Management of sepsis and septic shock

Management of Sepsis & Septic Shock International Guidelines

Dr. Samaresh Das

@Samaresh

Key Concepts of Sepsis

o Sepsis is the primary cause of death from infection, especially if not

recognized and treated promptly. Its recognition mandates urgent

attention.

o Sepsis is a syndrome shaped by pathogen factors and host factors

(eg, sex, race and other genetic determinants, age, comorbidities,

environment) with characteristics that evolve over time.

o What differentiates sepsis from infection is an aberrant or

dysregulated host response and the presence of organ dysfunction.

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Key Concepts of Sepsis

o Sepsis-induced organ dysfunction may be occult; therefore, its

presence should be considered in any patient presenting with

infection. Conversely, unrecognized infection may be the cause

of new-onset organ dysfunction.

o Any unexplained organ dysfunction should thus raise the

possibility of underlying infection.

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

JAMA. 2016;315(8):801-810. doi:10.1001/jama.2016.0287.

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Why sepsis again ?

Why new definition?

Why new scoring system ?

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Why Sepsis is revisited again !!!o Sepsis & its associated complications - major public

health and economic burden in the industrialized world.o Outcomes may have serious short- or long-term

consequences such as amputation, damage to organs, or

cognitive dysfunction.o In the US, treatment of a patient with sepsis may cost up

to $50,000, translating to an annual nationwide economic

burden of $17 billion

Tsertsvadze, Alexander, Royle, Pamela, Seedat, Farah, Cooper, Jennifer, Crosby, Rebecca and McCarthy,

N. D.. (2016) Community-onset sepsis and its public health burden : a systematic review. Systematic

Reviews, 5 . 81.

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o In European studies, the treatment of severe sepsis in 2002

was estimated to cost approximately 25,000 . Assuming an

incidence of 100,000 new cases per year, the UK’s National

Health Service (NHS) expenditure for treating these cases

would amount to £2.5 billion annually

o

Daniels R. The incidence, mortality and economic burden of sepsis. In: NHS Evid Emerg & Urgent Care. 2009.

Sepsis is the leading cause of death in non-coronary care , with a mortality rate between 30-50%

Why Sepsis is revisited again !!!

@Samaresh

Why Sepsis is revisited again !!!

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Why new definition?

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Why new definitions ?

o Definitions of sepsis and septic shock were last

revised in 2001.

o Considerable advances have since been made into

the pathobiology (changes in organ function,

morphology, cell biology, biochemistry, immunology,

and circulation), management, and epidemiology of

sepsis, suggesting the need for reexamination.

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To know what distinguishes sepsis from uncomplicated infection as simple infection (which could simply controlled by rest and cup of hot tea!! )

“We need to differentiate a straightforward infection from one that can cause organ dysfunction or death”

Why new definitions ?

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The old definitions

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o Nonspecific SIRS criteria such as pyrexia or neutrophilia will

continue to aid in the general diagnosis of infection.

oThese findings complement features of specific infections (eg, rash,

lung consolidation, dysuria, peritonitis) that focus attention toward

the likely anatomical source and infecting organism.

o However, SIRS may simply reflect an appropriate host response

that is frequently adaptive.

o Sepsis involves organ dysfunction, indicating a pathobiology more

complex than infection plus an accompanying inflammatory

response alone.


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o The Sepsis-3 authors deemed SOFA superior to SIRS in

predicting hospital mortality, with a SOFA score ≥2 identifying a 2-

to 25-fold increased mortality

o Unfortunately, SOFA is a relatively complex tool, as it scores 6

different organ system markers on a 1-4 scale for each system.

o An increase in 2 points from baseline signifies a higher risk for

in-hospital mortalityo qSOFA can be rapidly scored at the bedside without blood tests, and it is hoped that it will facilitate prompt identification of an infection that poses a greater threat to life.


