You are on page 1of 25

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® Tepaske 2007.................................... 13
Formulas...............................................4 Tepaske 2001.................................... 18
IMPACT Formulas: An Evidence- Tepaske 1997.................................... 23
Based Choice........................................5
Mechanisms of Action ........................5 Health Economic Analysis
Clinical Trial Outcomes ......................6 Mauskopf 2012.....................................9
Health Economic Outcomes...........7-8 Farber 2005....................................... 14
Braga 2005........................................ 15
Cancer Surgery Strickland 2005................................. 15
GI (Upper and Lower) Senkal 1997....................................... 21
Drover 2011....................................... 10
Marik 2010......................................... 11 Pre- and Postoperatively
Bozzetti 2007..................................... 12 Drover 2011....................................... 10
Waitzberg 2006................................. 13 Marik 2010......................................... 11
Gianotti 2002..................................... 16 Takeuchi 2007................................... 12
Braga 2002 (Arch Surg)................... 17 Waitzberg 2006................................. 13
Braga 1999 (Arch Surg)................... 19 Gianotti 2002..................................... 16
Braga 2002 (Arch Surg)......................1
Upper GI Braga 2002 (Surg)............................. 17
Marano 2013 ........................................9 Senkal 1999....................................... 18
Suzuki 2010....................................... 10 Snyderman 1999.............................. 19
Takeuchi 2007................................... 12 Braga 1999 (Arch Surg)................... 19
Farreras 2005................................... 14
Senkal 2005....................................... 16 Trauma
Senkal 1999....................................... 18 Farber 2005.......................................14
Braga 1999 (JPEN)............................ 20 Weimann 1998..................................20
Braga 1998........................................ 21 Chendrasekhar 1997.......................22
Senkal 1997....................................... 21 Bower 1995........................................24
Gianotti 1997..................................... 22
Kemen 1995....................................... 24
Daly 1995........................................... 23

Lower GI
Braga 2002 (Surg)............................. 17

Head and Neck


Felekis 2010...................................... 11
Snyderman 1999.............................. 19

3
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

5
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

44% 40% 47% 54% 47%

Anastomotic Wound Pneumonia Abdominal Urinary tract


leaks infections abscesses infections

(p=0.004) (p=0.005) (p<0.0001) (p=0.001) (p=0.0011)

6
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

$1,000 $961

$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.

7
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 COST POTENTIAL SAVINGS†

Formula Nosocomial Estimated Cost of ICU 1 100


POPULATION stay and
Cost* Pneumonia (%) ICU Cost** Patient Patients
formula

Trauma and burn


patients receiving $686 12 $79,200 $79,886 $11,374 $1,137,400
IMPACT® 1.5 formula

Trauma and burn


patients receiving $60 52 $91,200 $91,260
Promote®◊ formula

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, Mauskopf JA, Candrilli SD,
Grassia M, Petrillo M et al. Chevrou-Séverac H, Ochoa JB.
Ann Surg Oncol 2013; July 10 2013 DOI: Immunonutrition for patients
10.1245/s1043401330881. undergoing elective surgery for
Randomized controlled trial done to gastrointestinal cancer: Impact on
investigate the effect of early post-op hospital costs. WJSO 2012:10:136;
immunonutrition on outcomes in gastric doi:10.1186 1477-7819-10-136.
cancer patients undergoing gastrectomy
(n=109). Post-operative feedings were This study was completed to create a health
administered 6 hours post-op via jejunal economic model to determine the impact on
tube and continued until post-op day 7. hospital costs of immunonutrition (IMPACT®
Formulas were isonitrogenous and formulas) used in patients having major
isocaloric, however the study group tube elective surgery for gastrointestinal (GI)
feeding contained supplemental L-arginine, cancer). United States (US) hospital costs
n-3 fatty acids and nucleotides and the were taken from the Healthcare Cost and
control group received standard formula. Utilization Project’s Nationwide Inpatient
Infectious complications in the study group Sample (HCUP-NIP) database. These
were significantly lower than in the control costs were used to estimate the effect of
group (7.4% vs. 20%, p<0.05), as was the immunonutrition on hospital costs using
rate of anastomotic leak (3.7% vs 7.3%, reductions in length of stay (LOS) and risk
p<0.05). LOS for the intervention group was of complications from a meta-analysis of 14
3.2 days less than for the control group RCTs studying use of IMPACT® formulas in
(p=0.029). 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.

