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SHOCKSHOCK
September 6, 2005September 6, 2005
Andrew FiliatrautAndrew Filiatraut
In GeneralIn General
ShockShock Clinical syndrome defined as Clinical syndrome defined as
hypoperfusion hypoperfusion Hypotension and Cellular HypoxiaHypotension and Cellular Hypoxia
Elevated lactateElevated lactate OliguriaOliguria Hepatic/GI dysfunctionHepatic/GI dysfunction Mental status changes Mental status changes
In GeneralIn General
Four ClassificationsFour Classifications HypovolemicHypovolemic CardiogenicCardiogenic ObstructiveObstructive DistributiveDistributive
Septic, Addison’s, Anaphylactic, Neurogenic, Septic, Addison’s, Anaphylactic, Neurogenic, Thyrotoxicosis, Beriberi, Paget’s, Cirrhosis, Thyrotoxicosis, Beriberi, Paget’s, Cirrhosis, Chroinc Anemia, Osler-Weber-RenduChroinc Anemia, Osler-Weber-Rendu
Hemodynamic ProfilesHemodynamic Profiles
TYPETYPE BPBP C.O.C.O. PCWPPCWP SVRSVR
↓ ↓ Vol.Vol. ↓↓ ↓↓ ↓↓ ↑↑
CardioCardio ↓↓ ↓↓ ↑↑ ↑↑
TmpnaTmpnadd
↓ ↓ or Nor N ↓ ↓ or Nor N ↑ ↑ or Nor N ↑↑
P. E.P. E. ↓↓ ↓↓ ↓ ↓ or Nor N ↑↑
DistribDistrib ↓↓ ↑↑ ↓↓ ↓↓
Septic ShockSeptic Shock
EpidemiologyEpidemiology
751,000 cases of severe sepsis /year751,000 cases of severe sepsis /year Up to half develop shockUp to half develop shock Overall mortality rate of 45%Overall mortality rate of 45% CauseCause
Gram+ 35-40%Gram+ 35-40% Gram- 55-60%Gram- 55-60%
Slightly higher incidence in men, Slightly higher incidence in men, older adults (55-60 yrs)older adults (55-60 yrs)
DefinitionsDefinitions
InfectionInfection Inflammation against microorganismInflammation against microorganism
BacteremiaBacteremia Viable bacteria in bloodViable bacteria in blood
DefinitionsDefinitions
SIRSSIRS Evidence of inflammation Evidence of inflammation NOTNOT
necessarily infectionnecessarily infection 2 or more of the following2 or more of the following
Temp>38 or <36Temp>38 or <36 HR >90bpmHR >90bpm RR >20 or PaCo2 <32RR >20 or PaCo2 <32 WBC’s >12,000 or <4000 or >10% WBC’s >12,000 or <4000 or >10%
bandemiabandemia
DefinitionsDefinitions
SepsisSepsis systemic inflammatory response as a result of systemic inflammatory response as a result of
infectioninfection Severe SepsisSevere Sepsis
sepsis associated with organ dysfunctionsepsis associated with organ dysfunction Lactic acidosis, oliguria, mental status changeLactic acidosis, oliguria, mental status change
Septic shockSeptic shock sepsis-induced hypotension with presence of sepsis-induced hypotension with presence of
perfusion abnormalitiesperfusion abnormalities
DefinitionsDefinitions
Sepsis-induced hypotensionSepsis-induced hypotension SBP<90 or reduction of 40mm Hg from SBP<90 or reduction of 40mm Hg from
baseline without other causebaseline without other cause Multiple Organ Dysfunction Multiple Organ Dysfunction
SyndromeSyndrome Altered organ dysfunction in acutely ill Altered organ dysfunction in acutely ill
patient requiring intervention to patient requiring intervention to maintain homeostasismaintain homeostasis
PathophysiologyPathophysiology
PathophysiologyPathophysiology
Focus of infectionFocus of infection Pneumonia, UTI, cellulitits, abscess, indwelling Pneumonia, UTI, cellulitits, abscess, indwelling
devicedevice ICU:ICU: catheters, sinusitis, acalculus cholecystitis, catheters, sinusitis, acalculus cholecystitis,
C. diff, resistant organism, fungal infection C. diff, resistant organism, fungal infection Blood stream invasion or proliferation of Blood stream invasion or proliferation of
organism at siteorganism at site Exogenous toxin releaseExogenous toxin release Activation of endogenous mediatorsActivation of endogenous mediators
Molecular Mediators in Molecular Mediators in PathophysiologyPathophysiology
Three phasesThree phases InductionInduction Cytokine synthesis & secretionCytokine synthesis & secretion CascadeCascade
Molecular Mediators in Molecular Mediators in PathophysiologyPathophysiology
InductionInduction Interaction of microbial molecules with Interaction of microbial molecules with
hosthost Mediators activated that amplify & transmit Mediators activated that amplify & transmit
the microbial signal to other cells the microbial signal to other cells Ex LPS binds to LPS binding protein which is Ex LPS binds to LPS binding protein which is
detected by CD14 releasing TNF-alphadetected by CD14 releasing TNF-alpha Peptidoglycan & lipoteichoic acid of gram Peptidoglycan & lipoteichoic acid of gram
(+) induce similarly(+) induce similarly
Molecular Mediators in Molecular Mediators in PathophysPathophys
Cytokine cascadeCytokine cascade Activation & release of central mediatorsActivation & release of central mediators
TNF-alpha and IL-1TNF-alpha and IL-1 Release of secondary mediatorsRelease of secondary mediators
