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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