9
IMPACT® Clinical Study Reference

Drover JW, Dhaliwal R, Weitzel L, Suzuki D, Furukawa K, Kimura F,


Wischmeyer PE, Ochoa JB, Heyland DK. Shimizu H, Yoshidome H, Ohtsuka M,
Perioperative use of arginine– Kato A, Yoshitomi H, Miyazaki M.
supplemented diets: A systematic Effects of perioperative
review of the evidence. J Am Coll immunonutrition on cell-mediated
Surg 2011;212(3): 385-399. immunity, T helper type 1 (Th1)/Th2
differentiation, and Th17 response
Thirty-five randomized controlled trials after pancreaticoduodenectomy.
(n=3,438) of major elective surgical patients
Surgery 2010;148:573-581.
are reviewed in this meta-analysis to
compare outcomes with enteral nutrition In this prospective randomized study, 30
supplemented with arginine vs. standard pancreaticoduodenectomy patients were
formula. Twenty-five studies involved GI divided into three groups: A perioperative
surgery patients and the other 10 studies group received ORAL IMPACT®* containing
represented other elective surgical supplementary arginine, omega-3 fatty
procedures. Twenty-three of 35 studies acids and nucleotides for 5 days before
utilized IMPACT® formula administered surgery and at least 7 days of enteral
pre-, peri- or post-surgically. Although, no infusion after surgery. Another group
difference in mortality was noted, arginine- received the same immunonutrition
supplemented diets were associated with post-operatively only, and a third group
a 41% reduction in infectious complications was given total parenteral nutrition (TPN)
(p<0.00001 and a 2.38 day reduction in postoperatively.
length of stay (LOS) (p<0.00001), on average.
Tests for heterogeneity were not significant The primary endpoint was immune
in regards to reduced overall infectious responses and the perioperative
complications (p=0.11), but were significant immunonutrition group was found to have
in regards to reduced LOS (p<0.00001). significantly higher levels of lymphocyte
Sub-analyses found greater reductions in proliferation, natural killer cell activity,
infectious complications and LOS associated mRNA levels of T-bet, interferon-γ, related
with perioperative vs. pre- or post operative orphan receptor, and interleukin-17F.
use (p=0.03, p=0.001), and more benefit A secondary endpoint was the rate of
associated with IMPACT® formula vs. other infectious complications. The perioperative
immunonutrition formulas (p<0.0001). immunonutrition group was found to have
Authors support implementing use of a significantly lower rate of infectious
perioperative nutritional therapy containing complications than either of the two other
arginine and omega-3 fatty acids to support groups (10% vs 60% vs 60%, p<0.05). Of
considerable reduction in morbidity for additional interest, there was a statistically
high-risk elective surgery patients and a significant difference in SIRS days between
substantial reduction in costs for the the perioperative group and the TPN group
health care system. (2.4 vs 3.6 days, p<0.05).
Investigators concluded that
perioperative immunonutrition reduced
*IMPACT ADVANCED RECOVERY® Advanced Nutrition immunosuppression induced by a major
Drink is the oral form of IMPACT® formula offered in stressful surgical procedure.
the United States.

10
Marik P, Zaloga G. Felekis D, Eleftheriadou A, Papadakos
Immunonutrition in high-risk G, Bosinakou I, Ferekidou E, Kandiloros
surgical patients: A systematic D, Katsaragakis S et al.
review and analysis of the Effect of Perioperative Immuno-
literature. JPEN. 2010; 34(4): Enhanced Enteral Nutrition on
378-386. Inflammatory Response, Nutritional
Status, and Outcomes in Head and
This meta-analysis reviewed 21 prospective Neck Cancer Patients Undergoing
controlled trials (n=1,918) to evaluate the
Major Surgery. Nutr and Cancer
effect of immune-modulating nutrition
vs. control formula on clinical outcomes 2010; 62(8): 1105-1112.
of high-risk elective surgery patients.
A randomized, double-blinded, prospective
Sixteen of 21 studies utilized IMPACT®
study done to evaluate that immunonutrition
formula pre-, peri- or post-surgically
supplemented with arginine, RNA and n-3
with GI, Head & Neck or Cardiac surgery
fatty acids improves outcomes in head
patients. Studies were stratified by formula
and neck cancer patients with squamous
type and timing of initiation. Although
cell carcinoma undergoing surgery.
no difference was noted in mortality
Formulas were isocaloric and the study
across groups, intention-to-treat analyses
group received ORAL IMPACT® 5 days
showed immunonutrition associated with
prior to surgery and IMPACT® tube feeding
a 38%-61% reduction in hospital acquired
post-surgery. The control group received
infections (p<0.0001), a 9%-60% reduction
no supplemental nutrition before surgery
in wound complications (p=0.02), and on
and standard tube feeding post-surgery.
average, a 3 day reduction in hospital LOS
Major complications included pneumonia,
(p<0.001). Benefits were found to be similar
UTI, fistula and wound infection, and were
for peri- and postoperative use; however,
followed until discharge (median = 12
formulas containing both arginine and fish
days). Rate of major complications was
oil (as opposed to a single immunonutrient)
significantly lower in the immunonutrition
were required, presumably due to
vs. the standard group (5% vs. 25%; p<0.05).
synergistic effect. As the majority of studies
Perioperative IMPACT® in head and neck
utilized a product containing arginine,
cancer surgery patients may influence post-
fish oil, nucleotides and antioxidants, it is
operative outcomes by reducing infections
unclear if benefits can be extrapolated to
and wound complications.
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.

