patho physiology and icu management of septic shock

Patho-Physiology and Patho-Physiology and ICU Management of ICU Management of

Septic ShockSeptic Shock

Dr.T.R.ChandraShekaDr.T.R.ChandraShekarr Director critical Director critical care, care, K.R.Hospital, K.R.Hospital, BengaluruBengaluru

Case ScenarioCase Scenario 35 year old male patient brought to ICU with 3 35 year old male patient brought to ICU with 3

day old perforation, day old perforation, Posted for emergency Posted for emergency LapratomyLapratomy

Has chills with feverHas chills with fever Tachypneic- RR 40/mt, has respiratory distress, Tachypneic- RR 40/mt, has respiratory distress, Tense abdomen, bilateral crepts, Tense abdomen, bilateral crepts, Spo2 on 89% on room air.Spo2 on 89% on room air. Pulse 130/mt well felt, BP 80/60 mm Hg, Pulse 130/mt well felt, BP 80/60 mm Hg,

Restless,Restless, InvestigationsInvestigations WBC – 19,000 T.B 3.5, Enzymes NormalWBC – 19,000 T.B 3.5, Enzymes Normal SC-2.0 INR 2.0, Platelets 1.2 lac SC-2.0 INR 2.0, Platelets 1.2 lac

Lactate 5.0 SCVO2 60%, Lactate 5.0 SCVO2 60%,

Is he in septic shock ?Can we administer anaesthesia right now ?

Do you want to stabilise him before surgery ?

Is he in septic shock ?Can we administer anaesthesia right now ?

Do you want to stabilise him before surgery ?

Shock definition Shock definition

Shock Shock is defined as a life-threatening, is defined as a life-threatening, generalized generalized maldistributionmaldistribution of blood flow of blood flow resulting in failure to deliver and/or utilize resulting in failure to deliver and/or utilize adequate amounts of adequate amounts of oxygen,oxygen, leading to leading to tissue dysoxia.tissue dysoxia.

Hypotension [SBP Hypotension [SBP < < 90 mmHg, SBP decrease 90 mmHg, SBP decrease of 40 mmHg from baseline, or mean arterial of 40 mmHg from baseline, or mean arterial pressure (MAP) pressure (MAP) < < 65 mmHg], while commonly 65 mmHg], while commonly present, should present, should not be required to define not be required to define shockshock.. Shock requires evidence of inadequate Shock requires evidence of inadequate tissue perfusion on physical examinationtissue perfusion on physical examination..

Sepsis: Defining a Disease Continuum

A clinical response arising from a nonspecific insult, including 2 of the following:

•Temperature 38oC or 36oC•HR 90 beats/min•Respirations 20/min•WBC count 12,000/mm3 or 4,000/mm3 or >10% immature neutrophils

SIRSSystemic Inflammatory Response Syndrome

SIRS with a presumed or confirmed infectious process

SepsisSepsisSIRSSIRSInfectionInfectionSevere Severe SepsisSepsis

SEPTIC SHOCK

Inflammatory response to microorganisms or invasion of normally sterile tissues

SepsisSepsisSIRSSIRSInfection/Infection/TraumaTrauma

Severe Severe SepsisSepsis

Sepsis with 1 sign of organ failureCardiovascular ( hypotension) Lungs: (ARDS): Kidneys Liver Digestive Brain - confusion

SEPTICSEPTIC

ShockShock

HYPOTENSION despite adequate fluid resuscitation/Requiring Vasopressors or Inotropes

Relationship Of Infection, SIRS, Relationship Of Infection, SIRS, Sepsis Severe Sepsis and Septic Sepsis Severe Sepsis and Septic

ShockShock

SIRSINFECTION

PANCREATITIS

BURNS

TRAUMA

OTHER

SEPSIS

SEVERESEPSIS

SEPTICSHOCKBacteria

Fungus

Parasites

Virus

DefinitionsDefinitions

SIRS Sepsis

Severe Sepsis

Septic ShockInfection

DO WE REQUIRE TO CHANGE THE DEFINITION?

