1. SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

2. Objectives Review basic physiologic aspects of shock Review basic physiologic aspects of shock Define shock and its different categories Define shock and its different categories Describe management of shock Describe management of shock

3. What is Shock? Pathophysiology of shock Oxygen Demand > Supply

4. Definition of Shock Inadequate tissue perfusion to meet tissue demands Inadequate tissue perfusion to meet tissue demands Usually result of inadequate blood flow and/or oxygen delivery Usually result of inadequate blood flow and/or oxygen delivery Shock is not a blood pressure diagnosis Shock is not a blood pressure diagnosis

5. Determinants of Oxygen Delivery Oxygen Oxygen Delivery = Content x Cardiac output

6. Determinants of Oxygen Delivery Oxygen content = 1.34 (Hgb x SaO2) + (PaO2 x 0.003) Oxygen content = 1.34 (Hgb x SaO2) + (PaO2 x 0.003) SaO2: Oxygen saturation SaO2: Oxygen saturation Hgb: Hemoglobin concentration Hgb: Hemoglobin concentration PaO2: partial pressure Oxygen in plasma PaO2: partial pressure Oxygen in plasma To improve Oxygen content To improve Oxygen content Increase Hemoglobin concentration Increase Hemoglobin concentration Increase saturation Increase saturation

7. Determinants of Oxygen Delivery Cardiac output Cardiac output C.O. = Heart rate x stroke volume C.O. = Heart rate x stroke volume To improve Cardiac output To improve Cardiac output Increase Heart rate Increase Heart rate Increase Stroke Volume Increase Stroke Volume Preload – volume of blood in the ventricle Preload – volume of blood in the ventricle Afterload – resistance to contraction Afterload – resistance to contraction Contractility – force applied Contractility – force applied

8. Secondary Organ Dysfunction Respiratory failure Respiratory failure Tachypnea Tachypnea Decreased compliance Decreased compliance Pulm edema, pulm infiltrate, etc. Pulm edema, pulm infiltrate, etc. Increased resistance Increased resistance Diaphragm fatigue Diaphragm fatigue Central vs peripheral Central vs peripheral Demand >> supply Demand >> supply Inadequate O2 delivery Inadequate O2 delivery

9. Secondary Organ Dysfunction CNS – altered mental status CNS – altered mental status Renal insufficiency – pre-renal Renal insufficiency – pre-renal Coagulation abnormalities – DIC Coagulation abnormalities – DIC Hepatic/GI dysfunction – bowel ischemia Hepatic/GI dysfunction – bowel ischemia Endocrine – Calcium, hypo-adrenalism, vasopressin Endocrine – Calcium, hypo-adrenalism, vasopressin

10. Classification of Shock Hypovolemic Shock (#1 cause world wide) Hypovolemic Shock (#1 cause world wide) Dehydration, hemorrhagic Dehydration, hemorrhagic Cardiogenic Shock Cardiogenic Shock Pump failure, obstructive, L-R shunt Pump failure, obstructive, L-R shunt Distributive Shock Distributive Shock Neurogenic Neurogenic Anaphylaxis Anaphylaxis Septic Shock – All of the above Septic Shock – All of the above

11. Classification of Shock Compensated Compensated Organ perfusion is maintained Organ perfusion is maintained Uncompensated Uncompensated Circulatory failure with end organ dysfunction Circulatory failure with end organ dysfunction Irreverisble Irreverisble Irreparable loss of essential organs Irreparable loss of essential organs

12. Mechanical Requirements for Adequate Tissue Perfusion Fluid Fluid Pump Pump Vessels Vessels Flow Flow

13. Hypovolemic Shock #1 cause of death world wide #1 cause of death world wide Gastroenteritis Gastroenteritis Hemorrhagic – Trauma, GI bleed Hemorrhagic – Trauma, GI bleed

14. Diagnosis of Hypovolemic Shock Early Early Increase HR Increase HR Decrease perfusion Decrease perfusion Normal BP, decrease pulse pressure Normal BP, decrease pulse pressure Late Late Sign increase HR Sign increase HR Sign decrease perfusion Sign decrease perfusion Decrease BP Decrease BP End organ dysfunction End organ dysfunction

