Sepsis and Septic Shock

DR. MD. AHAD HOSSAINMD(phase A)

Dept. of Anesthesiology, BSMMU

Sepsis and Septic Shock

• Definitions

• Epidemiology

• Pathogenesis

• Principles of management

Definitions

• SIRS: systemic response to infection manifested by ≥ 2 of:– Temp > 38oC or < 36oC– HR > 90 b/m– RR > 20 /m or PaCO2 < 32 mmHg– WBC > 12 x 109/L, < 4 x 109/L or >10% band formSEPSIS: SIRS plus documented infection

• Septic shock: sepsis with hypotension despite adequate fluid resuscitation, with perfusion abnormalities that could include, but are not limited to, lactic acidosis, oliguria, and/or acute mental status.

ACCP/SCCM Consensus Conference: Bone et al, Chest 1992 101:1644

SIRS

• SIRS – systemic inflammatory response syndrome• Must have at least 2 of the following:– Temperature >38.5ºC or <36ºC– Heart rate >90 beats/min– Respiratory rate >20 breaths/min or PaCO2 <32

mmHg– WBC >12,000 cells/mm3, <4000 cells/mm3, or

>10 % immature (band) forms• SIRS is the body’s response to infection,

inflammation, stress.

Severe sepsis

• Severe sepsis is defined as sepsis plus organ dysfunction

• Hypo perfusion or hypotension• A major cause of organ failure in ICU • Severe sepsis is directly or indirectly

responsible for 75% of all ICU death

Infection

Parasite

Virus

Fungus

BacteriaTrauma

Burns

Sepsis SIRSSevereSepsis

SevereSIRS

Adapted from SCCM ACCP Consensus Guidelines

shock

BSI

Epidemiology

Severe sepsis incidence and mortality increase with age

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Angus Crit Care Med 29:1301, 2001

Mortality

Incidence

Organ dysfunction at time of severe sepsis recognition

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Pathogenesis

Bacterial infection

Sepsis and septic shock

Excessive host response

Host factors lead to cellular damage

Organ damage

Death

Management

Management of Sepsis

• Recognition• Supportive care• Source control• Antibiotics• Specific (adjunctive) therapy

Risk factors for sepsis• • Diabetes mellitus• • Immunodeficiency• • Trauma• • Burns• • Alcohol and substance abuse• • Chronic disease (heart,• lungs, kidneys, liver)• • Hematological disorders• • Recent surgery/invasive• procedure• • Invasive lines: intravenous• or arterial, urinary• catheters, nasogastric• tubes

Diagnostic Criteria for Sepsis

General variables• Fever (> 38.3°C)• Hypothermia (core temperature < 36°C)• Heart rate > 90/min–1 or more than two sd above

the normal value for age• Tachypnea• Altered mental status• Significant edema or positive fluid balance (> 20

mL/kg over 24 hr)• Hyperglycemia (plasma glucose > 140 mg/dL or

7.7 mmol/L) in the absence of diabetes

Inflammatory variable

• Leukocytosis (WBC count > 12,000 μL–1)• Leukopenia (WBC count < 4000 μL–1)• Normal WBC count with greater than 10% immature forms• Plasma C-reactive protein more than two sd above the

normal value• Plasma procalcitonin more than two sd above the normal

valueHemodynamic variables• Arterial hypotension (SBP < 90 mm Hg, MAP < 70 mm Hg,

or an SBP decrease > 40 mm Hg in adults

Organ dysfunction variables• Arterial hypoxemia (Pao2/Fio2 < 300)• Acute oliguria (urine output < 0.5 mL/kg/hr for at

least 2 hrs despite adequate fluid resuscitation)• Creatinine increase > 0.5 mg/dL or 44.2 μmol/L• Coagulation abnormalities (INR > 1.5 or aPTT >

60 s)• Ileus (absent bowel sounds)• Thrombocytopenia (platelet count < 100,000 μL–

1)• Hyperbilirubinemia (plasma total bilirubin > 4

mg/dL or 70 μmol/L)Tissue perfusion variables• Hyperlactatemia (> 1 mmol/L)• Decreased capillary refill or mottling

Severe Sepsis• Sepsis-induced hypotension• Lactate above upper limits laboratory normal• Urine output < 0.5 mL/kg/hr for more than 2 hrs

despite adequate fluid resuscitation• Acute lung injury with Pao2/Fio2 < 250 in the

absence of pneumonia as infection source • Acute lung injury with Pao2/Fio2 < 200 in the

presence of pneumonia as infection source normal >400

• Creatinine > 2.0 mg/dL (176.8 μmol/L)• Bilirubin > 2 mg/dL (34.2 μmol/L)• Platelet count < 100,000 μL• Coagulopathy (international normalized ratio > 1.5)

