Systemic Response to Injury and Metabolic Support

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Systemic Response to Injury and Metabolic
Support

• Yalaunda M. Thomas, MD
• Assistant Professor, Division of Critical Care,
  Trauma and Burn
• Department of General Surgery
• The Ohio State University Medical Center
• July 10, 2008

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Outline

• Systemic Inflammatory Response Syndrome
• Definitions
• Pro-Inflammatory and Counterregulatory phases
• Metabolism
• Nutrition
• Enteral
• Parenteral
• Formulations

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Systemic Response Syndrome (SIRS)

• Criteria requires 2 or more
• Temperature 38C or 36C
• Heart Rate 90 beats/min
• Respiratory Rate 20 breaths/min
• or PaCO2 32mmHg
• WBC 12,000 or 4000 or 10 bands

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More Definitions

• Infection microbial insult
• Sepsis SIRS Infection
• Severe Sepsis Sepsis Organ dysfunction
• Septic Shock Sepsis inadequate tissue
  perfusion (refractory hypotension)

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While we speak of SIRS, sepsis, severe sepsis or
septic shock as defined physiologic events, they
are really a continuum
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Inflammation and CNS

• Autonomic system
• HR,BP, RR, GI motility and temperature
• Autonomic system
• Reflex anti-inflammatory signaling

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CNS anti-inflammation reflex

• Hypothalamus receive message from mediators
  
• (ieTNF, IL-1)
• Vagus Nerve acetylcholine?Macrophage inhibition
• Macrophage inhibition decreased
  pro-inflammatory mediator production

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Hormones hypothalamic pituitary-adrenal axis

• Corticotrophin-releasing hormone (CRH)
• ACTH
• Cortisol (glucocorticoids)
• Pain, anxiety, inflammation or injury will cause
  a rise in any one of these hormones individually
  and as a result of ones effect on the other

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Rise in glucocorticoids.

• decrease in pro-inflammatory mediators (immune
  cell inhibition)
• increase in anti-inflammatory mediators (IL-10)
• stimulation of gluconeogenesis (liver)
• increased insulin resistance (muscle, fat)
• increased muscle protein breakdown (AA)
• increased fatty acids/triglyceride release

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What are these inflammation mediators??

• The list is long and growing..
• 1.Cytokines
• 2. Eicosanoids
• 3. Cell signaling pathways

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• Whilst not neglecting any of the
• earlier known mediators such as
• histamine, bradykinin,prostaglandins,
• leukotrienes and PAF,
• Mediators of Inflammation
• focuses on research into cytokines
• (tumour necrosis factors, interleukins,
  interferons),
• biological response modifiers
• interferon,G-CSF,mAbs
• and the family of cell adhesion
• promoting molecules
• CAMs, selectins.

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Cytokines
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Eicosanoids
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www.arthritis.co.za
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Cell signaling pathways ? immune cell response
to inflammation

• TLR2
• gram positive sepsis
• TLR4/CD14
• gram negative sepsis (LPS)
• TLR gene mutations associated with increased
  infection susceptibility

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Clinically..

• Early-goal directed therapy
• Source control
• Resuscitation
• fluids
• pressors
• steroids
• drotrecogina alfa (Xigris)
• COX inhibitors
• Organ dysfunction support
• ventilator Rx
• renal replacement Rx
• aortic balloon pump
• ECMO

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Xigris SEVERE SEPSIS Rx

• Activated Protein C
• Antithrombotic action (factors Va/VIIIa)
• Pro-fibrinolytic action (PAI-1)
• Anti-TNF (leukocyte-selectin thrombin)

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Xigris so how does that stuff work??
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Metabolism and the Inflammatory Response
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The healthy 70-kg man

• Less than 24hrs of glucose stores (Liver)
• Up to 2 weeks of protein stores
• (muscle/organ)
• More than 2 months fat stores

• The glucose obligate organs
• Brain
• RBC
• Kidney
• Kidney and brain could use ketones in extreme
  starvation

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Rise in glucocorticoids.

