بسم هللا الرحمن الرحيم

Management of Septic Shock

Dr. Ramadan Arafa; MSc, MRCPI

Physician; Fujairah Hospital

OVERVIEW

• Septic shock is the most common cause of mortality in the intensive care units.

• An analysis of a large sample from major US medical centers reported the incidence of severe sepsis is 3 cases/1000 population and 2.26 cases per 100 hospital discharges. Of these patients, 51.1% were admitted to ICU, and 17.3% were in an intermediate care or CCU (Angus 2001).

• The incidence of severe sepsis doubled over a 6-year period (2004-2009) (Gaieski 2013).

Etiology

Pathophysiology

How To Diagnose?

How To Manage?

Sepsis syndromes

Objectives

Sepsis syndromes

SIRS

Sepis

Severe sepsis-SIRS

Septic shock

MODS

(Systemic Inflammatory Response Syndrome)

is a systemic inflammatory response to non

specific insults.

SIRS

SIRS is either due to Infection or others

Clinically:1. hyperthermia >38°C or hypothermia <36°C2. tachycardia > 90 bpm3. tachypnea > 20 r.p.m. or PaCO2 <4.3 kPa4. neutrophilia >12000 or neutropenia <4000/uL or more

than 10% immature forms

Venn Diagram; Andre Kalil; septic shock 2015

Clinically?!

• Known or suspected infection, plus

• >2 SIRS Criteria.

Sepsis

The systemic inflammatory response to infection.

Severe sepsis-SIRS

• Severe sepsis resulting in at least one organ

failure

Clinically?!

• Sepsis plus >1 organ dysfunction.

Septic shock

•Sepsis induced shock with hypotension (SBP <90

mmHg or decreased > 40 mmHg from baseline

readings) despite adequate resuscitation plus;

presence of perfusion abnormalities which may

include lactic acidosis, oliguria, or an acute

alteration in mental status.

• Shock = inadequate tissue perfusion

– Decreased O2 delivery and decreased removal

of metabolites

• Tissue perfusion is determined by:

– Cardiac output (CO) = HR x SV

SV = function of preload, afterload,

contractility

– Systemic vascular resistance (SVR)

MODS

(multiple organ dysfunction syndrome)

The presence of altered organ function in an

acutely ill patient such that homeostasis cannot

be maintained without intervention.

SIRSsystemic

inflammatory response syndrome

SEPSISSIRS with a presumed or confirmed infectious process

Severe sepsisSepsis with ≥1 sign of organ failure

Septic shockSIRS + Infection + Organ Failure + Refractory Hypotension

Etiology

Pathophysiology

How To Diagnose?

How To Manage?

Sepsis syndromes

Objectives

Etiology

Caustive organisms

•Gram –ve the commonest

•Staph

•Candida

Sources of infection

• Endogenus source

1. Peritonitis

2. Perforated viscous

3. Gangrenous bowel

4. Genitourinary infection

• Exogenus source

Infected CVP

Predisposing factors

• Old age

• DM

• Corticosteroid therpy

• Malignancy

• Major surgery

Etiology

Pathophysiology

How To Diagnose?

How To Manage?

Sepsis syndromes

Objectives

It is not precisely understood, but it involves a

complex interaction between the pathogen

and the host's immune system.

Physiological response to localized infection:

o Influx of activated PMN leukocytes &

monocytes release of inflammatory

mediators

o Local vasodilatation & increased endothelial

permeability

o Activation of the coagulation cascade.

Pathophysiology

• The same occurs in septic shock but at

a systemic level.

