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IMPACT® FAMILY OF FORMULAS
Clinical Study
Reference
Evidence-Based Immunonutrition to Help Promote
Recovery in Surgical and Trauma Patients
Introduction
Cardiac Surgery
Guidelines Met by IMPACT®
Formulas...............................................4
IMPACT Formulas: An EvidenceBased Choice........................................5
Mechanisms of Action ........................5
Clinical Trial Outcomes ......................6
Health Economic Outcomes...........7-8
Tepaske 2007.................................... 13
Tepaske 2001.................................... 18
Tepaske 1997.................................... 23
Cancer Surgery
GI (Upper and Lower)
Drover 2011....................................... 10
Marik 2010......................................... 11
Bozzetti 2007..................................... 12
Waitzberg 2006................................. 13
Gianotti 2002..................................... 16
Braga 2002 (Arch Surg)................... 17
Braga 1999 (Arch Surg)................... 19
Upper GI
Marano 2013 ........................................9
Suzuki 2010....................................... 10
Takeuchi 2007................................... 12
Farreras 2005................................... 14
Senkal 2005....................................... 16
Senkal 1999....................................... 18
Braga 1999 (JPEN)............................ 20
Braga 1998........................................ 21
Senkal 1997....................................... 21
Gianotti 1997..................................... 22
Kemen 1995....................................... 24
Daly 1995........................................... 23
Health Economic Analysis
Mauskopf 2012.....................................9
Farber 2005....................................... 14
Braga 2005........................................ 15
Strickland 2005................................. 15
Senkal 1997....................................... 21
Pre- and Postoperatively
Drover 2011....................................... 10
Marik 2010......................................... 11
Takeuchi 2007................................... 12
Waitzberg 2006................................. 13
Gianotti 2002..................................... 16
Braga 2002 (Arch Surg)......................1
Braga 2002 (Surg)............................. 17
Senkal 1999....................................... 18
Snyderman 1999.............................. 19
Braga 1999 (Arch Surg)................... 19
Trauma
Farber 2005.......................................14
Weimann 1998..................................20
Chendrasekhar 1997.......................22
Bower 1995........................................24
Lower GI
Braga 2002 (Surg)............................. 17
Head and Neck
Felekis 2010...................................... 11
Snyderman 1999.............................. 19
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IMPACT® Clinical Study Reference
Introduction
Nestlé HealthCare Nutrition, Inc. leads the way in innovative products backed by
high levels of clinical research. This booklet provides health care professionals
with study summaries of the key clinical trials and meta-analyses providing
evidence for the role of IMPACT® formulas in supporting improved patient outcomes.
Guidelines Met By IMPACT® Formulas
Professional medical and multi-disciplinary organizations including Society
of Critical Care Medicine (SCCM), American Society for Parenteral and Enteral
Nutrition (A.S.P.E.N.) and European Society for Parenteral and Enteral Nutrition
(ESPEN) have acknowledged the vast body of evidence for the therapeutic use
of immune-modulating nutrients in the most recently published guidelines*.
CRITICAL CARE NUTRITION GUIDELINES1
E1. “Immune-modulating enteral formulations (supplemented with agents such
as arginine, glutamine, nucleic acids, omega-3 fatty acids, and antioxidants)
should be used for the appropriate patient population (major elective surgery,
trauma, burns, head and neck cancer, and critically ill patients on mechanical
ventilation), with caution in patients with severe sepsis.”
(Surgical ICU: Grade A; Medical ICU: Grade B)
Guideline references 8 studies using IMPACT® formulas
GUIDELINES ON ENTERAL NUTRITION: SURGERY 2
“Use EN preferably with immuno-modulating substrates (arginine, omega-3 fatty
acids and nucleotides) perioperatively independent of the nutritional risk for
those patients:
• undergoing major neck surgery for cancer (laryngectomy, pharyngectomy)
• undergoing major abdominal cancer surgery (oesophagectomy, gastrectomy,
and pancreatoduodenectomy)
• after severe trauma.”
(Grade A)
“Whenever possible start these formulae 5-7 days before surgery and continue
postoperatively for 5 to 7 days after uncomplicated surgery.” (Grade C)
Guideline references 18 studies using IMPACT® formulas
GUIDELINES ON NUTRITIONAL SUPPORT THERAPY DURING
ADULT ANTI-CANCER TREATMENT3
“Immune-enhancing enteral formulas containing mixtures of arginine, nucleic acids,
and essential fatty acids may be beneficial in malnourished patients undergoing
major cancer operations.” (Grade A)
Guideline references 10 studies using IMPACT® formulas
4
*The above statement does not constitute an endorsement of IMPACT formulas or
any other Nestlé HealthCare Nutrition products by SCCM, A.S.P.E.N. or ESPEN.
IMPACT® Formulas: An Evidence-Based Choice
Proper oral supplement and tube feeding formula selection is vital for surgical
and critically ill patients. Certain risks associated with major elective surgery
and trauma may be reduced by modifying specific nutrients in the diet. IMPACT®
formulas have been studied in a variety of surgical, critically ill and trauma
patients. The results of more than 40 positive-outcome studies, including several
meta-analyses, demonstrate that early feeding of IMPACT® formulas improves
patient outcomes by providing a blend of key nutrients–arginine, dietary
nucleotides and omega-3 fatty acids – shown to effectively modulate the immune
system and help improve outcomes in a variety of patient populations.
IMPACT® formulas have more Level 1 evidence, in more patients, with more
positive outcomes than any other immunonutrition formula.