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"WE NOW HAVE A SCIENTIFICALLY BASED CLASSIFICATION THAT

WILL GIVE THE CLINICIAN AT THE BEDSIDE NEW AND MORE

EFFECTIVE WAYS TO RECOGNIZE THE SEPTIC PATIENT AND THE

SEVERELY SEPTIC PATIENT SO AS TO AFFORD THE EARLIEST

POSSIBLE INTERVENTION,"

Timothy Buchman, MD, from Emory University in Atlanta

The care in sepsis is focused on prompt recognition and early treatment “Shift of focus from inflammation to Organ Dysfunction ”

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Sepsis

Sepsis is defined as life-threatening organ dysfunction

caused by a dysregulated host response to infection

o This new definition emphasizes the primacy of the

nonhomeostatic host response to infection, the

potential lethality that is considerably in excess of a

straightforward infection, and the need for urgent

recognition

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Here’s what has changed and how it will affect clinical practice

1. SIRS is no longer criterion for sepsis.

2. SIRS has been replaced with quick Sequential Organ

Failure Assessment (qSOFA) score

3. SOFA score is now used to clinically characterize

septic patients.

4. Severe sepsis is no more

5. Lactate is now part of septic shock criteria, along with

resistant hypotension.

Positive qSOFA= suspected infection plus ≥2 of the following:

1. Altered mental status (Glasgow Coma Scale score <15)

2. Systolic blood pressure ≤100 mm Hg3. Respiratory rate ≥22/min

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septic shock

Clinical construct of sepsis with persisting hypotension , requiring

vasopressors to maintain MAP ≥65 mm Hg and having a serum

lactate level >2 mmol/L (18 mg/dL)

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Clinical Criteria identifying patients with sepsis & septic shock

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Recommendations & Best Practice Statements

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Initial Resuscitaion with Sepsis & Septic Shock

1. Sepsis and septic shock are medical emergencies, treatment and resuscitation

should begin immediately (BPS).

2. Resuscitation for sepsis-induced hypoperfusion, at least 30 mL/kg of IV crystalloid

to be given within first 3 hours (strong recommendation, low quality of evidence).

3. Following initial fluid resuscitation, additional fluids be guided by frequent

reassessment of hemodynamic status (BPS).

Remarks: Reassessment should include a thorough clinical examination and evaluation of available

physiologic variables ( HR,BP, Spo2, RR, Temp, urine output, and other noninvasive or invasive

monitoring, as available.

4. Further hemodynamic assessment (such as assessing cardiac function) to

determine the type of shock if the clinical examination does not lead to a clear

diagnosis (BPS).

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Fluid resuscitation in Sepsis

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5. Suggest dynamic over static variables be used to predict fluid

responsiveness, where available (weak recommendation, low quality of

evidence).

6. Initial target MAP of 65 mmHg in patients with septic shock requiring

vasopressors (strong recommendation, moderate quality of evidence).

7. Suggest guiding resuscitation to normalize lactate in patients with

elevated lactate levels as a marker of tissue hypoperfusion (weak

recommendation, low quality of evidence).

Initial Resuscitaion with Sepsis & Septic Shock

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Screening for Sepsis & Sepsis performance Improvement

Hospitals and hospital systems should have a performance

improvement program for sepsis, including sepsis screening for

acutely ill, high risk patients (BPS).

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Diagnosis

o Appropriate routine microbiologic cultures (including blood) to be

obtained before starting antimicrobial therapy

Remarks: Appropriate routine microbiologic cultures always include at least two sets of

blood cultures (aerobic & anaerobic).

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Antimicrobial therapy

1. IV antimicrobials should be initiated ASAP after recognition and

within 1 hr for both sepsis and septic shock (strong

recommendation, moderate quality of evidence).

2. Empiric broad-spectrum therapy with one or more antimicrobials for

patients presenting with sepsis or septic shock to cover all likely

pathogens (including bacterial and potentially fungal or viral

coverage) (strong recommendation, moderate quality of evidence).

3. Systemic antimicrobial prophylaxis in patients with severe

inflammatory states of noninfectious origin (e.g., severe pancreatitis,

burn injury) (BPS).