15. Pathophysiology of Hypovolemic Shock Decrease intravascular volume Decrease intravascular volume Compensation – increase endogenous catecholamines Compensation – increase endogenous catecholamines Increase HR – increase C.O., O2 delivery Increase HR – increase C.O., O2 delivery Increase SVR – increase BP (esp diastolic) Increase SVR – increase BP (esp diastolic) Compensation for <15% dehydration Compensation for <15% dehydration

16. Cardiogenic Shock Pump failure/malfunction (decreased contractility)

17. Cardiogenic Shock Electrical Failure Electrical Failure Arrhythmias Arrhythmias Mechanical failure Mechanical failure Cardiomyopathy Cardiomyopathy Metabolic – acidosis Metabolic – acidosis Anatomic Anatomic Hypoxia/ischemia Hypoxia/ischemia Obstruction Obstruction

18. Cardiogenic Shock Symptoms Tachycardia Tachycardia Tachypnea Tachypnea Respiratory distress Respiratory distress Mental status change Mental status change Cool extremities Cool extremities Poor perfusion Poor perfusion Signs of dehydration Signs of dehydration

19. Cardiogenic Shock Obstruction of Flow Causes Causes Pericardial tamponade Pericardial tamponade Pulmonary embolism Pulmonary embolism Pulmonary hypertension Pulmonary hypertension

20. Cardiogenic Shock Obstruction of Flow Cardiac tamponade Causes Causes Pericarditis Pericarditis Post-traumatic Post-traumatic Post-cardiac surgery Post-cardiac surgery Complication of central line placement Complication of central line placement Recognition Recognition Tachycardia Tachycardia Low C.O., narrow pulse pressure (inc. diastole) Low C.O., narrow pulse pressure (inc. diastole) Inc. CVP, JVD Inc. CVP, JVD PULSUS PARADOXUS (>10mmHg) PULSUS PARADOXUS (>10mmHg) Muffled heart sounds (??rub) Muffled heart sounds (??rub) NO RALES NO RALES

21. Distributive Shock Abnormal vessel tone Abnormal vessel tone (decreased afterload)

22. Distributive Shock Vasodilitation Venous Pooling Decreased Afterload Maldistribution of regional blood flow

23. Distributive Shock Neurogenic or Anaphylactic Shock Neurogenic or Anaphylactic Shock Diminished or absent sympathetic tone Diminished or absent sympathetic tone Reduce peripheral vascular tone Reduce peripheral vascular tone Peripheral pooling of blood volume Peripheral pooling of blood volume Inadequate venous return Inadequate venous return Decreased perfusion, acidosis, hypotension Decreased perfusion, acidosis, hypotension

24. Septic Shock Terminology in Sepsis Terminology in Sepsis Infection = response to micro organism Infection = response to micro organism Bacteremia = bug in blood Bacteremia = bug in blood Systemic Inflammatory Response Syndrome (SIRS) Systemic Inflammatory Response Syndrome (SIRS) T>38, 38, <36 Increase HR Increase HR Increase RR, paCO2<32 Increase RR, paCO2<32 WBC>12,000, 10% bands WBC>12,000, 10% bands

25. Septic Shock Terminology in Sepsis Terminology in Sepsis Sepsis = SIRS as response to a known infection Sepsis = SIRS as response to a known infection Severe sepsis = Sepsis + organ dysfunction Severe sepsis = Sepsis + organ dysfunction Septic Shock = Sepsis + inadequate oxygen delivery Septic Shock = Sepsis + inadequate oxygen delivery Multiple Organ Dysfunction Syndrome (MODS) – organ dysfunction that requires intervention Multiple Organ Dysfunction Syndrome (MODS) – organ dysfunction that requires intervention

26. Septic Shock Components of Septic shock Components of Septic shock Decreased volume Decreased volume Decreased pump function Decreased pump function Abnormal vessel tone Abnormal vessel tone