• decrease in pro-inflammatory mediators (immune
  cell inhibition)
• increase in anti-inflammatory mediators (IL-10)
• stimulation of gluconeogenesis (liver)
• increased insulin resistance (muscle, fat)
• increased muscle protein breakdown (AA)
• increased fatty acids/triglyceride release

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• Glycogenolysis/gluconeogenesis to provide
  substrate inflammatory response
• Proteolysis (AA release) as a substrate for more
  gluconeogenesis
• Fatty acid release for ketogenesis or ATP
  generation

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Respiratory Quotient (RQ)

• Organ function and metabolism requires oxygen
  utilization with carbon dioxide production as a
  byproduct
• Metabolism of carbohydrates, fat and proteins are
  associated with different RQ

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• Equal utilization of carbs and fat
• RQVCO2/VO2 0.85
• Overfeeding (Carbohydrates only utilization)
• RQ 1
• Starvation (Fat only utilization)
• RQ0.7

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• Nitrogen balance is another method to assess
  nutritional state
• In the inflammatory state, nitrogen excretion is
  increased
• Negative nitrogen balance reflects protein
  breakdown

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Nutrition

• Your patient needs nutrition if
• There has been none in more than7-10days
• The duration of illness will be gt10 days
• Malnutrition (weight lossgt15 usual weight)

ACS Surgery Principles and Practice
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How much nutrition

• Harris-Benedict
• Anthropometrics
• Biochemical assays
• Indirect Calorimetry

• General rules of thumb
• No illness
• 25-30kcal/kg/day
• Moderately ill
• 30-35kgcal/kg/day
• Severely ill/Burn
• 40kcal/kg/day

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Nutrition content

• Carbohydrates (50-70 total calories)
• Proteins (up to 15-20 total calories)
• 0.8g/kg/day none stressed
• 1-1.5g/kg/day mod stressed
• 2g/kg/day severely stressed
• Fats (30 total calories)
• 1g/kg/day not needed daily

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Special Clinical Situations

• Renal Failure patients
• Adjust protein intake (poor nitrogen breakdown
  excretion)
• Concentrate total fluids (2cal enteral
  formulas)
• Ventilator dependent patients
• Difficult to wean/elevated PCO2
• Increase total fat calories, decrease
  carbohydrates (RQ)
• Burn patients(2nd/3rd degree)
• catabolic state up to a year from injury
• Increased protein and total caloric needs

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Route of nutrition

• Enteral
• Inexpensive
• Natural
• Gut protective
• IgA
• Bacterial translocation

• Enteral
• Inappropriate for high
• output fistulas
• Aspiration risks
• Nasogastric tube
• erosion

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Route of Nutrition

• Parenteral
• Not dependent on gut function
• No aspiration risks

• Parenteral
• Invasive
• Infection risks
• Expensive
• Gut atrophy without use

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Formulations

• TPN
• Dextrose
• 3.4 kcal/gram
• Protein
• 4 kcal/gram
• Fat
• 9 kcal/gram

• Remember
• GLUCOSE yields 4 kcal/gram
• (particularly important if calculating oral
  caloric intake)

Remember Glucose yields 4 kcal/gram (particula
rly important if calculating oral caloric intake)
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Formulations

• TPN standards
• D25 25g dextrose/100ml fluid 850kcal/L
• 4.25 AA 42.5g protein/L fluid
• 10 lipids solution 1.1 kcal/mL
• 20 lipids solution 2 kcal/mL

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• Trace elements
• Zinc (healing/dermatitis)
• Vitamins/Electrolytes
• Immune enhancers
• Glutamine fuel for immunocytes,
  enterocytes
• Arginine wound healing nitrogen
• retention/protein synthesis
• Omega-3 fatty acids
• decrease inflammatory response at cell
  membrane level

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• Questions ???