11
IMPACT® Clinical Study Reference

Takeuchi H, Ikeuchi S, Kawaguchi Y, Bozzetti F, Giannotti L, Braga M,


Kitagawa Y, Isobe Y, Kubochi K, Kitajima Di Carlo V, Mariani L.
Matsumoto S. Postoperative complications in
Clinical significance of gastrointestinal cancer patients: the
perioperative immunonutrition for joint role of the nutritional status
patients with esophageal cancer. and the nutritional support. Clin
World J Surg. 2007; 31: 2160-2167. Nutr. 2007; 26(6): 698-709.

Retrospective comparison of 40 patients A meta-analysis where 1,410 gastro-


undergoing elective esophagectomy for intestinal cancer surgery patients received
esophageal squamous cell carcinoma. either standard intravenous fluid, total
The 3 groups were randomized to: Group parenteral nutrition, standard enteral
A control (n=20) with a standard tube nutrition or immune-modulating enteral
feeding for 14 days postoperatively, Group nutrition (IMPACT® formula). Postoperative
B, (n=6) IMPACT® tube feeding for 14 days complications were recorded, as well as,
postoperatively or Group C (n=14) 5 days morbidity. Also noted were correlating
of preoperative IMPACT® and 14 days of factors of pancreatic surgery, advanced
postoperative IMPACT® tube feeding. Results age, weight loss, low serum albumin and
demonstrate that compared to the control nutrition support. Patients who received
group (A), the perioperative IMPACT® group enteral nutrition (specifically immune-
(C) had, on average, a significantly lower modulating nutrition) had significantly
incidence of incisional wound infection (0% reduced postoperative morbidity (p<0.001).
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.”

12
Tepaske R, Velthuis HT, Oudemans-Van Waitzberg DL, Saito H, Plank LD,
Straaten HM, Bossuyt PMM, Schultz JM, Jamieson GG, Jagannath P,
Eijsman L, Vroom M. Tsann-Long H, Mijares JM, Bihari D.
Glycine does not add to the Postsurgical infections are reduced
beneficial effects of perioperative with specialized nutrition support.
oral immune-enhancing nutrition World J Surg. 2006; 30:1592-1604.
supplements in high-risk cardiac
surgery patients. JPEN. 2007; 31(3): This article reviewed 17 studies (n=2,305)
173-180. where IMPACT® formula was used before
and/or after major elective surgery and
A prospective, randomized study to the clinical outcomes reported were
measure outcomes of the addition of included in this meta-analysis. Ten studies
glycine to an oral immune-enhancing compared preoperative or perioperative
nutrition supplement (ORAL IMPACT®+ IMPACT® formula provision vs. control and
glycine) as compared to a standard oral 7 studies looked at postoperative nutrition.
immune-enhancing nutrition supplement Fourteen studies examined IMPACT®
(ORAL IMPACT®) and a control group formula used with gastrointestinal (GI)
receiving standard nutrition. Each cancer surgeries. IMPACT® formula
nutrition supplement was administered supplementation was associated with
for a minimum of 5 preoperative days. significant reductions in postoperative
Patients (n=70) were 70 years of age or infectious complications (39-61%) and
older and were planned for mitral valve a significant decrease in hospital stay
surgery. Outcomes of morbidity, organ by an average of 2 days. Anastomotic
function and postoperative recovery leaks were found to be less prevalent
were analyzed. In both groups receiving in gastrointestinal surgery patients who
the ORAL IMPACT® formula, infectious received IMPACT® formula perioperatively.
morbidity was decreased (17%/23% vs. Overall, 500 mL-1 L of IMPACT® formula
50%) as compared to the control (p=0.02). 5-7 days preoperatively contributed to
Conclusions of the study were that use improved outcomes in GI, cardiac, and
of preoperative ORAL IMPACT® formula head/neck elective surgery patients.
reduces the rate of infectious morbidity
Cited by:
and results in more hemodynamic stability.
The addition of glycine did not result in any CRITICAL CARE NUTRITION
additional benefit. GUIDELINES1

