Patho-physiology And Icu Management Of Septic Shock

Patho-Physiology and ICU Management of Septic Shock

Dr.T.R.ChandraShekar Director critical care, K.R.Hospital, Bengaluru

Case Scenario 35 year old male patient brought to ICU with 3 day old perforation, Posted for emergency Lapratomy  Has chills with fever  Tachypneic- RR 40/mt, has respiratory Is he in septic shock ? distress,  Tense abdomen, bilateral crepts, Can we administer anaesthesia right now ?  Spo2 Do youon want to stabilise him before surgery ? 89% on room air.  Pulse 130/mt well felt, BP 80/60 mm Hg, Restless,  Investigations  WBC – 19,000 T.B 3.5, Enzymes 

Shock definition 

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Shock is defined as a life-threatening, generalized maldistribution of blood flow resulting in failure to deliver and/or utilize adequate amounts of oxygen, leading to tissue dysoxia. Hypotension [SBP < 90 mmHg, SBP decrease of 40 mmHg from baseline, or mean arterial pressure (MAP) < 65 mmHg], while commonly present, should not be required to define shock. Shock requires evidence of inadequate tissue perfusion on physical examination.

Sepsis: Defining a Disease Continuum Infection

SIRS

Severe Sepsis Sepsis

SEPTIC SHOCK

Inflammatory response to SIRS with a presumed or microorganisms or confirmed infectious process invasion of normally A clinical response arising from a nonspecific sterile tissues insult, including ≥ 2 of the following:

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

SIRS Systemic Inflammatory Response Syndrome

Infection/ Trauma

SIRS

Sepsis Severe Sepsis

SEPTIC Shock

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

HYPOTENSION despite adequate fluid resuscitation/Requiri ng Vasopressors or Inotropes

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

PANCREATITIS

SEVERE SEPSIS

INFECTION Bacteria

SEPTIC SHOCK

SIRS

BURNS

Fungus Parasites Virus

TRAUMA OTHER

Definitions DO WE REQUIRE TO CHANGE THE DEFINITION?

MODS

SIRS Infection

Sepsi Severe Septic s Sepsis Shock

2001 Sepsis Definitions Conference  Current

definitions will remain unchanged  However, will accept the uncertainty of definitions  SIRS Expanded list of SIRS andand symptoms expanded tosigns signs symptoms Although none of these is specific of sepsis, the unexplained presence of several in combination should raise suspicion of sepsis

Expanded signs of SIRS

General inflammatory General signs & symptoms reaction

Hemodynamic alterations

Altered WBC count Arterial hypotension Tachycardia Rigor– fever Increased CRP, Altered skin perfusion Tachypnea Decreased U.O PCT concentrations ositive fluid balance – edema Hyperlactatemia –

Signs of organ dysfunction Hypoxemia Coagulation abnormalities Altered mental status

Case Scenario 

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35 year old male patient brought to ICU with 3 day old perforation, Posted for emergency Lapratomy Has chills with fever Tachypneic- RR 40/mt, has respiratory Severe SEPSIS distress, Tense abdomen, bilateral crepts, Spo2 on 89% on room air. Pulse 130/mt well felt, BP 80/60 mm Hg, Restless, Investigations WBC – 19,000 T.B 3.5, Enzymes

Pathogenesis of shock Infectious trigger Interaction with human cells- macrophages Monocytes, Neutrophils, Endothelial cells Cytokines & inflammatory mediator cascade

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

Toll receptors

Toll receptors (TLR) 

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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

Toll receptors Pathogen-associated molecular patterns (PAMPs)

Host factors Immunosuppressed Chronic Health Issues – Extremes of age Diabetes, Liver Failure, Heart Malnutrition Disease, Alcohol, Drug Abuse Corticosteroids, Chemotherapy Malignancy Multiple invasive procedures HIV/AIDS or invasive lines

INFECTION/MICROBIAL TRIGGER PRO INFLAMMATORY Promotes-Inflammation Coagulation Inhibits-Anti-coagulants, Fibrinilysis. IL-1; TNF IL-6; IL-8

SIRS Systemic Inflammatory Response Syndrome

ANTI-INFLAMATORY Inhibits- Inflammation

MONOCYTE DERIVED CYTOKINES

S

Coagulation Immunosupression Anti-Inflammatories: IL-1ra; IL-4; IL-10

CARS

Compensatory Anti- Inflammatory Response Syndrome

SIRS

Infection

Immune Response Sepsis Uncontrolled Pro-inflammatory Mechanisms

Dysregulated anti-inflammatory Mechanisms

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

Why some patients do well others die ? Genetic predisposition Infection

HLA class III Wh genes TNF a gene promoter y?

