Metabolic responses that occur following trauma and its clinical implications to minimize morbidity and mortality. Mentor: Dr Saikat Saha MDS, OMFS, SIliguri, West Bengal, India Address: MAXFAC Center for Oral and Maxillofacial and Head & Neck Surgery, Siliguri Email : maxfacmail@gmail.com

1. METABOLIC RESPONSE TO
TRAUMA
Maxfac
Center for Cranio - Maxillofacial & Head and Neck Surgery, Siliguri
Contact us at : maxfacmail@gmail.com
Mentor & Guide :
Dr Saikat Saha MDS OMFS
Presenter : Dr Mukesh Chhetri BDS
Fellow Trainee at Maxfac

2. INTRODUCTION
SIRS/MODS
CRITERIAS
PHYSIOLOGIC RESPONSE
EBB PHASE vs FLOW PHASE
MEDIATORS OF RESPONSE
NEURO ENDORCRINE RESPONSE
LIPID DERIVED MEDIATORS
CYTOKINES
POLYMORPHONUCLEAR NEUTROPHILS
CLINICAL IMPLICATIONS
MODULATION OF RESPONSE
ADULT RESPIRATORY RESPONSE SYNDROME
NUTRITION AS THERAPY
DEEP VEIN THROMBOSIS
STRESS GASTRITIS
CONCLUSION

3. INJURY
HORMONES ANS CYTOKINES
STRESS RESPONSE(Cuthbertson)
+ -

4. SIRS- Systemic Inflammatory Response
Syndrome
Body’s response to infectious and non-infectious
causes.
Consists of two or more of the following:
1. Hyperthermia/Hypothermia.
2. Leucocytosis/Leucopenia.
3. Tachycardia.
4. Tachypnea.
MODS-Multiple Organ Dysfunction Syndrome
When the inflammatory response impairs
functions of organ/organ system.

5. SIRS Criteria(≥2 meets SIRS Critetria)
 Temp >38℃ (100.4℉) or <36℃ (96.8℉)
 Heart Rate >90
 Resp. Rate >20 or PaCO2 <32mmHg (4.3 kPa)
 WBC 12,000/mm3, 4000/mm3 or 10% Immature bands.
SEPSIS Criteria (SIRS + Source of Infection)
Suspected or Present source of infection.
SEVERE SEPSIS Criteria(Organ Dysfunction, Hypotension or
Hypoperfusion)
Severe sepsis with Hypotension despite adequate fluid resusciitation.
MODS Criteria
Evidence of ≥2 organ failing.
qSOFA (quick Sequential Organ Failure Assessment)score
for Sepsis
 Altered Mental Status (GCS <15)
 Respiratory rate ≥ 22
 Systolic BP ≤100
(a +ve score ≥2 suggests high risk of poor outcome in pts with suspected illness )

6. Local effects like Tissue Edema, Vasoconstriction and
Thrombosis
Distant effects(other mediators released into the systemic circulation
act at sites removed from injury ) like stimulation of ANS, prod. of
Hormones, Cytokines and Arachidonic Acid metabolites
Inflammatory Reaction
Tissue Damage

7. EBB PHASE(immediate, as long as24 hours
after injury)
•Reconstruction of body normal tissue
perfusion & efforts to protect normal
homeostasis
•Release of Catecholamines and vasoactive
hormones.
•↑HR + ↑Cardiac contractility → Cardiac
Output
•Peripheral and Splanchnic vasoconstriction
•↑Resp. rate → ↑oxygen delivery
•↑ Blood Glucose level
•Free Fatty acids are mobilized by catabolic
hormones(main source of energy for
peripheral tissues).
•Stored Hepatic glycogen depleted within 1
day.
• ↓ Total body energy & urinary nitrogen
excretion
•Hypotension due to ↓effective circulatory
volume
FLOW/CATABOLIC PHASE(may last for weeks)
•Metabolic emphasis on provision of
substrate for healing.
•↑ BMR → muscle catabolized to make
glucose.
•Catabolism → ↑83% -after skeletal trauma.
↑103% - in burn patients.
•Total body Nitrogen balance becomes –ve.
•Some earlier EBB changes reverse →
Diuresis may occur, HR may slow.
•Anabolic phase is the Late phase of flow
phase.

