Immunonutrition for patients undergoing elective surgery for gastrointestinal cancer: impact on hospital costs

Infectious and other types of complications following gastrointestinal cancer, head and neck cancer, and cardiac surgery are frequent and add significantly to patient morbidity as well as to hospital length of stay and costs[1, 2]. Published estimates of complication rates after surgery for patients with gastrointestinal cancer, head and neck cancer, and cardiac disease suggest that these rates range between 15% and 54%[3‐6]. Infectious complications include wound infections, abdominal abscess, pneumonia, urinary tract infections, and sepsis. Other types of complications include anastomotic leaks, acute renal failure, and cardiovascular events. Complications prolong the recovery period for the patient, require additional days in the hospital, may increase mortality and increase hospital costs[1].

Immunonutrition formulas composed of arginine, omega-3 fatty acids, and nucleotides improve host defenses, likely through the provision of key nutrients that maintain T-lymphocyte and other immune functions[5, 7]. Immunonutrition has been studied in multiple clinical trials, consistently showing reduced postsurgical infectious complications, and some studies also showing a decrease in selected noninfectious complications in patients undergoing elective surgery, including patients undergoing elective surgical interventions for gastrointestinal cancer. Several meta-analyses have summarized the results of these clinical trials, all demonstrating a 38%–62% risk reduction in infections and other complications[3‐9]. In particular, Waitzberg and colleagues[4] examined the relationship between hospital length of stay or postoperative infectious complications or anastomotic leak, a noninfectious complication, and the use of immunonutrition using a nutritionally complete formula containing supraphysiologic quantities of arginine, omega-3 fatty acids, and nucleotides (IMPACT®, Nestlé Science Health, Vevey, Switzerland). The results of the Waitzberg meta-analysis showed that, for all nutrition intervention strategies and for all surgical patients studied, use of immunonutrition resulted in lower postsurgical infectious complications, a lower rate of anastomotic leak, and shorter length of stay.

In this paper we evaluated the impact on per-patient hospital costs arising from the use of immunonutrition perioperatively (both before and after surgery) in patients undergoing elective surgery for gastrointestinal (GI) cancer using the results from Waitzberg and colleagues[4] applying estimates of the cost of care of this patient population derived from the Healthcare Cost and Utilization Project’s (HCUP’s) 2008 Nationwide Inpatient Sample (NIS)[10, 11].

Results of the HCUP NIS analyses of costs are presented in Table 2. The NIS data demonstrated that, for all patients undergoing elective surgery for gastrointestinal cancer in the US in 2008, the mean cost per stay for patients presenting with infectious complications (or presenting with infectious plus other complications) was $53,361 ($41,119), whereas for those without infectious complications (or without infectious plus other complications) it was $20.406 ($19,628). The average cost per hospital day was $2,948. However, the average cost per day and costs per stay were higher for those undergoing upper GI cancer surgery than for those undergoing lower GI cancer surgery. Also presented in Table 2 is the average length of stay for the populations of interest. Of note are the lower average length of stay and infectious complication rates for the combined upper and lower GI cancer surgery patients than those observed in the clinical trials reviewed by Waitzberg and colleagues[4].

When applying the HCUP NIS costs for hospital stays with and without infectious complications for the combined upper and lower GI population to the infectious complication rates with and without immunonutrition estimated in the Waitzberg meta-analysis, the mean cost per stay was $26,402 per patient in the control group and $22,743 per patient in the immunonutrition group, leading to $3,300 (rounded to the nearest $100) saved per patient due to immunonutrition use perioperatively attributable to the reduced complication rate. Using the estimated reduction in hospital length of stay of 2.18 days from Waitzberg’s meta-analysis gave an estimated reduction in cost of $6,000 (rounded to the nearest $100) per patient with immunonutrition when compared with standard nutritional supplementation (2.18*$2948)–$397. These results are presented in Table 3.

The first sensitivity analysis aimed at determining the baseline infectious complication rate at which cost savings from use of immunonutrition would offset the cost of therapy. As illustrated in Figure 1, net cost savings continued to be observed for infectious complication rates above 3.5%.