1. Diffuse endothelial disruption

2. Increased vascular permeability

3. Vasodilatation

4. Thrombosis of end organ capillaries

Infection

InflammatoryMediators

Endothelial Dysfunction

Vasodilation

Hypotension Vasoconstriction Edema

Maldistribution of Microvascular Blood Flow

Organ Dysfunction

Microvascular Plugging

Ischemia

Cell Death

Inadequate

Resuscitation

Preoperative

Illness

Trauma or

Operation

Tissue Injury

optimal oxygen

delivery and

support

Recovery

Excessive

Inflammatory

Response

SIRS/MODS

Pathogenesis of SIRS/MODS in surgical patients

Identifying Acute Organ Dysfunction

as a Marker of Severe Sepsis

Tachycardia

Hypotension

CVP

PAOP

Jaundice

Enzymes

Albumin

PT

Altered

Consciousness

Confusion

Psychosis

Tachypnea

PaO2 <70 mm Hg

SaO2 <90%

PaO2/FiO2 300

Oliguria

Anuria

Creatinine

Platelets

PT/APTT

Protein C

D-dimer

Rhabdomyolysis

Addison’s disease

Polyneuropathy

Etiology

Pathophysiology

How To Diagnose?

How To Manage?

Sepsis syndromes

Objectives

How To Diagnose?

• When you suspect sepsis in patient with predisposing factors, do not wait for septic shock

• The diagnosis of sepsis requires the taking of an EXCELLENT history, physical examination, appropriate laboratory tests, and a close follow-up of hemodynamic status

• Early recognition is live saving in such rapid overwhelming situation

Hyperdynamic- Warm-Early Septic Shock

Restlness & confusionVitals

1. fever more than 38 chills

2. Mild decrease ABP3. Tachycardia 4. Tachypnea

Skin warm ,dry ,flushedHigh cardiac output

Hypodynamic- Cold- Late Septic Shock

Semicomatosed Vitals

1. Temperature decreased

2. Tachycardia3. Tachypnea4. SBP<90mmHg

Oliguria & low COPMultiorgan failure start at

this stage

Work up…

Laboratory studies

o CBC

o Coagulation studies

o Blood, sputum, body fluids & urine cultures

o LFT, Renal and electrolytes

o Serum lactate

Imaging studies

o Chest radiography

o Abdominal radiography

o Others according to the suspected cause.

Complications of septic shock

• ARDS: starts 12-48 hours of the inciting event.

– Mild (mortality: 27%)

– moderate (mortality: 32%)

– severe (mortality: 45) (JAMA 2012)

• AKI: affects 40-70% of critically ill patients

• Chronic renal insufficiency

• DIC

• Mesentric ischemia

• Myocardial dysfunction and MI

• Liver failure

Etiology

Pathophysiology

How To Diagnose?

How To Manage?

Sepsis syndromes

Objectives

How To Manage?

How To Manage?

Goals:

Septic

• Identify and manage Infection Source

Shock • Adequate Resuscitation

MODS

• Support Dysfunctional Systems & Monitoring

Management principles

• Early recognition

• Early and adequate antibiotic therapy

• Source control

• Early hemodynamic resuscitation and continued

support

• Proper ventilator management with low tidal

volume in patients with ARDS

General measures

• Venous access

• Crystalloid infusion

• Central venous line insertion ?

• Urinary catheterization

• Oxygenation and ventilation. Low tidal volume

ventilation is associated with better outcome

• Within 6 hours of presentation to ER, intensive

monitoring of specific circulatory parameters with

the aggressive management of 5 key parameters

to specified targets to optimise oxygen delivery to

tissues and maintain hemodynamic stability.

(Rivers 2001)

Early goal directed therapy

(EGDT)

Effective Sepsis Management for Quality Patient Outcomes

• EGDT have been shown to be effective at improving patient costs and outcomes, including significant reductions in sepsis-related mortality.

• EGDT with the PreSep oximetry catheter has been shown to:

– Reduce sepsis-related mortality by 46%

– Reduce hospital length-of-stay by 5 days

– Reduce hospital charges by $5,882 per patient

– Guide therapy and enable early intervention

Continuous ScvO2 Monitoring, PreSepOximetry Catheter

The Vigileo monitor works with the PreSep catheter

The PreSep catheter is a triple lumen central venous oximetry catheter with an added capability for continuously monitoring ScvO2.