IL-6, IL-8, PAF, PG’s, leukotrienesIL-6, IL-8, PAF, PG’s, leukotrienes Activation of neutrophils, complement Activation of neutrophils, complement
system, vascular endothelial cellssystem, vascular endothelial cells Synthesis of acute phase reactantsSynthesis of acute phase reactants
Molecular Mediators in Molecular Mediators in PathophysPathophys
Parallel to SIRS is CARS Parallel to SIRS is CARS Compensatory Anti-inflammatory Compensatory Anti-inflammatory
Response SystemResponse System Attempts to down regulate the SIRS responseAttempts to down regulate the SIRS response IL-4, IL-10, transforming growth factor beta, IL-4, IL-10, transforming growth factor beta,
CSF, soluble receptors to TNF, antagonists to CSF, soluble receptors to TNF, antagonists to TNF-alpha and IL-1TNF-alpha and IL-1
If CARS reaction is severe it will manifest as If CARS reaction is severe it will manifest as anergy and infection susceptibilityanergy and infection susceptibility
Vasoactive Mediators in Vasoactive Mediators in PathophysPathophys
Nitric OxideNitric Oxide Produced by endotheliumProduced by endothelium Increased levels during shockIncreased levels during shock Actions at high levelsActions at high levels
Mediator of vasodilation & hypotensionMediator of vasodilation & hypotension Direct cellular toxicityDirect cellular toxicity Myocardial depressionMyocardial depression Increased permeabilityIncreased permeability
Clinical FeaturesClinical Features
Clinical FeaturesClinical Features
ConstitutionalConstitutional Hyper/hypothermiaHyper/hypothermia TachycardiaTachycardia TachypneaTachypnea Wide pulse pressureWide pulse pressure Mental status change Mental status change
Most likely obtundedMost likely obtunded
Clinical FeaturesClinical Features
CadiovascularCadiovascular Early, vasodilators predominateEarly, vasodilators predominate Cardiac output is increased with Cardiac output is increased with
tachycardiatachycardia CO=SV x HRCO=SV x HR i.e. Initially patients will have warm extremitiesi.e. Initially patients will have warm extremities
If not treated aggressively decompensation If not treated aggressively decompensation ensuesensues
Typically hypotension is not reversible with Typically hypotension is not reversible with fluids alonefluids alone
Clinical FeaturesClinical Features
PulmonaryPulmonary Sepsis is most common condition Sepsis is most common condition
associated with ARDSassociated with ARDS Lung edema from increased permeability Lung edema from increased permeability
Alveolar edemaAlveolar edema dyspnea, hypoxemia, opacities dyspnea, hypoxemia, opacities on CXRon CXR
B/L infiltrates, wedge pressure <18B/L infiltrates, wedge pressure <18 Endotoxin, TNF-alpha, IL-1, IL-6, IL-8, Endotoxin, TNF-alpha, IL-1, IL-6, IL-8,
bactericidal/permeability-increasing (BPI) proteinbactericidal/permeability-increasing (BPI) protein
Clinical FeaturesClinical Features
PulmonaryPulmonary ARDSARDS
B/L pulmonary infiltratesB/L pulmonary infiltrates PCWP <18 (non-cardiogenic pulm edema)PCWP <18 (non-cardiogenic pulm edema) PaO2/FiO2 <200PaO2/FiO2 <200
If PaO2/FiO2 >200, but <300 then ALIIf PaO2/FiO2 >200, but <300 then ALI
Clinical FeaturesClinical Features
RenalRenal Acute renal failure w/ azotemia, oliguria, Acute renal failure w/ azotemia, oliguria,
active urinary sedimentactive urinary sediment Hypotension/Dehydration, aminoglycosides, Hypotension/Dehydration, aminoglycosides,
pigmenturia (e.g. myoglobinuria)pigmenturia (e.g. myoglobinuria) Immune complex depositionImmune complex deposition
IgG, IgM,C3, bacterial antigens & antibodiesIgG, IgM,C3, bacterial antigens & antibodies Tubulointersitial diseaseTubulointersitial disease
S. pneumoniae, S. pyogenes, Legionella, S. pneumoniae, S. pyogenes, Legionella, salmonellosis, brucellosis, diptheriasalmonellosis, brucellosis, diptheria
Clinical FeaturesClinical Features
GastrointestinalGastrointestinal Accelerated apoptosis of GI epithelial cellsAccelerated apoptosis of GI epithelial cells
Can lead to blood loss anemiaCan lead to blood loss anemia Cholestatic jaundice (most frequent Cholestatic jaundice (most frequent
abnormality)abnormality) Transaminase/Alkaline phosphatase 1-3x Transaminase/Alkaline phosphatase 1-3x
normalnormal Bilirubin concentrations, usually not >10mg/dLBilirubin concentrations, usually not >10mg/dL
Hemolysis of RBC’s, hepatocellular dysfunction due Hemolysis of RBC’s, hepatocellular dysfunction due to endotoxinto endotoxin
Clinical FeaturesClinical Features
HematologicHematologic Minor blood loss secondary to erosions Minor blood loss secondary to erosions
in mucosal layer of stomach/duodenumin mucosal layer of stomach/duodenum Accelerated apoptosis of lymphocytesAccelerated apoptosis of lymphocytes
Possibly due to elevated glucocorticoids Possibly due to elevated glucocorticoids Most frequent changes are neutrophilia Most frequent changes are neutrophilia