Mechanisms of Action
The IMPACT® family of enteral formulas contains a unique blend of three
synergistic immunonutrients:
Arginine:
• Supports host immune response by promoting T-lymphocyte
growth and replication, and nitrogen retention.4-7
• Increases levels of hydroxyproline, the main precursor for
collagen, thereby playing a role during wound management.4-7
• Increases gut oxygenation and colonic microperfusion.8
• Stimulates synthesis of nucleotides in vitro.9
Dietary Nucleotides:
• Support replication of the rapidly dividing cells of the immune system, i.e.,
T-lymphocytes, by providing a source of purine and pyrimidine bases for
DNA/RNA production.10
Omega-3 Fatty Acids:
• Modulate cytokines to produce less inflammatory and less
immunosuppressive mediators.11.12
• Produce less inflammatory prostaglandins (PGE3) to help to
alleviate arginine deficiency by reducing induction of arginase I.13
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IMPACT® Clinical Study Reference
Clinical Trial Outcomes
Use of IMPACT® nutritional therapy has been shown to support improved
outcomes in a variety of ways. Significantly improved postoperative outcomes in
patients supplemented with IMPACT® formula have been measured, including:
• Hospital LOS reduction on average by 15% - 20% 14
• 39%-61% reduction in postoperative infectious complications: 15
- Anastomotic leaks: by 44% (p=0.004)
- Pneumonia: by 47% (p<0.0001)
- Wound infections: by 40% (p=0.005)
- Abdominal abscesses: by 54% (p=0.001)
- UTI: by 47% (p=0.011)
• Use of antibiotics reduced by 1.9–2.7 days16
In clinical trials conducted on the early enteral use of IMPACT® formulas in critically
ill patients, results also include significant reductions in:
• ICU LOS: on average, 4.5 days17
• Hospital LOS: 4.5-8 days17, 18
• Ventilator Days: on average, 4.5 days17
Clinical outcomes of IMPACT® Formulas include reductions in risk of:15
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44%
40%
47%
54%
47%
Anastomotic
leaks
Wound
infections
Pneumonia
Abdominal
abscesses
Urinary tract
infections
(p=0.004)
(p=0.005)
(p<0.0001)
(p=0.001)
(p=0.0011)
Health Economic Outcomes
IMPACT ® Nutritional Therapy Health Economic Model (Complications Method)
Potential Estimated Cost Savings in GI Cancer Surgery16,21*
$4,000
$3,810
$3,500
$3,240
$3,000
$2,671
$2,500
$2,101
$2,000
$1,531
$1,500
$961
$1,000
$500
$391
$0
0%
5%
10%
15%
20%
25%
30%
35%
Base Complication Rate
Potential estimated savings of $2,192 per patient stay
based on US average GI cancer surgery complication rate of 20.8%
These calculations are designed to help illustrate the potential cost savings to a facility with the use
of a specific immunonutrition formula. They are not intended to guarantee any specific reductions in
cost, infectious or other complication rates.
*The improvement in outcome shown by these calculations is based on the observed decrease in infectious
complications analyzed for perioperative use of IMPACT® Nutritional Therapy by Waitzberg et al. The
potential estimated cost savings shown by these calculations is based on hospital cost data from the HCUP
database computed in 2010 dollars. Formula cost is per published distributor prices.
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IMPACT® Clinical Study Reference
Health Economic Outcomes
IMPACT® Nutritional Therapy shown to help reduce nosocomial pneumonia
and reduce cost of care in trauma and burn patients20
INVESTMENT
POPULATION
Trauma and burn
patients receiving
IMPACT® 1.5 formula
Trauma and burn
patients receiving
Promote®◊ formula
POTENTIAL SAVINGS†
COST
Formula
Cost*
Nosocomial
Pneumonia (%)
Estimated
ICU Cost**
Cost of ICU
stay and
formula
1
Patient
100
Patients
$686
12
$79,200
$79,886
$11,374
$1,137,400
$60
52
$91,200
$91,260
Pneumonia is the second most frequent cause of readmission
for surgical patients21
*IMPACT® Nutritional Therapy has been associated with reduced cost of hospital care despite its higher purchase
price vs. standard formulas. Assumes patients received 14 days of isocaloric/isonitrogenous feedings of
IMPACT® 1.5 formula or Promote®. Formula cost in these financial calculations is based on the cost of formula
referenced in the study. Actual pricing will vary.
**Assumes cost of incremental care is $2400/day.
†These financial calculations are based on certain estimates and assumptions, are for illustrative purposes only
and are not a prediction or guarantee of savings at any specific institution.
Promote® is a registered trademark of Abbott Laboratories.
◊
8
Marano L, Profidia R, Pezzella M,
Grassia M, Petrillo M et al.
Ann Surg Oncol 2013; July 10 2013 DOI:
10.1245/s1043401330881.
Randomized controlled trial done to
investigate the effect of early post-op
immunonutrition on outcomes in gastric
cancer patients undergoing gastrectomy
(n=109). Post-operative feedings were
administered 6 hours post-op via jejunal
tube and continued until post-op day 7.
Formulas were isonitrogenous and
isocaloric, however the study group tube
feeding contained supplemental L-arginine,
n-3 fatty acids and nucleotides and the
control group received standard formula.
Infectious complications in the study group
were significantly lower than in the control
group (7.4% vs. 20%, p<0.05), as was the
rate of anastomotic leak (3.7% vs 7.3%,
p<0.05). LOS for the intervention group was
3.2 days less than for the control group
(p=0.029).
Mauskopf JA, Candrilli SD,
Chevrou-Séverac H, Ochoa JB.
Immunonutrition for patients
undergoing elective surgery for
gastrointestinal cancer: Impact on
hospital costs. WJSO 2012:10:136;
doi:10.1186 1477-7819-10-136.
This study was completed to create a health
economic model to determine the impact on
hospital costs of immunonutrition (IMPACT®
formulas) used in patients having major
elective surgery for gastrointestinal (GI)
cancer). United States (US) hospital costs
were taken from the Healthcare Cost and
Utilization Project’s Nationwide Inpatient
Sample (HCUP-NIP) database. These
costs were used to estimate the effect of
immunonutrition on hospital costs using
reductions in length of stay (LOS) and risk
of complications from a meta-analysis of 14
RCTs studying use of IMPACT® formulas in
GI cancer surgery patients (n=889).
Meta-analysis estimates show perioperative
use of IMPACT® resulted in savings per
patient of $6000 when costs were based
on reduction in LOS, and a $3300 savings
when costs were based on a reduction in
infectious complications. The sensitivity
analysis showed cost savings were present
for baseline complication rates above
3.5%. When US baseline rates for LOS and
infectious complications for upper and
lower GI cancer surgery were inserted
in the model, cost savings continued to
present (range, $1200 to $6300).
Use of immunonutrition for patients
undergoing elective surgery for GI cancer
was concluded an effective and cost-saving
intervention.