MODS

Although none of these is specific of sepsis, the unexplained presence of several in

combination should raise suspicion of sepsis

2001 Sepsis Definitions 2001 Sepsis Definitions ConferenceConference

Current definitions will remain Current definitions will remain unchangedunchanged

However, will accept the uncertainty However, will accept the uncertainty of definitionsof definitions

SIRS expanded to signs and symptomsSIRS expanded to signs and symptomsExpanded list of SIRS signs and symptoms

Arterial hypotensionTachycardia

Altered skin perfusionDecreased U.O

Hyperlactatemia –

Altered WBC countIncreased CRP,

PCT concentrations

Rigor– feverTachypnea

Positive fluid balance – edema

General signs & symptomsGeneral inflammatory reaction

Hemodynamic alterations

Signs of organ dysfunction Signs of organ dysfunction

HypoxemiaCoagulation abnormalities

Altered mental status

Expanded signs of SIRSExpanded signs of SIRS





Lactate 5.0 SCVO2 60%, Lactate 5.0 SCVO2 60%,

Severe SEPSISSevere SEPSIS

Pathogenesis of shockPathogenesis of shock

Microcirculatory Mitochondrial dysfunction

Cardiac dysfunction, Microemboli, Microvasular injury, increased Nitric oxide- Vasoplegia

Cytokines & inflammatory mediator cascade

Interaction with human cells- macrophages Monocytes, Neutrophils, Endothelial cells

Infectious trigger

Toll receptorsToll receptors

Toll receptors (TLR)Toll receptors (TLR)

Key mediators of the innate immune system

Expressed on macrophage, dendritic cells, neutrophils, endothelial cells and mucosal epithelial cells

TLR are transmembrane proteins with the ability to promote signaling pathways downstream, triggering cytokine release and neutrophil activation and stimulating endothelial cells

Toll receptorsToll receptors

Pathogen-associated molecular patterns (PAMPs)

Host factorsImmunosuppressed

Extremes of ageMalnutrition

Alcohol, Drug AbuseMalignancyHIV/AIDS

Chronic Health Issues – Diabetes, Liver Failure, Heart

Disease, Corticosteroids, ChemotherapyMultiple invasive procedures

or invasive lines

PRO INFLAMMATORYPromotes-InflammationCoagulationInhibits-Anti-coagulants,Fibrinilysis.IL-1; TNF IL-6; IL-8

ANTI-INFLAMATORY

Inhibits- Inflammation

Coagulation

ImmunosupressionAnti-Inflammatories:IL-1ra; IL-4; IL-10

S

MONOCYTE DERIVED CYTOKINES

INFECTION/MICROBIAL TRIGGERINFECTION/MICROBIAL TRIGGER

SIRS CARS

Systemic Inflammatory Response Syndrome

Compensatory Anti- Inflammatory Response Syndrome

Crit Care Med 2000, 28(4):N105-N113 with modification

Infection

Immune Response

Sepsis

Uncontrolled Pro-inflammatoryMechanisms

Dysregulated anti-inflammatoryMechanisms

SIRS

MODS/MOF

Death

Why some patients do well Why some patients do well others die ?others die ?

Infection

Toxins

Host defenses InadequateOverwhelming infection

Death

Sepsis Excessive

Survival

MODSAdequate

Coordinated

Infection control

Survival

Why?

Why?

Unregulated

Host factors

Delayed therapy

Genetic predisposition

HLA class III genes TNF a gene promoter

Role of Role of Nitric OxideNitric Oxide

L – arginineL – arginine

eNOS iNOSeNOS iNOSnNOSnNOS

NONO

EndotheliumEndothelium

Neurones

Neurones

MacrophagesSmooth muscleEndothelium

MacrophagesSmooth muscleEndothelium

Vasoplegia-Hypotension

Coagulation in SepsisCoagulation in Sepsis

Bernard GR, et al. New Engl J Med, 2001;344:699-709.

Inflammatory Responseto Infection

Thrombotic Responseto Infection

Fibrinolytic Responseto Infection

Endothelium

TAFI

PAI-1

Suppressedfibrinolysis

Neutrophil

Monocyte

IL-6IL-1TNF

Bacterial, viral, fungal or parasitic infection/endotoxin

Bacterial, viral, fungal or parasitic infection/endotoxin

IL-6

Tissue Factor

Tissue Factor

COAGULATION CASCADE

Factor Va

Factor VIIIa

THROMBIN

FibrinFibrin clot

Coagulation

Inflammation

Fibrinolysis

Micro-emboli

Inflammatory Response

CARDIOVASCULAR FAILURE

Vasodilatation (nitric oxide release)HypovolemiaMyocardial dysfunctionCell metabolism alterationDecrease vascular resistance

Tachycardia, Hypotension, Hypoperfusion

Final pathway in sepsisFinal pathway in sepsisVasoplegia , Cardiac dysfunction, Capillary leak

Hypovolemia,Maldistribution Microemboli

Microcirculatory Mitochondrial Dysfunction syndrome(MMDS)

Cell death-Organ injury –MODS- Death

Sepsis is a disease of the microcirculation

Why the microcirculation is important in shockWhy the microcirculation is important in shock..

It is where oxygen exchange It is where oxygen exchange takes place.takes place.

It plays a central role in the It plays a central role in the

immune system.immune system. During sepsis and shock it the During sepsis and shock it the

first to go and last to recover.first to go and last to recover.