27. Septic Shock Therapy for Caridovascular Support Therapy for Caridovascular Support PreloadVolume ContractilityInotropes AfterloadVasodilators

28. Septic Shock Etiologies Inflammatory: too much, too little Inflammatory: too much, too little Coagulation pathway: DIC-bleeding, pro- coagulant, microthombosis Coagulation pathway: DIC-bleeding, pro- coagulant, microthombosis Multiple organ system failure Multiple organ system failure

29. Recognition of Septic Shock Early – warm shock – similar to neurogenic shock Early – warm shock – similar to neurogenic shock Late – Cold shock – similar to cardiogenic shock Late – Cold shock – similar to cardiogenic shock

30. Diagnosis of Septic Shock Establish presence of infection Establish presence of infection Inc. HR, normal or dec. BP & perfusion Inc. HR, normal or dec. BP & perfusion Latic acidosis Latic acidosis Muti-organ dysfunction Muti-organ dysfunction

31. Early vs Late Septic Shock EarlyLate Heart rate TachycardiaTachycardia/bradycardia Blood pressure Normaldecreased PeripheralPerfusionWarm/cool Dec./inc. pulses Cool Dec. pulses

32. Early vs Late Septic Shock EarlyLate End-organ: skin Dec. cap refill Very dec. cap Refill Brain Irritable, restless Lethargic, unresponsive KidneysOliguria Oliguria, anuria

33. Treatment Strategies in Shock

34. Principles of Resuscitation Increase Oxygen Delivery\ Increase Oxygen Delivery\ Increase Oxygen content Increase Oxygen content Increase Cardiac output Increase Cardiac output Increase blood pressure Increase blood pressure Decrease Demand Decrease Demand Sedation/analgesia Sedation/analgesia Intubation Intubation

35. Initial Treatment in Shock Airway Airway Supplemental oxygen, intubation Supplemental oxygen, intubation Carefull with cardiovascular collapse post intubation due to positive thoracic pressure decrease venous return Carefull with cardiovascular collapse post intubation due to positive thoracic pressure decrease venous return Breathing Breathing Circulation Circulation Intravenous access – go early, go IO Intravenous access – go early, go IO Volume expansion (40cc/kg NS, repeat prn) Volume expansion (40cc/kg NS, repeat prn) Carefull with cardiogenic shock (5cc/kg then reassess) Carefull with cardiogenic shock (5cc/kg then reassess) Optimize cardiac function, oxygenation Optimize cardiac function, oxygenation

36. Restoration of Circulation Volume Fluids, fluids, fluids Crystalloids vs Colloids

37. Restoration of Circulation Volume Crystalloids Crystalloids NS is the fluid of choice, availability NS is the fluid of choice, availability Rapid redistribution out of intravascular space – capillary leak Rapid redistribution out of intravascular space – capillary leak

38. Restoration of Circulation Volume Colloids: albumin, blood Colloids: albumin, blood Albumin Albumin Worsening of edema due to cap leak in early sepsis Worsening of edema due to cap leak in early sepsis Blood Blood Great volume expanders Great volume expanders Side effects: with massive transfusion >1.5 blood volumes Side effects: with massive transfusion >1.5 blood volumes Risk of infection Risk of infection Dilutional thrombocytopenia and factors V & VIII Dilutional thrombocytopenia and factors V & VIII Calcium binding hemodynamic instability (citrate) Calcium binding hemodynamic instability (citrate)

39. Restoration of Circulation Volume – Fluid Choices Based on: Based on: Type of deficit Type of deficit Urgency of repletion Urgency of repletion Pathophysiology of shock Pathophysiology of shock

40. Restoration of Circulation Volume – Fluid Choices Crystalloids for initial resuscitation Crystalloids for initial resuscitation Colloids/PRBC’s to replace blood loss Colloids/PRBC’s to replace blood loss