13
IMPACT® Clinical Study Reference

Farber MS, Moses K, Korn M. Farreras N, Artigas V, Cardona D,


Reducing costs and patient Rius X, Trias M, Gonzalez JA.
morbidity in the enterally fed Effect of early postoperative
intensive care unit patient. JPEN. enteral immunonutrition on wound
2005; 29(1 Suppl): S62-S69. management in patients undergoing
surgery for gastric cancer. Clin Nutr.
Clinical trial of predominantly trauma 2005; 24: 55-65.
patients prospectively identified to be
enterally fed with IMPACT® 1.5 formula A prospective, randomized study to
and compared with a historical cohort determine the effect of early postoperative
of similarily identified patients receiving enteral immunonutrition (IMPACT®
standard nutrition. No differences in formula) on wound management
mean calories or protein received, days to in patients undergoing surgery for
feeding initiation or days to goal rate were gastric cancer. Sixty-six patients were
observed between groups. randomized to receive IMPACT® formula
A reduction in nosocomial pneumonia or an isocaloric, isonitrogenous control
(12% in IMPACT® 1.5 formula patients vs. formula. The wound management process
52% in those on standard feeding, p=0.01) was analyzed, as well as, development
was shown. Although not statistically of surgical wound management
significant, the patients receiving IMPACT® complications in sixty patients. Those
1.5 formula required 3 fewer days of patients who received IMPACT® formula
ventilator support and had a 5 day shorter had significantly increased hydroxyproline
ICU stay, on average, than those receiving levels (p=0.0018) and decreased incidence
standard feeding. of wound management complications
(p=0.005). Authors concluded that
Using previously published costs of ICU early provision of IMPACT® formula
care, cost of formulas and the difference postoperatively improves wound
in length of ICU stay, an economic analysis management substrates and decreases
identified a savings of $11,374 for each wound complications.
patient receiving IMPACT® 1.5 formula.
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, Strickland A, Brogan A, Krauss J,
Schmid A, Nespoli L, Di Carlo V. Martindale R, Cresci G.
Hospital resources consumed Is the use of specialized nutritional
for surgical morbidity: effects of formulations a cost-effective
preoperative arginine and n-3 fatty strategy? A national database
acid supplementation on costs. evaluation. JPEN. 2005; 29
Nutrition. 2005; 21: 1078-1086. (1 Suppl): S81-91.
This article uses results from a This article uses a current review on
prospective, randomized, placebo- the literature of published outcomes
controlled study22 of preoperative of studies using clinical outcomes with
immunonutrition supplementation immune-modulating diets to determine
(IMPACT® formula) to calculate hospital the potential economic benefit associated
costs for post-operative complications, with the use of specialized nutritional
and analyze for the possibility of formulations in elective surgical trauma
cost savings in upper and lower GI and medical patients. Data was obtained
cancer patients. A blinded cost-analysis from a large national database of 126
for hospital length of stay (LOS) and member hospitals and over 1 million
in-patient resource utilization for patients. Data was collected on patient
infectious and non-infectious type, subservice, complication, mean
complications were referenced to the length of stay, mean cost and incremental
National List of Sanitary Costs, Italian cost per complication (if experienced). For
Ministry of Health. Mean cost the medical patient population, specialized
of treating infectious complications nutritional formulations found a 51%
was significantly lower in the IMPACT® decrease in infectious complications
formula vs. conventional group and decreased length of stay of 9.7
(p=0.05). Because patients receiving days resulting in a net cost savings of
preoperative IMPACT® formula had $2,066 per patient. Net cost savings for
significantly fewer infectious surgical and trauma patients was $688
complications and significantly shorter and $308 per patient respectively. This
LOS, total cost per patient was €5668 data demonstrated that specialized
vs. €7092 for conventional treatment. formulations are a cost-effective way to
Preoperative immunonutrition with improve clinical outcomes while reducing
IMPACT® formula resulted in a net resource consumption.
hospital savings per patient of €1424, Cited by:
as compared to conventional care.
GUIDELINES ON ENTERAL
Cited by:
NUTRITION: SURGERY 2
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2