Rescue of the microcirculation = resuscitation end-pointRescue of the microcirculation = resuscitation end-point

TIME TIME isis

TISSUETISSUE

Oxygen Don’t Go Oxygen Don’t Go Where the Blood Won’t Flow!Where the Blood Won’t Flow!

From these two statements three things are obviousEarly therapy before mitochondria gets damaged.

Macro circulation should be optimised first.Micro circulation optimisation to prevent

Mitochondrial injury is the target

Resuscitation end pointsResuscitation end points

CVP 8–12 mm HgCVP 8–12 mm Hg

(MAP) >=65 mm Hg(MAP) >=65 mm Hg

Urine output >=to 0.5 Urine output >=to 0.5 mL/kg/hrmL/kg/hr

SCVO2(superior vena SCVO2(superior vena cava) >=70% or SVO2 cava) >=70% or SVO2 >= 65%, >= 65%,

Lactate < 2 mmol/LLactate < 2 mmol/L

SCVO2 > 70%SCVO2 > 70%

Micro circulationMacro circulation

Tissue hypoperfusion can persist despite normal vital sign.

Normal Lactate and SCVO2 Normal Lactate and SCVO2 despite MMDSdespite MMDS

No extraction of oxygen-No extraction of oxygen-mitochondrial damagemitochondrial damage

Shunting of blood away from Shunting of blood away from microcirculationmicrocirculation

Although ScvOAlthough ScvO22 tracked SvO tracked SvO22, it is , it is tended to 7 ± 4 % highertended to 7 ± 4 % higher

Management of Sepsis the Management of Sepsis the bottom line isbottom line is

Blood to be oxygenated Blood to be oxygenated Have Adequate pressure Have Adequate pressure Deliver this blood into Deliver this blood into

microcirculation early before microcirculation early before Mitochondria are damagedMitochondria are damaged

DO2 –oxygen delivery DO2 –oxygen delivery with adequate pressurewith adequate pressure

Arterial oxygen content X Cardiac out Arterial oxygen content X Cardiac out putput

SaO2/Pao2 x Hb%SaO2/Pao2 x Hb%MV/ oxygen therapy

PEEP

Blood transfusion

ContractilityInotropes

Preload Fluids

HRPacing

Isoproterenol

Afterload

Vasodialators

Oxygen to mitochondriaOxygen to mitochondria

Patient may have defective oxygen Patient may have defective oxygen extraction or oxygen may not reach extraction or oxygen may not reach the cells due to micro emboli or the cells due to micro emboli or shunting of blood.shunting of blood.

Defective extraction may be due to Defective extraction may be due to Mitochondrial injury.Mitochondrial injury.

Shunting of bloodShunting of bloodO2

lactateCO2

vvaa

Micro-Emboli

Maldistribution

MMDS- PreventionMMDS- Prevention

Optimize Macro-circulation.Optimize Macro-circulation. rhAPC- Prevents coagulation rhAPC- Prevents coagulation

enhances fibrinolysis.enhances fibrinolysis. VasodilatorsVasodilators

Microcirculation Monitoring at bedside is difficultTherapeutically Not much can be done at MM level

Except early and protocol based treatment

War on SepsisSurviving Sepsis Campaign- Phase II Surviving Sepsis Campaign- Phase II 25% reduction in sepsis mortality within 5 years 25% reduction in sepsis mortality within 5 years

- by 2009- by 2009

Society of Critical Care Medicine, European Society of Intensive Society of Critical Care Medicine, European Society of Intensive CareCareMedicine, International Sepsis Forum + Institute of Healthcare Medicine, International Sepsis Forum + Institute of Healthcare ImprovementImprovement

Even with the ‘best’ parameters it is not always easy to make the right decision.………

EGDTEGDT

Suspected infectionBlood cultures

Obtain two or more BCsOne or more BCs should be percutaneous

One BC from each vascular access device in place more than equal to 48 hrsCulture other sites as clinically indicated.

Other diagnostic/imaging as indicated

Appropriate Empirical Antibiotics with in 1 hr/

source control

Host factors/ local antibiogram/ suspected siteCombination antibiotics/ right dose

