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Systemic Response to Injury & Metabolic Support. a review of Schwartz’s Principles of Surgery- Chapter 1 L. Coughlin, M.D. July 7, 2008. Introduction. Inflammatory response to injury to restore tissue function Eradicate invading microorganisms Local- limited duration, restores function

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systemic response to injury metabolic support

Systemic Response to Injury & Metabolic Support

a review of Schwartz’s Principles of Surgery- Chapter 1

L. Coughlin, M.D.

July 7, 2008

  • Inflammatory response to injury
    • to restore tissue function
    • Eradicate invading microorganisms
  • Local- limited duration, restores function
  • Major
    • overwhelming inflammatory response
    • Potential multi-organ failure
    • Adversely impacts patient survival
clinical spectrum of sirs

Identifiable source of microbial insult

SIRS = 2 or more:

Temp ≥38˚C or ≤36˚C

HR ≥ 90 bpm

RR ≥ 20 breaths/min or PaCO2 ≤ 32 mmHg or mechanical ventilation

WBC ≥ 12,000/µL or ≤ 4000/µL or ≥ 10% band forms


Infection + SIRS

Severe Sepsis

Sepsis + Organ Dysfunction

Septic Shock

Sepsis + Cardiovascular Collapse (requires vasopressors)

Clinical Spectrum of SIRS
  • Humoral – inflammatory mediators in the circulation can induce fever and anorexia i.e. TNF-α
  • Neural – parasympathetic vagal stimulation attenuates the inflammatory response via Ach release
    • Reduces HR, increases gut motility, dilates arterioles, constricts pupils, and decreases inflammation
    • Reduces macrophage activation
    • Reduces macrophage release of pro-inflammatory mediators (TNF-α, IL-1, IL-18)
hormone signaling
Hormone Signaling
  • Hormone classifications
    • polypeptide (cytokine, insulin)
    • amino acid (epinephrine, serotonin, or histamine)
    • fatty acid (cortisol, leukotrienes)
  • Pathways
    • Receptor Kinases – insulin
    • Guanine nucleotide binding (G-protein) - prostaglandins
    • Ligand Gated ion channels
adrenocorticotropic hormone
Adrenocorticotropic Hormone
  • Synthesized anterior pituitary
  • Regulated by circadian signals
  • Pattern is dramatically altered in injured patients
  • Elevation is proportional to injury severity
  • Released by: pain, anxiety, vasopressin,

