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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