or neutropenia, thrombocytopenia, DICor neutropenia, thrombocytopenia, DIC
Clinical FeaturesClinical Features
Hematologic Hematologic NeutrophiliaNeutrophilia
Most commonMost common Left shiftLeft shift
Demargination & release of less mature Demargination & release of less mature granulocytes from BMgranulocytes from BM
C3a causes release of neutrophil releasing C3a causes release of neutrophil releasing substancesubstance
Sustained neutrophilia is secondary to CSFs Sustained neutrophilia is secondary to CSFs
Clinical FeaturesClinical Features
Hematologic continuedHematologic continued NeutropeniaNeutropenia
Increases mortalityIncreases mortality Increased peripheral use of cells, damage to cells by Increased peripheral use of cells, damage to cells by
bacterial byproducts, depression of marrow by bacterial byproducts, depression of marrow by inflammatory mediatorsinflammatory mediators
Morphological changes of WBC’s in sepsisMorphological changes of WBC’s in sepsis Toxic granulations, Dohle bodies, vacuolizationToxic granulations, Dohle bodies, vacuolization
Functional changes of WBC’s Functional changes of WBC’s Increased phagocytic/cytotoxic activitiesIncreased phagocytic/cytotoxic activities
Clinical FeaturesClinical Features
Hematologic continuedHematologic continued RBC production & survival are RBC production & survival are
decreaseddecreased Usually does not cause anemia unless Usually does not cause anemia unless
infection is prolongedinfection is prolonged Low serum Fe concentrationsLow serum Fe concentrations
Decrease by 50%Decrease by 50% Influx into liver & other reticuloendothelial Influx into liver & other reticuloendothelial
cellscells
Clinical FeaturesClinical Features
Hematologic continuedHematologic continued ThrombocytopeniaThrombocytopenia
Usual a consequence of DICUsual a consequence of DIC May be early sign of bacteremiaMay be early sign of bacteremia
Inhibition of thrombopoiesis, increased platelet Inhibition of thrombopoiesis, increased platelet turnover, increased endothelial adherence, turnover, increased endothelial adherence, increased destructionincreased destruction
Clinical FeaturesClinical Features
DICDIC Clotting & fibrinolytic systems activatedClotting & fibrinolytic systems activated
Consumption of coagulation factors & plateletsConsumption of coagulation factors & platelets Clotting system activated through the extrinisic Clotting system activated through the extrinisic
clotting system by bacteria, viruses, fungi, clotting system by bacteria, viruses, fungi, endo/exotoxinsendo/exotoxins
Gram(-) precipitate DIC more readily than gram (+)Gram(-) precipitate DIC more readily than gram (+) Fibrinolytic system is activated by tissue type Fibrinolytic system is activated by tissue type
plasminogen activator plasminogen activator As sepsis progresses, increase release of plasminogen As sepsis progresses, increase release of plasminogen
activator inhibitor type 1activator inhibitor type 1
Clinical FeaturesClinical Features
DIC continuedDIC continued Two formsTwo forms
CompensatedCompensated ““slower” generalized activationslower” generalized activation Bleeding prevented by increasing coagulation factor Bleeding prevented by increasing coagulation factor
production in liver, release of platelets from reserve, production in liver, release of platelets from reserve, synthesis of inhibitors at accelerated ratesynthesis of inhibitors at accelerated rate
DecompensatedDecompensated Clinical bleeding and/or thrombosisClinical bleeding and/or thrombosis Thrombocytopenia, prolonged PT/PTT, decreased Thrombocytopenia, prolonged PT/PTT, decreased
fibrinogen & antithrombin III, increased fibrin fibrinogen & antithrombin III, increased fibrin monomer/fibrin split products/D-dimermonomer/fibrin split products/D-dimer
Clinical FeaturesClinical Features
EndocrineEndocrine HyperglycemiaHyperglycemia
Increased catecholamines, cortisol, glucagon, Increased catecholamines, cortisol, glucagon, peripheral insulin resistance, impaired glucose use, peripheral insulin resistance, impaired glucose use, decreased insulin secretiondecreased insulin secretion
Significant risk for adverse outcomeSignificant risk for adverse outcome Must maintain tight control w/insulin infusion to keep b/w Must maintain tight control w/insulin infusion to keep b/w
80-100 mg/dl 80-100 mg/dl (NEJM Nov 8, 2001; vol 345, #19)(NEJM Nov 8, 2001; vol 345, #19)
HypoglycemiaHypoglycemia Assoc. w/S. pneumoniae, S. aureus, S. pyogenes, Assoc. w/S. pneumoniae, S. aureus, S. pyogenes,
Listeria, Neisseria meningitidis, H. flu, Listeria, Neisseria meningitidis, H. flu, EnterobacteriaceaeEnterobacteriaceae
Clinical FeaturesClinical Features
Acid/BaseAcid/Base Early in sepsis Early in sepsis resp alkalosis resp alkalosis Metabolic acidosis suggests inadequate Metabolic acidosis suggests inadequate
