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SHOCK SHOCK NGA B. PHAM, MD, FAAP NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON EGLESTON 2006 2006

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

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

SHOCK SHOCK

NGA B. PHAM, MD, FAAPNGA B. PHAM, MD, FAAP

CRITICAL CARE MEDICINECRITICAL CARE MEDICINE

CHILDREN’S HEALTHCARE OF ATLANTACHILDREN’S HEALTHCARE OF ATLANTA

EGLESTONEGLESTON

20062006

Page 2: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

ObjectivesObjectives

Review basic physiologic aspects of Review basic physiologic aspects of shockshock

Define shock and its different Define shock and its different categoriescategories

Describe management of shockDescribe management of shock

Page 3: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

What is Shock?What is Shock?Pathophysiology of shockPathophysiology of shock

OxygenOxygen

Demand > SupplyDemand > Supply

Page 4: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Definition of ShockDefinition of Shock

Inadequate tissue perfusion to meet Inadequate tissue perfusion to meet tissue demandstissue demands

Usually result of inadequate blood Usually result of inadequate blood flow and/or oxygen deliveryflow and/or oxygen delivery

Shock is not a blood pressure Shock is not a blood pressure diagnosisdiagnosis

Page 5: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Determinants of Oxygen DeliveryDeterminants of Oxygen Delivery

OxygenOxygenDelivery = Content x Cardiac Delivery = Content x Cardiac

outputoutput

Page 6: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Determinants of Oxygen DeliveryDeterminants of Oxygen Delivery

Oxygen content = 1.34 (Hgb x SaO2) + Oxygen content = 1.34 (Hgb x SaO2) + (PaO2 x 0.003)(PaO2 x 0.003)

SaO2: Oxygen saturationSaO2: Oxygen saturation Hgb: Hemoglobin concentrationHgb: Hemoglobin concentration PaO2: partial pressure Oxygen in plasmaPaO2: partial pressure Oxygen in plasma

To improve Oxygen contentTo improve Oxygen content Increase Hemoglobin concentrationIncrease Hemoglobin concentration Increase saturationIncrease saturation

Page 7: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Determinants of Oxygen DeliveryDeterminants of Oxygen Delivery

Cardiac outputCardiac output C.O. = Heart rate x stroke volumeC.O. = Heart rate x stroke volume

To improve Cardiac outputTo improve Cardiac output Increase Heart rateIncrease Heart rate Increase Stroke VolumeIncrease Stroke Volume

Preload – volume of blood in the ventriclePreload – volume of blood in the ventricle Afterload – resistance to contractionAfterload – resistance to contraction Contractility – force appliedContractility – force applied

Page 8: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Secondary Organ DysfunctionSecondary Organ Dysfunction

Respiratory failureRespiratory failure TachypneaTachypnea Decreased complianceDecreased compliance

Pulm edema, pulm infiltrate, etc.Pulm edema, pulm infiltrate, etc. Increased resistanceIncreased resistance Diaphragm fatigueDiaphragm fatigue

Central vs peripheralCentral vs peripheral Demand >> supplyDemand >> supply Inadequate O2 deliveryInadequate O2 delivery

Page 9: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Secondary Organ DysfunctionSecondary Organ Dysfunction

CNS – altered mental statusCNS – altered mental status Renal insufficiency – pre-renalRenal insufficiency – pre-renal Coagulation abnormalities – DICCoagulation abnormalities – DIC Hepatic/GI dysfunction – bowel Hepatic/GI dysfunction – bowel

ischemiaischemia Endocrine – Calcium, hypo-Endocrine – Calcium, hypo-

adrenalism, vasopressinadrenalism, vasopressin

Page 10: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Classification of ShockClassification of Shock

Hypovolemic Shock (#1 cause world Hypovolemic Shock (#1 cause world wide)wide) Dehydration, hemorrhagicDehydration, hemorrhagic

Cardiogenic ShockCardiogenic Shock Pump failure, obstructive, L-R shuntPump failure, obstructive, L-R shunt

Distributive ShockDistributive Shock NeurogenicNeurogenic AnaphylaxisAnaphylaxis

Septic Shock – All of the aboveSeptic Shock – All of the above

Page 11: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Classification of ShockClassification of Shock