In the second sensitivity analysis, the infectious complication rates, length of stay, and costs per day and per stay with and without infectious complications were taken from the 2008 HCUP NIS data analysis to show the impact on cost savings for the combined population as well as upper and lower GI cancer patients separately, using more recent data on length of stay and infectious complication rates. As presented in Table 3, the results show that the cost savings are lower when using the infectious complication rates and length of stay from the total HCUP NIS GI cancer surgery population and the lower GI cancer surgery population but higher for the upper GI cancer surgery population because of the higher hospital costs for the upper GI patients.

Multiple studies (>20), including those studies performed in patients undergoing elective surgery for gastrointestinal cancers, support the use of immunonutrition as a low-risk strategy that effectively and significantly decreases the risk of postsurgical complication in patients undergoing major elective surgery[4, 5]. The analyses presented in this paper have demonstrated that the use of perioperative (both before and after surgery) immunonutrition also may be cost saving based on a meta-analysis of available trials in GI cancer patients using a single immunonutrition formula. Cost savings with the use of immunonutrition have been previously reported. However, the applicability of these studies has been limited due to the fact that their analysis is done on either a single clinical trial for perioperative[12] or preoperative immunonutrition[1, 13] or of a hospital database for different patient populations[14].

The estimated net cost savings was calculated through two different approaches based on either a decrease in infectious complication rate or in hospital length of stay resulting from the use of immunonutrition. Interestingly, even though a significant decrease in cost was evident through either method, cost savings estimates based on decrease in the infectious complication rate were lower than estimates based on reduced hospital length of stay. This suggests that immunonutrition may bring additional benefits beyond reduction in risk of infectious complications, including a reduced risk of noninfectious complications (such as the reduction in anastomotic leak shown in the Waitzberg and colleagues[4] meta-analysis), decreased severity of complications (such as a more limited infection), or speedier recovery in patients who do not develop complications. Indeed, some clinical observations suggest that the use of immunonutrition results in improved hemodynamics, including decreased accumulation of lactate and base deficit, enhanced tissue oxygenation, and improved T-lymphocyte function[15]. These physiologic benefits may translate into clinical benefits that are difficult to quantify but nonetheless may result in a shorter length of stay.

Our results using the incremental costs associated with infectious complications were sensitive to the baseline infectious complication rate, suggesting that cost savings would decrease in patient populations or hospitals with lower infectious complication rates. However, cost savings are estimated with the use of immunonutrition when the infectious complication rate is above 3.5%.

Our study has some limitations. First, noninfectious complications were not included in the estimates that were based solely on estimated reductions in infectious complication rates, although the Waitzberg and colleagues[4] meta-analysis indicated a possible significant reduction in the noninfectious complication, anastomotic leak (Table 1). However, the estimates based on hospital length of stay would capture the effects of any reductions in noninfectious complication. Second, the studies included in the meta-analysis were completed over 10 years ago, and surgical techniques and postoperative management have evolved since then. Our sensitivity analysis using the 2008 HCUP NIS data was performed to assess the impact of more recent estimates of infectious complication rates and hospital length of stay in the US to address this limitation. Third, we used results from a meta-analysis published in 2006. However, more recent meta-analyses have estimated similar reduction in infectious complication rates and reductions in hospital length of the stay for those taking immunonutrition perioperatively for gastrointestinal surgery[5‐9]. For example, the Marimuthu and colleagues[9] meta-analysis, which included data from several more recent clinical trials, estimated a relative risk (RR) for infectious complications of 0.53 and a reduction in hospital length of stay of 2.71 days for those receiving immunonutrition perioperatively. Their meta-analysis showed a lower impact on length of stay when only preoperative immunonutrition was provided (1.46 days), but a similar impact on length of stay when only postoperative immunonutrition was provided (2.44 days). Conversely, they showed a greater impact on infectious complication rates with only preoperative immunonutrition (RR = 0.48) and a lower impact with only postoperative immunonutrition (RR = 0.68) than that estimated for perioperative immunonutrition.

Our study, which used pooled data from multiple clinical trials, demonstrates that a comparatively small investment in immunonutrition support both before and after surgery for both upper and lower gastrointestinal cancer surgery patients is likely to be more than offset by the estimated savings due to reduced infectious complications and/or hospital length of stay. Thus, the use of immunonutrition support may be a valuable addition to other strategies used by hospitals to control postsurgical infectious complications, improve patient outcomes, and reduce hospital costs.