SHOCK SHOCK September 6, 2005 Andrew Filiatraut. In General Shock Shock Clinical syndrome defined as hypoperfusion Clinical syndrome defined as hypoperfusion

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


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


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


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


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


ConstitutionalConstitutional Hyper/hypothermiaHyper/hypothermia TachycardiaTachycardia TachypneaTachypnea Wide pulse pressureWide pulse pressure Mental status change Mental status change

Most likely obtundedMost likely obtunded


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


▪ ▪ 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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


PathophysiologyPathophysiology Autonomic Nervous SystemAutonomic Nervous System

ParasympatheticParasympathetic Cranial Nerves & 2-4Cranial Nerves & 2-4thth sacral segments sacral segments

(splanchnic nerves)(splanchnic nerves)


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


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

Documents

SHOCK SHOCK September 6, 2005 Andrew Filiatraut. In General Shock Shock Clinical syndrome defined as hypoperfusion Clinical syndrome defined as hypoperfusion