perfusion, impaired hepatic clearance of perfusion, impaired hepatic clearance of lactate/pyruvate, increased glycolysislactate/pyruvate, increased glycolysis
Hypoxemia often present due to Hypoxemia often present due to vent/perfusion mismatchvent/perfusion mismatch
Clinical FeaturesClinical Features
CutaneousCutaneous Direct bacterial involvementDirect bacterial involvement
Cellulitis, erysipelas, fasciitisCellulitis, erysipelas, fasciitis Lesions as a consequence of Lesions as a consequence of
sepsis/hypotension/DICsepsis/hypotension/DIC Acrocyanosis & necrosis of peripheral tissueAcrocyanosis & necrosis of peripheral tissue
Lesions secondary to intravascular Lesions secondary to intravascular infectioninfection
Microemboli &/or immune complex vasculitisMicroemboli &/or immune complex vasculitis
DiagnosisDiagnosis
DiagnosisDiagnosis
Pt presents withPt presents with Hypotension not responsive to fluid bolusHypotension not responsive to fluid bolus Inadequate perfusionInadequate perfusion Complaints attributable to a serious infectionComplaints attributable to a serious infection Hot flushed skinHot flushed skin Mental obtundation or agitationMental obtundation or agitation Widened pulse pressureWidened pulse pressure HyperventilationHyperventilation DysthermiaDysthermia **beware of the old, young, **beware of the old, young,
immunocompromisedimmunocompromised
DiagnosisDiagnosis
Differential DiagnosisDifferential Diagnosis Other causes of shockOther causes of shock
CardiogenicCardiogenic NeurogenicNeurogenic HypovolemicHypovolemic AnaphylacticAnaphylactic Obstructive (PE, tamponade)Obstructive (PE, tamponade) Endocrine (adrenal insufficiency, thyroid Endocrine (adrenal insufficiency, thyroid
storm)storm)
DiagnosisDiagnosis
H & PH & P Basic lab and x-rays are Basic lab and x-rays are usuallyusually
successful in identification of sourcesuccessful in identification of source CNSCNS
Meningitis (nuchal rigidity, MS change, Meningitis (nuchal rigidity, MS change, petechiae)petechiae)
Brain abscess, sub/epi dural empyemas Brain abscess, sub/epi dural empyemas Viral CNS infectionsViral CNS infections
DiagnosisDiagnosis
PulmonaryPulmonary Acute bacterial pneumoniaAcute bacterial pneumonia
Intra-abdominal processesIntra-abdominal processes Most common source of infection leading to Most common source of infection leading to
sepsissepsis Acute pancreatitsAcute pancreatits CholangitisCholangitis Septic abortion/endometritis/myometritisSeptic abortion/endometritis/myometritis PyelonephritisPyelonephritis Occult AbscessOccult Abscess
SkinSkin Cellulitis (S.aureus, S.pyogenes)Cellulitis (S.aureus, S.pyogenes) Decubitus ulcer(s)Decubitus ulcer(s)
DiagnosisDiagnosis
No obvious sourceNo obvious source EndocarditisEndocarditis Primary bacteremiaPrimary bacteremia
S.aureus, S.pneumoniae, N.meningitidisS.aureus, S.pneumoniae, N.meningitidis Asplenia Asplenia
Salmonella, H flu, S pneumo, N. meningitidisSalmonella, H flu, S pneumo, N. meningitidis IVD users, Pseudomonas & gram(-) bacteriaIVD users, Pseudomonas & gram(-) bacteria
Skin abscess from “popping”Skin abscess from “popping”
DiagnosisDiagnosis
Ancillary StudiesAncillary Studies CBCCBC DIC panel (PT,PTT,fibrinogen,D-dimer, ATIII)DIC panel (PT,PTT,fibrinogen,D-dimer, ATIII) CMP (include Mag, Ca, Phosphate)CMP (include Mag, Ca, Phosphate) Lactate levelLactate level ABGABG UAUA CXRCXR Cultures (blood, urine)Cultures (blood, urine) If H&P suggestIf H&P suggest
LP, CT (abd . . .)LP, CT (abd . . .) ConsiderConsider
CRP, pro-calcitonin, IL-6 levelCRP, pro-calcitonin, IL-6 level
Standard TreatmentStandard Treatment
Standard TreatmentStandard Treatment
ABC’s!ABC’s! Maintain O2 sat’s above 90%Maintain O2 sat’s above 90%
Hemodynamic StabilizationHemodynamic Stabilization Rapid fluid administrationRapid fluid administration
Rate of 0.5L of NS every 5-10minRate of 0.5L of NS every 5-10min May require 2-6L in initial stabilization phaseMay require 2-6L in initial stabilization phase Be careful with heart failure patientsBe careful with heart failure patients Monitor response with BP, HR, RR, mental Monitor response with BP, HR, RR, mental
status, urine output (1cc/kg/hr), CVP, skin status, urine output (1cc/kg/hr), CVP, skin perfusionperfusion
Standard TreatmentStandard Treatment
▪ ▪ Inotropic supportInotropic support If no response to fluids or signs of fluid If no response to fluids or signs of fluid
overload presentoverload present Goal is to keep MAP above 65 mm HgGoal is to keep MAP above 65 mm Hg
Dopamine 5-20 micrograms/kg/minDopamine 5-20 micrograms/kg/min Beta-1, dopaminergic and alpha adrenergic Beta-1, dopaminergic and alpha adrenergic
activityactivity NorepinephrineNorepinephrine
