NUTRITION IN TRAUMA AND GUT SPECIFIC RESUSCITATION

Warko Karnadihardja 2011

RECENT ISSUES

The gut is one of the first organs exposed to shock and the last to be resuscitated in circulatory failure Impairment of the gut plays a central roles in the pathogenesis of infection, sepsis and even MODS
Heyland, Dhaliwal & Suchner. 2005

TRAUMA CARE

Trauma is a multi system disease and as such, benefits from almost any advance in medical science We can provide better management for trauma victims, as we learn more about physiology and biochemistry of various organ systems

MAJOR TRAUMA
Associated with Severe hemorrhage Low-flow conditions Tissue destruction and debris Gut bacterial translocation

Leading to: Massive dyshomeostasis of immunoinflammatory response

THE RESPONSE
Starts within minutes following the traumatic impact Characterized by the immediate activation of monocytes and granulocytes Leukocytic activation leads to an increased synthesis and release of inflammatory and antiinflammatory mediators

Blood cytokine level during the first 24 hours following trauma and hemorrhagic shock

Faist E, Angele MK. In: Baue AE, et al. MOF. Springer 2000.

MASSIVE DYSHOMEOTASIS INDUCED BY MAYOR TRAUMA

Faist E, Angele M & Wichmann M, Trauma 5th edit. 2004

Release of Mediators
First Hit
POST INJURY

Second Hit Lung

Systemic Activation of Inflammatory Cells Primed Inflammatory Cells Primed WBCs Primed WBCs Primed WBCs
SYSTEMIC RELEASE OF TOXIC MEDIATORS

INITIAL INSULT Local Activation of Inflammatory Cells Systemic Release of Cytokines

Liver
Gut Other Organs

LOCAL TISSUE RESPONSE

Demling et al. Surg Clin North Am 74(3); 1994.

GENERALIZED TISSUE INJURY

Postinjury Hypermetabolism:

The Stage for MOF

Macroendocrine

O2 Deprivation/Injury
Tissue Necrosis Inflammation Sensory Perception

Evans & Park. Blackwell 1997.

Pituitary
Hypothalamus Adrenal
Microendocrine
Catechols Cortisol Glucagon

Injury Stress Response

IL1 TNF TXA2 PGE2 LTB4 PAF O2OH Proteases

Neutrophil

Gut Barrier

Bacteria/Endotoxin Translocation

Macrophage Endothelium

EARLY ENTERAL VS PARENTERAL NUTRITION IN MAJOR TRAUMA (ATI 15-40)

( 11 PRCT, 2 META ANALYSIS, 1 MODEL)

Reduced septic morbidity Increase lymphocytic count Increase anastomotic strength in peritonitis model Support wound healing

Moore EE, Jones TN : J Trauma 1986 Moore FA, Moore EE, Jones TN: J Trauma. 1989 Kudsk KA, Croce MA, Fabian TC et al : Ann Surg 1992 Moore FA, Feliciano DV, Andrassy RJ et al : Ann Surg. 1992 Khalili TM, Navarro RA, Meddleton J et al : An J Surg. 2001

Bowel rest/NPO Malnutrition Stress

Mucosal cell turnover

Cardiac failure Shock Vasopressors

Mesenteric blood flow

Achlorhydria Antacids H2 Antagonists

Gastric pH

Intestinal obstruction, Ileus, Blind loop, Opiates, Ca channel blockers Motility

Mucosal atrophy Mucosal sloughing

Intestinal bacterial overgrowth

Breakdown mucosal barrier

Translocation of bacteria and toxins

Schematic Representation of the Effect of Critical Illness on Gastrointestinal Function

Rolandelli RH & Koruda MJ : Surg. Crit. Care, 1994

THE ROLE OF GUT IN DYSFUNCTION INFLAMMATION TO MOF

Gut: The Starter for MOF Liver: The Motor for MOF
Liver

Shock
Gut Bacteria Endotoxin

Kupffer Cell

PGE2 = IL1 =

Immune Stress

C3a,C5a

TNF

Injured Tissue

Delayed Enteral Feeding

O2

ATN ARDS

Enteral Nutrition
Evans & Park. Blackwell 1997.

HOW GUT DYSFUNCTION HAPPENS IN MAJOR TRAUMA ?