15
IMPACT® Clinical Study Reference

Senkal M, Haaker R, Linseisen J, Gianotti L, Braga M, Nespoli L,


Wolfram G, Homann HH, Stehle P. Radaelli G, Beneduce A, Di Carlo V.
Preoperative oral supplementation Randomized controlled trial of
with long-chain omega-3 fatty acids preoperative oral supplementation
beneficially alters phospholipid with a specialized diet in patients
fatty acid patterns in liver, gut with gastrointestinal cancer.
mucosa, and tumor tissue. JPEN. Gastroenterology. 2002; 122:
2005; 29(4): 236-240. 1763-1770.
In this study, 40 patients undergoing A prospective, randomized study of 305
gastrointestinal surgery were well nourished patients with cancer of
prospectively randomized to receive ORAL the gastrointestinal tract comparing
IMPACT® formula 5 days preoperatively or either ORAL IMPACT® formula 5 days
an isocaloric diet, in addition to their oral preoperatively, ORAL IMPACT® formula 5
hospital diet. The supplemented IMPACT® days preoperatively plus, IMPACT® formula
formula provided 3.3 g of polyunsaturated jejunally postoperatively, or no nutrition
eicosapentaenoic acid (EPA) and before or after surgery. A significantly
docosahexaenoic acid (DHA). During decreased infection rate (p=0.006 p=0.02)
surgery, samples of liver, gut mucosa and and length of hospital stay (p=0.008
tumor were obtained and analyzed for p=0.03) occurred in both IMPACT® formula
EPA/DHA content. Compared to the control treatment groups. Thus, using IMPACT®
group, IMPACT® formula supplemented formula preoperatively was as effective
patients had increased levels of EPA and as perioperative immunonutrition in
DHA in liver tissue, gut mucosa and tumor improving outcomes in well nourished
tissue (p<0.05), which indicates a possible patients and is superior to conventional
effect on post-operative inflammatory treatment.
response after abdominal surgery. Cited by:
GUIDELINES ON NUTRITIONAL
SUPPORT THERAPY DURING ADULT
ANTI-CANCER TREATMENT3

16
Braga M, Gianotti L, Nespoli L, Braga M, Gianotti L, Vignali A,
Radaelli G, Di Carlo V. Di Carlo V.
Nutritional approach in Preoperative oral arginine and n-3
malnourished surgical patients. fatty acid supplementation improves
Arch Surg. 2002; 137: 174-180. the immunometabolic host response
and outcome after colorectal
Prospective, randomized, controlled trial resection for cancer. Surgery. 2002;
of 150 patients requiring major elective 132: 805-814.
surgery of the GI tract for malignancy. All
enrolled patients were malnourished with A prospective, randomized, controlled trial
≤10% body mass loss and randomized of 200 patients with colorectal neoplasm
to 3 groups. Group 1 (Perioperative requiring surgical resection. The 4 groups
Treatment Group) was supplemented were randomized to: Group 1, perioperative
preoperatively with 1 liter per day ORAL supplementation with ORAL IMPACT®
IMPACT® formula for 7 consecutive days formula for 5 days preoperatively +
and tube fed with IMPACT® formula post- ORAL IMPACT® or IMPACT® tube feeding
operatively. Group 2 (Preoperative Group) postoperatively; Group 2, preoperative
was supplemented with 1 liter per day of ORAL IMPACT® for 5 days; Group 3 (control),
ORAL IMPACT® formula for 7 consecutive iosnitrogenous/caloric oral supplement
days preoperatively and standard formula preoperatively for 5 days; and Group 4; no
post-op. Group 3 (Control Group) received supplementation before or after surgery
standard tube feeding post-operatively. All (conventional therapy). Immune response
diets were isocaloric and isonitrogenous. (p<0.05), gut oxygenation (p<0.01) and
Results reveal that the perioperative microperfusion (p<0.02) were found to
treatment group experienced decreased be significantly better for Groups 1 and
complications (p=0.02), and both treatment 2. Overall, Groups 1 and 2 fed IMPACT®
groups had a reduced length of hospital formula both perioperatively and
stay as compared to the control group preoperatively had outcomes of decreased
(p=0.01, p=0.001). infectious complications (p<0.02 p<0.04);
Cited by: reductions in antibiotic therapy days
(p<0.005, p<0.004) and length of hospital
GUIDELINES ON NUTRITIONAL stay (p<0.0005) as compared to the control
SUPPORT THERAPY DURING ADULT
ANTI-CANCER TREATMENT3 and conventional therapy groups.
Cited by:
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2 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 Senkal M, Zumtobel V, Bauer KH,