Beta-1 and alpha adrenergic stimulationBeta-1 and alpha adrenergic stimulation Short term vasopressin infusion (0.04 units/min Short term vasopressin infusion (0.04 units/min
for 4-16h)for 4-16h) Vasodilatory septic shockVasodilatory septic shock
Standard TreatmentStandard Treatment
End pointsEnd points Early goal directed therapy provides Early goal directed therapy provides
significant benefit & improves outcomesignificant benefit & improves outcome Rivers et al. NEJM vol. 345:1368, 2001Rivers et al. NEJM vol. 345:1368, 2001
Maintain CVP b/w 8-12Maintain CVP b/w 8-12 Hct 30%Hct 30% SVO2 >70%SVO2 >70% Reduction in mortality from 44% in control Reduction in mortality from 44% in control
group to 29% in intervention groupgroup to 29% in intervention group
Standard TreatmentStandard Treatment
Empiric Antimicrobial TherapyEmpiric Antimicrobial Therapy Start ASAPStart ASAP TryTry to get culture samples before to get culture samples before Select based on adequate coverage of Select based on adequate coverage of
potential pathogenspotential pathogens Should cover gram +/- Should cover gram +/- Give maximum dose allowed Give maximum dose allowed Give IVGive IV
Empiric Antibiotics in SepsisEmpiric Antibiotics in Sepsis
Table 32-3Table 32-3
Standard TreatmentStandard Treatment
Removal of Source of InfectionRemoval of Source of Infection Indwelling catheters Indwelling catheters send tip for send tip for
cultureculture Replace Foley cathetersReplace Foley catheters Intra-abdominal or soft tissue sites of Intra-abdominal or soft tissue sites of
pus require urgent drainagepus require urgent drainage
Standard TreatmentStandard Treatment
Initial Baseline Assessment & Continued Initial Baseline Assessment & Continued Monitoring (again goal directed)Monitoring (again goal directed) Some use serum lactate to monitor responseSome use serum lactate to monitor response ABG’s to monitor ventilation & perfusionABG’s to monitor ventilation & perfusion 2 large bore IV’s 2 large bore IV’s
Consider central line earlyConsider central line early If requiring vasoactive drugs consider pulm If requiring vasoactive drugs consider pulm
artery thermal-dilution catheterartery thermal-dilution catheter Other monitoring gadgetsOther monitoring gadgets
Sublingual capnography, gastric pH tonometry, Sublingual capnography, gastric pH tonometry, muscle oximetry, bioimpedance determination of COmuscle oximetry, bioimpedance determination of CO
New Innovative TherapiesNew Innovative Therapies
Innovative TherapyInnovative Therapy
Based in premise that neutralizing Based in premise that neutralizing bacterial toxins, cytokines, & other bacterial toxins, cytokines, & other mediators could stop or slow the mediators could stop or slow the syndromesyndrome
Innovative TherapiesInnovative Therapies
CorticosteroidsCorticosteroids Meta-analysis has shown physiologic Meta-analysis has shown physiologic
doses of hydrocortisone improves doses of hydrocortisone improves outcomesoutcomes
(200-300mg/d) for 5-7 days (200-300mg/d) for 5-7 days Then tapered for 5-7 daysThen tapered for 5-7 days
Early studies (proir to 1989) used high doses and Early studies (proir to 1989) used high doses and had increased mortalityhad increased mortality
Those published after 1997 (5)used lower doses and Those published after 1997 (5)used lower doses and reported improved survival similar to that of reported improved survival similar to that of Activated Protein CActivated Protein C
Annal of Internal Med 2004;141:47-56Annal of Internal Med 2004;141:47-56
Innovative TherapyInnovative Therapy
Activated Protein C (Xigris)Activated Protein C (Xigris) Inactivates Factors Va and VIIIaInactivates Factors Va and VIIIa Inhibits thrombin (decreases inflammation)Inhibits thrombin (decreases inflammation)
Inhibits platelet activation, neutrophil Inhibits platelet activation, neutrophil recruitment, and mast cell degranulationrecruitment, and mast cell degranulation
Blocks cytokine productionBlocks cytokine production Inhibits cell adhesionInhibits cell adhesion Anti-apoptotic actionsAnti-apoptotic actions
Apoptosis (i.e. GI epithelial cell) induces anergyApoptosis (i.e. GI epithelial cell) induces anergy
Innovative TherapyInnovative Therapy
SummarySummary To date the only treatments shown to To date the only treatments shown to
produce benefitproduce benefit Early goal directed hemodynamic Early goal directed hemodynamic
stabilizationstabilization Tight control of blood glucose with insulinTight control of blood glucose with insulin Activated protein CActivated protein C
““Efficacy and Safety of Recombinant Human Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis” NEJM Activated Protein C for Severe Sepsis” NEJM 2001, vol. 344; 699-7092001, vol. 344; 699-709
Cardiogenic ShockCardiogenic Shock
Cardiogenic ShockCardiogenic Shock
