. Thus, this parameter reflects the ability of the treatment studied to prevent the occurrence of complications. The complication costs per patient spread over all patients of a group (complication costs multiplied by the number of patients with complications/all patients) were calculated. Cost-effectiveness analysis was performed by dividing per-patient costs of clinical nutrition and costs of treating postoperative complications with the percentage of complication-free patients; thus, the cost of achieving 1 complication-free patient per group was obtained. Sensitivity analysis was used to evaluate the effect on results when certain underlying parameters were being changed. In this context, we analyzed whether the exclusion of either nonsurviving patients or patients with anastomotic leak had a major impact on the cost effectiveness-outcome. There was 1 nonsurviving patient in both groups.
Statistical Analysis
Ninety-two patients underwent gastroesophageal resection (44 in the conventional group, 48 in the preoperative group), 54 patients underwent pancreatic resection (26 in the conventional group, 28 patients in the preoperative group), and 58 patients underwent colorectal resection (32 in the conventional group, 26 in the preoperative group). A total of 139 postoperative complications occurred in 85 patients. Twenty-eight patients had > 1 complication (14 in the preoperative group, 14 in the conventional group). Table I reports outcome variables in both groups. Table II reports postoperative complications in detail.
The supplemented diet was administered before surgery according to the
study protocol. Additionally, all patients received a certain volume of IV
glucose and electrolyte solution in the postoperative course. The cost of Oral
Impact in Italy was
The mean LOS for patients without complication was similar in both groups
according to the type of surgery. The cost of in-hospital routine care per day
for patients without complications was
Table IV reports the costs of patients with complication in both groups. A differentiation according to infectious or noninfectious complications is shown in Table V.
Table VI shows the total
costs and the diagnosis-related-group (DRG) reimbursement rates. Summing up
all costs for both groups resulted in a substantial total net savings of
Cost-effectiveness analysis shows an economic advantage for the
preoperative group (Table VII).
When the analysis was limited to infectious complications, cost-effectiveness
was
In view of increasing international concerns over exploding costs in medical care, the decision process for adopting the use of new products for routine treatment should not only weigh clinical benefits and risks but also consider whether these benefits are worth the health care resources used. This decision-making process should be informed by cost-effectiveness analyses of clinical trials.16,17 Among the proposed strategies to reduce postoperative morbidity and its related costs, artificial nutrition is recognized as an important part of the patient care, particularly for patients undergoing major surgery for cancer of the GI tract.14,18,19 Recently, the main focus of clinical nutrition has moved from the issue of energy and nitrogen requirement to the pharmacologic effects of specific key nutrients that seem to modulate both immune and inflammatory responses and gut function after surgery.5,7,8 Despite promising results from randomized clinical trials,10,11 the high cost of these new nutritional products may be considered a major drawback for their wide and routine use. In 2 cost-effectiveness analyses, it has been shown that the significant reduction in postoperative infections by perioperative immunonutrition translated into a substantial cost savings and an improved cost-effectiveness when compared with a standard diet.11,12 In a post hoc analysis, we found that clinical outcome was improved also in a subgroup of patients who received solely the preoperative supplementation because they did not tolerate the early postoperative jejunal infusion.20 Two subsequent randomized clinical trials confirmed that preoperative oral immunonutrition was as effective as perioperative immunonutrition in well-nourished patients with GI cancer.13,21 The current economic analysis was performed on a clinical study that we have previously reported.13 This approach may have several advantages: (1) the economic analysis can be done in shorter time and with low costs; (2) available results from the clinical research can be used without producing duplicates; and (3) in an early state of clinical evidence, it is not yet advisable to include economic analysis in a clinical study as long as the expected clinical effects are not clearly and statistically demonstrated. On the other hand, such analysis could have a theoretical disadvantage because clinical and statistical analyses are finished and the study has been unblinded. Thus, further evaluations may be biased in favor of verum or placebo group. To minimize this potential disadvantage, the cost analysis was carried out by a blinded economist in a blinded fashion.
The results of the present economic analysis support that preoperative
immunonutrition could be the dominant nutrition support strategy in
well-nourished patients undergoing major GI surgery for cancer. In fact,
preoperative immunonutrition resulted in a positive cost-effectiveness ratio
with a net savings of The results of the present study per se could stimulate the transition of preoperative oral immunonutrition into routine practice. In fact, patients can be easily prepared for surgery in a short period of time (5 days), and no postoperative prolonging of immunonutrition is required, thus avoiding any potential side effects of early jejunal feeding. We have to reiterate, however, that the sole preoperative approach may be optimal, clinically and economically, exclusively for well-nourished patients. In malnourished patients, it appeared that perioperative immunonutrition was clinically more beneficial than the sole preoperative immunonutrition.22 This might be explained by the fact that malnourished patients exhibit a marked impairment of the immune response, in addition to energy and nitrogen needs, and thus a prolonged administration of immune-enhancing substrates is required. Some general limitations of economic analyses should be noticed on the transferability of the present clinical and economic data, which may also influence their reproducibility. Comparable cost savings by the routine use of preoperative immunonutrition might be achieved in hospitals where the same type of operations are performed on a similar scale and complication rate. The economic parameters that we used for the present analysis may differ from country to country according to the type of health care system and reimbursement rates. The present analysis is only based on calculation of hospital resources spent. The assessment of community associated costs, including sick leave, rehabilitation, and full recovery of physical and social performance, would probably even magnify our findings even more.
The results of the present economic analysis support use of preoperative immunonutrition as an important nutrition support strategy in well-nourished patients prior to major gastrointestinal surgery for cancer. Preoperative immunonutrition resulted in a positive cost-effectiveness ratio, with a net saving of  3260 per patient. Received for publication August 2, 2004. Accepted for publication August 26, 2004.
Journal of Parenteral and Enteral Nutrition, Vol. 29, No. 1 suppl,
S57-S61 (2005) This article has been cited by other articles:
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-3 fatty acids, and RNA (immunonutrition) had a
significant reduction of both postoperative infections and length of hospital
stay when compared with patients fed with a standard enteral
formula.
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MATERIALS AND METHODS
RESULTS
