Metabolic Response to Trauma

Presented by Dr. Mohammed haneef

INTRODUCTION ClASSIFICATION FEATURES OF METABOLIC RESPONSE FACTORS MEDIATING METABOLIC RESPONSE CONSEQUENCES OF METABOLIC RESPONSE FACTORS MODIFYING METABOLIC RESPONSE APPLIED ASPECTS

• Following accidental or deliberate injury, a characteristic series of changes occurs, both locally at the site of injury and within the body generally; these changes are intended to restore the body to its pre-injury condition.• The magnitude of the metabolic response is generally

proportional to the severity of tissue injury and the presence of ongoing stimulation but can be modified by additional factors such as infection• The response to injury has probably evolved to aid

recovery,by mobilizing substrates and mechanisms of preventing infection, and by activating repair processes• Although the metabolic response aims to return an

individual to health, a major response can damage organs distant to the injured site itself.• In modern surgery, a major goal is to minimize the metabolic

response to surgery in order to shorten recovery times.

• Classically, these responses have been described as stress response, a term coined by the scottish chemist CUTHBERTSON in 1932.

• Intial response is directed at maintaining adequate substrate suppy to the vital organs, in particular oxygen and energy

• When the inflammatory response impairs function of organs or organ systems, the term multiple organ dysfunction syndrome is applied (MODS)

• SIRS, systemic infalmatory response syndrome is a the term used to describe the body’s response to infections and noninfectious causes and consists of two or more of the following• Hyper/hypo thermia• Leukopenia/ leukocytosis• Tachycardia• Tachyapnea

Classification• Aller and colleagues propose a modern perspective on the

metabolic events associated with the inflammatory response to major trauma• the "ischemia/reperfusion phenotype” –phenotype represents the

immediate, nervous system-related alteration in response to injury, in which neuronal and humoral responses and edema formation predominate. This phase is characterized by regulating the metabolic supply to cells via the least elaborate mechanism:diffusion.

• the "leukocytic phenotype“ – is characterized as the intermediate (or "immune") phase of the metabolic response to trauma. This phase is characterized by leukocytic and bacterial infiltration of previously damaged tissues, which occurs in an edematous, oxygen-poor environment. The resulting post-shock hypercatabolism and hypermetabolism is related to a hyperdynamic response with increased body temperature, increased oxygen consumption, glycogenolysis,lipolysis, proteolysis and futile substrate cycling

• The “ Angeogenic phase “- third ("angiogenic") phenotype is defined as the late (or"endocrine") phase of systemic response to injury. This phase is characterized by a return of oxidative metabolism,favoring angiogenesis in damaged tissues and organs. This process creates a capillary bed that facilitates tissue repair and regeneration

Ebb and Flow phases

• Trauma causes major alterations in energy and protein metabolism.• The response to trauma can be divided into the ebb

phase and the flow phase. The ebb phase occurs immediately after trauma and lasts from 24-48 hours followed by the flow phase. After this, comes the anabolism phase and finally, the fatty-replacement phase.

• Unmodified metabolic response

• Ebb phase -phase of metabolic response to acute stress• Flow phase - phase of metabolic response after operation• Anbolic phase - recovery from operation

Time

Ener

gy E

xpen

ditu

re Ebb PhaseEbb

PhaseFlow

PhaseFlow

Phase

Metabolic Response to Trauma:Ebb Phase (upto 24 hours)• Characterized • Hypovolemic shock• reversible • Irreversible

• Release of Catacholamines/ vasoactive hormones• Cardiac Output• Peripheral Vasoconstriction• Respiratory Rate• Delivery of Maximum oxygen Levels• Blood Glucose• Mobilization of free Fatty acids

Fonseca : Oral and Maxillofacial Trauma Vol.1

Metabolic Response to Trauma:Flow Phase (may last for weeks) Catecholamines basal metabolic Rates Glucocorticoids Glucagon• Release of cytokines, lipid mediators• Acute phase protein production

Fonseca : Oral and Maxillofacial Trauma Vol.1

Anabolic phase• Recovery• restoration of lean body mass, weight and well being

Metabolic Response to Trauma

Fatty Deposits

Liver & Muscle (glycogen)

Muscle (amino acids)

Fatty Acids

Glucose

Amino Acids

Endocrine Response

• Endocrine response in the form of increased catecholamines, glucocorticoids and glycogen, leads to mobilization of tissue energy reserves. These calorie sources include fatty acids and glycerol from lipid reserves, glucose from hepatic glycogen (muscle glycogen can only provide glucose for the involved muscle) and gluconeogenic precursors (eg, amino acids) from muscle.