• Parameters

– CVP 8-12 mmHg

– MAP > 65mmHg and / or SBP > 90 mmHg

– Urine output > 0.5 ml/kg/hr

– Mixed venous oxygen saturation >65% / ScvO2 >70%

– Haematocrit >30%

• Interventions

– Reduce work of breathing by early use of mech. Vent

– Fluid resuscitation

– Use of vasoactive agents: noradrenaline, dobutamine

– Transfusion

ScvO2

O2 delivery

Cardiac output

HR SV

preload

Bleeding

Fluid shift

afterload

Vascular resistance

contractility

Heart disease

Hb

BleedingHemodilution

Anemia

Oxygenation

SaO2

FiO2

Vent

O2

consumption

Metabolic demands

Fever

Anxiety

Pain

Shivering

Muscle activitySt joseph 2008

• In critically ill patients, it is crucial to

maintain the balance between

oxygen consumption and oxygen

delivery

International guidelines for management of severe sepsis and

septic shock 2012

The Society of Critical Care Medicine The European Society of Intensive Care Medicine 2013

Initial Resuscitation and Infection Issues

A. Initial Resuscitation:

1. We recommend the protocolized, quantitative

resuscitation of patients with sepsis- induced tissue

hypoperfusion (defined in this document as

hypotension persisting after initial fluid challenge or

blood lactate concentration ≥ 4 mmol/L).

This protocol should be initiated as soon as

hypoperfusion is recognized and should not be delayed

pending ICU admission.

During the first 6 hr of resuscitation, the goals of initial

resuscitation of sepsis-induced hypoperfusion should

include all of the following (grade 1C):

a) CVP 8–12 mm Hg

b) MAP ≥ 65 mm Hg

c) Urine output ≥ 0.5 mL/kg/hr

d) ScvO2 or SvO2 70% or 65%, respectively.

2. We suggest targeting resuscitation to normalize

lactate in patients with elevated lactate levels

B. Screening for Sepsis and Performance

Improvement

1. Routine screening of potentially infected

seriously ill patients for severe sepsis to allow

earlier implementation of therapy (grade 1C).

2. Hospital–based performance improvement

efforts in severe sepsis (UG).

C. Diagnosis

1. Cultures as clinically appropriate before antimicrobial therapy if no significant delay (> 45 mins) in the start of antimicrobial(s) (grade 1C). At least 2 sets of blood cultures to be obtained before antimicrobial therapy with at least 1 drawn percutaneously and 1 drawn through each vascular access device, unless the device was recently (<48 hrs) inserted (grade 1C).

2. Invasive candidiasis should be in differential diagnosis of cause of infection.

3. Imaging studies performed promptly to confirm a potential source of infection (UG).

D. Antimicrobial Therapy

1. Administration of effective IV antimicrobials within the first hour of recognition of septic shock (grade 1B) and severe sepsis without septic shock (grade 1C) as the goal of therapy.

2. - 2a. Initial empiric anti-infective therapy of one or more drugs that have activity against all likely pathogens (bacterial and/or fungal or viral) and that penetrate in adequate concentrations into tissues presumed to be the source of sepsis (grade 1B).

– 2b. Antimicrobial regimen should be reassessed daily for potential de-escalation (grade 1B).

3. Use of low procalcitonin levels or similar biomarkers to assist the clinician in the discontinuation of empiric antibiotics in patients who initially appeared septic, but have no subsequent evidence of infection (grade 2C).

4a. Combination empirical therapy for neutropenic patients with severe sepsis (grade 2B) and for patients with difficult-to-treat, multi-drugresistant bacterial pathogens such as Acinetobacter and Pseudomonas spp. (grade 2B).

For patients with severe infections associated with respiratory failure and septic shock, combination therapy with an extended spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone is for P. aeruginosa bacteremia (grade 2B).

A combination of beta-lactam and macrolide for patients with septic shock from bacteremic Streptococcus pneumoniaeinfections (grade 2B).

4b. Empiric combination therapy should not be administered for more than 3–5 days. De-escalation to the most appropriate single therapy should be performed as soon as the susceptibility profile is known (grade 2B).

