Associate Prof. DrHuda 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
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
Severe Sepsis SIRS + Blood Infection Plus Organ Failure
Septic Shock SIRS or Sepsis PlusHypotension (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
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 ProductAdministration 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
DopamineDopamine is capable of stimulating:1. Cardiac ß1-receptors2. Peripheral α-receptors3. 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 possible 3) Full sterile technique ( mask, gown, gloves ) 4) Antibiotics Treatment of Pneumonia: 1) Good Oral Hygiene 2) Aspiration Precaution: ↑ HOB 45 ˚ 3) Antibiotics Treatment of Intra-abdominal infections: 1) Cholecystitis, diverticulitis, gut ischemia, abscess, pancreatitis, appendicitis, UTI ( change catheter ) 2) Mini-invasive surgery vs. surgery 3) 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 response2. Undrainable foci of infection3. Immunologic deficiencies4. Neutropenia
Interrupt InflammatoryMediators Activated Protein C: 1) Reduced mortality rate in sever sepsis and septic shock 2) Very expensive therapy Corticosteroid therapy: 1) Persistent Hypotension 2) Non responder to ACTH stimulation test Glucose control: 1. Keep glucose < 150 mg/dl 2. Use Intravenous insulin protocol
Drotrecogin alfa DoseContinuous 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 ( ( EGDTEarly detection and treatment: Decreases mortality rate
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 BundleIs defined as a group of interventionsrelated to a disease process that, whenexecuted together, result in betteroutcomes than when implementedindividually
Sepsis BundleReduces mortality and ICU stayif implemented within 6 hours