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6. Suggest empiric combination therapy (using at least two antibiotics

of different antimicrobial classes) aimed at the most likely bacterial

pathogen(s) for the initial management of septic shock (weak


7. Suggest combination therapy not to be routinely used for ongoing

treatment of most other serious infections, including bacteremia and

sepsis without shock (weak recommendation, low quality of

evidence).

8. Recommendation against combination therapy for the routine

treatment of neutropenic sepsis/bacteremia (strong



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9. If combination therapy used for septic shock, de-escalate with

discontinuation of combination therapy within first few days in

response to clinical improvement and/or evidence of infection

resolution. (BPS).

10. Suggest duration 7 to 10 days is adequate for most serious

infections associated with sepsis and septic shock (weak


11. Suggest longer courses are appropriate in patients who have a slow

clinical response, undrainable foci of infection,bacteremia with Staph.

aureus, some fungal and viral infections, or immunologic deficiencies,

including neutropenia (weak recommendation, low quality of

evidence).


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12. Suggest Shorter courses for those with rapid clinical resolution

following effective source control of intra-abdominal or urinary

sepsis (weak recommendation, low quality of evidence).

13. Daily assessment for de-escalation of therapy (BPS).

14. Suggest procalcitonin levels to support shortening the duration

of antimicrobial therapy (weak recommendation, low quality of

evidence).

15. Suggest procalcitonin levels to support the discontinuation of

empiric antibiotics , who initially appeared to have sepsis, but

subsequently have limited clinical evidence of infection (weak



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Source Control

1. Specific anatomic diagnosis of infection requiring emergent source

control should be identified ASAP & required source control

intervention should be implemented ASAP after the diagnosis is

made (BPS).

2. Prompt removal of intravascular access devices that are a possible

source of sepsis or septic shock after other vascular access has

been established (BPS).

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Fluid Therapy

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Fluid Therapy1. Fluid challenge technique be applied where fluid administration is

continued as long as hemodynamic factors continue to improve

(BPS).

2. Crystalloids as the fluid of choice for initial resuscitation and

subsequent intravascular volume replacement (strong


3. Suggest either balanced crystalloids or saline (weak


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4. Suggest using albumin in addition to crystalloids (weak


5. Against using hydroxyethyl starches for intravascular volume

replacement in patients with sepsis or septic shock (strong

recommendation, high quality of evidence).

6. Suggest using crystalloids over gelatins when resuscitating

patients with sepsis or septic shock (weak recommendation,

low quality of evidence)

Fluid Therapy

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Vasopressor use for Septic Shock

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Vasoactive medication 1. Norepinephrine as the first-choice vasopressor (strong recommendation,

moderate quality of evidence).

2. Suggest adding either vasopressin (up to 0.03 U/min) (weak

recommendation, moderate quality of evidence) or epinephrine (weak

recommendation, low quality of evidence) to norepinephrine with the intent

of raising mean arterial pressure to target, or adding vasopressin (up to 0.03

U/min) (weak recommendation, moderate quality of evidence) to decrease

norepinephrine dosage.

3. Suggest using dopamine as an alternative vasopressor agent to

norepinephrine in highly selected patients (e.g., patients with low risk of

tachyarrhythmias and absolute or relative bradycardia) (weak


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4. Against using low-dose dopamine for renal protection (strong


5. Suggest using dobutamine in patients with persistent

hypoperfusion despite adequate fluid loading and vasopressor

(weak recommendation, low quality of evidence)

6. Suggest arterial catheter placed as soon as practical if resources

are available on patients requiring vasopressors

(weak recommendation, very low quality of evidence).

Vasoactive medication

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Corticostroids

Suggest against using IV hydrocortisone if adequate fluid resuscitation

and vasopressor are able to restore hemodynamic stability

If not achievable, suggest IV hydrocortisone at a dose of 200 mg per day

(weak recommendation, low quality of evidence).

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Blood Products

1. RBC transfusion only when Hb < 7.0 g/dL in adults in the absence

of extenuating circumstances, such as myocardial ischemia,

severe hypoxemia, or acute hemorrhage (strong recommendation,

high quality of evidence).