Sepsis

Toxins

Host factors

Wh y?

Delayed therapy

Excessiv Inadequate Overwhelmi Host defenses ng infection Unregulat eed

MODS

Survival Death

Adequate Coordinated

Infection control Survival

Death

Role of Nitric Oxide Endotheli um

L – arginine

eNOS

Macrophag es Smooth muscle Endotheliu m

iNOS nNOS

Neurone s

NO

VasoplegiaHypotension

Coagulation in Sepsis Endothelium

COAGULATION CASCADE

Tissue Factor Bacterial, viral, fungal or parasitic infection/end otoxin

IL-6 IL-1 TNFα

Factor VIIIa

Coagulation Inflammatio n

Suppressed fibrinolysis

Inflammatory Response THROMBIN

TAFI Fibrin clot

Bacterial, viral, fungal or parasitic infection/end otoxin

Inflammatory Response to Infection

PAI-1

Factor Va

Monocyte

Tissue Factor

Fibrinolysi s

Neutrophil

Fibrin

Micro-emboli

IL-6

Thrombotic Response to Infection

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

Fibrinolytic Response to Infection

CARDIOVASCULAR FAILURE Vasodilatation (nitric oxide release) Hypovolemia Myocardial dysfunction Cell metabolism alteration Decrease vascular resistance

Tachycardia, Hypotension, Hypoperfusion

Final pathway in sepsis

Vasoplegia , Cardiac dysfunction, Capillary le Hypovolemia,Maldistribution Microemboli

Microcirculatory Mitochondrial Dysfunction syndrom (MMDS)

Cell death-Organ injury –MODS- Death

Sepsis is a disease of the microcirculation

Why the microcirculation is important in shock. 

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It is where oxygen exchange takes place. It plays a central role in the immune system. During sepsis and shock it the first to go and last to recover.

ue of the microcirculation = resuscitation end-point

TIME is

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

From these two statements three things are obvious

arly therapy before mitochondria gets damage Macro circulation should be optimised first. Micro circulation optimisation to prevent Mitochondrial injury is the target

Resuscitation end points Micro circulation

Macro circulation

CVP 8–12 mm Hg (MAP) >=65 mm Hg Urine output >=to 0.5 mL/kg/hr SCVO2(superior vena cava) >=70% or SVO2 >= 65%,

Lactate < 2 mmol/L SCVO2 > 70%

Tissue hypoperfusion can persist despite normal vital sign.

Normal Lactate and SCVO2 despite MMDS 

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No extraction of oxygenmitochondrial damage Shunting of blood away from microcirculation Although ScvO2 tracked SvO2, it is tended to 7 ± 4 % higher

Management of Sepsis the bottom line is   

Blood to be oxygenated Have Adequate pressure Deliver this blood into microcirculation early before Mitochondria are damaged

DO2 –oxygen delivery with adequate pressure Arterial oxygen content X Cardiac out put HR Pacing Isoproterenol

SaO2/Pao2 x Hb% MV/ oxygen therapy PEEP

Blood transfusi on

Contractility Inotropes

Preload Fluids

Afterload Vasodialators

Oxygen to mitochondria 

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Patient may have defective oxygen extraction or oxygen may not reach the cells due to micro emboli or shunting of blood. Defective extraction may be due to Mitochondrial injury. Shunting of blood O2

a

v lactate CO2

Micro-Emboli Maldistribution

MMDS- Prevention  

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Optimize Macro-circulation. rhAPC- Prevents coagulation enhances fibrinolysis. Vasodilators

Microcirculation Monitoring at bedside is difficult Therapeutically Not much can be done at MM leve Except early and protocol based treatment

War on Sepsis

Surviving Sepsis Campaign- Phase II 25% reduction in sepsis mortality within 5 years - by 2009

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

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

EGDT

Suspected infection Blood cultures

Obtain two or more BCs One or more BCs should be percutaneous One BC from each vascular access device in place more than equal to 48 hrs Culture other sites as clinically indicated. Other diagnostic/imaging as indicated

SBP< 90 even after 20-30ml/kg fluid or Lactate > 4mmol/l

Appropriate Empirical Antibiotics with in 1 hr/ source control

Host factors/ local antibiogram/ suspected site Combination antibiotics/ right dose