Straaten HM, Heisterkamp SH, Van Deventer Marpe B, Wolfram G, et al.
SJH, Ince C, Eÿsman León, Jozef Kesecioglu. Outcome and cost-effectiveness
Effect of preoperative oral immune- of perioperative enteral
enhancing nutritional supplement immunonutrition in patients
on patients at high risk of infection undergoing elective upper
after cardiac surgery: a randomized gastrointestinal tract surgery:
placebo-controlled trial. Lancet. a prospective randomized trial.
2001; 358(9283): 696-701. Archives of Surgery. 1999; 134:
1309-1316.
A prospective, randomized, double-blind,
placebo-controlled study of 50 patients A prospective, randomized, double-blind
scheduled for coronary artery bypass. The trial of 154 patients undergoing surgery
preoperative treatment group consumed 1 for cancer of the upper gastrointestinal
liter of an oral immune-enhancing nutritional tract. In the study, patients were
supplement (ORAL IMPACT®) for at least randomized to receive ORAL IMPACT®
5 days prior to surgery. The control group formula or an isonitrogenous, isocaloric
received an isocaloric, isonitrogenous amount
supplement for 5 days prior to surgery.
of a control nutritional supplement. After
Patients in both groups consumed 1 liter
surgery, patients requiring tube feeding
received either an immune-enhancing or an each day by mouth. Following surgery,
isocaloric, isonitrogenous control formula patients who consumed the ORAL IMPACT®
until extubation. Study group patients had formula were started on IMPACT® formula
significantly higher preoperative expression and patients who consumed the standard
of HLA-DR epitopes on monocytes (109%) control were started on a standard tube
than those in the control group compared feeding formula. All patients were fed via
with baseline (p=0.01). Post-op concentration needle-catheter jejunostomy, initiated 12
of IL-6 was significantly lower in the study hours after surgery and continued on the
group than in the control group (p=0.032). prescribed diet for at least 5 days after
Patients receiving ORAL IMPACT® had a surgery. Patients who received IMPACT®
significant reduction in total infectious formula had significantly fewer infections
complications (p=0.013), and had significantly occurring after postoperative day 3
fewer cases of pneumonia (p=0.047). (p=0.04), and fewer complications overall
Investigators concluded preoperative (48% reduction, p=0.05) than patients who
intake of an immune-enhancing nutritional received the standard diet.
supplement for 5-10 days enhanced the
outcome of high-risk cardiac patients Cited by:
undergoing surgery, improved preoperative GUIDELINES ON ENTERAL
host defense and reduced the number of NUTRITION: SURGERY 2
postoperative infections.
Cited by:

GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2

18
Snyderman CH, Kachman K, Braga M, Gianotti L, Vignali A,
Molseed L, et al. Radaelli G, Mari G, Di Carlo V.
Reduced postoperative infections Perioperative immunonutrition
with an immune-enhancing in patients undergoing cancer
nutritional supplement. surgery. Results of a randomized
Laryngoscope. 1999; 109: 915-921. double-blind phase 3 trial. Archives
of Surgery. 1999; 134: 428-433.
A prospective, randomized, double-blind,
study of 136 head and neck cancer One hundred and seventy-one patients
patients who received IMPACT® formulas who required major surgery for gastric,
pre- and postoperatively or postoperatively pancreatic or colorectal cancer were
alone versus a standard formula pre- and randomized in a double-blind fashion to
post-operatively or postoperatively alone. receive either a formula supplemented
IMPACT® formula-fed patients (pre- and with arginine, omega-3 fatty acids and
postoperatively and post-operatively dietary nucleotides (IMPACT® formula,
only) had nearly half as many infections n=102), or an isocaloric, isonitrogenous
compared to patients in the standard control (n=104). For seven days prior to
formula groups (p=0.02 p=0.04). There was surgery, patients consumed 1 liter/day
no difference in length of stay; however, of either the control or the supplemented
there was a trend toward shorter length formula. After surgery, patients received
of ICU stay and potential cost savings for the same preoperative formulas via jejunal
patients fed IMPACT® formula. feeding and continued on the formula for
Cited by: 7 days. Patients who received the IMPACT®
formula perioperatively had significant
GUIDELINES ON ENTERAL reduction in postoperative infection (9/85
NUTRITION: SURGERY 2 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, Weimann A, Bastian L, Bischoff WE,