2. Against the use of erythropoietin for treatment of anemia

associated with sepsis (strong recommendation, moderate quality

of evidence).

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3. Suggest against FFP in the absence of bleeding or planned

invasive procedures (weak recommendation, very low quality of

evidence).

4. Suggest platelet transfusion in < 10,000/mm3 (10 × 109/L) in

the absence of apparent bleeding & < 20,000/mm3 (20 ×

109/L) if significant risk of bleeding. Higher platelet counts

(≥50,000/mm3 [50 x 109/L]) are advised for active bleeding,

surgery, or invasive procedures (weak recommendation, very

lowquality of evidence).

Blood Products

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ImmunoglbulinsSuggest against use of IV immunoglobulins in patients with

sepsis or septic shock (weak recommendation, low quality of

evidence).

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Blood purification

No recommendation regarding the use of blood purification

techniques.

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Anticoagulants

1. Against the use of antithrombin for the treatment of sepsis and

septic shock (strong recommendation, moderate quality of

evidence).

2. No recommendation regarding the use of thrombomodulin or

heparin for the treatment of sepsis or septic shock.

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Mechanical ventilation 1. Target Vt of 6 mL/kg predicted body weight with sepsis-induced

ARDS (strong recommendation, high quality of evidence).

2. Upper limit for plateau pressures of 30 cmH2O (strong


3. Suggest higher PEEP in adult patients with sepsis-induced

moderate to severe ARDS (weak recommendation, moderate quality

of evidence).

4. Suggest recruitment maneuvers (weak recommendation, moderate

quality of evidence).

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5 . Prone over supine ventilation ( Pao2/Fio2 ratio < 150) (strong


6. Against using ( HFOV) (strong recommendation, moderate quality

of evidence).

7. No recommendation regarding the use of noninvasive ventilation

8. Suggest using neuromuscular blocking agents for ≤ 48 with P:F

< 150 mm Hg (weak recommendation, moderate quality of evidence).

9. Conservative fluid strategy for patients who do not have evidence

of tissue hypoperfusion (strong recommendation, moderate quality

of evidence).

Mechanical ventilation

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10. Against ß-2 agonists for the treatment of patients with sepsis-

induced ARDS without bronchospasm(strong recommendation,


11. Against the routine use of the PA catheter (strong recommendation,

high quality of evidence).

12. Suggest lower tidal volumes over higher tidal volumes in adult

patients with sepsis-induced respiratory failure without ARDS (weak



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13. Mechanically ventilated sepsis patients with head up between 30

& 45 degrees to limit aspiration risk & to prevent VAP(strong


14. SBT in ventilated patients with sepsis who are ready for weaning

(strong recommendation, high quality of evidence).

15. Using a weaning protocol in ventilated patients who can tolerate

weaning (strong recommendation, moderate quality of evidence).

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Sedation and Analgesia

Continuous or intermittent sedation to minimized in mechanically

ventilated sepsis patients, targeting specific titration end points

(BPS).

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Glucose Control1. Protocolized approach to control glucose , commencing insulin

dosing when two consecutive blood glucose levels are > 180 mg/dL.

Target an upper blood glucose level ≤180 mg/dL (strong


2. Blood glucose every 1 to 2 hours until glucose values and insulin

infusion rates are stable, then every 4 hours thereafter in patients

receiving insulin infusions (BPS).

3. Glucose levels obtained with point-of-care testing of capillary blood

be interpreted with caution because may not accurately estimate

arterial blood or plasma glucose values (BPS).

4. Suggest use of arterial blood rather than capillary blood for point-

of-care testing using glucose meters if patients havearterial

catheters (weak recommendation, low quality of evidence).

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Renal replacement Therapy

1. Suggest either continuous or intermittent renal replacement

therapy (RRT) be used in patients with sepsis and AKI(weak


2. Suggest using continuous therapies to facilitate management of

fluid balance in hemodynamically unstable septic patients

(weak recommendation, very low quality of evidence).

3. Suggest against the use of RRT in patients with sepsis and

acute kidney injury for increase in creatinine or oliguria without

other definitive indications for dialysis (weak recommendation,

low quality of evidence).