CompensatedCompensated Organ perfusion is maintainedOrgan perfusion is maintained

UncompensatedUncompensated Circulatory failure with end organ Circulatory failure with end organ

dysfunctiondysfunction

IrreverisbleIrreverisble Irreparable loss of essential organsIrreparable loss of essential organs

Page 12: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Mechanical Requirements for Mechanical Requirements for Adequate Tissue PerfusionAdequate Tissue Perfusion

FluidFluid PumpPump VesselsVessels FlowFlow

Page 13: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Hypovolemic ShockHypovolemic Shock

#1 cause of death world wide#1 cause of death world wide GastroenteritisGastroenteritis Hemorrhagic – Trauma, GI bleedHemorrhagic – Trauma, GI bleed

Page 14: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Diagnosis of Hypovolemic ShockDiagnosis of Hypovolemic Shock

EarlyEarly Increase HRIncrease HR Decrease perfusionDecrease perfusion Normal BP, decrease pulse pressureNormal BP, decrease pulse pressure

LateLate Sign increase HRSign increase HR Sign decrease perfusion Sign decrease perfusion Decrease BPDecrease BP End organ dysfunctionEnd organ dysfunction

Page 15: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Pathophysiology of Pathophysiology of Hypovolemic ShockHypovolemic Shock

Decrease intravascular volumeDecrease intravascular volume Compensation – increase Compensation – increase

endogenous catecholaminesendogenous catecholamines Increase HR – increase C.O., O2 deliveryIncrease HR – increase C.O., O2 delivery Increase SVR – increase BP (esp Increase SVR – increase BP (esp

diastolic)diastolic) Compensation for <15% dehydrationCompensation for <15% dehydration

Page 16: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Cardiogenic ShockCardiogenic Shock

Pump failure/malfunctionPump failure/malfunction

(decreased contractility)(decreased contractility)

Page 17: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Cardiogenic ShockCardiogenic Shock

Electrical FailureElectrical Failure ArrhythmiasArrhythmias

Mechanical failureMechanical failure CardiomyopathyCardiomyopathy Metabolic – acidosisMetabolic – acidosis AnatomicAnatomic Hypoxia/ischemiaHypoxia/ischemia ObstructionObstruction

Page 18: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Cardiogenic ShockCardiogenic ShockSymptomsSymptoms

TachycardiaTachycardia TachypneaTachypnea Respiratory distressRespiratory distress Mental status changeMental status change Cool extremitiesCool extremities Poor perfusionPoor perfusion Signs of dehydrationSigns of dehydration

Page 19: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Cardiogenic ShockCardiogenic ShockObstruction of FlowObstruction of Flow

CausesCauses Pericardial tamponadePericardial tamponade Pulmonary embolismPulmonary embolism Pulmonary hypertensionPulmonary hypertension

Page 20: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Cardiogenic ShockCardiogenic ShockObstruction of FlowObstruction of Flow

Cardiac tamponadeCardiac tamponade CausesCauses

PericarditisPericarditis Post-traumaticPost-traumatic Post-cardiac surgeryPost-cardiac surgery Complication of central line placementComplication of central line placement

RecognitionRecognition TachycardiaTachycardia Low C.O., narrow pulse pressure (inc. diastole)Low C.O., narrow pulse pressure (inc. diastole) Inc. CVP, JVDInc. CVP, JVD PULSUS PARADOXUS (>10mmHg)PULSUS PARADOXUS (>10mmHg) Muffled heart sounds (??rub)Muffled heart sounds (??rub) NO RALESNO RALES

Page 21: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Distributive ShockDistributive Shock

Abnormal vessel toneAbnormal vessel tone

(decreased afterload)(decreased afterload)

Page 22: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Distributive ShockDistributive Shock

Vasodilitation Vasodilitation Venous PoolingVenous Pooling

Decreased Decreased AfterloadAfterload

Maldistribution of regional blood flowMaldistribution of regional blood flow

Page 23: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Distributive ShockDistributive Shock