Initial resuscitation of sepsis: therapeutic goals

• Central venous pressure: 8 – 12 mmHg• Mean arterial pressure: ≥ 65 mmHg• Urine output: 0.5 mL/kg/h• Central venous (SVC) or mixed venous

oxygen saturation: ≥ 70%

Immediate management of severe sepsis

• Give high-concentration oxygen•Take blood cultures• Give intravenous antibiotics(appropriate to likely organism)• Volume-resuscitate• Measure Hb and lactate• Measure urine output• Control source of infection

SURVIVING SEPSIS CAMPAIGN BUNDLES

TO BE COMPLETED WITHIN 3 HOURS:• 1) Measure lactate level• 2) Obtain blood cultures prior to

administration of antibiotics• 3) Administer broad spectrum

antibiotics• 4) Administer 30 mL/kg crystalloid for

hypotension or lactate 4mmol/L

TO BE COMPLETED WITHIN 6 HOURS: 5) Apply vasopressors (for hypotension that does

not respond to initial fluid resuscitation) to maintain a mean arterial pressure (MAP) 65

mm Hg In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate 4 mmol/L (36 mg/dL):

- Measure central venous pressure (CVP)* - Measure central venous oxygen saturation

(ScvO2)* Remeasure lactate if initial lactate was elevated* *Targets for quantitative resuscitation included in

the guidelines are CVP of 8 mm water. ScvO2 of 70%, and normalization of lactate

Hemodynamic Support and Adjunctive Therapy

Fluid Therapy of Severe Sepsis1. initial fluid of choice in the resuscitation of severe sepsis and septic shock.2. albumin -patients require substantial amounts

of crystalloids.3.(SSC) recommend against the use of hydroxyethyl starches(HES) for fluid resuscitation of severe sepsis and septic shock.

Vasopressors1. (MAP) of 65 mm Hg.2. Norepinephrine - first choice 3. Epinephrine -added to and potentially substituted for norepinephrine.4. Low dose vasopressin is not recommended5. Dopamine as an alternative vasopressor agent to norepinephrine. 6. Low-dose dopamine should not be used for renal protection.7. All patients requiring vasopressors have an arterial catheter placed as soon as practical if resources are available (UG).

Corticosteroids

1. Not using intravenous hydrocortisone to treat adult septic shock patients if adequate fluid resuscitation and vasopressortherapy are able to restore hemodynamic stability.In case this is not achievable, we suggestintravenous hydrocortisone alone at a dose of 200 mg per day.

2. Corticosteroids not be administered for the treatment of sepsis in the absence of shock.

Sites of infection in critically ill patients

Sites of infection Investigations and commentsMajorIntravenous lines (particularly

If the patient develops sepsis, replace any lines that have not been changed for > 4 days

Lungs High risk of nosocomial pneumonia in intubated patients. After ICU stay > 3–4 days, particularly ifantibiotics are given, the nasopharynx becomes colonised with Gram-negative bacteria, whichmigrate to the lower respiratory tract. Prophylaxis with parenteral and enteral antibiotics (selectivedecontamination of the digestive tract) reduces the incidence of nosocomial pneumonia

Urinary tract Urine culture (but this is a relatively unusual source in unexplained sepsis)

Abdomen Consider intra-abdominal abscess or necrotic gut in patients who have had abdominal surgeryPancreatitis, acute cholecystitis or perforated peptic ulcer may develop as a complication of criticalillness. Ultrasound, CT, aspiration of collections of fluid/pus and laparotomy may be required

OtherHeart valves

Transthoracic or transoesophageal echocardiogram

Meningitis Lumbar puncture after checking coagulation and platelet count

Joints &bones X-ray, gallium or technetium white cell scanNasal sinuses, ears,retropharyngeal space

Clinical examination, plain X-ray, CT

Genitourinary tract (particularlypost-partum)

PV examination, ultrasound

Gastrointestinal tract PR examination, stool culture, Clostridium difficile toxin, sigmoidoscopy

Issues in the rational choice of antibiotics

EFFICACY• Spectrum of activity• Pharmacokinetics & pharmacodynamics• Patterns of resistance TOXICITYCOST

Choosing antibiotics in sepsis

• There is no, single, “best” regimen• Consider the site of the infection• Consider which organisms most often cause

infection at that site• Choose antibiotic(s) with the appropriate

spectrum• After obtaining cultures, give antibiotics

quickly and empirically at appropriate dose

Inadequate treatment of bloodstream infectionsincreases ICU mortality

Ibrahim et al, Chest 2000 118:146

“Non-antibiotic” therapy for sepsis

• Low dose steroids• Intensive insulin therapy

– tight glycaemic control• Activated protein C• Goal directed therapy

Other Supportive Therapy of Severe Sepsis

• Glucose control• Renal replacement therapy• Bicarbonate therapy• Deep vein thrombosis prophylaxis• Stress ulcer prophylaxis• Nutrition