Always look at you

Antibiotics local organisms and resistance patterns

Early antibiotic therapy Right dose

Case Scenario 35 year old male patient brought to ICU with 3 day old perforation, Posted for emergency Lapratomy  Has chills with fever 3l of oxygen RBM, Two BC  TachypneicRR 40/mt, has respiratory Inj Meoropenem 500mg tid+ Inj Metrogyl 100 ml tid distress,  Tense abdomen, bilateral crepts,  Spo2 on 89% on room air.  Pulse 130/mt well felt, BP 80/60 mm Hg, Restless,  Investigations  WBC – 19,000 T.B 3.5, Enzymes 

Suspected infection Blood cultures SBP< 90 even after 20-30ml/kg fluid or Lactate > 4mmol/l Appropriate Empirical Antibiotics with in 1 hr/ source control

CVP 8-12 Decrease Oxygen consumption

MAP >6090mmHg

SCVO2 < 70%

Goal achieved

< 8 Fluids NS, RL/ Colloid

< 60-90 Vasopressors Noradrenaline/dopamine

< 30 HCt-Packed cells SCVO2< 70% Inotrope Dobutamine SCVO2 >70%

Fluid Therapy: Fluid Challenge 

Fluid challenge in patients with suspected hypovolemia may be given 500 - 1000 mL of crystalloids over 30 mins  300 - 500 mL of colloids over 30 mins  Repeat based on response and tolerance  Input is typically greater than output due to venodilation and capillary leak  Most patients require continuing Grade E aggressive fluid Dellinger, et. al. Crit Care Med 2004, 32: 858-873. resuscitation during the 

Suspected infection Blood cultures SBP< 90 even after 20-30ml/kg fluid or Lactate > 4mmol/l Appropriate Empirical Antibiotics with in 1 hr/ source control

CVP 8-12 Decrease Oxygen consumption

MAP >6090mmHg

SCVO2 < 70%

Goal achieved

< 8 Fluids NS, RL/ Colloid

< 60-90 Vasopressors Noradrenaline/dopamine

< 30 HCt-Packed cells SCVO2< 70% Inotrope Dobutamine SCVO2 >70%

Vasopressors   

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MAP >=65 mm Hg. Noradrenaline or dopamine as the first choice Adrenaline/ Vasopressin be the first chosen alternative agent in septic shock that is poorly responsive to norepinephrine or dopamine. Low-dose dopamine not be used for renal protection. Arterial catheter placed Inotropic Therapy Dobutamine -myocardial dysfunction

Suspected infection Blood cultures SBP< 90 even after 20-30ml/kg fluid or Lactate > 4mmol/l Appropriate Empirical Antibiotics with in 1 hr/ source control

CVP 8-12 Decrease Oxygen consumption

MAP >6090mmHg

SCVO2 < 70%

Goal achieved

< 8 Fluids NS, RL/ Colloid

< 60-90 Vasopressors Noradrenaline/dopamine

< 30 HCt-Packed cells SCVO2< 70% Inotrope Dobutamine SCVO2 >70%

Case Scenario 

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35 year old male patient brought to ICU with 3 day old perforation, Posted for emergency Lapratomy Has chills 1-2with litrs fever NS/ RL still hypotensive TachypneicRR 40/mt, and hasadrenaline respiratory Add noradrenaline distress, BP 130/70 mmHg, lactate 3 mmol/l, SCVO2 68% CVP 8 cmsbilateral H20/ UO 1ml/kg/mt Tense abdomen, crepts, If he continues to improve for first 6 hrs Spo2 onplan 89% on room air. for his surgery. I may to administer anesthesia Pulse 130/mt well felt, BP 80/60 mm Hg, Restless, Investigations WBC – 19,000 T.B 3.5, Enzymes

EGDT

Steroids 

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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 not recommended. Steroid therapy may be weaned once vasopressors are no longer required.

Supportive care 

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Deep vein thrombosis prophylaxis. Stress ulcer prophylaxis. Glucose control. Maintain a Plateau pressure of less than equal to 30 cmH2O and low tidal volume 4-6 ml/kg of Predicted body weight for mechanically ventilated patients .

Conclusions  

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Sepsis is a disease of microcirculation. Oxygen Don’t Go Where the Blood Won’t FlowOptimise the Macrocirculation first. Monitoring microcirculation at bedside is difficult- Lactate/ SCVO2 are most important parameters to be monitored, validated by studies. Treatment –SS guidelines

Thank you