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IMPACT® Clinical Study Reference
Drover JW, Dhaliwal R, Weitzel L,
Wischmeyer PE, Ochoa JB, Heyland DK.
Perioperative use of arginine–
supplemented diets: A systematic
review of the evidence. J Am Coll
Surg 2011;212(3): 385-399.
Thirty-five randomized controlled trials
(n=3,438) of major elective surgical patients
are reviewed in this meta-analysis to
compare outcomes with enteral nutrition
supplemented with arginine vs. standard
formula. Twenty-five studies involved GI
surgery patients and the other 10 studies
represented other elective surgical
procedures. Twenty-three of 35 studies
utilized IMPACT® formula administered
pre-, peri- or post-surgically. Although, no
difference in mortality was noted, argininesupplemented diets were associated with
a 41% reduction in infectious complications
(p<0.00001 and a 2.38 day reduction in
length of stay (LOS) (p<0.00001), on average.
Tests for heterogeneity were not significant
in regards to reduced overall infectious
complications (p=0.11), but were significant
in regards to reduced LOS (p<0.00001).
Sub-analyses found greater reductions in
infectious complications and LOS associated
with perioperative vs. pre- or post operative
use (p=0.03, p=0.001), and more benefit
associated with IMPACT® formula vs. other
immunonutrition formulas (p<0.0001).
Authors support implementing use of
perioperative nutritional therapy containing
arginine and omega-3 fatty acids to support
considerable reduction in morbidity for
high-risk elective surgery patients and a
substantial reduction in costs for the
health care system.
*IMPACT ADVANCED RECOVERY® Advanced Nutrition
Drink is the oral form of IMPACT® formula offered in
the United States.
10
Suzuki D, Furukawa K, Kimura F,
Shimizu H, Yoshidome H, Ohtsuka M,
Kato A, Yoshitomi H, Miyazaki M.
Effects of perioperative
immunonutrition on cell-mediated
immunity, T helper type 1 (Th1)/Th2
differentiation, and Th17 response
after pancreaticoduodenectomy.
Surgery 2010;148:573-581.
In this prospective randomized study, 30
pancreaticoduodenectomy patients were
divided into three groups: A perioperative
group received ORAL IMPACT®* containing
supplementary arginine, omega-3 fatty
acids and nucleotides for 5 days before
surgery and at least 7 days of enteral
infusion after surgery. Another group
received the same immunonutrition
post-operatively only, and a third group
was given total parenteral nutrition (TPN)
postoperatively.
The primary endpoint was immune
responses and the perioperative
immunonutrition group was found to have
significantly higher levels of lymphocyte
proliferation, natural killer cell activity,
mRNA levels of T-bet, interferon-γ, related
orphan receptor, and interleukin-17F.
A secondary endpoint was the rate of
infectious complications. The perioperative
immunonutrition group was found to have
a significantly lower rate of infectious
complications than either of the two other
groups (10% vs 60% vs 60%, p<0.05). Of
additional interest, there was a statistically
significant difference in SIRS days between
the perioperative group and the TPN group
(2.4 vs 3.6 days, p<0.05).
Investigators concluded that
perioperative immunonutrition reduced
immunosuppression induced by a major
stressful surgical procedure.
Marik P, Zaloga G.
Immunonutrition in high-risk
surgical patients: A systematic
review and analysis of the
literature. JPEN. 2010; 34(4):
378-386.
This meta-analysis reviewed 21 prospective
controlled trials (n=1,918) to evaluate the
effect of immune-modulating nutrition
vs. control formula on clinical outcomes
of high-risk elective surgery patients.
Sixteen of 21 studies utilized IMPACT®
formula pre-, peri- or post-surgically
with GI, Head & Neck or Cardiac surgery
patients. Studies were stratified by formula
type and timing of initiation. Although
no difference was noted in mortality
across groups, intention-to-treat analyses
showed immunonutrition associated with
a 38%-61% reduction in hospital acquired
infections (p<0.0001), a 9%-60% reduction
in wound complications (p=0.02), and on
average, a 3 day reduction in hospital LOS
(p<0.001). Benefits were found to be similar
for peri- and postoperative use; however,
formulas containing both arginine and fish
oil (as opposed to a single immunonutrient)
were required, presumably due to
synergistic effect. As the majority of studies
utilized a product containing arginine,
fish oil, nucleotides and antioxidants, it is
unclear if benefits can be extrapolated to
immune-modulating formulas of differing
composition. Although optimal timing is
a matter for further research, authors
suggest beginning immunonutrition 5 days
preoperatively and continuing into the
postoperative period, when feasible.
Felekis D, Eleftheriadou A, Papadakos
G, Bosinakou I, Ferekidou E, Kandiloros
D, Katsaragakis S et al.
Effect of Perioperative ImmunoEnhanced Enteral Nutrition on
Inflammatory Response, Nutritional
Status, and Outcomes in Head and
Neck Cancer Patients Undergoing
Major Surgery. Nutr and Cancer
2010; 62(8): 1105-1112.
A randomized, double-blinded, prospective
study done to evaluate that immunonutrition
supplemented with arginine, RNA and n-3
fatty acids improves outcomes in head
and neck cancer patients with squamous
cell carcinoma undergoing surgery.
Formulas were isocaloric and the study
group received ORAL IMPACT® 5 days
prior to surgery and IMPACT® tube feeding
post-surgery. The control group received
no supplemental nutrition before surgery
and standard tube feeding post-surgery.
Major complications included pneumonia,
UTI, fistula and wound infection, and were
followed until discharge (median = 12
days). Rate of major complications was
significantly lower in the immunonutrition
vs. the standard group (5% vs. 25%; p<0.05).
Perioperative IMPACT® in head and neck
cancer surgery patients may influence postoperative outcomes by reducing infections
and wound complications.
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IMPACT® Clinical Study Reference
Takeuchi H, Ikeuchi S, Kawaguchi Y,
Kitagawa Y, Isobe Y, Kubochi K, Kitajima
Matsumoto S.
Clinical significance of
perioperative immunonutrition for
patients with esophageal cancer.
World J Surg. 2007; 31: 2160-2167.
Bozzetti F, Giannotti L, Braga M,
Di Carlo V, Mariani L.
Postoperative complications in
gastrointestinal cancer patients: the
joint role of the nutritional status
and the nutritional support. Clin
Nutr. 2007; 26(6): 698-709.