8.  Postoperatively
 Glucose utilization reduced due to insulin resistance, ↑ in FFA and triglycerides.
due to catecholamine release
 Metabolic response maintained by catabolic hormones glucagon, catecholamines
and corticosteroids and insulin resistance.
 Cytokines, Oxygen radicals and other mediators>>anabolic(wound healing) +
catabolic(peripheral tissues like muscle, fat and skin)
 Amino acids(synthesis of acute phase proteins+ wound healing) eg. Essential +
Non Essential(glutamine, alanine, arginine)
 Corticoid withdrawal phase: transition from catabolic to anabolic, 3-8 days
after uncomplicated elective surgery, ↓net nitrogen excretion & appropriate
potassium-nitrogen balance.
 Early anabolic phase(few weeks to few months)
Beginning of diuresis & oral intake request
Positive nitrogen balance>> Max of 4g/day to protein
synthesis of approx. 25g/day & Body mass gain of 100g/day.
 Late anabolic phase(weeks to several months)-final phase of the recovery
period, gradual restoration of body protein, fat stores and normalization of
Positive Nitrogen balance.

9. BRAIN
INJURY
Brain injury with
multisystem trauma
Risk of Death more than
doubles
(Neurological + Deranged
metabolism + other
interventions like Steroids,
Systemic Dehydration, Muscle
Paralysis, Hypoventilation,
Hypothermia, Hyperbaric O2
therapy, Barbiturate coma )
CLASSIC FAT
EMBOLISM
SYNDROME (LONG
BONE #)
Fatty acids + Triglycerides
globules
Enter venous sinusoids
at # site
Enter lungs
Damage pulmonary vasculature
Activate platelets+ Aggregate+
Attach to fat globule
Consumptive Coagulopathy
(DIC)
With Pulmonary lipase forms
FREE FATTY ACIDS

10. Mediators of Response
Sympathetic activity
Lipolysis within adipose tissue
Energy source of Gluconeogenesis
plasma conc. of epinephrine, nor.
Epinephrine, vasopressin,
dopamine
Affects blood glucose levels
Inhibits uptake of glucose by tissues
Glucagon secretion
In liver

11. Muscle Breakdown Protein catabolism AA release
Pituitary release
ACTH (corticotropin)
Stimulates adrenal cortex
Glucocorticoid hormnone
Epinephrine + Cortisol Aldosterone

12. ↑superoxide production
↑platelet aggregation
Altered pulmonary vascular
reactivity
Changes in the endothelial
permeability
 ↑ Cyclooxygenase
products
Thromboxane A2>> ↑ Neutrophil
agggregration
Prostacyclin >>pulmonary hypoxic
vasoconstriction + systemic
vasodilation
 ↑ Lipooxygenase
products>>permeability of
pulmonary vascular bed
 Platelet Activating
Factor (PAF)
Phospholipid metabolite
released by PMNs and other
cells
Act at the endothelial surface

13. TNF
Interleukins
IL-1
IL-2
IL-6
IL-8
Interferons
Growth factors
GM-CSF
PDGFs
TNF(Tumor Necrosis Factor)
 Most proximal mediator
 Originally described as catabolic
factor Cachetin
 2 forms
 Actions:
◦ Influences cellular attraction (loc. Infl. resp)
◦ Leukocyte migration
◦ Systemic hypotension
◦ Promote muscle catabolism
◦ Free fatty acid release
◦ Hepatic synthesis of acute phase reactants
Interleukins
 Polypeptides released from lymphocytes
 IL-1: Originally Pyrexin
 Few hours after injury in circulation
 Actions:
◦ Activation of resting T lymp. & Macrophage
◦ Induction of Haematopoietic Gr. Factor.
◦ Stimulation of chemotaxis of PMNs
◦ Synthesis of Collagen and Collagenases
◦ Fever & change in protein metabolism.
◦ Produces PGs in Hypothallamus>alters set
point of thermoregulator>antiPG agents
like aspirin block fever effect
◦ Byproducts: ↑ proteolysis of muscle, induce
hepatic protein synthesis.
IL-6: B cell differentiation factor
◦ In severe injury, predictor of adverse
outcome & mortality