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Bicarbonate Therapy

suggest against the use of NaHCo3 to improve hemodynamics

or to reduce vasopressor requirements in patients with

hypoperfusion-induced lactic acidemia with pH ≥ 7.15 (weak


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Venous Thromboprophylaxis

1. Pharmacologic prophylaxis (UFH or LMWH) against VTE in the absence

of contraindications (strong recommendation, moderate evidence).

2. LMWH rather than UFH for VTE prophylaxis in the absence of

contraindications to the use of LMWH (strong recommendation,


3. Suggest combination pharmacologic VTE prophylaxis and mechanical

prophylaxis, whenever possible (weak recommendation,low quality of

evidence).

4. Suggest mechanical prophylaxis when pharmacologic VTE is

contraindicated (weak recommendation, low quality of evidence).

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Stress Ulcer Prophylaxis

1. To be given to patients with sepsis or septic shock who have

risk factors for GI bleeding (strong recommendation, low


2. Suggest using either PPI or H-2 receptor antagonists when

stress ulcer prophylaxis is indicated (weak recommendation,

low quality of evidence).

3. Recommendation against stress ulcer prophylaxis in patients

without risk factors for GI bleeding (BPS).

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Nutrition

1. Against the early parenteral nutrition alone or parenteral nutrition

in combination with enteral feedings (but rather initiate early

enteral nutrition) in critically ill patients with sepsis or septic

shock who can be fed enterally (strong recommendation, moderate


2. Against parenteral nutrition alone or in combination with enteral

feeds (but rather to initiate IV glucose and advance enteral feeds

as tolerated) over the first 7 days in critically ill patients with

sepsis or septic shock for whom early enteral feeding is not

feasible (strong recommendation, moderate quality of evidence).

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3. Suggest early initiation of enteral feeding rather than a complete

fast or only IV glucose (weak recommendation, low quality of

evidence).

4. Suggest either early trophic/hypocaloric or early full enteral feeding

in critically ill patients with sepsis or septic shock; if

trophic/hypocaloric feeding is the initial strategy, then feeds

should be advanced according to patient tolerance (weak


Nutrition

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5. Against the use of omega-3 fatty acids as an immune supplement

(strong recommendation, low quality of evidence).

6. Suggest against routinely monitoring gastric residual volumes (weak

recommendation, low quality of evidence). suggest measurement of gastric residuals

in patients with feeding intolerance or who are considered to be at high risk of aspiration (weak

recommendation, very low quality of evidence).Remarks: This

recommendation refers to nonsurgical critically ill patients with

sepsis or septic shock.

7. Suggest prokinetic agents in critically ill patients with sepsis or

septic shock and feeding intolerance (weak recommendation, low


8. Suggest post-pyloric feeding tubes with feeding intolerance / at high

risk of aspiration (weak recommendation, low quality of evidence).

Nutrition

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9. Against the use of IV selenium (strong recommendation, moderate


10. Suggest Against the use of arginine to treat sepsis and septic

shock (weak recommendation, low quality of evidence).

11. Against the use of glutamine to treat sepsis and septic shock

(strong recommendation, moderate quality of evidence).

12. No recommendation about the use of carnitine for sepsis and

septic shock.

Nutrition

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Setting Goals of Care

1. Goals of care and prognosis be discussed with patients and

families (BPS).

2 . Goals of care be incorporated into treatment and end-of-life

care planning, utilizing palliative care principles

where appropriate (strong recommendation, moderate quality

of evidence).

3. Suggest that goals of care be addressed as early as feasible,

but no later than within 72 hours of ICU admission (weak

recommendation, low quality of evidence

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Take Home points

o Early recognition screening

o Early resuscitation with Crystaloid 30ml/kg( albumin )

o Culture and Abx ASAP

o MAP & CO : Vasopressor ( NE) / lactate

o Frequent Volume assessment / Dynamic measures

o Once stable – De-escalate

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Thanks

Management of sepsis and septic shock

Healthcare

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