Neurogenic or Anaphylactic ShockNeurogenic or Anaphylactic Shock Diminished or absent sympathetic Diminished or absent sympathetic

tonetone Reduce peripheral vascular toneReduce peripheral vascular tone Peripheral pooling of blood volumePeripheral pooling of blood volume Inadequate venous returnInadequate venous return Decreased perfusion, acidosis, Decreased perfusion, acidosis,

hypotensionhypotension

Page 24: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Septic ShockSeptic Shock

Terminology in SepsisTerminology in Sepsis Infection = response to micro organismInfection = response to micro organism Bacteremia = bug in bloodBacteremia = bug in blood Systemic Inflammatory Response Systemic Inflammatory Response

Syndrome (SIRS)Syndrome (SIRS) T>38, <36T>38, <36 Increase HRIncrease HR Increase RR, paCO2<32Increase RR, paCO2<32 WBC>12,000, <4,000, >10% bandsWBC>12,000, <4,000, >10% bands

Page 25: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Septic ShockSeptic Shock

Terminology in SepsisTerminology in Sepsis Sepsis = SIRS as response to a known Sepsis = SIRS as response to a known

infectioninfection Severe sepsis = Sepsis + organ Severe sepsis = Sepsis + organ

dysfunctiondysfunction Septic Shock = Sepsis + inadequate Septic Shock = Sepsis + inadequate

oxygen deliveryoxygen delivery Multiple Organ Dysfunction Syndrome Multiple Organ Dysfunction Syndrome

(MODS) – organ dysfunction that requires (MODS) – organ dysfunction that requires interventionintervention

Page 26: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Septic ShockSeptic Shock

Components of Septic shockComponents of Septic shock Decreased volumeDecreased volume Decreased pump functionDecreased pump function Abnormal vessel toneAbnormal vessel tone

Page 27: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Septic ShockSeptic Shock

Therapy for Caridovascular SupportTherapy for Caridovascular Support

PreloadPreload VolumeVolume

ContractilityContractility InotropesInotropes

AfterloadAfterload VasodilatorsVasodilators

Page 28: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Septic ShockSeptic Shock

EtiologiesEtiologies Inflammatory: too much, too littleInflammatory: too much, too little Coagulation pathway: DIC-bleeding, Coagulation pathway: DIC-bleeding,

pro-coagulant, microthombosispro-coagulant, microthombosis Multiple organ system failureMultiple organ system failure

Page 29: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Recognition of Septic ShockRecognition of Septic Shock

Early – Early – warm shock warm shock – similar to – similar to neurogenic shockneurogenic shock

Late – Late – Cold shock Cold shock – similar to – similar to cardiogenic shockcardiogenic shock

Page 30: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Diagnosis of Septic ShockDiagnosis of Septic Shock

Establish presence of infectionEstablish presence of infection Inc. HR, normal or dec. BP & Inc. HR, normal or dec. BP &

perfusionperfusion Latic acidosisLatic acidosis Muti-organ dysfunctionMuti-organ dysfunction

Page 31: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Early vs Late Septic ShockEarly vs Late Septic Shock

EarlyEarly LateLate

Heart rateHeart rate TachycardiaTachycardia Tachycardia/Tachycardia/

bradycardiabradycardia

Blood Blood pressurepressure

NormalNormal decreaseddecreased

PeripheralPeripheral

PerfusionPerfusionWarm/coolWarm/cool

Dec./inc. Dec./inc. pulsespulses

CoolCool

Dec. pulsesDec. pulses

Page 32: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Early vs Late Septic ShockEarly vs Late Septic Shock

EarlyEarly LateLate

End-organ: End-organ: skinskin

Dec. cap refillDec. cap refill Very dec. capVery dec. cap

RefillRefill

BrainBrain Irritable, Irritable, restlessrestless

Lethargic, Lethargic, unresponsiveunresponsive

KidneysKidneys OliguriaOliguria Oliguria, Oliguria, anuriaanuria

Page 33: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Treatment Strategies in Treatment Strategies in ShockShock

Page 34: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Principles of ResuscitationPrinciples of Resuscitation

Increase Oxygen Delivery\Increase Oxygen Delivery\ Increase Oxygen contentIncrease Oxygen content Increase Cardiac outputIncrease Cardiac output Increase blood pressureIncrease blood pressure

