Septic Shock

Dr. Mohammad Abdul MatinMRCP(Ire), MRCP(UK), FACP, FRCP(Edin)

Consultant, Internal Medicine

Agenda:

Define ShockDifferent type of Shock with

mechanismSeptic Shock : DefineClassification/Terminology in

septic ShockPathophysiology of sepsisDiagnosis and work upManagement of septic

shock(Surviving Sepsis Campaign -2012 guideline)

What is shock ?

Shock is the term to describe acute circulatory failure with inadequate or inappropriately distributed tissue perfusion resulting in generalized cellular hypoxia and/ or an inability of the cells to utilize oxygen.

Decreased Tissue Perfusion

Tissue Ischemia

Organ or System Dysfunction

Key hemodynamic Parameter of shock:Patients develop shock when there is a problem with one or more of the key elements that contribute to perfusion

Blood Pressure

Cardiac Output(Decreased in

Cardiogenic Shock)

Systemic Vascular Resiatance

(Decreased in Distributive Shock)

Heart RateStroke Volume

Preload (Decreased in Hypovolemic

Shock)

Contractility Afterload

Common clinical features of shock:

Hypotension:SBP Less than 90 mm HgDBP Less than 60 mm Hg Acute decrease in SBP of more than 40 mm

HgLack of MAP response to initial fluid challenge

End organ dysfunction due to Hypo- perfusion:

Decreased Urine OutputChange in mental statusIncreased serum lactic acid level

Types/causes of shock:

Hypovolemic ObstructiveExogenous lossesEndogenous losses

Obstruction to outflow e.g. Pulmonary embolismRestricted Cardiac Filling (e.g. Cardiac tamponade, Tension Pneumothorax)

Cardiogenic Distributivee.g. Ischemic Myocardial Injury

(e.g. sepsis, anaphylaxis)Vascular dilatationSequestrationmyocardial depressionArteriovenous shunting

Understanding the cause of shock is

important as clinician can decide which parameter needs to be supported or corrected and also to know the underlying problem that require therapy.

In all types of shock the therapeutic goals are to support tissues and organs that are dysfunctional due to hypoperfusion.

Perfusion is often improved by some combination of intravenous fluids, vasopressor and inotropic agents and treatment of the underlying cause.

Septic shock

Define Sepsis: Sepsis is an exaggerated inflammatory response to an infectious stimulus and is characterized by a severe catabolic reaction, widespread endothelial dysfunction and release of inflammatory agents.

Epidemiology:

Incidence rises exponentially after age 65

Mortality increased with co-morbidities like DM, CKD, chronic heart diseases, continued systemic signs of sepsis (persistent hypotension despite multiple liters of fluids) and persistent deficit in oxygen delivery.

Pathophysiology:

Complex dysregulation of both inflammation and coagulation.

Primary cellular injury results from infections or the host’s immune response to the infection.

Cytokines(TNF-alpha, IL-1) activate leukocytes and promote leukocyte adhesion, diapedesis and degranulation with resultant endothelial cell damage.

Endothelial damage leads to tissue factor expression and activation of the clotting cascade.

Cont…..pathophysiology

Inflammatory cascade induced by sepsis results in vasodilatation and capillary leak, which decreases effective circulatory volume, which leads to an increase in heart rate as a means to maintain effective Blood Pressure.

Later in sepsis, there is myocardial dysfunction with decreased contractility, which exacerbate sepsis induced hypotension.

Hypotension, microthrombi and abnormal tissue oxygen utilization result in further cellular ischemia, cell death, and release of additional inflammatory mediators.

Terminology in Sepsis/ Classification of Sepsis:

Infection: Invasion of normally sterile host tissue by microorganism

Bacteraemia: Viable bacteria in blood

Systemic Inflammatory Response syndrome(SIRS):SIRS results from variety of clinical insults (inflammatory

or infectious) and is manifested by two or more of the following:

Temperature >38*C or <36*C HR >90 beats/minute RR>20 breaths/minute WBC >12x10*9/L, <4*X10*9/L or >10% immature

forms

Sepsis: SIRS + suspected infection

Terminology……Cont…Severe Sepsis: Sepsis associated with

hypoperfusion or organ dysfunction and manifested by systemic effect like hypotension, decreased urine output or lactic acidosis or an acute alteration in mental status.

Septic Shock: severe sepsis with hypotension(systolic BP 90 mmHg or a reduction of 40 mmHg from baseline) in the absence of other causes of hypotension and despite adequate fluid resuscitation( means require vasopressor agent to maintain BP).