angiotensin II, cholecystokinin, catecholamines, and pro-inflammatory cytokines

  • ACTH signals increase glucocorticoid production
  • Cortisol – elevated following injury,
    • duration of elevation depends on severity of injury
  • Potentiates hyperglycemia
    • Hepatic gluconeogenesis
    • Muscle and adipose tissue –> induces insulin resistance
    • Skeletal m.–> protein degradation, lactate release
    • Adipose -> reduces release of TG, FFA, glycerol
exogenous administration
Exogenous administration
  • Adrenal suppression in the acutely ill
    • Acute Adrenal Insufficiency
    • Atrophy of the adrenal glands
    • Weakness, n/v, fever, hypotension
    • Hypoglycemia, hyponatremia, hyperkalemia
  • Immunosuppression
    • Thymic involution, decreased T-killer and NK fcn, graft vs host rxns, delayed hypersensitivity responses, inability of monocyte intracellular killing, inhibition of superoxide reactivity and chemotaxis in neutrophils
    • Down regulates pro-inflammatory cytokine production (TNF-α, IL-1, IL-6)
    • Increases anti-inflammatory mediator IL-10
    • Useful in septic shock, surgical trauma, and CABG
macrophage inhibitory factor
Macrophage Inhibitory Factor
  • Glucocorticoid antagonist
  • produced by anterior pituitary & T-lymphocytes
  • Reverses immunosuppressive effects of glucocorticoids
  • Potentiates G- and G+ septic shock
  • Experimentally improves survival
growth hormone
Growth Hormone
  • During stress -> protein synth, fat mobilization, and skeletal cartilage growth
  • 2˚ to release of insulin-like growth factor (IGF1)
  • Injury reduces IGF1 levels
  • IGF1 inhibited by pro-inflammatory cytokines
    • TNF-α, IL-1α, IL-6
  • GH admin to pediatric burn patients shows improvement in their clinical course
  • Severe injury activates the adrenergic system
  • Norepi and Epi immed. increase 3-4 fold and remain elevated 24-48hrs after injury
  • Epinephrine
    • hepatic glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis
    • Decreases insulin and glucagon secretion
    • Peripheral- lipolysis, insulin resistance in skeletal m.
    • = stress induced hyperglycemia
epinephrine other effects
Epinephrine – other effects
  • Increase secretion of T3, T4, and renin
  • Reduces release of aldosterone
  • Enhances leukocyte demargination and lymphocytosis
  • Synthesized, stored, released from the adrenal zona glomerulosa
  • Maintains intravascular volume
    • Conserves sodium
    • Eliminates potassium and hydrogen ions
    • Acts on the early distal convoluted tubules
  • Deficiency- hypotension, hyperkalemia
  • Excess- edema, HTN, hypokalemia, metab alkalosis
  • Stress inhibited release + peripheral insulin resistance = hyperglycemia
  • Injury has 2 phases of insulin release
    • Within hours- release is suppressed
    • Later- normal/xs insulin production with peripheral insulin resistance
  • Activated lymphocytes have insulin receptors -> enhanced Tcell proliferation and cytotoxicity
  • Tight control of glucose levels esp. in diabetics significantly reduces mortality after injury
acute phase proteins
Acute Phase Proteins
  • Nonspecific markers
  • Produced by hepatocytes
  • Response to injury, infection, inflammation
  • Induced by IL-6
  • C-reactive protein best reflects inflammation
    • No diurnal variation, not affected by feeding
    • Affected only by preexisting hepatic failure
    • Accuracy surpasses that of ESR
inflammatory mediators
Inflammatory Mediators
  • Heat Shock Proteins
  • Reactive Oxygen Metabolites
  • Eicosanoids
  • Fatty Acid Metabolites
  • Kallikrein-Kinin System
  • Serotonin
  • Histamine
  • Cytokines
heat shock proteins
Heat Shock Proteins
  • Induced by hypoxia, trauma, heavy metals, and hemorrhage
  • Intracellularly modify and transport proteins
    • Steroids
  • Requires gene induction by a transcription factor
  • ACTH sensitive
  • Production seems to decline with age
reactive oxygen metabolites
Reactive Oxygen Metabolites
  • Short-lived
  • Cause tissue injury by oxidation of unsaturated fatty acids within cell membranes
  • Produced by anaerobic glucose oxidation and reduction to superoxide anion in leukocytes
  • Further metabolized to hydrogen peroxide and hydroxyl radicals
  • Cells are protected by oxygen scavengers – glutathione and catalases
  • In ischemia- production of oxygen metabolites are activated but nonfunctional due to no oxygen supply. After reperfusion, large amounts are produced causing injury




  • Secreted by nucleated cells (not lymphocytes)
  • Induced by hypoxic injury, direct tissue injury, endotoxin, norepinephrine, vasopressin, ang II, bradykinin, serotonin, ACh, cytokines, histamine
  • Diverse systemic effects
  • Adverse effects include acute lung injury, pancreatitis, renal failure
  • NSAIDs acetylate COX which reduce prostaglandin levels
eicosanoid effects
Pancreas – glucagon secretion- PGD2, PGE2

