Sepsis


Sepsis: 1991

Sepsis: 2001

Sepsis: 2015




Evidence



Sepsis: pathophysiology and clinical management BMJ 2016

Crit Care Med 2013; 41:580–637 

Crit Care Med 2013; 41:580–637 

Crit Care Med 2013; 41:580–637 

Crit Care Med 2013; 41:580–637 

Crit Care Med 2013; 41:580–637 

Crit Care Med 2013; 41:580–637 

Crit Care Med 2013; 41:580–637 

  • With co-mobodities Mortality is high with Sepsis
  • Definition:
    • Surviving Sepsis Definition of Sepsis
    • SIRS2: 7 % mortality, increases to 15% with SIRS4
  • Pathophysiology
    • Proinflammatory Concept: IL-6, TNF mediated endothelial injury
    • Pro-coagulation concept: Endothelial Damage causing pro coagulation 
    • Mitochondrial Dysfunction Concept: Leading to Lactic Acidosis
    • Endothelial Injury causes NO release; diffuses to smooth muscle causing vasodilatation
  • Surviving Sepsis Campaign in co-ordination with Elli (pharmacy) (2000 - 2002): 5 positive studies
    • Early Goal Directed Therapy (Rivers Protocol): Proof of Concept Study NEJM 2001
      • Resuscitation Strategy:
        • Central Line / A-Line
        • CVP > 8 
        • MAP > 65
        • ScvO2 >70 (RBC transfusion if  Hct <10) 
    • Intensive Insulin Therapy
      • Mean 103 vs 153 mean glucose
      • Relatively better sepsis mortality
    • Activated Protein C 
      • As sepsis mortality was going down, APC did not do as well. 
      • First study (PROWESS study)
        • Sickest of the sick patient did have mortality improvement at day 28. (27 vs 30 % mortality in two groups)
      • It was based on the pro-coagulant phenomenon. Could that be due to lack of Protein C. 
    • Low dose Steroids (JAMA 2002, Multi-centric study in France)
      • Improved mortality in subset of patient in ACTH non-responders only 
    • Low Tidal Volume Stratedy (LTVS) ARDSNeTT
    • Clinical Studies
      • Prospective RCT
      • Post hoc analysis of PRCT
      • Lars Retrospective database analyes
        • Clinical Database
        • Administrative Database
    • SIRS Criteria in Severe Sepsis
      • SIRS 2 defining criteria missed 1/8 patients
    • Abx
      • Time Dependent Kinetics (B-lactam and Vanc)
      • Concentration-dependent Kinetics (FQ, Aminoglycosides)
    • Early Source Control 
  • Newer Study
    • EGDT had controversies
      • CVP as a measure of cardiac filling volume ?
        • Normal CVP 3-5 (target was 8-10)
        • Drawback was positive fluid balance and worse outcomes 
          • Posthoc analyze of VAAST study 
        • Fluid Resuscitation in Sepsis (Ann Itern Med 2014)
          • Certain IV fluid had more mortality 
        • Lactate Guided Resuscitation
          • <45 ml/kg of fluid resuscitation
          • PaO2 of < 30 mmHg is needed for lactic acidosis
          • Hgb < 5 is needed for lactic acidosis (NEJM Lactic Acidosis)
          • So, Lactate in sepsis is less likely due to hypoxemia vs anemia
          • Severe sepsis with BB
            • Cleared Lactate Faster
            • So, possible Lactate is due to Epinephrine in Severe Sepsis 
      • Ideal MAP target?
        • No difference in DA vs NE in mortality (NEJM 2010, Study from France)
        • More adverse events with DA; Hence, NE is a go to drug
        • VASSST (Cric Care Med 2009, no difference in outcome in patients not receiving steroids)
          • Vasopression is not a good drugs due to risk of ischemia 
        • MAP 65 vs 85 had mo difference in mortality (NEJM 2014)
          • MAP 65 had more renal failure (if they had baseline high BP)
      • ScvO2 as a reliable target?
        • Initial concept derived from Cardiac Failure and Hemorrhage
        • Restrospective review of Surviving Sepsis 
  •  SIRS / SEPSIS / SEVERE SEPSIS / SEPTIC SHOCK -- 2/2 infections in one of the following 7 systems – worsening/resolving/resolved – Pan-culture, Pan Physical Exam – Rx (see reference)

                                               i.     CNS
                                              ii.     URT including Sinus
                                            iii.     LRT including PNA
                                            iv.     Hepatobiliary
                                              v.     GI (gastroenteritis, colitis, intra-abdominal abscess)
                                            vi.     KUB (UTI, Pyelonephritis, PID)
                                           vii.     Skin and Joints


Reference:      

1. Diagnostic Criteria for Sepsis, Severe Sepsis, Septic Shock (Table NEJM 2013

2. Treatment of Sepsis (NEJM 2013)

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