Refractory Shock: Shock unresponsive to conventional therapy (IVF + inotropes/ vasopressor) within one hour.

Presentation in case of Sepsis

SIRS with infectionSeptic ShockGeneral symptoms:

Diagnosis of sepsis:Clinical features of SepsisPyrexia and rigors or rarely hypothermiaNausea, vomitingVasodilatation, warm peripheriesBounding pulseRapid capillary refillHypotensionOther signs: - Jaundice - Coma, stupor - Bleeding due to coagulopathy (e.g. from vascular puncture site, GI tract and surgical wound) - Rash and meningism - Hyperglycemia and in more severe cases

hypoglcemia

Diagnosis of sepsis: cont,,,,,

Diagnosis is often difficult in elderly

Classic signs may not be present all the time

Mild confusion, tachycardia and tachypnoea may be the only clues, sometimes associated with unexplained hypotension, reduction in urine output, a rising plasma creatinine and glucose intolerance.

Sepsis and Multi organ failure (MOF) orMultiple organ dysfunction syndrome(MODS)

Sepsis is the commonest cause of death in non-coronary adult ICU.

Mortality rates are high and are closely related to the severity of illness and the number of organs that fail.

Those who die are overwhelmed by persistent or recurrent sepsis, with fever, intractable hypotension and failure of multiple organs

Sequential failure of vital organs occur but the pattern of organ dysfunction is variable

Most cases the lungs are the first to be affected (Acute lung injury-ALI, Acute Respiratory Distress Syndrome-ARDS) in association with cardiovascular instability and deteriorating renal function.

Gastrointestinal failure happenCentral Nervous system involvesFinally cardiovascular collapse

supervenes.

CAP is the commonest cause of sepsis requiring admission to ICU

Patient develops ARDS

CT chest finding in ARDS

Examinations:BPPulsePeripheral warmnessTemperatureRR- tachypneaHypoxiaOliguriaMetabolic acidosisFocus of infection

Investigations:

Blood test: CultureImaging

Management:

Management principle:

To treat infectionOptimize tissue perfusion

How we can do that ?Control source of infectionInstituting early and appropriate antibiotic

therapyOptimizing oxygen delivery by correcting hypoxiaIVF – using crystalloid to maintain adequate

preloadStarting vasoactive agent to maintain perfusion

pressure for persistent hypotension despite adequate fluid resuscitation

Transfusion of packed RBC if needed

Source Control and Antibiotic Therapy:Source of infection should be identified and

controlled (removal of infected device or abscess drainage)

Blood and other specimen should be collected for C/S before starting antibiotics

Broad spectrum empiric antibiotics based on the site of infection should be started within 1 hour

Delay in initiation or choice of inappropriate antibiotics is associated with increased mortality rate.

Antibiotics needs modified once C/S result available

Management of Septic Shock: Requires hemodynamic monitoring and high

dependency facilities ABC-

- Check the airway is clear

- Give high flow oxygen, if

refractory hypoxia, intubate and ventilate.

- Insert large bore peripheral venous

canula to begin fluid resuscitation.

- Insert central line and arterial line Early goal directed resuscitation: during the first 6

hours after recognition (in patients with hypotension and serum lactate more than 4 mmol/L)

Resuscitation goals include:

- MAP more than 65 mmHg

- Target CVP of 8-12 mmHg (12-15 mmHg if ventilated)

- Central venous O2 saturation (ScvO2) equal or more than 70%

- Urine output equal or more than 0.5 mL/kg/h

Source Identification: - Within first 6 hours of presentation - Blood culture before antibiotic therapy - Culture all sites as clinically indicated - imaging studies performed promptly for any source.

Broad spectrum antibiotics: - Within 1 hour of diagnosis - Daily assessment of antimicrobial therapy with

microbiology and clinical data - Antibiotic therapy guided by clinical response; Normally 7-10 days but longer if response is

slow, unreliable source of infection or immunological deficiencies

Source Control: - Abscess drainage - Tissue debridement - Removal of IV access devices if

potentially infected

IV fluids - Crystalloids as the initial fluid of choice in the

resuscitation of severe sepsis and septic shock

- Against the use of hydroxyethyl starches for fluid resuscitation of severe sepsis and septic shock

- Albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids

- Initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (1 L of crystalloid or 300-500 ml colloid). More rapid administration and greater amounts of fluid may be needed in some patients .