Might as complications of :

Abdominal compartment syndrome (ACS) when intra-abdominal pressure (IAP) exceeds 25 cm H2O (Urinary bladder pressure) Gastroparesis Impaired mucosal perfusion : shock results in disproportionate splanchnic vasoconstriction Impaired intestinal transit: shock, bowel manipulation and sepsis demonstrate impaired small bowel transit Impaired gut absorptive capacity of small bowel: absorption of glucose and amino acid is depressed after trauma and sepsis.
Moore FA & Weisbroodt NW, 2003

Stress Stratification by Metabolic Criteria

Stress Level Urine Nitrogen ( g/day) Plasma Lactate (mM/L) Plasma Glucose (mg/dl) Insulin Resistance Oxygen Consumption (mL/min/m2)

Low Mid High

< 10 10 20 > 20

< 1.5 1.5 3.0 >3

< 150 150-250 > 250

No Some Yes

< 140 140-180 > 180

Van der Berghe et al, 2001: Maintaining glucose levels below 110 mg/dL reduce mortality and morbidity in ICU and in-hospital

STRESS INDUCED HYPERGLYCEMIA

Acute or new hyperglycemia may occur after : Myocardial infarction Congestive heart failure Cerebral vascular accident Cardiopulmonary bypass Burns Major surgery or major trauma

GLUCOSE CONTROL BY INSULIN FOR CRITICALLY ILL SURGICAL PATIENTS

Hyperglycemia associated with insulin resistance, is common among criticall ill pts, even those who do not have diabetes. It is a known factor for poor prognosis in hospitalized pts

GUT-SPECIFIC RESUSCITATION
THE GOALS : Early optimizing gut perfusion Prevent reperfusion injury THE PROTOCOL Earlier use of PRBC, instead of aggressive use of crystaloids to avoid problematic bowel edema Or to use new blood substitutes and / or hypertonic saline or colloids
Moore FA & Weisbroodt NW, 2003

The Problems of Open Abdomen

Have a high in-hospital mortality: 20%-30% in most series Usually are heralded by a high ISS:25 9 And high serum lactate levels indicative of severe ischemia
Stone PA et.al.; J.Trauma 2004; 57:1082-1086

J Trauma, Dec 2008.65. 1520-152

SUPPORTED

In part, by Large scale collaborative project award (U54-GM 62119) from the National Institute of General Medical Sciences. National Institute of Health

CONTRIBUTIONS
1.

2.

3.

4.

George E. OKoeje : Depart of Surgery, University of Washington Seattle, Washington Joseph Cusheri : Depart of Surgery, University of Washington Seattle, Washington Ronald V.Maier : Depart of Surgery, University of Washington Seattle, Washington Marilyn Shelton : Depart of Hospitality and Nutrition, Harbor view Medical Center, Seattle, Washington

CONTRIBUTIONS
5.

6.

7.

Ernest E. Moore : Depart of Surgery, Univ of Colorado, Denver, Colorado Stephen F.Lowry, VMDNJ-RWJ Medical School, New Brunswich, New Jersey Brain G Harbredit, Depart of Surgery, Univ of Kentucky, Louisville, Kentucky

INTRODUCTION

Severely injured pts have marked metabolic derangements, generally characterized by increased substrate utilization and protein catabolism Specialized nutritional support is beneficial and improves important clinical outcomes in the critically ill
Heyland DK et al : JPEN, 2003; 27, 74-83

PROTOCOL GOALS
STANDARDS OPERATING PROCEDURE (SOP)
1.

To optimize patient outcome through enhancing tolerance of EN support and minimizing the complications

2.

To generate guidelines that is based upon the best available evidence

For Nutritional Support of the Trauma Patients

Selection of the pts for nutritional support 2. Approach to initiation 3. Route of administration 4. Nutrient formulation 5. Nutritional support monitoring This set of guidelines is evidence-based where possible and devised for pts with severe multisystem injury, who have been resuscitated from marked physiologic derangements
1.

SOP

FORMULATION

Protein needs are initially : 1,5 to 2,0 g protein/kg/d Caloric needs : 25 to 30 kcal/kg/d Monitor :

PN lipids : limited to 1 g/kg/d ( EN lipids) = less than 30% of total kcal

Occult and potentially excessive calories Hyperglycemia Excess CO2 production Fluid/electrolytes Blood stream infection

May AK et al : Ann Surg 1999; 65:560-574, Dissonaike S et al. Crit Care 2007; 11; R114

SUPPLEMENTATION

Recommendation:

Specific Nutrients (additional)

Standard high protein 1 kcal/ml formula When limiting volumes following large volume resuscitation, open abdomens and ongoing diuresis Higher caloric density 1,5-2.0 kcal/m
Glutamine Arginine Ribonucleic acids Omega-3 /fatty acids