Liver – glucagon stimulated glucose production- PGE2

Adipose – lipolysis- PGE2

Bone – resorption- PGE2, PGF2α, PGI2

Parathyroid – PTH secretion- PGE2

Pulmonary – Bronchoconstriction- PGF2α, TXA2, LTC4, LTD4, LTE4

Immune – suppress lymphocytes- PGE2


platelet aggregation- TXA2

Capillary leakage- PGE2, LT

PMN adherence and activation- LT


Prolactin- PGE1




Renal – renin secretion- PGE2, PGI2

GI – cytoprotective- PGE2

Eicosanoid Effects
fatty acid metabolites
Fatty Acid Metabolites
  • Omega 6 FA – precursors of inflammatory mediators (LT, PG, platelet activating, factor)
    • found in enteral nutrition formulas
  • Substituting Omega 3 FA attenuate the inflammatory response
    • Reduces TNFα, IL6, PGE2
    • Reduces the metabolic rater, normalizes glucose metabolism, attenuates weight loss, improves nitrogen balance, reduces endotoxin induced acute lung injury, minimizes reperfusion injury to the myocardium, small intestine, and skeletal muscles.
kallikrein kinin system
Kallikrein-Kinin System
  • Bradykinins are potent vasodilators
  • Stimulated by hypoxic and ischemic injury
    • Hemorrhage, sepsis, endotoxemia, tissue injury
    • Magnitude proportional to severity of injury
  • Produced by kininogen degradation by kallikrein
  • Kinins increase capillary permeability (edema), pain, inhibit gluconeogenesis, renal vasodilation, incr bronchoconstriction
  • In clinical trials, bradykinin antagonists help reverse G- sepsis, but do not improve survival
  • Present in intestinal chromaffin cells & platelets
  • Vasoconstriction, bronchoconstriction, platelet aggregation
  • Myocardial chronotrope and ionotrope
  • Unclear role in inflammation
  • Stored in neurons, skin, gastric mucosa, mast cells, basophils, and platelets
  • H1 – bronchoconstriction, increases intestinal motility and myocardial contractility
  • H2 – inhibits histamine release
  • H1/H2 – hypotension, decreased venous return/peripheral blood pooling, increased capillary permeability, myocardial failure.
  • Most potent mediators of inflammation
  • Local- eradicate microorganisms, promote wound healing
  • Overwhelming response- hemodynamic instability (septic shock) or metabolic derangements (muscle wasting)
  • Uncontrolled- end-organ failure, death
  • Self-regulatory production of anti-inflammatory cytokines, but inappropriate release may render the patient immunocompromised and susceptible to infection
tumor necrosis factor
Tumor Necrosis Factor α
  • Secreted from monocytes, macrophages, Tcells
  • Responds early, T ½ < 20min
  • Potent evocation of cytokine cascade
  • Induces muscle catabolism/cachexia, coagulation, PGE2, PAF, glucocorticoids, eicosanoids
  • Circulating TNF receptors compete with cellular receptors and may act as a counter regulatory system to prevent excessive TNF-α activity
interleukin 1
  • Released by activated macrophages, endothelial cells
  • IL1α- cell membrane associated
  • IL1β- circulation
  • Synergistic with TNF- α
  • T ½ = 6 min
  • Induces febrile response by stimulating PG activity in the anterior hypothalamus
  • Release of β-endorphins after surgery reduce perception of pain
interleukin 2
  • Promotes T-lymphocyte proliferation, Ig production, gut barrier integrity
  • T ½ < 10 min
  • Major injury or perioperative blood transfusions reduce IL-2 activity leading to a transient immunocompromised state
  • Regulates lymphocyte apoptosis
interleukin 4
  • Produced by type 2 T Helper lymphocytes
  • Important in antibody-mediated switching and antigen presentation
  • Induces class switching to promote IgE & IgG4
    • Important in allergic and antihelmintic responses
  • Anti-inflammatory- downregulates IL-1, TNF-α, IL-6, IL-8 and oxygen radical production
  • Increases macrophage susceptibility to anti-inflammatory effects of glucocorticoids
interleukin 5
  • Released from T lymphocytes, eosinophils, mast cells and basophils
  • Promotes eosinophil proliferation and airway inflammation
interleukin 6
  • Induced by IL-1 and TNF-α