41. Treatment of Shock Cardiac Support AlphaDopamineBeta Epinephrine Norepinephrine Dobutamine Neosynephrine

42. InotropesAgent Site of Action DoseMcg/kg/minEffects DopamineDopaminergicBeta Alpha > Beta 1-35-1011-20 Renal vasodilation Inotrope/vasoconstriction Increase perip. Vasc. resistance Dobutamine Beta 1 & 2 1-20InotropeVasodilation Epineprhine Beta > alpha 0.05 – 1.0 Inotrope, vasoconstriction Tachycardia Norepinephrine Alpha > beta 0.05 – 1.0 Profound vasoconstriction inotrope NitroprussideVasodilator (art > venous) 0.5 – 1.0 Vasodilation Milranone Phosphodiesterase inhibitor 0.5 – 0.75 Inotropevasodilation

43. “New” Therapies in Septic Shock Vasopressin Vasopressin Steroids Steroids Activated protein C (Xigris) in Septic Shock Activated protein C (Xigris) in Septic Shock

44. New” “ Therapies in Septic Shock Vasopressin Unclear mechanism of action Unclear mechanism of action Bridging vascular instability in high exogenous catecholamines requirement septic shock, therefore decrease side effects of toxic dosage of catecholamines Bridging vascular instability in high exogenous catecholamines requirement septic shock, therefore decrease side effects of toxic dosage of catecholamines Also shows greater blood flow diversion from non-vital to vital organs Also shows greater blood flow diversion from non-vital to vital organs

45. New” “ Therapies in Septic Shock Vasopressin Dosage 0.01 – 0.04U/min up to 0.08U/min Dosage 0.01 – 0.04U/min up to 0.08U/min

46. New” “ Therapies in Septic Shock Steroids Hypo-adrenalism: abnormal hypothalamus-pituitary-adrenal axis Hypo-adrenalism: abnormal hypothalamus-pituitary-adrenal axis At risk of adrenal insufficiency – in the presence of catecholamine requirement At risk of adrenal insufficiency – in the presence of catecholamine requirement Fluid refractory shock Fluid refractory shock Normal BP, cold shock Normal BP, cold shock Low BP, cold shock Low BP, cold shock Dosage – stress dose Dosage – stress dose Hydrocortisone 150 mg/m2 ivp Hydrocortisone 150 mg/m2 ivp

47. New” “ Therapies in Septic Shock Steroids Glucocorticoid function – immune response Fall in circulating lymphocytes Fall in circulating lymphocytes Inhibits neutrophils migration to the inflammatory sites Inhibits neutrophils migration to the inflammatory sites Inhibits macrophages secretion Inhibits macrophages secretion Promotes eosinophilic apoptosis Promotes eosinophilic apoptosis Modulates cytokines production Modulates cytokines production

48. New” “ Therapies in Septic Shock Steroids Glucocorticoid function – Cardiovascular Modulate vascular reactivity to angiotensin II and to catecholamines -Not fully understood mechanism Modulate vascular reactivity to angiotensin II and to catecholamines -Not fully understood mechanism Modulate vascular permeability and production of NO and other vasodilator factor Modulate vascular permeability and production of NO and other vasodilator factor INCREASE IN BLOOD PRESSURE

49. New” “ Therapies in Septic Shock Steroids Glucocorticoid production in stress Maintain homeostasis Maintain homeostasis Normalize vascular reactivity Normalize vascular reactivity Modulate inflammatory response Modulate inflammatory response

50. New” “ Therapies in Septic Shock Activated Protein C (Xigris) Recombinant Human Activated Protein C Recombinant Human Activated Protein C Prevent DIC cascade with antithrombotic activity by inhibiting factors Va & VIIIa Prevent DIC cascade with antithrombotic activity by inhibiting factors Va & VIIIa May exerts anti-inflammatory effects by inhibiting TNF and by blocking leukocytes adhesions May exerts anti-inflammatory effects by inhibiting TNF and by blocking leukocytes adhesions Side effects Side effects Bleeding Bleeding Pediatric trial terminated early (03/04) due to no benefit to known risk of bleeding Pediatric trial terminated early (03/04) due to no benefit to known risk of bleeding