- Monitor for any fluid overload.

Vasopressors

- Vasopressor therapy initially to target a mean arterial pressure (MAP) of 65 mm Hg .

- Norepinephrine as the first choice vasopressor.

- Vasopressin 0.03 units/minute can be added to norepinephrine (NE) with intent of either raising MAP or decreasing NE dosage .

- Dopamine as an alternative vasopressor agent to norepinephrine only in highly selected patients (eg, patients with low risk of tachyarrhythmias and absolute or relative bradycardia).

- Phenylephrine is not recommended in the treatment of septic shock except in circumstances where (a) norepinephrine is associated with serious arrhythmias, (b) cardiac output is known to be high and blood pressure persistently low or (c) as salvage therapy when combined inotrope/vasopressor drugs and low dose vasopressin have failed to achieve MAP target.

- All patients requiring vasopressors have an arterial catheter placed as soon as practical if resources are available

Inotropic Therapy - A trial of dobutamine infusion up to 20 micrograms/kg/min be

administered or added to vasopressor (if in use) in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion, despite achieving adequate intravascular volume and adequate MAP

Corticosteroids - Not using intravenous hydrocortisone to treat adult septic

shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (see goals for Initial Resuscitation). In case this is not achievable, we suggest intravenous hydrocortisone alone at a dose of 200 mg per day.( 50 mg Q 6 hourly)

- In treated patients hydrocortisone tapered when vasopressors are no longer required (grade 2D).

- Corticosteroids not be administered for the treatment of sepsis in the absence of shock (grade

Blood Product Administration - Once tissue hypoperfusion has resolved and in the absence of

extenuating circumstances, such as myocardial ischemia, severe hypoxemia, acute hemorrhage, or ischemic heart disease, we recommend that red blood cell transfusion occur only when hemoglobin concentration decreases to <7.0 g/dL to target a hemoglobin concentration of 7.0 –9.0 g/dL in adults.

- Fresh frozen plasma not be used to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures (grade 2D).

- In patients with severe sepsis, administer platelets prophylactically when counts are <10,000/mm3 (10 x 109/L) in the absence of apparent bleeding.

- We suggest prophylactic platelet transfusion when counts are < 20,000/mm3 (20 x 109/L) if the patient has a significant risk of bleeding.

- Higher platelet counts (≥50,000/mm3 [50 x 109/L]) are advised for active bleeding, surgery, or invasive procedures.

Recombinanat activated protein C : has anti-inflammatory, anticoagulant and profibrinolytic properties. It was used in severe sepsis. No more recommended to use it.

Ventilation: - a low tidal volume and limitation of inspiratory plateau

pressure strstegy for ALI/ARDS - Minimum amount of PEEP - Head of bed elevation in mechanically ventilated

patients unless contrindicated - Prone positioning in ALI/ARDS - Avoid routine use of pulmonary artery catheters Glucose Control - A protocolized approach to blood glucose management

in ICU patients with severe sepsis commencing insulin dosing when 2 consecutive blood glucose levels are >180 mg/dL. This protocolized approach should target an upper blood glucose ≤180 mg/dL rather than an upper target blood glucose ≤ 110 mg/dL.

- Blood glucose values be monitored every 1–2 hrs until glucose values and insulin infusion rates are stable and then every 4 hrs thereafter.

Renal Replacement Therapy: Continuous hemofiltration is the preferred method.

DVT prophylaxis: low dose UFH or LMWH, unless contraindicated, compression stockings when heparin is contraindicated.

Stress Ulcer prophylaxis: H2 blocker or PPIs

Nutrition

Consideration of limitation of support: - Discuss goals of care and prognosis with patients

and families. - Incorporate goals of care into treatment and end-of-

life care planning, utilizing palliative care principles where appropriate.

How to monitor in ICU:

Continuous Assessment in ICU/HDU:

Arterial lineExamine frequently Ask Yourself for:Fluid managementIs circulation adequate? Urine output?Gas exchange ? ARDS ?, CxR ABGAny new focus ?Follow the test resultsAdequate nutrition

Mortality in Sepsis:Mortality

Bacteraemia 15-20%

Bacterimia plus Shock 30-40%

Shock plus ARDS 40-60%

Poor prognostic features in Sepsis syndrome

Age more than 60Multiorgan failureRenal failureRespiratory FailureHepatic failureHypothermia or LeucopeniaHAIDICUnderlying Disease(Malignacy,

Immunocompromised)

Thanks