  • Levels are detectable within 60 min of injury, peak 4-6 hours, and persist up to 10 days
  • Levels are proportional to extent of tissue injury
  • Pro-inflammatory
    • Mediates hepatic acute phase response during injury and convalescence
    • Induces and prolongs neutrophil activity
  • Anti-inflammatory
    • Attenuate TNF-α and IL-1 activity
    • Promote release of circulating TNF- α receptors & IL-1 antagonists
interleukin 8
  • Released from monocytes, macrophages, T lymphocytes
  • Activity similar to IL-6
  • Chemoattractant for PMNs, basophils, eosinophils, and lymphocytes, activates PMNs
  • Proposed biomarker for risk of multiple organ failure
interleukin 10
  • Anti-inflammatory
  • Released from T lymphocytes
  • Down-regulates TNF-α activity
  • Also attenuates IL-18 mRNA in monocytes
  • Studies in animal sepsis and ARDS models suggest induced IL-10 decreases the systemic inflammatory response and reduces mortality
interleukin 12
  • Promotes differentiation of type 1 T Helper cells
  • Promotes PMN and coagulation activation
  • In primate studies, IL-12 induces inflammatory responses independent of TNF-α and IL-1
  • In animal studies of fecal peritonitis and burns, IL-12 administration increases survival, whereas IL-12 neutralization increases mortality
interleukin 13
  • Similar to IL-4, overall anti-inflammatory
  • Modulates macrophage function
  • Unlike IL-4, has no effect on T lymphocytes
  • Inhibits NO production
  • Inhibits pro-inflammatory cytokines
  • Attenuates leukocyte interaction with activated endothelial surfaces
interleukin 15
  • Derived from macrophages
  • Shares receptor components with IL-2, and shares promoting lymphocyte activation/prolif.
  • In neutrophils, it induces IL-8 and nuclear factor кB -> enhanced phagocytosis against fungal infections
interleukin 18
  • Formerly IFN-γ-inducing factor
  • Produced by macrophages
  • Pro-inflammatory, similar to IL-12
  • Increased levels are pronounced (especially in G- sepsis) and can last up to 21 days
  • Helper T lymphocytes activated by bacterial antigens, IL-2, IL-12, or IL-18 produce IFN-γ
  • IFN-γ can induce IL-2, IL-12, or IL-18
  • Detectable in circulation by 6 hrs and remain elevated for up to 8 days
  • Activate circulating and tissue macrophages
  • Induces acute lung inflammation by activating alveolar macrophages after surgery or trauma
granulocyte macrophage colony stimulating factor
Granulocyte-Macrophage Colony-Stimulating Factor
  • Delays apoptosis of macrophages and PMNs
  • Promotes the maturation and recruitment of PMNs in inflammation and perhaps wound healing
  • May contribute to organ injury such as ARDS
  • Peri-operative GM-CSF undergoing major oncologic procedures and burn patients demonstrate enhances neutrophil counts and fcn
high mobility group box 1
High Mobility Group Box 1
  • DNA transcription factor
  • Expressed 24-48 hrs after injury
  • Associated with weight loss, food aversion, shock, SIRS and Sepsis
  • Peak levels are associated with ARDS and death
cell signaling pathways
Cell Signaling Pathways
  • Heat Shock Proteins
    • produced in response to ischemia/injury
    • HS Factors are activated upon injury, undergo conformational changes, translocate into the nucleus, and bind HSP promoter regions
    • Attenuate inflammatory response
  • Ligand Gated Ion Channels
    • When activated by a ligand, a rapid influx of ions cross the cell membrane. i.e. neurotransmitters
cell signaling pathways43
Cell Signaling Pathways
  • G-protein receptors
    • Largest family of signaling receptors
    • Adjacent effector protein activated receptor
    • Second messengers – cAMP or calcium
    • Can result in gene transcription or activation of phospholipase C
  • Tyrosine Kinases
    • When activated, receptors dimerize, phosphorylate, and recruit secondary signaling molecules
    • Used in gene transcription and cell proliferation
    • i.e. insulin, PGDF, IGF-1
cell signaling pathways44
Cell Signaling Pathways