A state of decreased cardiac A state of decreased cardiac output(CO) producing inadequate output(CO) producing inadequate tissue perfusion despite adequate or tissue perfusion despite adequate or excessive circulating volume excessive circulating volume
Cardiogenic shockCardiogenic shock
EtiologyEtiology AMI AMI
Pump failure (40% of LV involved)Pump failure (40% of LV involved) Mechanical complications (MR,VSD,free wall rupture)Mechanical complications (MR,VSD,free wall rupture) RV infarctionRV infarction
Depression of contractilityDepression of contractility Sepsis, myocarditis, contusionSepsis, myocarditis, contusion
Mechanical obstructionMechanical obstruction AS, hypertrophic CM, MS, LA myxomaAS, hypertrophic CM, MS, LA myxoma
Regurgitation of LV outputRegurgitation of LV output AI, chordal ruptureAI, chordal rupture
PathophysiologyPathophysiology
AMI cell death loss of contractile AMI cell death loss of contractile function function
Decreased CO/SV Decreased CO/SV tachycardia/hypotension decreased tachycardia/hypotension decreased coronary perfusion/diastolic filling time coronary perfusion/diastolic filling time
Further ischemia SNS/Renin-Further ischemia SNS/Renin-Angiotension System activation Angiotension System activation
Increased SVR and myocardial O2 Increased SVR and myocardial O2 consumptionconsumption
Cardiogenic ShockCardiogenic Shock
Clinical FeaturesClinical Features PEPE
HypoperfusionHypoperfusion Skin mottling, obtundedSkin mottling, obtunded
+/-hypotension (SBP<90)+/-hypotension (SBP<90) May be compensated (pulse pressure <20, ST) or pre-May be compensated (pulse pressure <20, ST) or pre-
existing hypertensionexisting hypertension Tachypnea, rales (clear if RV), JVDTachypnea, rales (clear if RV), JVD MurmurMurmur
MR (chordae tendinea rupture): holosystolic at apex MR (chordae tendinea rupture): holosystolic at apex going to axillagoing to axilla
VSD: holosystolic at L parasternalVSD: holosystolic at L parasternal
Cardiogenic ShockCardiogenic Shock
Ancillary StudiesAncillary Studies ECG: ischemia/infarction,electrolyte ECG: ischemia/infarction,electrolyte
abnormality,drug toxicityabnormality,drug toxicity CXR: helps r/o other causes (pneumonia, aortic CXR: helps r/o other causes (pneumonia, aortic
dissection, pericardial effusion)dissection, pericardial effusion) Labs: BNP, cardiac enzymes, ABG, lactate, Labs: BNP, cardiac enzymes, ABG, lactate,
electrolytes, serum drug levelselectrolytes, serum drug levels Echo: ventricular/valve dysfunctionEcho: ventricular/valve dysfunction HD monitoring (table 33-3): invasive vs HD monitoring (table 33-3): invasive vs
bioimpedancebioimpedance
Cardiogenic ShockCardiogenic Shock
Differential DiagnosisDifferential Diagnosis AMIAMI PEPE COPDCOPD PneumoniaPneumonia Aortic dissectionAortic dissection TamponadeTamponade Acute valvular insufficiencyAcute valvular insufficiency HemorrhageHemorrhage SepsisSepsis Drug OD of negative inotropic/chronotropic agentDrug OD of negative inotropic/chronotropic agent
Cardiogenic ShockCardiogenic Shock
TreatmentTreatment ABC’s firstABC’s first IV access/cardiac monitor/art line/foleyIV access/cardiac monitor/art line/foley Correct hypoxia/hypovolemia/rhythm Correct hypoxia/hypovolemia/rhythm
disturbance/electrolyte abnormalities/acid-base disturbance/electrolyte abnormalities/acid-base alterationsalterations
HypotensionHypotension Dopamine,dobutamineDopamine,dobutamine Fluid bolus if RV involvedFluid bolus if RV involved Acute MR consider dobutamine and nitroprussideAcute MR consider dobutamine and nitroprusside IABPIABP
Cardiogenic ShockCardiogenic Shock
Treatment continuedTreatment continued Thrombolytic therapyThrombolytic therapy
Better outcomes if followed by Better outcomes if followed by revascularizationrevascularization
Intraaortic balloon conterpulsionIntraaortic balloon conterpulsion Decreases afterload, increases diastolic BPDecreases afterload, increases diastolic BP
Early revascularizationEarly revascularization Most important life saving interventionMost important life saving intervention
Cardiogenic ShockCardiogenic Shock
Treatment continuedTreatment continued Inotropic agentsInotropic agents
DopamineDopamine First line agentFirst line agent 2.5-5 micrograms/kg/min beta-12.5-5 micrograms/kg/min beta-1 5-10 alpha & beta-15-10 alpha & beta-1 10-20 alpha10-20 alpha
DobutamineDobutamine Use for signs of poor perfusion when SBP>90Use for signs of poor perfusion when SBP>90 2-20micrograms/kg/min2-20micrograms/kg/min
NorepinephrineNorepinephrine Use only when inadequate response to other pressorsUse only when inadequate response to other pressors 2 micrograms/min and titrate to response2 micrograms/min and titrate to response
MilrinoneMilrinone 50 microgram/kg bolus followed by 0.5microgram/kg/min infusion—50 microgram/kg bolus followed by 0.5microgram/kg/min infusion—
watch BP!watch BP!