SBP< 90 even after20-30ml/kg fluid or Lactate > 4mmol/l

Antibiotics Antibiotics

Always look at you

local organisms and resistance patterns

Early antibiotic therapy Right dose





Lactate 5.0 SCVO2 60%, K+4.5Lactate 5.0 SCVO2 60%, K+4.5

3l of oxygen RBM, Two BCInj Meoropenem 500mg tid+ Inj Metrogyl 100 ml tid




source control

CVPCVP

MAPMAP

Goal achievedGoal achieved

SCVO2SCVO2

< 8 Fluids NS, RL/ Colloid

8-12

>60-90mmHg

< 60-90Vasopressors

Noradrenaline/dopamine

< 60-90Vasopressors


<70%

< 30 HCt-Packed cellsSCVO2< 70%

InotropeDobutamine


InotropeDobutamine

SCVO2 >70%

DecreaseOxygen

consumption

DecreaseOxygen

consumption

Fluid challenge in patients with suspected Fluid challenge in patients with suspected hypovolemia may be givenhypovolemia may be given 500 - 1000 mL of crystalloids over 30 mins500 - 1000 mL of crystalloids over 30 mins 300 - 500 mL of colloids over 30 mins300 - 500 mL of colloids over 30 mins Repeat based on response and toleranceRepeat based on response and tolerance Input is typically greater than output due to Input is typically greater than output due to

venodilation and capillary leakvenodilation and capillary leak Most patients require continuing aggressive fluid Most patients require continuing aggressive fluid

resuscitation during the first 24 hours of resuscitation during the first 24 hours of managementmanagement

Fluid Therapy: Fluid Fluid Therapy: Fluid ChallengeChallenge

Grade E

Dellinger, et. al. Crit Care Med 2004, 32: 858-873.




source control

CVPCVP

MAPMAP


SCVO2SCVO2


8-12

>60-90mmHg

< 60-90Vasopressors


< 60-90Vasopressors


<70%


InotropeDobutamine


InotropeDobutamine

SCVO2 >70%

DecreaseOxygen

consumption

DecreaseOxygen

consumption

VasopressorsVasopressors MAP >=65 mm Hg. MAP >=65 mm Hg. Noradrenaline or dopamine as the first choice Noradrenaline or dopamine as the first choice Adrenaline/ Vasopressin be the first chosen Adrenaline/ Vasopressin be the first chosen

alternative agent in septic shock that is poorly alternative agent in septic shock that is poorly responsive to norepinephrine or dopamine. responsive to norepinephrine or dopamine.

Low-dose dopamine Low-dose dopamine not be usednot be used for renal for renal protection. protection.

Arterial catheter placed Arterial catheter placed Inotropic TherapyInotropic Therapy Dobutamine -myocardial dysfunction Dobutamine -myocardial dysfunction Do not use a strategy to increase cardiac Do not use a strategy to increase cardiac

index to predetermined supranormal levelsindex to predetermined supranormal levels




source control

CVPCVP

MAPMAP


SCVO2SCVO2


8-12

>60-90mmHg

< 60-90Vasopressors


< 60-90Vasopressors


<70%


InotropeDobutamine


InotropeDobutamine

SCVO2 >70%

DecreaseOxygen

consumption

DecreaseOxygen

consumption





Lactate 5.0 SCVO2 60%, K+4.5Lactate 5.0 SCVO2 60%, K+4.5

1-2 litrs NS/ RL still hypotensiveAdd noradrenaline and adrenaline

BP 130/70 mmHg, lactate 3 mmol/l, SCVO2 68%CVP 8 cms H20/ UO 1ml/kg/mt

If he continues to improve for first 6 hrsI may plan to administer anesthesia for his surgery.

EGDTEGDT

SteroidsSteroids

Treat patients who still require vasopressors despite fluid replacement with hydrocortisone 200-300 mg/day, for 7 days in three or four divided doses or by continuous infusion.

ACTH stimulation test is ACTH stimulation test is notnot recommended.recommended.

Steroid therapy may be weaned once Steroid therapy may be weaned once vasopressors are no longer required.vasopressors are no longer required.

Supportive careSupportive care

Deep vein thrombosis prophylaxis.Deep vein thrombosis prophylaxis. Stress ulcer prophylaxis.Stress ulcer prophylaxis. Glucose control.Glucose control. Maintain a Plateau pressure of Maintain a Plateau pressure of

less than equal to 30 cmH2O and less than equal to 30 cmH2O and low tidal volume 4-6 ml/kg of low tidal volume 4-6 ml/kg of Predicted body weight for Predicted body weight for mechanically ventilated patientsmechanically ventilated patients . .

Conclusions Conclusions Sepsis is a disease of microcirculation. Sepsis is a disease of microcirculation. Oxygen Don’t Go Oxygen Don’t Go

Where the Blood Won’t Flow- Where the Blood Won’t Flow- Optimise the Macrocirculation first.Optimise the Macrocirculation first.

Monitoring microcirculation at Monitoring microcirculation at bedside is difficult- Lactate/ SCVO2 bedside is difficult- Lactate/ SCVO2 are most important parameters to are most important parameters to be monitored, validated by studies.be monitored, validated by studies.

Treatment –SS guidelinesTreatment –SS guidelines

Thank youThank you

patho physiology and icu management of septic shock

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