5. Duration of therapy typically 7–10 days; longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection, bacteremia with S. aureus; some fungal and viral infections or immunologic deficiencies, including neutropenia (grade 2C).

6. Antiviral therapy initiated as early as possible in patients with severe sepsis or septic shock of viral origin (grade 2C).

7. Antimicrobial agents should not be used in patients with severe inflammatory states determined to be of noninfectious cause (UG).

E. Source Control

1. A specific anatomical diagnosis of infection requiring consideration for emergent source control be sought and diagnosed or excluded as rapidly as possible, and intervention be undertaken for source control within the first 12 hr after the diagnosis is made, if feasible (grade 1C).

2. When infected peripancreatic necrosis is identified as a potential source of infection, definitive intervention is best delayed until adequate demarcation of viable and nonviable tissues has occurred (grade 2B).

3. When source control in a severely septic patient

is required, the effective intervention associated

with the least physiologic insult should be used (eg,

percutaneous rather than surgical drainage of an

abscess) (UG).

4. If intravascular access devices are a possible

source of severe sepsis or septic shock, they should

be removed promptly after other vascular access

has been established (UG).

F. Infection Prevention

1a. Selective oral decontamination and selective digestive

decontamination should be introduced and investigated as a

method to reduce the incidence of VAP; This infection

control measure can then be instituted in health care

settings and regions where this methodology is found to be

effective (grade 2B).

1b. Oral chlorhexidine gluconate be used as a form of

oropharyngeal decontamination to reduce the risk of VAP in

ICU patients with severe sepsis (grade 2B).

G. Fluid Therapy of Severe Sepsis

1. We recommend against using hydroxymethyl

starch for fluid resuscitation in severe sepsis and

septic shock (grade1B).

2. We suggest the use of albumin in the fluid

resuscitation of severe sepsis and septic shock

when patients require substantial amounts of

crystalloids (grade 2C).

4. Initial fluid challenge in a minimum of 30 mL/kg

of crystalloids (a portion of this may be albumin

equivalent). More rapid administration and greater

amounts of fluid may be needed in some patients

(grade 1C).

5. Fluid challenge technique be applied wherein

fluid administration is continued as long as there is

hemodynamic improvement either based on

dynamic or static variables (UG).

H. Vasopressors

1. Vasopressor therapy initially to target a MAP of 65 mm Hg

(grade 1C).

2. Norepinephrine as the first choice vasopressor (grade 1B).

3. Epinephrine (added to and potentially substituted for

norepinephrine) when an additional agent is needed to

maintain adequate blood pressure (grade 2B).

4. Vasopressin 0.03 units/minute can be added to

norepinephrine (NE) with intent of either raising MAP or

decreasing NE dosage (UG).

5. Low dose vasopressin is not recommended as the

single initial vasopressor for treatment of sepsis-

induced hypotension and vasopressin doses higher than

0.03-0.04 units/minute should be reserved for salvage

therapy (failure to achieve adequate MAP with other

vasopressor agents) (UG).

6. 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) (grade 2C).

7. 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 (grade 1C).

8. Low-dose dopamine should not be used for

renal protection (grade 1A).

9. All patients requiring vasopressors have an

arterial catheter placed as soon as practical if

resources are available (UG).

I. Inotropic Therapy

1. Dobutamine infusion up to 20 mcg/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 (grade 1C).

J. Corticosteroids

1. Not using IV hydrocortisone to treat adult septic

shock patients if adequate fluid resuscitation and

vasopressor therapy are able to restore hemodynamic

stability . In case this is not achievable, we suggest IV

hydrocortisone at a dose of 200 mg/ day (grade 2C).

2. Not using the ACTH stimulation test to identify adults

with septic shock who should receive hydrocortisone

(grade 2B).

3. In treated patients hydrocortisone tapered when

vasopressors are no longer required (grade 2D).

4. Corticosteroids not be administered for the

treatment of sepsis in the absence of shock (grade 1D).