Retrospective comparison of 40 patients
undergoing elective esophagectomy for
esophageal squamous cell carcinoma.
The 3 groups were randomized to: Group
A control (n=20) with a standard tube
feeding for 14 days postoperatively, Group
B, (n=6) IMPACT® tube feeding for 14 days
postoperatively or Group C (n=14) 5 days
of preoperative IMPACT® and 14 days of
postoperative IMPACT® tube feeding. Results
demonstrate that compared to the control
group (A), the perioperative IMPACT® group
(C) had, on average, a significantly lower
incidence of incisional wound infection (0%
compared to 30%, p=0.031); significantly
shorter length of ICU stay (5.5 days vs. 7
days, p=0.047) and a significantly shorter
duration of postoperative SIRS response
(p=0.046). Postoperative lymphocyte
counts in group C were somewhat higher
than group A (p=0.07) and significantly
higher than group B (p=0.03). Authors note
that preoperative oral supplementation
with an immune-modulating formula
“may be crucial for rapid improvement
of lymphocyte counts, which is related to
activation of the host defense mechanisms
after esophagectomy.”
A meta-analysis where 1,410 gastrointestinal cancer surgery patients received
either standard intravenous fluid, total
parenteral nutrition, standard enteral
nutrition or immune-modulating enteral
nutrition (IMPACT® formula). Postoperative
complications were recorded, as well as,
morbidity. Also noted were correlating
factors of pancreatic surgery, advanced
age, weight loss, low serum albumin and
nutrition support. Patients who received
enteral nutrition (specifically immunemodulating nutrition) had significantly
reduced postoperative morbidity (p<0.001).
12
Tepaske R, Velthuis HT, Oudemans-Van
Straaten HM, Bossuyt PMM, Schultz JM,
Eijsman L, Vroom M.
Glycine does not add to the
beneficial effects of perioperative
oral immune-enhancing nutrition
supplements in high-risk cardiac
surgery patients. JPEN. 2007; 31(3):
173-180.
A prospective, randomized study to
measure outcomes of the addition of
glycine to an oral immune-enhancing
nutrition supplement (ORAL IMPACT®+
glycine) as compared to a standard oral
immune-enhancing nutrition supplement
(ORAL IMPACT®) and a control group
receiving standard nutrition. Each
nutrition supplement was administered
for a minimum of 5 preoperative days.
Patients (n=70) were 70 years of age or
older and were planned for mitral valve
surgery. Outcomes of morbidity, organ
function and postoperative recovery
were analyzed. In both groups receiving
the ORAL IMPACT® formula, infectious
morbidity was decreased (17%/23% vs.
50%) as compared to the control (p=0.02).
Conclusions of the study were that use
of preoperative ORAL IMPACT® formula
reduces the rate of infectious morbidity
and results in more hemodynamic stability.
The addition of glycine did not result in any
additional benefit.
Waitzberg DL, Saito H, Plank LD,
Jamieson GG, Jagannath P,
Tsann-Long H, Mijares JM, Bihari D.
Postsurgical infections are reduced
with specialized nutrition support.
World J Surg. 2006; 30:1592-1604.
This article reviewed 17 studies (n=2,305)
where IMPACT® formula was used before
and/or after major elective surgery and
the clinical outcomes reported were
included in this meta-analysis. Ten studies
compared preoperative or perioperative
IMPACT® formula provision vs. control and
7 studies looked at postoperative nutrition.
Fourteen studies examined IMPACT®
formula used with gastrointestinal (GI)
cancer surgeries. IMPACT® formula
supplementation was associated with
significant reductions in postoperative
infectious complications (39-61%) and
a significant decrease in hospital stay
by an average of 2 days. Anastomotic
leaks were found to be less prevalent
in gastrointestinal surgery patients who
received IMPACT® formula perioperatively.
Overall, 500 mL-1 L of IMPACT® formula
5-7 days preoperatively contributed to
improved outcomes in GI, cardiac, and
head/neck elective surgery patients.
Cited by:
CRITICAL CARE NUTRITION
GUIDELINES1
13
IMPACT® Clinical Study Reference
Farber MS, Moses K, Korn M.
Reducing costs and patient
morbidity in the enterally fed
intensive care unit patient. JPEN.
2005; 29(1 Suppl): S62-S69.
Clinical trial of predominantly trauma
patients prospectively identified to be
enterally fed with IMPACT® 1.5 formula
and compared with a historical cohort
of similarily identified patients receiving
standard nutrition. No differences in
mean calories or protein received, days to
feeding initiation or days to goal rate were
observed between groups.
A reduction in nosocomial pneumonia
(12% in IMPACT® 1.5 formula patients vs.
52% in those on standard feeding, p=0.01)
was shown. Although not statistically
significant, the patients receiving IMPACT®
1.5 formula required 3 fewer days of
ventilator support and had a 5 day shorter
ICU stay, on average, than those receiving
standard feeding.
Using previously published costs of ICU
care, cost of formulas and the difference
in length of ICU stay, an economic analysis
identified a savings of $11,374 for each
patient receiving IMPACT® 1.5 formula.
Farreras N, Artigas V, Cardona D,
Rius X, Trias M, Gonzalez JA.
Effect of early postoperative
enteral immunonutrition on wound
management in patients undergoing
surgery for gastric cancer. Clin Nutr.
2005; 24: 55-65.
A prospective, randomized study to
determine the effect of early postoperative
enteral immunonutrition (IMPACT®
formula) on wound management
in patients undergoing surgery for
gastric cancer. Sixty-six patients were
randomized to receive IMPACT® formula
or an isocaloric, isonitrogenous control
formula. The wound management process
was analyzed, as well as, development
of surgical wound management
complications in sixty patients. Those
patients who received IMPACT® formula
had significantly increased hydroxyproline
levels (p=0.0018) and decreased incidence
of wound management complications
(p=0.005). Authors concluded that
early provision of IMPACT® formula
postoperatively improves wound
management substrates and decreases
wound complications.
Cited by:
GUIDELINES ON NUTRITIONAL
SUPPORT THERAPY DURING ADULT
ANTI-CANCER TREATMENT3
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
14
Braga M, Gianotti L, Vignali A,
Schmid A, Nespoli L, Di Carlo V.