  • Janus Kinase/Signal Transduction and Activator of Transcription (JAK-STAT)
    • IL-6, IL-10, IL-12, IL-13, IFN-γ
    • Ligand binds to the receptor, receptor dimerizes, enzymatic activation via phosphorylation propagates through the JAK domain and recruits STAT to the cytosolic receptor portion.
    • STAT dimerizes and translocates into the nucleus as a transcription factor
    • Suppressors of cytokine signaling (SOCS) block JAK-STAT
tumor necrosis factor45
Tumor Necrosis Factor
  • Apoptosis - normal fcn of cellular disposal w/o activating the immune/inflammatory system
  • 2 receptors
    • TNFR-1 : inflammation, apoptosis, circulatory shock
    • TNFR-2 : no inflammation or shock
  • CD95 (Fas) receptor similar structure to TNFR-1
    • Initiates apoptosis
cell mediated inflammation
Cell Mediated Inflammation
  • Platelets
    • Source of eicosanoids and vasoactive mediators
    • Clot is a chemoattractant for PMNs/monocytes
    • Modulate PMN endothelium adherence
    • Migration occurs within 3 hrs of injury
      • Mediated by serotonin, PAF, PGE2
  • Eosinophils
    • Migrate to parasitic infection and allergen challenge to release cytotoxic granules
    • Reside in the GI, lung, and GU tissues
    • Activated by IL-3, GM-CSF, IL-5, PAF, and anaphylatoxins C3a and C5a
cell mediated inflammation47
Cell Mediated Inflammation
  • Lymphocytes
    • T-helpers produce IL-3, TNF-α, GM-CSF
      • TH1: IFN-γ, IL-2, IL-12
      • TH2: IL-4, IL-5, IL-6, IL-9, IL-10, IL-13
      • Severe infection – shift toward more TH2
  • Mast Cells
    • First responders to injury
    • Produce histamine, cytokines, eicosanoids, proteases, chemokines, TNF-α (stored in granules)
    • Cause vasodilation, capillary leakage, and recruit immunocytes
cell mediated inflammation48
Cell Mediated Inflammation
  • Monocytes
    • Downregulation of receptor TNFR is clinically and experimentally correlated with CHF, nonsurvival in sepsis
  • Neutrophils
    • Modulate acute inflammation
    • Maturation is stimulated by G-CSF
    • Rolling (L-selectin (fast), P-selectin (slow)
    • Adhesion/transmigration – ICAM 1, 2, PECAM 1, VCAM 1, CD18
endothelium mediated injury
Endothelium-Mediated Injury
  • Neutrophil-Endothelium Interaction
    • Increased vascular permeability – facilitate oxygen delivery and immunocyte migration
    • Accumulation of neutrophils at injury sites can cause cytotoxicity to vital organs
    • Ischemia-reperfusion injury potentiates this response by releasing oxygen metabolites and lysosomal enz.
    • Neutrophils – rolling 10-20min (p-selectin), >20min
nitric oxide
Nitric Oxide
  • Derived from endothelial surfaces responding to Ach, hypoxia, endotoxin, cellular injury, or shear stresses of circulating blood
  • T ½ = seconds
  • Reduces microthrombosis, mediates protein synthesis in hepatocytes
  • Formed from oxidation of L-arginine via NOS (+calmodulin, Ca2+, NADPH)
prostacyclin pgi2
Prostacyclin (PGI2)
  • Endothelium derived in response to shear stress and hypoxia
  • Vasodilator
  • Platelet deactivation (increases cAMP)
  • Clinically used to reduce pulmonary hypertension (especially pediatric)
  • Produced as a response to a variety of factors – injury, anoxia, thrombin, IL-1, vasopressin
  • ET-1 is a potent vasoconstrictor, 10x more potent than angiotensin II
platelet activating factor
Platelet Activating Factor
  • Phospholipid component of cell membranes, constitutively expressed at low levels
  • Released by PMNs, platelets, mast cells, monocytes during acute inflammation
  • Further activates PMNs and platelets
  • Increases vascular permeability
  • PAF antagonists reduce ischemia/reperfusion injury
metabolism during fasting
Metabolism During Fasting
  • Comparable to changes seen in acute injury
  • Requires 25-40 kcal/kg/day of carbs, protein, fat
  • Normal adult body contains 300-400g carbs (glycogen) – 75-100g hepatic, 200-250g muscle (not available systemically due to deficiency of G6P)
metabolism during fasting55
Metabolism During Fasting