15.  Modulation of response
1. Anticytokine antibodies & Specific cytokine receptor antagonists:
block some cytokine effects on target tissues.
2. Ibuprofen: Inhibits eicosanoids production>> ↓ fever.
3. IIT(Intensive Insulin Therapy): requires maintenance of blood glucose
levels below 110 mg/dl.
4. Role of glucocorticoid: Low dose corticosteroid therapy>>↓ duration of shock
state, improve short term survival.
Hydrocortisone therapy attenuates stress
response & ↓ Hospital acquired pneumonia.
5. Human activated protein C (drotrecogin alfa activated): Targets
procoagulant & generalized inflammatory response occurring during
sepsis.
 Adult Respiratory Distress Syndrome:
Acute illness characterized by non-cardiogenic pulmonary edema>>Refractory
hypoxaemia>>Damage to alveolar-capillary interface>>Intrapulmonary
shunting of blood>>↑ Pulmonary vascular pressure>>Surfactant depletion.
Treatment: Mechanical Ventilation( Low tidal volume ventilation 6mL/kg
predicted body weight> Traditional tidal volumes 12mL/kg)
Alternative therapies: High frequency oscillatory ventilation, Prone
positioning, ECLS(ExtraCorporeal lLfe Support), ECMO(ExtraCorporeal Membrane
Oxygenation).

16.  Enteric Nutrition > Parenteral Nutrition
 ↓Enteric org. resp. for bacterial translocation
 Stimulation of enterocyte brush border & gut- associated
lymphoid tissue>> ↓cytokine prod., ↓ bact. proliferation.
 Arginine+Glutamine+Nucleic acid>>enhance immune system.
 Omega 3 UFA> Omega 6 UFA- ↑ immune system.
 Vit A,C,E, trace element Selenium>>antioxidant, prevent free
radical damage.
 ‘Immunonutrition’: enteric diet-Omega 3 FA + gamma linolenic
acid + antioxidants, Eicosapentaenoic acid + gamma linolenic
acid+antioxidants

17.  Hypercoagulable state exists immediately after sever traumatic injury.
 Hypercoagulable state + Pt. immobility + Direct venous injury = Virchow’s triad for
venous thrombosis.
Tissue injury
Tissue thromboplastin
Factor VII Enzyme Factor VIIa
Prophylaxis: Subcutaneous mixed/Low mol. Wt Heparin (full duration of hospital stay or
when fully mobile)
Except in specific Contraindications like: Intracranial Haemorrhage, known peptic ulcer,
solid organ laceration, haematoma.
Alternative sequential compression device on limbs.
Chemo prohpylaxis contraindicated in pt with Traumatic Brain injury with intracranial
haemorrhage(3-4 times chance of having DVT)
Stress Gastritis
Left untreated>>GI bleeding
Stress factor>> head injury, mechanical ventilation, abnormal
coagulation profiles
Prophylaxis: histamine 2 receptor antagonists/PPI

18. Injury produces a series of physiologic changes mediated by local and systemic agents
and systemic effects, mainly cytokines, hormones, and activation of the sympathetic
nervous system.
The metabolic response aims to promote substrate delivery to the injured organs and
promote healing.
However, in the setting of severe trauma, these responses can result in organ injury,
particularly to the lungs.
These consequences can produce significant morbidity and mortality. An appreciation of
nuances of the metabolic response allows the clinician to support the patient through
the physiologic changes associated with the stress response caused by injury.

19. Thank You
Maxfac
Center for Cranio - Maxillofacial & Head and Neck Surgery, Siliguri
Contact us at : maxfacmail@gmail.com
Mentor & Guide :
Dr Saikat Saha MDS OMFS
Dr Mukesh Chhetri BDS
Fellow Trainee at Maxfac