Hospital resources consumed
for surgical morbidity: effects of
preoperative arginine and n-3 fatty
acid supplementation on costs.
Nutrition. 2005; 21: 1078-1086.
Strickland A, Brogan A, Krauss J,
Martindale R, Cresci G.
Is the use of specialized nutritional
formulations a cost-effective
strategy? A national database
evaluation. JPEN. 2005; 29
(1 Suppl): S81-91.
This article uses results from a
prospective, randomized, placebocontrolled study22 of preoperative
immunonutrition supplementation
(IMPACT® formula) to calculate hospital
costs for post-operative complications,
and analyze for the possibility of
cost savings in upper and lower GI
cancer patients. A blinded cost-analysis
for hospital length of stay (LOS) and
in-patient resource utilization for
infectious and non-infectious
complications were referenced to the
National List of Sanitary Costs, Italian
Ministry of Health. Mean cost
of treating infectious complications
was significantly lower in the IMPACT®
formula vs. conventional group
(p=0.05). Because patients receiving
preoperative IMPACT® formula had
significantly fewer infectious
complications and significantly shorter
LOS, total cost per patient was €5668
vs. €7092 for conventional treatment.
Preoperative immunonutrition with
IMPACT® formula resulted in a net
hospital savings per patient of €1424,
as compared to conventional care.
This article uses a current review on
the literature of published outcomes
of studies using clinical outcomes with
immune-modulating diets to determine
the potential economic benefit associated
with the use of specialized nutritional
formulations in elective surgical trauma
and medical patients. Data was obtained
from a large national database of 126
member hospitals and over 1 million
patients. Data was collected on patient
type, subservice, complication, mean
length of stay, mean cost and incremental
cost per complication (if experienced). For
the medical patient population, specialized
nutritional formulations found a 51%
decrease in infectious complications
and decreased length of stay of 9.7
days resulting in a net cost savings of
$2,066 per patient. Net cost savings for
surgical and trauma patients was $688
and $308 per patient respectively. This
data demonstrated that specialized
formulations are a cost-effective way to
improve clinical outcomes while reducing
resource consumption.
Cited by:
Cited by:
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
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IMPACT® Clinical Study Reference
Senkal M, Haaker R, Linseisen J,
Wolfram G, Homann HH, Stehle P.
Preoperative oral supplementation
with long-chain omega-3 fatty acids
beneficially alters phospholipid
fatty acid patterns in liver, gut
mucosa, and tumor tissue. JPEN.
2005; 29(4): 236-240.
Gianotti L, Braga M, Nespoli L,
Radaelli G, Beneduce A, Di Carlo V.
Randomized controlled trial of
preoperative oral supplementation
with a specialized diet in patients
with gastrointestinal cancer.
Gastroenterology. 2002; 122:
1763-1770.
In this study, 40 patients undergoing
gastrointestinal surgery were
prospectively randomized to receive ORAL
IMPACT® formula 5 days preoperatively or
an isocaloric diet, in addition to their oral
hospital diet. The supplemented IMPACT®
formula provided 3.3 g of polyunsaturated
eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA). During
surgery, samples of liver, gut mucosa and
tumor were obtained and analyzed for
EPA/DHA content. Compared to the control
group, IMPACT® formula supplemented
patients had increased levels of EPA and
DHA in liver tissue, gut mucosa and tumor
tissue (p<0.05), which indicates a possible
effect on post-operative inflammatory
response after abdominal surgery.
A prospective, randomized study of 305
well nourished patients with cancer of
the gastrointestinal tract comparing
either ORAL IMPACT® formula 5 days
preoperatively, ORAL IMPACT® formula 5
days preoperatively plus, IMPACT® formula
jejunally postoperatively, or no nutrition
before or after surgery. A significantly
decreased infection rate (p=0.006 p=0.02)
and length of hospital stay (p=0.008
p=0.03) occurred in both IMPACT® formula
treatment groups. Thus, using IMPACT®
formula preoperatively was as effective
as perioperative immunonutrition in
improving outcomes in well nourished
patients and is superior to conventional
treatment.
Cited by:
GUIDELINES ON NUTRITIONAL
SUPPORT THERAPY DURING ADULT
ANTI-CANCER TREATMENT3
16
Braga M, Gianotti L, Nespoli L,
Radaelli G, Di Carlo V.
Nutritional approach in
malnourished surgical patients.
Arch Surg. 2002; 137: 174-180.
Prospective, randomized, controlled trial
of 150 patients requiring major elective
surgery of the GI tract for malignancy. All
enrolled patients were malnourished with
≤10% body mass loss and randomized
to 3 groups. Group 1 (Perioperative
Treatment Group) was supplemented
preoperatively with 1 liter per day ORAL
IMPACT® formula for 7 consecutive days
and tube fed with IMPACT® formula postoperatively. Group 2 (Preoperative Group)
was supplemented with 1 liter per day of
ORAL IMPACT® formula for 7 consecutive
days preoperatively and standard formula
post-op. Group 3 (Control Group) received
standard tube feeding post-operatively. All
diets were isocaloric and isonitrogenous.
Results reveal that the perioperative
treatment group experienced decreased
complications (p=0.02), and both treatment
groups had a reduced length of hospital
stay as compared to the control group
(p=0.01, p=0.001).
Cited by:
GUIDELINES ON NUTRITIONAL
SUPPORT THERAPY DURING ADULT
ANTI-CANCER TREATMENT3
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
Braga M, Gianotti L, Vignali A,
Di Carlo V.
Preoperative oral arginine and n-3
fatty acid supplementation improves
the immunometabolic host response
and outcome after colorectal
resection for cancer. Surgery. 2002;
132: 805-814.
A prospective, randomized, controlled trial
of 200 patients with colorectal neoplasm
requiring surgical resection. The 4 groups
were randomized to: Group 1, perioperative
supplementation with ORAL IMPACT®
formula for 5 days preoperatively +
ORAL IMPACT® or IMPACT® tube feeding
postoperatively; Group 2, preoperative
ORAL IMPACT® for 5 days; Group 3 (control),
iosnitrogenous/caloric oral supplement
preoperatively for 5 days; and Group 4; no
supplementation before or after surgery
(conventional therapy). Immune response
(p<0.05), gut oxygenation (p<0.01) and
microperfusion (p<0.02) were found to
be significantly better for Groups 1 and
2. Overall, Groups 1 and 2 fed IMPACT®
formula both perioperatively and
preoperatively had outcomes of decreased
infectious complications (p<0.02 p<0.04);
reductions in antibiotic therapy days
(p<0.005, p<0.004) and length of hospital
stay (p<0.0005) as compared to the control
and conventional therapy groups.