Anaphylactic ShockAnaphylactic Shock
Anaphylactic ShockAnaphylactic Shock
Severe systemic hypersensitivity Severe systemic hypersensitivity with multisystem involvementwith multisystem involvement
Life-threatening release of mediators Life-threatening release of mediators by mast cells and basophilsby mast cells and basophils
Anaphylactic ShockAnaphylactic Shock
PathophysiologyPathophysiology 4 classic mechanisms4 classic mechanisms
1. cross-linking of 2 IgE molecules on a mast 1. cross-linking of 2 IgE molecules on a mast cell or basophil by a multivalent antigencell or basophil by a multivalent antigen
2. reaction of IgM & IgG to cell surface 2. reaction of IgM & IgG to cell surface antigensantigens
3. soluble antigen-antibody complexes 3. soluble antigen-antibody complexes activating complementactivating complement
4. activation of T lymphocytes4. activation of T lymphocytes
Anaphylactic ShockAnaphylactic Shock
PathophysiologyPathophysiology Classic anaphylaxisClassic anaphylaxis
2 separate exposures2 separate exposures First the antigen or hapten-protein complex is First the antigen or hapten-protein complex is
processed by macrophage & dendritic cellsprocessed by macrophage & dendritic cells Presented externally with MHC-2Presented externally with MHC-2 T helper cells recognize and stimulate plasma T helper cells recognize and stimulate plasma
cells to produce IgEcells to produce IgE Second exposure recognized by these IgE Second exposure recognized by these IgE
antibodies triggers degranulation of mast cells antibodies triggers degranulation of mast cells and basophils and basophils
Anaphylactic ShockAnaphylactic Shock
PathophysiologyPathophysiology Complement mediated reactionComplement mediated reaction
Occur after administration of blood products Occur after administration of blood products secondary to immune complexessecondary to immune complexes
C3a & C5a cause degranulationC3a & C5a cause degranulation
Non-immunologic anaphylaxis Non-immunologic anaphylaxis (anaphylactoid)(anaphylactoid)
Exogenous substances directly degranulate mast Exogenous substances directly degranulate mast cellscells
Radiocontrast dye, opiates, depolarinzing drugs, Radiocontrast dye, opiates, depolarinzing drugs, dextransdextrans
Anaphylactic ShockAnaphylactic Shock
PathophysiologyPathophysiology ASA/NSAIDSASA/NSAIDS
Non-mast cell processNon-mast cell process Modulate cyclooxygenase-arachidonic acid Modulate cyclooxygenase-arachidonic acid
metabolismmetabolism Idiopathic anaphylaxisIdiopathic anaphylaxis
Diagnosis of exclusionDiagnosis of exclusion
Anaphylactic ShockAnaphylactic Shock
Clinical FeaturesClinical Features Diffuse urticaria & angioedemaDiffuse urticaria & angioedema +/- abd pain or cramping, N/V, diarrhea, +/- abd pain or cramping, N/V, diarrhea,
bronchospasm, rhinorrhea, conjunctivitis, bronchospasm, rhinorrhea, conjunctivitis, dysrhythmias, hypotensiondysrhythmias, hypotension
c/o “lump” in the throat heralds life-c/o “lump” in the throat heralds life-threatening laryngeal edemathreatening laryngeal edema
Usually begin w/in 60 minutes of exposureUsually begin w/in 60 minutes of exposure Faster the onset the more severe the reactionFaster the onset the more severe the reaction Biphasic phenomenon Biphasic phenomenon
Second release of mediators clinically evident 3-4h Second release of mediators clinically evident 3-4h after the initial manifestations clearafter the initial manifestations clear
Anaphylactic ShockAnaphylactic Shock
DiagnosisDiagnosis History and physicalHistory and physical
2 or more body systems involved2 or more body systems involved DifferentialDifferential
Vasovagal reaction, status asthmaticus, seizure, Vasovagal reaction, status asthmaticus, seizure, epiglottitis, hereditary angioedema, FB airway epiglottitis, hereditary angioedema, FB airway obstruction, carcinoid, mastocytosis, non-IgE drug obstruction, carcinoid, mastocytosis, non-IgE drug reactions, AMI, dysrhythmias reactions, AMI, dysrhythmias
Anaphylactic ShockAnaphylactic Shock
TreatmentTreatment First LineFirst Line
ABC’sABC’s Epinephrine, oxygen, fluids (NS 1-2L)Epinephrine, oxygen, fluids (NS 1-2L)
Epi 0.1mg in 10cc NS over 5-10minutes IV if signs Epi 0.1mg in 10cc NS over 5-10minutes IV if signs of CV collapseof CV collapse
If refractive start infusion: 1mg in 500ccD5W If refractive start infusion: 1mg in 500ccD5W at 1-4 micrograms/minat 1-4 micrograms/min
Less severe, give 0.3-0.5 mg IM in the thighLess severe, give 0.3-0.5 mg IM in the thigh decontaminationdecontamination
Anaphylactic ShockAnaphylactic Shock
TreatmentTreatment Second LineSecond Line
CorticosteroidsCorticosteroids Methylprednisolone 125mg IVMethylprednisolone 125mg IV 2mg/kg in children2mg/kg in children
AntihistaminesAntihistamines Diphenhydramine (H1) 25-50mg IVDiphenhydramine (H1) 25-50mg IV Ranitidine or cimetidine(H2) Ranitidine or cimetidine(H2)
Avoid cimetidine in elderly, renal/hepatic Avoid cimetidine in elderly, renal/hepatic failure, or if patient is on beta blockerfailure, or if patient is on beta blocker
Anaphylactic ShockAnaphylactic Shock
TreatmentTreatment Second LineSecond Line
Agents for bronchospasmAgents for bronchospasm AlbuterolAlbuterol Ipratropium bromideIpratropium bromide Magnesium 2g IV over 20-30minutesMagnesium 2g IV over 20-30minutes