Vignali A, Gentilini O, Zerbi A, Grotz M, Hansel M, Lotz J,
Di Carlo V. Trautwein C, Tusch G, Shlitt HJ, Regel G.
Artificial nutrition after major Influence of arginine, omega-3 fatty
pancreatic resection: results of a acids and nucleotide-supplemented
prospective, randomized clinical enteral support on systemic
Trial. JPEN. 1999; 23(1): S2. inflammatory response syndrome
and multiple organ failure in patients
An extension of earlier, prospective, after severe trauma. Nutrition. 1998;
randomized trials of patients undergoing 14(2): 165-172.
surgery for pancreatic cancer. In
the study, 182 patients undergoing In this prospective, randomized, double-
pancreaticoduodenectomy were blind trial, 32 patients with multiple severe
randomized to receive IMPACT® formula, injuries were randomized to receive
standard enteral feeding or total IMPACT® formula or an isonitrogenous,
parenteral nutrition (TPN). Postoperative isocaloric control. Patients also received
nutrition was initiated within 6 hours after TPN initially. During the course of the
surgery. Each of the groups received the study, patients who received IMPACT®
same amount of calories and nitrogen per formula had fewer numbers of days with
day. Despite the invasive surgery, early SIRS (8.3 days/patient versus 13.3 days/
postoperative enteral feeding was well patient on the control). During the high-risk
tolerated and did not increase the rate of period of 8-14 days after trauma, patients
complications. Compared to the TPN group, on IMPACT® formula had less than half
there was a 36% reduction in number of the incidence of SIRS (3.0 days with SIRS/
patients with infectious complications and patient versus 6.2 days with SIRS/patient
the hospital stay was 4 days shorter for on the control). Patients who received
patients fed IMPACT® formula (p<0.05). IMPACT® formula also had a significant
Both findings were statistically significant. reduction in MOF score during this critical
Patients with pancreatic resection who period. High-risk patients who receive
receive IMPACT® formula as part of an IMPACT® formula are less likely to develop
early enteral nutrition program have fewer SIRS or MOF than patients who receive
infection-related complications and a standard enteral feeding following
shorter length of hospitalization. severe trauma.
Cited by:

CRITICAL CARE NUTRITION


GUIDELINES1

GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2

20
Braga M, Gianotti, Vignali A, Senkal M, Mumme A, Eickhoff U,
Cestari A, Bisagni P, Di Carlo V. Geier B, Spath G, Wulfert D,
Artificial nutrition after major Joosten U, Frei A, Kemen M.
abdominal surgery: IMPACT of Early postoperative
route of administration and immunonutrition: clinical outcome
composition of the diet. Crit Care and cost-benefit analysis in surgical
Med. 1998; 26(1): 24-30. patients. Crit Care Med. 1997; 25(9):
1489-1496.
A prospective, randomized trial of 166
patients undergoing surgery for gastric A prospective, randomized, multi-center
or pancreatic cancer randomized to study of 164 patients with upper GI
receive IMPACT® formula, standard enteral cancer who underwent major surgery and
formula or total parenteral nutrition (TPN). received early postoperative feeding with
The nutritional regimens were isocaloric IMPACT® formula or an isonitrogenous,
and isonitrogenous. Patients receiving isocaloric control formula without
IMPACT® formula had the fewest number supplemental arginine, dietary nucleotides
of postoperative infections (p<0.05) and or fish oil. Patients who received IMPACT®
a shorter hospital stay compared to the formula had 53% fewer infectious and
standard formula or TPN. In sub-groups wound complications occurring after day
of malnourished patients and patients five postoperatively (p<0.05). The average
who received homologous transfusions, cost for treating complications was 32%
administration of IMPACT® formula lower for the IMPACT® formula group.
compared more favorably than TPN at
Cited by:
reducing severity of infection and length
of hospital stay (p<0.05). This study GUIDELINES ON ENTERAL
included data from a 1995 study published NUTRITION: SURGERY 2
in Infusionsther Transfusionmed with an
additional 89 patients.
Cited by:
GUIDELINES ON NUTRITIONAL
SUPPORT THERAPY DURING ADULT
ANTI-CANCER TREATMENT3