Decrease DemandDecrease Demand Sedation/analgesiaSedation/analgesia IntubationIntubation

Page 35: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Initial Treatment in ShockInitial Treatment in Shock

AAirwayirway Supplemental oxygen, intubationSupplemental oxygen, intubation

Carefull with cardiovascular collapse post intubation Carefull with cardiovascular collapse post intubation due to positive thoracic pressure decrease venous due to positive thoracic pressure decrease venous returnreturn

BBreathingreathing CCirculationirculation

Intravenous access – go early, go IOIntravenous 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, oxygenationOptimize cardiac function, oxygenation

Page 36: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Restoration of CirculationRestoration of CirculationVolumeVolume

Fluids, fluids, fluidsFluids, fluids, fluidsCrystalloids vs ColloidsCrystalloids vs Colloids

Page 37: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Restoration of CirculationRestoration of CirculationVolumeVolume

CrystalloidsCrystalloids NS is the fluid of choice, availabilityNS is the fluid of choice, availability Rapid redistribution out of intravascular Rapid redistribution out of intravascular

space – capillary leakspace – capillary leak

Page 38: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Restoration of CirculationRestoration of CirculationVolumeVolume

Colloids: albumin, bloodColloids: albumin, blood AlbuminAlbumin

Worsening of edema due to cap leak in early Worsening of edema due to cap leak in early sepsissepsis

BloodBlood Great volume expandersGreat volume expanders Side effects: with massive transfusion >1.5 Side effects: with massive transfusion >1.5

blood volumesblood volumes Risk of infectionRisk of infection Dilutional thrombocytopenia and factors V & VIIIDilutional thrombocytopenia and factors V & VIII Calcium binding hemodynamic instability (citrate)Calcium binding hemodynamic instability (citrate)

Page 39: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Restoration of CirculationRestoration of CirculationVolume – Fluid ChoicesVolume – Fluid Choices

Based on:Based on: Type of deficitType of deficit Urgency of repletionUrgency of repletion Pathophysiology of shockPathophysiology of shock

Page 40: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Restoration of CirculationRestoration of CirculationVolume – Fluid ChoicesVolume – Fluid Choices

Crystalloids for initial resuscitationCrystalloids for initial resuscitation Colloids/PRBC’s to replace blood lossColloids/PRBC’s to replace blood loss

Page 41: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

Treatment of ShockTreatment of ShockCardiac SupportCardiac Support

AlphaAlpha DopamineDopamine BetaBeta

EpinephrineEpinephrine

NorepinephrineNorepinephrine DobutamineDobutamine

NeosynephrineNeosynephrine

Page 42: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

InotropesInotropes

AgentAgent Site of ActionSite of Action DoseDose

Mcg/kg/minMcg/kg/minEffectsEffects

DopamineDopamine DopaminergicDopaminergic

BetaBeta

Alpha > BetaAlpha > Beta

1-31-3

5-105-10

11-2011-20

Renal vasodilationRenal vasodilation

Inotrope/vasoconstrictionInotrope/vasoconstriction

Increase perip. Vasc. resistanceIncrease perip. Vasc. resistance

DobutamineDobutamine Beta 1 & 2Beta 1 & 2 1-201-20 InotropeInotrope

VasodilationVasodilation

EpineprhineEpineprhine Beta > alphaBeta > alpha 0.05 – 1.00.05 – 1.0 Inotrope, vasoconstrictionInotrope, vasoconstriction

TachycardiaTachycardia

NorepinephriNorepinephrinene

Alpha > betaAlpha > beta 0.05 – 1.00.05 – 1.0 Profound vasoconstrictionProfound vasoconstriction

inotropeinotrope

NitroprussideNitroprusside VasodilatorVasodilator

(art > venous)(art > venous)0.5 – 1.00.5 – 1.0 VasodilationVasodilation

MilranoneMilranone Phosphodiesterase Phosphodiesterase inhibitorinhibitor

0.5 – 0.750.5 – 0.75 InotropeInotrope

vasodilationvasodilation

Page 43: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

““New” Therapies in Septic ShockNew” Therapies in Septic Shock

VasopressinVasopressin SteroidsSteroids Activated protein C (Xigris) in Septic Activated protein C (Xigris) in Septic