  • A healthy 70kg adult will use 180 g /d of glucose to support obligate glycolytic cells (neurons, RBCs, PMNs, renal medulla, skeletal m.)
  • Glucagon, Norepi, vasopressin, AngII promote utilization of glycogen stores
  • Glucagon, Epi, and cortisol promote gluconeogenesis
  • Precursors include lactate (sk.m., rbc, pmn), glycerol, and aa (ala, glutamine)
metabolism of simple starvation
Metabolism of Simple Starvation
  • Lactate is not sufficient for glucose demands
  • Protein must be degraded (75 g/d) for hepatic gluconeogenesis
  • Proteolysis from decreased insulin and increased cortisol
  • Elevated urinary nitrogen (7 -> 30 g/d)
metabolism of prolonged starvation
Metabolism of Prolonged Starvation
  • Proteolysis is reduced to 20g/d and urinary nitrogen excretion stabilizes to 2-5g/d
  • Organs (myocardium, brain, renal cortex, sk.m) adapt to ketone bodies in 2-24 days
  • Kidneys utilize glutamine and glutamate in gluconeogenesis
  • Adipose stores provide up to 40% calories (approx 160 g FFA and glycerol)
    • Stimulated by reduced insulin and increased glucagon and catecholamines
metabolism following injury
Metabolism Following Injury
  • Magnitude of expenditure is proportional to the severity of injury
  • Changes in
    • Lipid Absorption
    • Lipid Oxidation
    • Carbohydrate metabolism
lipid absorption
Lipid Absorption
  • Oxidation of 1g fat = 9 kcal energy
  • Dietary lipids require pancreatic lipase and phospholipase to hydrolyze TG into FFA and monoglycerides within the duodenum
  • After gut absorption, enterocytes resynthesize TG from monoglycerides + fatty acyl-CoA
  • Long chain TG (>12 carbons) enter the circulation as chylomicrons. Shorter FA chains directly enter portal circulation and are transported via albumin
  • Under stress, hepatocytes utilize FFA as fuel
  • Systemically TG and chylomicrons are used from hydrolysis with lipoprotein lipase (suppressed by trauma and sepsis)
fatty acid oxidation
Fatty Acid Oxidation
  • FFA + acyl-CoA = LCT are transported across the mitochondrial inner membrane via the carnitine shuttle
  • Medium-chain TG (MCT) 6-12 carbons long, freely cross the mitochondrial membrane
  • Fatty acyl-CoA undergoes β-oxidation to acetyl-CoA to enter TCA cycle for oxidation to ATP, CO2, and water
  • Excess acetyl-CoA is used for ketogenesis
carbohydrate metabolism
Carbohydrate Metabolism
  • Carbohydrates + pancreatic intestinal enzymes yield dimeric units (sucrase, lactase, maltase)
  • Intestinal brush border disaccharidases break them into simple hexose units which are transported into the intestinal mucosa
  • Glucose and galactose are absorbed via a sodium dependent active transport pump
  • Fructose absorption via facilitated diffusion
carbohydrate metabolism62
Carbohydrate Metabolism
  • 1g carbohydrate = 4 kcal energy
  • IV/parenteral nutrition 3.4 kcal/g dextrose
  • In surgical patients dextrose administration is to minimize muscle wasting
  • Glucose can be utilized in a variety of pathways – phosphorylation to G6P then glycogenesis or glycogenolysis, pyruvic acid pathway, or pentose shunt
protein and amino acid metabolism
Protein and Amino Acid Metabolism
  • Average adult protein intake 80-120 g/day
    • every 6 g protein yields 1 g nitrogen
    • 1g protein = 4 kcal energy
  • Following injury, glucocorticoids increase urinary nitrogen excretion (>30g/d), peak at 7d, persist 3-7 wks
nutrition in the surgical patient
Nutrition in the Surgical Patient
  • Nutritional assessment to determine the severity of deficiencies/excess
  • Wt loss, chronic illnesses, dietary habits, quality/quantity of food, social habits, meds
  • Physical exam – loss of muscle/adipose tissue, organ dysfunction
  • Biochemical – Cr excretion, albumin, prealbumin, total lymphocyte count, transferrin
surgical nutrition
Surgical Nutrition
  • Support the requirements for protein synthesis
  • Nonprotein calorie : nitrogen ratio = 150:1
  • A lower rate of 80-100:1 may be beneficial in some critically ill or hypermetabolic patients
  • Basal Energy Expenditure (BEE):