Flow phase

Phenomenon Effect

catecholamine glucagon cortisol insulin

cardiac output

core body temperature

aldosterone ADH

IL1, IL6, TNF spillage from wound

consumption of glucose, FFA, amino acid

O2 consumption

fluid retention

systemic inflammatory response

N or glucoseN or FFAnormal lactate

CO2 production

heat production

multi-organ failure

Metabolic response

Sequence of events

surgical problem infection

operation

bleeding tissue traumabacterial contamination

necrotic debris

local inflammatory response

wound healing

recovery

hypermetabolism

muscle wastingimmunosuppressionorgan failure

mortality

*

*mortality

food deprivation

wound pain

infection

immobility

Ebb phase

Flow phase

Anabolic phase

*acute stress

Comparison of metabolic response between ebb and flow phase

Ebb phase Flow phase

Blood glucose level N or

Glucose production N

Free fatty acid level N or

Insulin concentration N or

Catecholamine

Comparison of metabolic response between ebb and flow phase (con’t)

Ebb phase Flow phase

Glucagon

Blood lactate level N

Oxygen consumption

Cardiac output

Core temperature

Strategy to attenuate metabolic response to surgery

During ebb phase•Prompt fluid and blood replacement to maintain blood pressure•Adequate oxygen supply and ventilation•Cardiovascular support by inotropes•Antibiotics

During flow phase•Nutritional support•Warm room temperature•Mobilization•Hemodialysis•Timely intervention for complication

• Neuroendocrine Response• Lipid Derived Mediators• Cytokines

• Upregulation of sympathoadrenal axis• epinephrine inhibition of Glucose

uptake• nor epinephrine promotes glucagon

secreation• Vasopressin promotes lipolysis

• dopamine gluconeogenesis

• Stimulation of hypothalamic – pituitary axix

Cytokine Mediated response• Polypeptide hormones, protein mediators• Act locally (paracrine)/ systemically (endocrine)• Responsible for • Fever• Leucocytosis• Hypotension• malaise

• Important cytokines:• TNF• IL-1• IL-2• IL-6• IL-8

• Released by:• Monocytes• Lymphocytes• Marcophages

Lipid derived mediators• Act by:• Enhanced superoxide production• Enchanced platelet aggregation• Changes in endothelial permeability• Altered pulmonary vascular reactivity

Metabolic Response to Overfeeding

• Hyperglycemia• Hypertriglyceridemia• Hypercapnia• Fatty liver• Hypophosphatemia, hypomagnesemia,

hypokalemia Trauma or critically ill patients should not be overfed. Alterations in

serum glucose and lipid levels, development of fatty liver, and electrolyte shifts have been associated with overfeeding.

Macronutrients during StressCarbohydrate

•At least 100 g/day needed to prevent ketosis•Carbohydrate intake during stress should be

between 30%-40% of total calories•Glucose intake should not exceed

5 mg/kg/min

Barton RG. Nutr Clin Pract 1994;9:127-139 ASPEN Board of Directors. JPEN 2002; 26 Suppl 1:22SA

Macronutrientes during Stress

Fat

•Provide 20%-35% of total calories•Maximum recommendation for intravenous lipid

infusion: 1.0 -1.5 g/kg/day•Monitor triglyceride level to ensure adequate

lipid clearance

Barton RG. Nutr Clin Pract 1994;9:127-139ASPEN Board of Directors. JPEN 2002;26 Suppl 1:22SA

Macronutrients during Stress

Protein

•Requirements range from 1.2-2.0 g/kg/day during stress

•Comprise 20%-30% of total calories during stress

Barton RG. Nutr Clin Pract 1994;9:127-139 ASPEN Board of Directors. JPEN 2002;26 Suppl 1:22SA

Determining Protein Requirements for Hospitalized Patients

Stress Level

Calorie:Nitrogen Ratio

Percent Potein / Total Calories

Protein / kg Body Weight

No Stress

< 15% protein

0.8 g/kg/day

Moderate Stress

15-20% protein

1.0-1.2 g/kg/day

1.5-2.0 g/kg/day

> 20% protein

Severe Stress

• Calorie-to-nitrogen ratios can be used to prevent lean body mass from being utilized as a source of energy. Therefore, in the non-stressed patient, less protein is necessary to maintain muscle as compared to the severely stressed patient.