Cited by:
GUIDELINES ON NUTRITIONAL
SUPPORT THERAPY DURING ADULT
ANTI-CANCER TREATMENT3
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
17
IMPACT® Clinical Study Reference
Tepaske R, te Velthuis H, Oudemans-van
Straaten HM, Heisterkamp SH, Van Deventer
SJH, Ince C, Eÿsman León, Jozef Kesecioglu.
Effect of preoperative oral immuneenhancing nutritional supplement
on patients at high risk of infection
after cardiac surgery: a randomized
placebo-controlled trial. Lancet.
2001; 358(9283): 696-701.
A prospective, randomized, double-blind,
placebo-controlled study of 50 patients
scheduled for coronary artery bypass. The
preoperative treatment group consumed 1
liter of an oral immune-enhancing nutritional
supplement (ORAL IMPACT®) for at least
5 days prior to surgery. The control group
received an isocaloric, isonitrogenous amount
of a control nutritional supplement. After
surgery, patients requiring tube feeding
received either an immune-enhancing or an
isocaloric, isonitrogenous control formula
until extubation. Study group patients had
significantly higher preoperative expression
of HLA-DR epitopes on monocytes (109%)
than those in the control group compared
with baseline (p=0.01). Post-op concentration
of IL-6 was significantly lower in the study
group than in the control group (p=0.032).
Patients receiving ORAL IMPACT® had a
significant reduction in total infectious
complications (p=0.013), and had significantly
fewer cases of pneumonia (p=0.047).
Investigators concluded preoperative
intake of an immune-enhancing nutritional
supplement for 5-10 days enhanced the
outcome of high-risk cardiac patients
undergoing surgery, improved preoperative
host defense and reduced the number of
postoperative infections.
Cited by:
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
18
Senkal M, Zumtobel V, Bauer KH,
Marpe B, Wolfram G, et al.
Outcome and cost-effectiveness
of perioperative enteral
immunonutrition in patients
undergoing elective upper
gastrointestinal tract surgery:
a prospective randomized trial.
Archives of Surgery. 1999; 134:
1309-1316.
A prospective, randomized, double-blind
trial of 154 patients undergoing surgery
for cancer of the upper gastrointestinal
tract. In the study, patients were
randomized to receive ORAL IMPACT®
formula or an isonitrogenous, isocaloric
supplement for 5 days prior to surgery.
Patients in both groups consumed 1 liter
each day by mouth. Following surgery,
patients who consumed the ORAL IMPACT®
formula were started on IMPACT® formula
and patients who consumed the standard
control were started on a standard tube
feeding formula. All patients were fed via
needle-catheter jejunostomy, initiated 12
hours after surgery and continued on the
prescribed diet for at least 5 days after
surgery. Patients who received IMPACT®
formula had significantly fewer infections
occurring after postoperative day 3
(p=0.04), and fewer complications overall
(48% reduction, p=0.05) than patients who
received the standard diet.
Cited by:
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
Snyderman CH, Kachman K,
Molseed L, et al.
Reduced postoperative infections
with an immune-enhancing
nutritional supplement.
Laryngoscope. 1999; 109: 915-921.
A prospective, randomized, double-blind,
study of 136 head and neck cancer
patients who received IMPACT® formulas
pre- and postoperatively or postoperatively
alone versus a standard formula pre- and
post-operatively or postoperatively alone.
IMPACT® formula-fed patients (pre- and
postoperatively and post-operatively
only) had nearly half as many infections
compared to patients in the standard
formula groups (p=0.02 p=0.04). There was
no difference in length of stay; however,
there was a trend toward shorter length
of ICU stay and potential cost savings for
patients fed IMPACT® formula.
Cited by:
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
Braga M, Gianotti L, Vignali A,
Radaelli G, Mari G, Di Carlo V.
Perioperative immunonutrition
in patients undergoing cancer
surgery. Results of a randomized
double-blind phase 3 trial. Archives
of Surgery. 1999; 134: 428-433.
One hundred and seventy-one patients
who required major surgery for gastric,
pancreatic or colorectal cancer were
randomized in a double-blind fashion to
receive either a formula supplemented
with arginine, omega-3 fatty acids and
dietary nucleotides (IMPACT® formula,
n=102), or an isocaloric, isonitrogenous
control (n=104). For seven days prior to
surgery, patients consumed 1 liter/day
of either the control or the supplemented
formula. After surgery, patients received
the same preoperative formulas via jejunal
feeding and continued on the formula for
7 days. Patients who received the IMPACT®
formula perioperatively had significant
reduction in postoperative infection (9/85
in the supplemented group compared to
21/86 in the control group, p=0.02). There
was also significant reduction in length of
hospitalization for the group that received
IMPACT® formula (p=0.01).
Cited by:
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
19
IMPACT® Clinical Study Reference
Braga M, Gianotti L, Balzano G,
Vignali A, Gentilini O, Zerbi A,
Di Carlo V.
Artificial nutrition after major
pancreatic resection: results of a
prospective, randomized clinical
Trial. JPEN. 1999; 23(1): S2.
An extension of earlier, prospective,
randomized trials of patients undergoing
surgery for pancreatic cancer. In
the study, 182 patients undergoing
pancreaticoduodenectomy were
randomized to receive IMPACT® formula,
standard enteral feeding or total
parenteral nutrition (TPN). Postoperative
nutrition was initiated within 6 hours after
surgery. Each of the groups received the
same amount of calories and nitrogen per
day. Despite the invasive surgery, early
postoperative enteral feeding was well
tolerated and did not increase the rate of
complications. Compared to the TPN group,
there was a 36% reduction in number of
patients with infectious complications and
the hospital stay was 4 days shorter for
patients fed IMPACT® formula (p<0.05).
Both findings were statistically significant.