men = 66.47 + 13.75(W) + 5(H) – 6.76(A) kcal/d

women = 655.1 + 9.56(W) + 1.85(H) – 4.68 (A) kcal/d

W= wt in kg, H= Ht in cm, A= age in years

enteral feeding
Enteral Feeding
  • Less expensive and risks than parenteral
  • Reduced intestinal atrophy
  • 44% reduction in infections over parenteral in the critically ill
  • Healthy patients without malnutrition undergoing uncomplicated surgery can tolerate 10 d of maintenance IV fluids only before significant protein catabolism begins
initiation of enteral feeding
Initiation of Enteral Feeding
  • Immediately after adequate fluid resuscitation (UOP)
  • Not absolute prerequisites: presence of bowel sounds, passage of flatus or stool
  • Gastric residuals of >200ml in 4-6 hrs or abdominal distention requires cessation/lowering the rate
enteral formulas
Enteral Formulas
  • Low-residue isotonic
    • caloric density 1.0kcal/ml, 1500-1800 ml/day
    • Provide carbs, protein, lytes, water, fat, water sol vitamins, calorie:Nitrogen of 150:1.
    • No fiber bulk = minimum residue
    • Standard for stable patients with an intact GI tract
  • Isotonic with fiber
    • Soluble and insoluble fiber (soy)
    • Delay GI transit time and reduce diarrhea
    • Not contraindicated in the critically ill
enteral formulas69
Enteral Formulas
  • Immune-Enhancing
    • Glutamine, argenine, omega-3 FA, nucleotides, beta-carotene.
    • Benefits not consistent in trials
    • Expensive
  • Calorie-Dense
    • 1.5-2 kcal/ml, higher osmolality (ok for intragastric feeding)
    • for fluid restriction/inability to tolerate larger volumes
  • High-Protein
    • Isotonic and nonisotonic available
    • calorie:Nitrogen ratio of 80-120:1
enteral formulas70
Enteral Formulas
  • Elemental
    • Contain predigested nutrients, small peptides
    • Limited complex carbs and fat (long/med chains)
    • Easily absorbed, but limited long term use
    • High osmolality = slow infusion or diluted
    • Expensive
  • Renal-Failure
    • Lower fluid volume, K, phos, and Mg
    • Essential aa, high calorie : nitrogen ratio, no vitamins
enteral formulas71
Enteral Formulas
  • Pulmonary-Failure
    • Fat content is increased to 50% of total calories
    • Reduces CO2 production and ventilation burden
  • Hepatic-Failure
    • 50% of aa are branched chains (Leu, Ile, Val)
    • Potentially reverses encephalopathy
    • Controversial, no clear benefits in trials
enteral access
Enteral Access
  • Nasogastric Tube - requires intact mental status and laryngeal reflexes to reduce aspiration
    • Difficult to place, requires radiographic confirmation
    • If required >30 d, convert to PEG
    • Problems: clogging, kinking, inadvertent removal
  • Percutaneous Endoscopic Gastrostomy –
    • Impaired swallowing/obstruction, major facial trauma
    • Contraindications: ascites, coagulophathy, gastric varices, gastric neoplasm, lack of suitable location
    • Tubes can be use for 12-24 mos
    • Requires endoscopic transillumination of abdominal wall and passage of catheter into an insufflated stomach
    • Complications in 3% of cases: infection, peritonitis, aspiration/pneumonia, leaks, dislodgement, bowel perforation, enteric fistulas, bleeding
percutaneous endoscopic gastrostomy jejunostomy
Percutaneous Endoscopic Gastrostomy-Jejunostomy
  • Feeding administered past the pylorus
  • Cannot tolerate gastric feedings/signif aspiration
  • Passes a catheter through an existing PEG past the pylorus into the duodenum
  • Long term malfunction >50% due to retrograde tube migration into the stomach, kinking, clogging
direct percutaneous endoscopic jejunostomy
Direct Percutaneous Endoscopic Jejunostomy
  • Same technique as PEG placement but requires an enteroscope/colonscope to reach the jejunum
  • Less malfunction than PEG-J