ShockShock

Page 44: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

New” “ Therapies in Septic ShockNew” “ Therapies in Septic ShockVasopressinVasopressin

Unclear mechanism of actionUnclear mechanism of action Bridging vascular instability in high Bridging vascular instability in high

exogenous catecholamines exogenous catecholamines requirement septic shock, therefore requirement septic shock, therefore decrease side effects of toxic dosage decrease side effects of toxic dosage of catecholaminesof catecholamines

Also shows greater blood flow Also shows greater blood flow diversion from non-vital to vital diversion from non-vital to vital organsorgans

Page 45: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

New” “ Therapies in Septic ShockNew” “ Therapies in Septic ShockVasopressinVasopressin

Dosage 0.01 – 0.04U/min up to Dosage 0.01 – 0.04U/min up to 0.08U/min0.08U/min

Page 46: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

New” “ Therapies in Septic ShockNew” “ Therapies in Septic ShockSteroidsSteroids

Hypo-adrenalism: abnormal Hypo-adrenalism: abnormal hypothalamus-pituitary-adrenal axishypothalamus-pituitary-adrenal axis

At risk of adrenal insufficiency – in the At risk of adrenal insufficiency – in the presence of catecholamine presence of catecholamine requirementrequirement Fluid refractory shockFluid refractory shock Normal BP, cold shockNormal BP, cold shock Low BP, cold shockLow BP, cold shock

Dosage – stress doseDosage – stress dose Hydrocortisone 150 mg/m2 ivpHydrocortisone 150 mg/m2 ivp

Page 47: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

New” “ Therapies in Septic ShockNew” “ Therapies in Septic ShockSteroidsSteroids

Glucocorticoid function – immune Glucocorticoid function – immune responseresponse

Fall in circulating lymphocytesFall in circulating lymphocytes Inhibits neutrophils migration to the Inhibits neutrophils migration to the

inflammatory sitesinflammatory sites Inhibits macrophages secretionInhibits macrophages secretion Promotes eosinophilic apoptosisPromotes eosinophilic apoptosis Modulates cytokines production Modulates cytokines production

Page 48: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

New” “ Therapies in Septic ShockNew” “ Therapies in Septic ShockSteroidsSteroids

Glucocorticoid function – CardiovascularGlucocorticoid function – Cardiovascular Modulate vascular reactivity to Modulate vascular reactivity to

angiotensin II and to catecholamines -angiotensin II and to catecholamines -Not fully understood mechanismNot fully understood mechanism

Modulate vascular permeability and Modulate vascular permeability and production of NO and other production of NO and other vasodilator factorvasodilator factor

INCREASE IN BLOOD PRESSUREINCREASE IN BLOOD PRESSURE

Page 49: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

New” “ Therapies in Septic ShockNew” “ Therapies in Septic ShockSteroidsSteroids

Glucocorticoid production in stressGlucocorticoid production in stress Maintain homeostasisMaintain homeostasis Normalize vascular reactivityNormalize vascular reactivity Modulate inflammatory responseModulate inflammatory response

Page 50: SHOCK NGA B. PHAM, MD, FAAP CRITICAL CARE MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA EGLESTON2006

New” “ Therapies in Septic ShockNew” “ Therapies in Septic ShockActivated Protein C (Xigris)Activated Protein C (Xigris)

Recombinant Human Activated Protein Recombinant Human Activated Protein CC Prevent DIC cascade with antithrombotic Prevent DIC cascade with antithrombotic

activity by inhibiting factors Va & VIIIaactivity by inhibiting factors Va & VIIIa May exerts anti-inflammatory effects by May exerts anti-inflammatory effects by

inhibiting TNF and by blocking leukocytes inhibiting TNF and by blocking leukocytes adhesionsadhesions

Side effectsSide effects BleedingBleeding Pediatric trial terminated early (03/04) due Pediatric trial terminated early (03/04) due

to no benefit to known risk of bleedingto no benefit to known risk of bleeding