25-50mg/kg in children25-50mg/kg in children Glucagon Glucagon
1 mg IV q 5min until response followed by 1 mg IV q 5min until response followed by infusion 5-15 micrograms/min if patient on beta infusion 5-15 micrograms/min if patient on beta blockers with refractive hypotensionblockers with refractive hypotension
Anaphylactic ShockAnaphylactic Shock
DispositionDisposition Unstable patients admit to ICUUnstable patients admit to ICU If patient received epi-observe for 4hIf patient received epi-observe for 4h
Consider distance from care, someone to go Consider distance from care, someone to go home with, comorbidities, agehome with, comorbidities, age
Good discharge instructions is a mustGood discharge instructions is a must Send with epipen, short course of Send with epipen, short course of
antihistamines and steroidsantihistamines and steroids
Neurogenic ShockNeurogenic Shock
Neurogenic ShockNeurogenic Shock
Acute spinal cord injuryAcute spinal cord injury Disruption of sympathetic outflowDisruption of sympathetic outflow Hypotension & bradycardiaHypotension & bradycardia Majority caused by blunt traumaMajority caused by blunt trauma
MVA, falls, sportsMVA, falls, sports Cervical region most commonly injuredCervical region most commonly injured Penetrating injury (10-15% of cases)Penetrating injury (10-15% of cases)
GSW’s and stab woundsGSW’s and stab wounds
Neurogenic ShockNeurogenic Shock
PathophysiologyPathophysiology 33 bony vertebrae33 bony vertebrae
Anterior body, posterior arch, sup/inf articular Anterior body, posterior arch, sup/inf articular processes, pedicles, laminaeprocesses, pedicles, laminae
Spinal cord is cylindrical arising from base of Spinal cord is cylindrical arising from base of brain & covered by 3 layers of meninges & CSFbrain & covered by 3 layers of meninges & CSF
31 pairs of spinal nerves exit the canal via 31 pairs of spinal nerves exit the canal via intervertebral foramen intervertebral foramen
Spinal nerves are formed by ant/post nerve rootsSpinal nerves are formed by ant/post nerve roots
Neurogenic ShockNeurogenic Shock
PathophysiologyPathophysiology Spinal cord contains white & gray matterSpinal cord contains white & gray matter
White: nerve fibers running up & down in cord tractsWhite: nerve fibers running up & down in cord tracts Gray: nerve cellsGray: nerve cells
Autonomic Nervous SystemAutonomic Nervous System SympatheticSympathetic
Outflow tracts in lateral gray horns of 1Outflow tracts in lateral gray horns of 1stst thoracic to 2 thoracic to 2ndnd lumbarlumbar
Controlled by hypothalamusControlled by hypothalamus Lateral hornLateral hornanterior nerve rootanterior nerve rootganglia of paraspinal ganglia of paraspinal
sympathetic trunksympathetic trunktravel throughout the bodytravel throughout the body
Neurogenic ShockNeurogenic Shock
PathophysiologyPathophysiology Autonomic Nervous SystemAutonomic Nervous System
ParasympatheticParasympathetic Cranial Nerves & 2-4Cranial Nerves & 2-4thth sacral segments sacral segments
(splanchnic nerves)(splanchnic nerves)
Neurogenic ShockNeurogenic Shock
Clinical featuresClinical features Hypotensive with warm,dry skinHypotensive with warm,dry skin Bradycardic ususallyBradycardic ususally HypothermicHypothermic These symptoms last 1-3 weeksThese symptoms last 1-3 weeks
Neurogenic ShockNeurogenic Shock
TreatmentTreatment ABCDE’sABCDE’s Investigate all other possible sources of hypotension & Investigate all other possible sources of hypotension &
bradycardiabradycardia Infuse crystalloids rapidlyInfuse crystalloids rapidly
Attempt to keep MAP 85-90mm Hg for the first 7 days to Attempt to keep MAP 85-90mm Hg for the first 7 days to minimize secondary cord injuryminimize secondary cord injury
Dopamine & dobutamine may be helpfulDopamine & dobutamine may be helpful Severe bradycardia can be treated with atropine or pacingSevere bradycardia can be treated with atropine or pacing Steroids are not indicated in the treatment of neurogenic Steroids are not indicated in the treatment of neurogenic
shock per seshock per se Indicated in blunt injury with neuro deficits if started within 8h Indicated in blunt injury with neuro deficits if started within 8h
(30mg/kg bolus then 45 mins later infuse at 5.4mg/kg/h for (30mg/kg bolus then 45 mins later infuse at 5.4mg/kg/h for 23h)23h)
QuestionsQuestions
1. In cardiogenic shock the PCWP is 1. In cardiogenic shock the PCWP is A. DecreasedA. Decreased B. IncreasedB. Increased C. NormalC. Normal
QuestionsQuestions
2. SIRS is defined as inflammation 2. SIRS is defined as inflammation secondary to infection secondary to infection
A. TrueA. True B. FalseB. False
3. Which is not a parameter used to 3. Which is not a parameter used to define ARDS define ARDS
A. Bilateral infiltrates on CXRA. Bilateral infiltrates on CXR B. PCWP>18B. PCWP>18 C. PaO2/FIO2 <200C. PaO2/FIO2 <200
4. What is considered the first line 4. What is considered the first line inotrope in cardiogenic shock inotrope in cardiogenic shock
A. DopamineA. Dopamine B. DobutamineB. Dobutamine C. MilrinoneC. Milrinone
5.5. Which is not considered a first line Which is not considered a first line agent in treatment of anaphylaxisagent in treatment of anaphylaxis
A. EpiA. Epi B. OxygenB. Oxygen C. albuterolC. albuterol
AnswersAnswers
1. B1. B 2. B2. B 3. B3. B 4. A4. A 5. C5. C