  • Kinking/clogging reduced by placing larger caliber catheters
surgical gastrostomy and jejunostomy
Surgical Gastrostomy and Jejunostomy
  • With complex abdominal trauma/laparatomy there may be an opportunity for placement
  • Contraindication: distal obstruction, severe intestinal wall edema, radiation enteritis, inflammatory bowel disease, ascites, severe immunodeficiency, bowel ischemia
  • Adverse effects: abdominal/bowel distention, cramps, pneumotosis intestinalis, small bowel necrosis
parenteral nutrition
Parenteral Nutrition
  • Continuous infusion of hyperosmolar carbs, proteins, fats and other nutrients through a catheter into the SVC
  • Optimal > 100-150 kcal/g nitrogens
  • Higher rates of infection compared to enteral
  • Studies with parenteral nutrition and complete bowel rest results in increased stress hormone and inflammatory responses
parenteral nutrition rationale
Parenteral Nutrition Rationale
  • Seriously ill patients with malnutrition, sepsis or surgery/trauma when use of the GI tract for feeding is not possible
    • Short bowel syndrome after massive resection
    • Prolonged paralytic ileus (>7 days)
    • Severe intestinal malabsorption
    • Functional GI disorders – esophageal dyskinesia
    • Etc.
total parenteral nutrition
Total Parenteral Nutrition
  • Central parenteral nutrition, aka TPN
  • Requires access to a large diameter vein
  • Dextrose content is high (15-25%)
peripheral parenteral nutrition
Peripheral Parenteral Nutrition
  • Lower osmolality
  • Reduced dextrose (5-10%)
  • Protein (3%)
  • Not appropriate for severe malnutrition due to need for larger volumes of some nutrients
  • Shorter periods, < 2 wks
parenteral nutrition80
Parenteral Nutrition
  • Dextose 15-25%
  • Amino acids 3-5%
  • Vitamins (Vit K is not included)
  • Lipid emulsions to prevent essential FA deficiency (10-15% of calories)
  • Prepared by the pharmacy from commercially available kits
  • If prolonged – supplement trace minerals
    • Zinc (eczematous rash), copper (microcytic anemia), chromium (glucose intolerance)
parenteral nutrition81
Parenteral Nutrition
  • Insulin supplement to insure glucose tolerance
  • IV fluids/electrolytes if high fluid losses
  • Freq. monitor fluid status, vital signs, UOP, electrolytes, BUN, and LFTs. Glucose q6h
  • Hyperglycemia – pt with impaired glc tolerance or high infusion rate
    • Tx- volume replacement, correct electrolytes, insulin
    • Avoid by monitoring daily fluid balance, glc, & lytes
  • Overfeeding – results in CO2 retention and respiratory insufficiency
  • Hepatic steatosis
  • Cholestasis and gallstones
  • Hepatic abnormalities – serum transaminase, alk phos and bilirubin
  • Intestinal - atrophy from disuse, bacterial overgrowth, reduced lymphoid tissue and IgA production, impaired gut immunity
special formulations
Special Formulations
  • Glutamine and Arginine
    • Glutamine – nonessential aa, comprises 66% of free amino acids
    • During stress glu is depleted and shunted as a fuel source to visceral organs and tumors
    • Inconclusive data for benefits of increased supplementation
    • Arginine – nonessential aa, promotes net nitrogen retention and protein synthesis in the critically ill/injured. Benefits still under investigation.
  • Omega-3 Fatty Acids
    • Canola or fish oil. Displaces omega-6 FAs, theoretically reducing pro-inflammatory responses
  • Nucleotides
    • ? Increase cell proliferation, DNA synthesis, T Helper cell function

The material in this presentation was directly adapted from:

E. Lin, S. E. Calvano, and S. F. Lowry. Chapter 1. Systemic Response to Injury and Metabolic Support. In Schwartz's Principles of Surgery, 8th ed. F. C. Brunicardi, D. K. Andersen , T. R. Billiar, D. L. Dunn, J. G. Hunter, R. E. Pollock, eds. McGraw-Hill Professional, 2004.