Patients with pancreatic resection who
receive IMPACT® formula as part of an
early enteral nutrition program have fewer
infection-related complications and a
shorter length of hospitalization.
Weimann A, Bastian L, Bischoff WE,
Grotz M, Hansel M, Lotz J,
Trautwein C, Tusch G, Shlitt HJ, Regel G.
Influence of arginine, omega-3 fatty
acids and nucleotide-supplemented
enteral support on systemic
inflammatory response syndrome
and multiple organ failure in patients
after severe trauma. Nutrition. 1998;
14(2): 165-172.
In this prospective, randomized, doubleblind trial, 32 patients with multiple severe
injuries were randomized to receive
IMPACT® formula or an isonitrogenous,
isocaloric control. Patients also received
TPN initially. During the course of the
study, patients who received IMPACT®
formula had fewer numbers of days with
SIRS (8.3 days/patient versus 13.3 days/
patient on the control). During the high-risk
period of 8-14 days after trauma, patients
on IMPACT® formula had less than half
the incidence of SIRS (3.0 days with SIRS/
patient versus 6.2 days with SIRS/patient
on the control). Patients who received
IMPACT® formula also had a significant
reduction in MOF score during this critical
period. High-risk patients who receive
IMPACT® formula are less likely to develop
SIRS or MOF than patients who receive
standard enteral feeding following
severe trauma.
Cited by:
CRITICAL CARE NUTRITION
GUIDELINES1
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
20
Braga M, Gianotti, Vignali A,
Cestari A, Bisagni P, Di Carlo V.
Artificial nutrition after major
abdominal surgery: IMPACT of
route of administration and
composition of the diet. Crit Care
Med. 1998; 26(1): 24-30.
A prospective, randomized trial of 166
patients undergoing surgery for gastric
or pancreatic cancer randomized to
receive IMPACT® formula, standard enteral
formula or total parenteral nutrition (TPN).
The nutritional regimens were isocaloric
and isonitrogenous. Patients receiving
IMPACT® formula had the fewest number
of postoperative infections (p<0.05) and
a shorter hospital stay compared to the
standard formula or TPN. In sub-groups
of malnourished patients and patients
who received homologous transfusions,
administration of IMPACT® formula
compared more favorably than TPN at
reducing severity of infection and length
of hospital stay (p<0.05). This study
included data from a 1995 study published
in Infusionsther Transfusionmed with an
additional 89 patients.
Senkal M, Mumme A, Eickhoff U,
Geier B, Spath G, Wulfert D,
Joosten U, Frei A, Kemen M.
Early postoperative
immunonutrition: clinical outcome
and cost-benefit analysis in surgical
patients. Crit Care Med. 1997; 25(9):
1489-1496.
A prospective, randomized, multi-center
study of 164 patients with upper GI
cancer who underwent major surgery and
received early postoperative feeding with
IMPACT® formula or an isonitrogenous,
isocaloric control formula without
supplemental arginine, dietary nucleotides
or fish oil. Patients who received IMPACT®
formula had 53% fewer infectious and
wound complications occurring after day
five postoperatively (p<0.05). The average
cost for treating complications was 32%
lower for the IMPACT® formula group.
Cited by:
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
Cited by:
GUIDELINES ON NUTRITIONAL
SUPPORT THERAPY DURING ADULT
ANTI-CANCER TREATMENT3
21
IMPACT® Clinical Study Reference
Gianotti L, Braga M, Vignali A, Balzano
G, Zerbi A, Bisagni P, Di Carlo V.
Effect of route of delivery and
formulation of postoperative
nutritional support in patients
undergoing major operations for
Malignant Neoplasms. Arch Surg.
1997; 132: 1222-1230.
Prospective, randomized, controlled trial
of 260 post-upper GI surgical cancer
patients who received standard enteral
feeding, IMPACT® formula or TPN. Patients
who received IMPACT® formula had a
significantly lower sepsis score than
patients on either standard enteral or TPN
(p<0.01). Mean hospital LOS was shorter
for patients in the IMPACT® formula group
compared to either of the other groups
(16.1 days for the IMPACT® formula group
versus 19.2 days for the standard enteral
and 21.6 days for TPN, p=0.004 p=0.01).
IMPACT® formula favorably affects host
immune response resulting in infectious
complications that are less severe
compared to infectious complications that
occur in patients who receive standard
enteral or TPN.
Chendrasekhar A, Fagerli JC,
Prabhakar G, Landreth K,
Timberlake GA.
Evaluation of an enhanced diet
in patients with severe closed head
injury. Crit Care Med. 1997; 25(1): A80.
A prospective, randomized, dual center
trial of 20 patients with severe closed
head injury who received IMPACT® formula
or a standard enteral formula. Following
one week of the two different nutrition
support regimens, IMPACT® formula-fed
patients had significant improvements
in various immune parameters (p<0.05).
Patients who received IMPACT® formula
had a significant reduction in infection
rate compared to patients who received
the standard formula (9.1% versus 100%,
p<0.0001). The authors concluded IMPACT®
formula improves antigen processing to
promote immune function and thereby
reduce risk of infection in severe closed
head injury patients.
Cited by:
CRITICAL CARE NUTRITION
GUIDELINES1
GUIDELINES ON NUTRITIONAL
SUPPORT THERAPY DURING ADULT
ANTI-CANCER TREATMENT3
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
* TraumaCal® is no longer available.
22
Tepaske R, Thio S, Eysman l,
van Deventer L, Ince C, et al.
Perioperative immunonutrition
in “high risk” cardiac surgery
patients improves immunological
parameters and clinical outcome.
Presented at the european society
of surgical infection meeting, Oslo,
June 1997.
A prospective, randomized, placebo
controlled double-blind study of 50
patients undergoing heart surgery.
Patients consumed ORAL IMPACT®
formula or an isocaloric control
formula for 5 – 10 days before
surgery. Patients who received ORAL
IMPACT® formula had significantly
fewer lower respiratory tract infections
(0 of 22 vs. 5 of 23, p=0.022) and 65%
reduction in total infections compared
to the group that received the
control formula (p=0.009).
Daly JM, Weintraub FN, Shou J,
Rosato EF, Lucia M.
Enteral nutrition during
multimodality therapy in upper
gastrointestinal cancer patients.
Ann Surg. 1995; 221(4): 327-338.