21
IMPACT® Clinical Study Reference

Gianotti L, Braga M, Vignali A, Balzano Chendrasekhar A, Fagerli JC,


G, Zerbi A, Bisagni P, Di Carlo V. Prabhakar G, Landreth K,
Effect of route of delivery and Timberlake GA.
formulation of postoperative Evaluation of an enhanced diet
nutritional support in patients in patients with severe closed head
undergoing major operations for injury. Crit Care Med. 1997; 25(1): A80.
Malignant Neoplasms. Arch Surg.
1997; 132: 1222-1230. A prospective, randomized, dual center
trial of 20 patients with severe closed
Prospective, randomized, controlled trial head injury who received IMPACT® formula
of 260 post-upper GI surgical cancer or a standard enteral formula. Following
patients who received standard enteral one week of the two different nutrition
feeding, IMPACT® formula or TPN. Patients support regimens, IMPACT® formula-fed
who received IMPACT® formula had a patients had significant improvements
significantly lower sepsis score than in various immune parameters (p<0.05).
patients on either standard enteral or TPN Patients who received IMPACT® formula
(p<0.01). Mean hospital LOS was shorter had a significant reduction in infection
for patients in the IMPACT® formula group rate compared to patients who received
compared to either of the other groups the standard formula (9.1% versus 100%,
(16.1 days for the IMPACT® formula group p<0.0001). The authors concluded IMPACT®
versus 19.2 days for the standard enteral formula improves antigen processing to
and 21.6 days for TPN, p=0.004 p=0.01). promote immune function and thereby
IMPACT® formula favorably affects host reduce risk of infection in severe closed
immune response resulting in infectious head injury patients.
complications that are less severe
compared to infectious complications that
occur in patients who receive standard
enteral or TPN.
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, Daly JM, Weintraub FN, Shou J,
van Deventer L, Ince C, et al. Rosato EF, Lucia M.
Perioperative immunonutrition Enteral nutrition during
in “high risk” cardiac surgery multimodality therapy in upper
patients improves immunological gastrointestinal cancer patients.
parameters and clinical outcome. Ann Surg. 1995; 221(4): 327-338.
Presented at the european society
of surgical infection meeting, Oslo, A prospective, randomized, double-blind
June 1997. study of 60 patients with upper GI cancer
who underwent abdominal surgery and
A prospective, randomized, placebo received early postoperative feeding with
controlled double-blind study of 50 either IMPACT® formula or TraumaCal®
patients undergoing heart surgery. formula*. Patients fed IMPACT® formula
Patients consumed ORAL IMPACT® had 77% fewer infectious and wound
formula or an isocaloric control complications (p<0.005) and had a six day
formula for 5 – 10 days before shorter mean length of hospitalization
surgery. Patients who received ORAL than patients in the TraumaCal® group
IMPACT® formula had significantly (p=0.02).
fewer lower respiratory tract infections Cited by:
(0 of 22 vs. 5 of 23, p=0.022) and 65%
reduction in total infections compared GUIDELINES ON NUTRITIONAL
SUPPORT THERAPY DURING ADULT
to the group that received the ANTI-CANCER TREATMENT3
control formula (p=0.009).
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, Bower RH, Cerra FB, Bershadsky B,


Mumme A, Dauphin AK, Baier J, Licari JJ, Hoyt DB, Jensen GL,
Windeler J, Neumann H, Van Buren CT, Rothkopf MM, Daly JM,
Zumtobel V. Adelsgerg BR.
Early postoperative enteral Early administration of a formula
nutrition with arginine, omega-3 (IMPACT®) supplemented with
fatty acids and ribonucleic acid- arginine, nucleotides, and fish oil in
supplemented diet versus placebo intensive care unit patients: results
in cancer patients: an immunologic of a multicenter, prospective,
evaluation of impact. Crit Care Med. randomized, clinical trial. Crit Care
1995; 23(4): 652-659. Med. 1995; 23(3): 436-449.
Randomized clinical trial of 42 patients A prospective, randomized, double-blind
with upper gastrointestinal malignancies multi-center study of 326 critically ill,
who received either IMPACT® formula or ICU tube-fed patients (84% trauma, 12%
an isonitrogenous and isocaloric control MICU, 4% SICU) who received either
formula postoperatively to evaluate the IMPACT® formula or Osmolite®◊ HN.
effects of providing early postoperative Patients fed IMPACT® formula who met all
feeding on the immune system. Enteral requirements for study completion had
feeding of IMPACT® formula significantly a 28% reduction (eight days) in length of
improved immune function as measured hospital stay, as compared to the control
by Immunoglobin M (IgM) (p<0.05) and group (p<0.05). IMPACT® formula-fed
Immunoglobin G (IgG) (p<0.05), as well patients who were septic had a ten day
as, significantly higher T-lymphocyte shorter hospital stay (p<0.05) and a 60%
concentrations (p<0.05) compared to lower incidence of new infections
standard enteral feeding. compared to septic patients fed
Cited by: Osmolite® HN (p<0.01).
Cited by:
GUIDELINES ON ENTERAL
NUTRITION: SURGERY 2 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.

References:
1. McClave SA et al. Guidelines for the provision and assessment of nutrition support therapy in the
adult critically ill patient: Society of Critical Care Medicine and American Society for Parenteral
and Enteral Nutrition. JPEN. 2009; 33(3): 277-316.
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
anticancer treatment and in hematopoietic cell transplantation. JPEN. 2009; 33(5): 472-500.
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
Care Clin 2010; 26(3): 491-500.
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
and Metab Care. 2001; 4(1): 57-64.
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.
www.NestleHealthScience.us
1-800-422-ASK2 (2752)
Unless otherwise noted, all trademarks are
owned by Société des Produits Nestlé S.A.,
Vevey, Switzerland. ©2014 Nestlé.
IPCT-10366 - 0714