5. When hydrocortisone is given, use continuous flow

(grade 2D).

6. Steroids may be indicated in the presence of a

history of steroid therapy or adrenal dysfunction !!

K. Blood Product Administration

1. Once tissue hypoperfusion has resolved and in the

absence of extenuating circumstances, such as

myocardial ischemia, severe hypoxemia, acute

hemorrhage, or ischemic coronary artery disease,

we recommend that RBCs transfusion occur when

the Hb concentration decreases to < 7.0 g/dL to

target a Hb concentration of 7.0 to 9.0 g/dL in adults

(grade 1B).

2. We recommend not using erythropoietin as a specific treatment of anemia associated with severe sepsis (grade 1B).

3. We suggest that FFP not be used to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures (grade 2D). No studies suggest that correction of more severe coagulation abnormalities benefits patients who are not bleeding.

4. We recommend against antithrombinadministration for the treatment of severe sepsis and septic shock (grade 1B).

5. In patients with severe sepsis, we suggest that

platelets be administered prophylactically when:

– counts are ≤ 10,000/mm3 in the absence of apparent

bleeding

– counts are ≤ 20,000/mm3 if the patient has a

significant risk of bleeding.

– platelet counts ≥ 50,000/mm3 if the patient has active

bleeding, surgery, or invasive procedures (grade 2D).

L. Immunoglobulins

1. We suggest not using IV immunoglobulins in

adult patients with severe sepsis or septic

shock (grade 2B). Large RCTs found no benefit

M. Recombinant activated protein C

1. It is no longer available for treating patients

with severe sepsis or septic shock

N. Glucose Control

1. We recommend a protocolized approach to blood glucose management in ICU patients with severe sepsis, commencing insulin dosing when two consecutive RBS levels are > 180 mg/dL. This approach should target an upper blood glucose level ≤ 180 mg/dL rather than an upper target blood glucose ≤ 110 mg/dL (grade 1A).

2. We recommend blood glucose values be monitored every 1-2 hrs until glucose values and insulin infusion rates are stable, then every 4 hrsthereafter (grade 1C).

3. We recommend that capillary glucose levels to be

interpreted with caution, as such measurements

may not accurately estimate arterial blood or

plasma glucose values (UG).

O. Renal Replacement Therapy

1. Continuous RRT and intermittent hemodialysis are equivalent in patients with severe sepsis and acute renal failure (grade 2B).

2. Use continuous therapies to facilitate management of fluid balance in hemodynamically unstable septic patients (grade 2D).

P. Bicarbonate Therapy

1. Not using sodium bicarbonate therapy for the purpose of improving hemodynamics or reducing vasopressor requirements in patients with hypoperfusion-induced lactic acidemia with pH ≥7.15 (grade 2B).

Q. Deep Vein Thrombosis Prophylaxis

1. Patients with severe sepsis receive daily pharmacoprophylaxis against VTE (grade 1B). Daily SC LMWH is more preferred than twice daily UFH or three times daily UFH. If creatinineclearance is <30 mL/min, use dalteparin (grade 1A) or another form of LMWH that has a low degree of renal metabolism (grade 2C) or UFH (grade 1A).

2. Patients with severe sepsis be treated with a combination of pharmacologic therapy and intermittent pneumatic compression devices whenever possible (grade 2C).

3. Septic patients who have a contraindication for

heparin use not receive pharmacoprophylaxis

(grade 1B), but receive mechanical prophylactic

treatment, such as graduated compression stockings

or intermittent compression devices (grade 2C),

unless contraindicated. When the risk decreases

start pharmacoprophylaxis (grade 2C).

R. Stress Ulcer Prophylaxis

1. Stress ulcer prophylaxis using H2 blocker or PPI

be given to patients with severe sepsis/septic

shock who have bleeding risk factors (grade 1B).

2. When stress ulcer prophylaxis is used, PPIs rather

than H2RA (grade 2D)

3. Patients without risk factors do not receive

prophylaxis (grade 2B).

Thank you

Questions ???