IMMUNE ENHANCED SUPPLEMENTATION

The beneficial effect in severely injured humans are uncertain

Mendez C et al: J Trauma 1997, 42: 933-940 Kudsk KA et al : Ann Surg 1996; 224: 531-540

Combined supplementation of EN formula with arginine, omega-3 fatty acids and glutamine does not reduce mortality, infections, or organ failure in critically ill pts This constrasts with demonstrated reduction in infections complications when are used in elective surgical pts

Heyland DK et al: JAMA, 2001; 286: 944-953

IMMUNE ENHANCED SUPPLEMENTATION

Arginine increases nitric oxide (NO) production, while beneficially influencing innate immune function and infections outcomes in elective surgery pts Is detrimental in critically ill pts with sepsis

Sucher U, Heyland DK, Peter K: Br J Nutr 2002: 87 (S1), S121-S132

GUT-SPECIFIC RESUSCITATION
THE GOALS : Early optimizing gut perfusion Prevent reperfusion injury THE PROTOCOL Earlier use of PRBC, instead of aggressive use of crystalloids to avoid problematic bowel edema Or to use new blood substitutes and / or hypertonic saline or colloids
Moore FA & Weisbroodt NW, 2003

MONITORING NUTRITIONAL SUPPORT

INCLUDES Bedside assessment of the patient tolerance Daily evaluation by the dietician to ensure nutritional targets Biochemical monitoring The effect of massive resuscitation and marked fluid shifts during initial post injury week generally preclude the use of serum marker and body weight as indications

MONITORING NUTRITIONAL SUPPORT

Once the patient enters an anabolic state, sufficient substrate is needed to rebuild proteins, heal wound, and restore muscle mass

MONITORING GI TOLERANCE

High gastric residual volumes have often been considered a marker for gastric in tolerance of EN, reflux and broncho pulmonary aspiration of GI contents Other manifestations:
Poor gastric emptying Abdominal distention Abdominal tenderness Diarrhea Gastric ileus, infections colitis, intestinal ischemia and necrosis ( < 1%)

MONITORING GI TOLERANCE

Gastric aspirates are obtained every 4 to 6 hours

Residual volume of > 300 ml, mandates cessation of feeding with reassessment of residual volume 2 hours later

Gutt M, McFe J : Br J Surg 2010; 97:1629-1636

Gutt M, McFe J : Br J Surg 2010; 97:1629-1636

Gutt M, McFe J : Br J Surg 2010; 97:1629-1636

PLACEBO COCKTAIL VS GSN COCKTAIL

GSN COCKTAIL

Multivitamine capsules : 1 capsule daily (Forcevol) Probiotic capsules : 3 x 1 capsule Trevis Prebiotic powder : oligofructosa 16 g/day in two divided doses Glutamine IV : dipeptiven 100 ml daily Oral : glutamine Ox 5 g powder sachets 20 g/day in four divided dose Orally or via NGT

METABOLIC RESUSCITATION OF G.I.T

By providing adequate nutrition in KEY THERAPEUTIC STRATEGY general Immunomodulatory substrates specifically to maintain gut barrier integrity

The vicious cycle of oxygen free radical production in critically ill patient
Infection Surgery, trauma SIRS Ischemia/ reperfusion OFR Macrophage activation (liver) OFR Tissue injury OFR Cytokines Monocytes/ leucocytes activation Cytokines Hypoperfusion

Endotoxin, bacteria
Sepsis OFR

Inflammation OFR

Heyland, Dhaliwal & Suchners, 2005

POTENTIAL ROLES AND SITES OF ACTION OF IMMUNO NUTRIENTS IN SEPSIS

Sepsis

Free fatty acid

Arginine n-3 PUFAs Gut n-3 PUFAs Glutamine SCFAs Glutamine release

Macrophages

n-3 PUFAs

Cytokines and stress hormones

Immune response Adipose tissue Muscle Liver OKG Glutamine

CONCLUSION

The gut of is one the first organs exposed to shock and the last to e resuscitated in circulatory failure Impairment of the gut plays central role in the pathogenesis of infection, sepsis and even MODS Metabolic resuscitation of the gut by adequate nutrition in general and specific immunomodulating substrates to maintain gut barrier integrity and function will have to be considered

CONCLUSION

Enhancing the recovery of gut function or curtailing the period of gut failure, might be associated with improvements in patient outcomes The return of adequate gut function can be expedited with the use of GSN preparations This was associated with an attenuation of the acute phase response, decreased septic complications and a tendency towards improved survival