• Nitrogen balance can be affected by the biological value of the protein as well as by growth, caloric balance, sepsis, surgery, activity (bed rest and lack of muscle use can promote nitrogen excretion), and by renal function.

Role of Glutamine in Metabolic Stress

•Considered “conditionally essential” for critical patients

•Depleted after trauma•Provides fuel for the cells of the immune system

and GI tract•Helps maintain or restore intestinal mucosal

integrity

Smith RJ, et al. JPEN 1990;14(4 Suppl):94S-99S; Pastores SM, et al. Nutrition 1994;10:385-391Calder PC. Clin Nutr 1994;13:2-8; Furst P. Eur J Clin Nutr 1994;48:607-616 Standen J, Bihari D. Curr Opin Clin Nutr Metab Care 2000;3:149-157

• Glutamine is one of the few nutrients included in the category of conditionally-essential amino acids.• Glutamine is the body’s most abundant amino acid and is

involved in many physiological functions. Plasma glutamine levels decrease drastically following trauma.• It has been hypothesized that this drop occurs because

glutamine is a preferred substrate for cells of the gastrointestinal cells and white blood cells. • Glutamine helps maintain or restore intestinal mucosal

integrity.

Role of Arginine in Metabolic Stress

• Provides substrates to immune system• Increases nitrogen retention after metabolic stress• Improves wound healing in animal models• Stimulates secretion of growth hormone and is a

precursor for polyamines and nitric oxide• Not appropriate for septic or inflammatory patients.

Barbul A. JPEN 1986;10:227-238; Barbul A, et al. J Surg Res 1980;29:228-235

Key Vitamins and Minerals Vitamin AVitamin CB VitaminsPyridoxineZinc

Vitamin EFolic Acid,Iron, B12

Wound healing and tissue repairCollagen synthesis, wound healingMetabolism, carbohydrate utilizationEssential for protein synthesisWound healing, immune function, protein synthesisAntioxidantRequired for synthesis and replacement of red blood cells

• Micronutrient, trace element, vitamin, and mineral requirements of metabolically stressed patients seem to be elevated above the levels for normal healthy people.• There are no specific dosage guidelines for

micronutrients and trace elements, but there are plausible theories supporting their increased intake.• This slide lists some of these nutrients along with the

rationale for their inclusion.

Factors influencing the Extent and Duration of the Metabolic Response

• Pain and Fear • Surgical Factors:

• Type of surgery• Region• Duration• Preoperative support

• Extent of the trauma and degree of resuscitation• Post traumatic complications:

• Hemorrhage• Hypoxia • Sepsis and Fever• Re-operation

• Pre-existing nutritional status• Age and sex• Anaesthetic considerations

Methods to Minimize the Metabolic Response• Replace blood and fluid losses• Maintain Oxygenation• Give adequate nutrition• Provide Analgesia• Avoid Hypothermia

Consequences of the Response

• Limiting injury

• Initiation of repair processes

• Mobilization of substrates

• Prevention of infection

• Distant organ damage

Strategy to attenuate metabolic response to surgeryPrinciples

• No effective strategy to attenuate metabolic response• Supportive measures are available• Perfect surgery is essential

Strategy to attenuate metabolic response to surgeryDuring ebb phase

• Prompt fluid and blood replacement to maintain blood pressure

• Adequate oxygen supply and ventilation• Cardiovascular support by inotropes• Antibiotics

Strategy to attenuate metabolic response to surgeryDuring flow phase

• Nutritional support• Warm room temperature• Mobilization• Hemodialysis• Timely surgery for complication

References• Fonseca trauma Vol.1• Metabolic response to trauma (The journal of Bone and Joint Surgery)• Clinical aspects of the metabolic response to trauma

(The american Journal of Clinical Nutrition: Vol.3, Number 3)• Metabolic response to trauma

( Australian journal of physiotherapy)• Manipulating the metabolic response to injury

(British medical bulletin 1999;55 (no.1): 181-195)• The metabolic response to stress: an overview and update

(Anesthesiology 73:308-327, 1980)