A prospective, randomized, double-blind
study of 60 patients with upper GI cancer
who underwent abdominal surgery and
received early postoperative feeding with
either IMPACT® formula or TraumaCal®
formula*. Patients fed IMPACT® formula
had 77% fewer infectious and wound
complications (p<0.005) and had a six day
shorter mean length of hospitalization
than patients in the TraumaCal® group
(p=0.02).
Cited by:
GUIDELINES ON NUTRITIONAL
SUPPORT THERAPY DURING ADULT
ANTI-CANCER TREATMENT3
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
Osmolite® is a registered trademark of
Abbott Laboratories.
◊
23
IMPACT® Clinical Study Reference
Kemen M, Senkal M, Homann HH,
Mumme A, Dauphin AK, Baier J,
Windeler J, Neumann H,
Zumtobel V.
Early postoperative enteral
nutrition with arginine, omega-3
fatty acids and ribonucleic acidsupplemented diet versus placebo
in cancer patients: an immunologic
evaluation of impact. Crit Care Med.
1995; 23(4): 652-659.
Bower RH, Cerra FB, Bershadsky B,
Licari JJ, Hoyt DB, Jensen GL,
Van Buren CT, Rothkopf MM, Daly JM,
Adelsgerg BR.
Early administration of a formula
(IMPACT®) supplemented with
arginine, nucleotides, and fish oil in
intensive care unit patients: results
of a multicenter, prospective,
randomized, clinical trial. Crit Care
Med. 1995; 23(3): 436-449.
Randomized clinical trial of 42 patients
with upper gastrointestinal malignancies
who received either IMPACT® formula or
an isonitrogenous and isocaloric control
formula postoperatively to evaluate the
effects of providing early postoperative
feeding on the immune system. Enteral
feeding of IMPACT® formula significantly
improved immune function as measured
by Immunoglobin M (IgM) (p<0.05) and
Immunoglobin G (IgG) (p<0.05), as well
as, significantly higher T-lymphocyte
concentrations (p<0.05) compared to
standard enteral feeding.
A prospective, randomized, double-blind
multi-center study of 326 critically ill,
ICU tube-fed patients (84% trauma, 12%
MICU, 4% SICU) who received either
IMPACT® formula or Osmolite®◊ HN.
Patients fed IMPACT® formula who met all
requirements for study completion had
a 28% reduction (eight days) in length of
hospital stay, as compared to the control
group (p<0.05). IMPACT® formula-fed
patients who were septic had a ten day
shorter hospital stay (p<0.05) and a 60%
lower incidence of new infections
compared to septic patients fed
Osmolite® HN (p<0.01).
Cited by:
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
Cited by:
CRITICAL CARE NUTRITION
GUIDELINES1
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2
24
References to nutritional guidelines in this document do not constitute endorsements by or on
behalf of any organization.
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adult critically ill patient: Society of Critical Care Medicine and American Society for Parenteral
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2. Weimann A et al. ESPEN guidelines on enteral nutrition: surgery including organ
transplantation. Clin Nutr. 2006; 25: 224-244.
3. August DA et al. A.S.P.E.N. Clinical Guidelines: nutrition support therapy during adult
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4. Ochoa JB et al. A rational use of immune enhancing diets: when should we use dietary arginine
supplementation? NCP 2004; 19 (3): 216-225.
5. Zhu X et al. Immunosuppression and infection after major surgery: a nutritional deficiency. Crit
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6. Wu G et al. Arginine metabolism and nutrition in growth, health and disease. Amino Acids 2009;
3(0) 153-168.
7. de Aguilar- Nascimento JE et al. Role of enteral nutrition and pharmaconutrition in conditions
of splanchnic hypoperfusion. Nutrition 2010; 26(4): 354-358.
8. Barbul A. Arginine biochemistry, physiology and therapeutic implications. JPEN.
1986; 10: 227-238.
9. Yamauchi K et al. Glutamine and arginine affect Caco-2 proliferation by promotion of nucleotide
synthesis. Nutrition. 2002; 18: 329-333.
10.Grimble GK et al. Nucleotides as immunomodulators in clinical nutrition. Curr Opin in Clin Nutr
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11.Calder PC. Polyunsaturated fatty acids and inflammation. Prostaglandins, Leukotrienes and
Essential Fatty Acids. 2006; 75: 197-202.
12.Mizock BA. Nutritional support in acute lung injury and acute respiratory distress syndrome.
NCP. 2001; 16: 319-328.
13.Bansal V et al. Interactions between fatty acids and arginine metabolism: implications for the
design of immune enhancing diets. JPEN. 2005; 29(1): S75-S80.
14.Drover JW et al. Perioperative use of arginine-supplemented diets: a systematic review of the
evidence. J Am Coll Surg; 2011; 212 (3): 385-399.
15.Waitzberg DL et al. Postsurgical infections are reduced with specialized nutrition support.
World J Surg. 2006; 30: 1592-1604.
16.Braga M et al. Preoperative oral arginine and n-3 fatty acid supplementation improves the
immunometabolic host response and outcomes after colorectal resection for cancer. Surg.
2002; 132(5): 805-814.
17.Atkinson S et al. A prospective, randomized, double-blind, controlled clinical trial of enteral
immunonutrition in the critically ill. Crit Care Med. 1998; 25: 1164-1172.
18.Bower RH et al. Early enteral administration of a formula (IMPACT formula) supplemented
with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter,
prospective, randomized, clinical trial. Crit Care Med. 1995; 23(3): 436-449.
19.HCUP Nationwide Inpatient Sample (NIS). Healthcare Cost and Utilization (HCUP). 2008. Agency
for Healthcare Research and Quality, Rockville, MD. www.hcup-us.ahrq.gov/nisoverview.jsp.
20.Farber MS et al. Reducing costs and patient morbidity in the enterally fed intensive care unit
patient. JPEN. 2005; 29(1 Suppl): S62-S69.
21.Jencks SF et al. Rehospitalization among patients in the Medicare free-for-service program.
NEJM 2009; 360: 1418-1428.
22.Gianotti L et al. Randomized controlled trial of preoperative oral supplementation with a
specialized diet in patients with gastrointestinal cancer. Gastroenterol 2002; 122: 1763-1770.
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