Associate Prof. Dr

Huda NasserMD, FARCSIFaculty of Medicine –Aleppo University

Agenda

Clinical syndromes related to sepsis Septic shock, pathogenesis, manifestations Goals of treatment of septic shock Initial resuscitation with fluid Stabilize hemodynamics with pressors Antibiotics Interruption of inflammatory mediators Early goal directed therapy

Bacteremia

Transient Infection in the blood

Systemic Inflammatory Response Syndrome ( SIRS (

Trigger: infectious or non-infectious (e.g., pancreatitis, crush injuries, and certain drug ingestions such as salicylates)

Cause: release of inflammatory mediators

Can be self limited or can progress to severe sepsis and septic shock

Systemic Inflammatory Response Syndrome

Sepsis

SIRS + Blood Infection

Severe Sepsis

SIRS + Blood Infection

Plus

Organ Failure

Septic Shock

SIRS or Sepsis

Plus

Hypotension (SBP< 90) or Lactate ≥ 4 mmol/L

Refractory Hypotension

Systolic blood pressure < 90 mm Hg after a crystalloid-fluid challenge.

Dose of fluid Challenge: 20 to 30 ml per kilogram of body weight over 60 minutes

Example: (70 kg) fluid challenge= 1.5-2.0 L

Septic Shock

Is caused by the systemic release of mediators that usually are triggered by circulating bacteria or their products

Or caused by systemic mediators triggered by noninfectious causes

Refractory Hypotension MUST be present

Clinical Manifestation of Shock

Septic Shock: Goals of Treatment

Septic Shock-Initial Resuscitation

Appropriate large-volume fluid administration to compensate for the decrease in vascular tone and dilated ventricular capacity.

First Goal: CVP = 8-12 cm H2Oa) Crystalloid fluid Administrationb) Central venous pressure monitorc) During first 6 hours

Fluid Therapy

We recommend fluid resuscitation with either natural/artificial colloids or crystalloids.

There is no evidence-based support for one type of fluid over another (grade 1B).

A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004; 350:2247-2256.

Stabilize Hemodynamics

Second goal is: 65 ≤ MAP ≤ 90a) Norepinephrine or Dopamine IV dripb) Arterial line monitorc) During first 6 hours

Third goal is: ScvO2 ≥ 70 %a) Blood transfusion to keep Hct ≥ 30 %b) Use Inotropic agent to improve cardiac indexc) Central venous monitor of O2 saturationd) During first 6 hours

Blood Product Administration

Give red blood cells when hemoglobin decrease to < 7 g/dl to target a hemoglobin of 7.0-9.0 g/dl in adults

Do not use erythropoietin to treat sepsis related anemia

Norepinephrine Dose

0.2-1.5 mcg/kg/min

Large dose: 3.3 mcg/kg/min have been used because of the alpha-receptor down-regulation in sepsis.

Norepinephrine versus Dopamine

Two recent trials have shown that a significantly greater proportion of patients treated with norepinephrine were resuscitated successfully, as opposed to the patients treated with dopamine.

Norepinephrine should be used early and should not be withheld as a last resort in patients with severe sepsis who are in shock.

Critical Care Medicine 2000;28,2758-2765 Chest 1993;103,1826-1831

Dopamine

Dopamine is capable of stimulating:

1. Cardiac ß1-receptors 2. Peripheral α-receptors 3. Dopaminergic receptors in renal, splanchnic,

and other vascular beds.

Bicarbonate Therapy

Do not use bicarbonate for the purpose of improving hemodynamics or reducing vasopressor requirements when treating hypoperfusion-induced lactic acidemia with PH ≥ 7.15

Control of Underlying Infection

Replacement of Central and Arterial lines:1) Infected lines or old lines ( ≥ 7 days )2) Avoid Femoral Vein if possible3) Full sterile technique ( mask, gown, gloves )4) AntibioticsTreatment of Pneumonia:1) Good Oral Hygiene2) Aspiration Precaution: HOB 45 ˚↑3) AntibioticsTreatment of Intra-abdominal infections:1) Cholecystitis, diverticulitis, gut ischemia, abscess, pancreatitis, appendicitis,

UTI ( change catheter )2) Mini-invasive surgery vs. surgery3) Antibiotics

Blood Cultures ( BCs (

Obtain ≥ 2 BCs ≥ 1 BC should be percutaneous One BC from each vascular access device in

place > 48 Should be obtained very early

Obtain Lactate level with blood culture

Empiric Antibiotics: Broad Spectrum

Must be broad-spectrum agents and must cover

gram-positive, gram-negative, and anaerobic bacteria.

Empiric Antibiotics: First Hour

Should be started within the first hour of recognition of septic shock and severe sepsis

Appropriate cultures should be obtained

before initiating antibiotic therapy

Blood cultures should not significantly delay antibiotic therapy

Empiric Antibiotics: Selection

Host defenses, potential sources of infection, and most likely organisms

Antibiotic experienced patient: use aminoglycoside rather than a quinolone or cephalosporin for gram-negative coverage

Antibiotic resistance patterns of both the hospital itself and its referral base (i.e., nursing homes)

Empiric Antibiotics: Duration

Should not be administered for > 3-5 days De-escalation to the most appropriate single

therapy should be performed as soon as the susceptibility profile is known

Anti-Fungal

If candidemia is a likely cause Risk factors for Candidemia: TPN, Propofol,

DM, HIV, Chemotherapy

Empirical antifungal therapy (e.g., fluconazole, amphotericin B, or echinocandin)

Specific Antibiotics: Duration

Typically 7-10 days Longer courses in patients: 1. Slow clinical response 2. Undrainable foci of infection 3. Immunologic deficiencies 4. Neutropenia

Interrupt Inflammatory Mediators

Activated Protein C:1) Reduced mortality rate in sever sepsis and septic

shock2) Very expensive therapyCorticosteroid therapy:1) Persistent Hypotension2) Non responder to ACTH stimulation testGlucose control:1. Keep glucose < 150 mg/dl2. Use Intravenous insulin protocol

Activated Protein C

Drotrecogin alfa Dose

Continuous infusion of 24 mcg/kg/hour for 96 hours

Contraindications to Use of Recombinant Human Activated Protein C (rhAPC(

Active internal bleeding Recent (within 3 months) hemorrhagic stroke Recent (within 2 months) intracranial or intraspinal surgery, or severe head

trauma Trauma with an increased risk of life-threatening bleeding Presence of an epidural catheter Intracranial neoplasm or mass lesion or evidence of cerebral herniation Known hypersensitivity to rhAPC or any component of the product The committee recommends that platelet count be maintained at ≥30,000 during

infusion of rhAPC.

Physicians' Desk Reference, 61st Edition. Montvale, NJ, Thompson PDR, 2007, Page 1829

EARLY GOAL-DIRECTED THERAPY ( EGDT (

Early detection and treatment:

Decreases mortality rate

Septic Shock

Fluid Dose: First Golden 6 Hours

A 500-ml bolus of crystalloid ( NS ) was given every 30 minutes to achieve a central venous pressure of 8 to 12 mm Hg

Central venous catheter capable of measuring central venous oxygen saturation (Edwards Lifesciences, Irvine, Calif.)

Sepsis Bundle

Is defined as a group of interventions related to a disease process that, when executed together, result in better outcomes than when implemented individually

Sepsis Bundle

Reduces mortality and ICU stay if implemented within 6 hours

Thank you