SEPSIS M H MUMTAZ 992020 1 INCIDENCE USA

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SEPSIS M H MUMTAZ 9/9/2020 1

SEPSIS M H MUMTAZ 9/9/2020 1

INCIDENCE USA 750, 000 Whole wold 18 millions Mortality 1400 /day Growth rate 1.

INCIDENCE USA 750, 000 Whole wold 18 millions Mortality 1400 /day Growth rate 1. 5%/year Mortality rate 30%-50% s. sepsis 50%-60% s. shock Cost $ 22, 000 /case 9/9/2020 2

Introduction Complex interaction between; 1, micro-organisms = Bacteraemia 2, toxins = toxaemia 3, immune

Introduction Complex interaction between; 1, micro-organisms = Bacteraemia 2, toxins = toxaemia 3, immune system = SIRS 9/9/2020 3

Pathophysiology Bacteraemia+Toxins+Immune. s. 1. cytokines production SIRS 2. PGs activation 3, activation of coagulation

Pathophysiology Bacteraemia+Toxins+Immune. s. 1. cytokines production SIRS 2. PGs activation 3, activation of coagulation lead to; - 1, generalised endothelial injury ^ permeability___oedaema. ischaemia 2, coagulopathy M. O. F. 9/9/2020 4

Markers of Infection n 1, Bacterial products as markers a, bacterial products endotoxins exotoxins

Markers of Infection n 1, Bacterial products as markers a, bacterial products endotoxins exotoxins enzymes lipids b, bacterial DNA, RNA PCR (multiplex PCR, real time PCR) 2, Pro-inflammatory factors a, acute phase proteins, ( CRP) 9/9/2020 5

Markers of infection n b, proxima markers of the innate immune response 1 L-6,

Markers of infection n b, proxima markers of the innate immune response 1 L-6, 1 L-8, C 3 a, s. PLA 2, c, macrophage products procalcitonin (Pct), neupterins, d, Neutrophil products Elastase, lactoferrin, e, coagulation markers tissue plasminogen activator (TPA) 9/9/2020 6

THERAPY 1, SPECIFIC a, antimicrobials b, Drotrecogin alpha(activated) 2, SUPPORTIVE (organ support) a, Haemodynamic

THERAPY 1, SPECIFIC a, antimicrobials b, Drotrecogin alpha(activated) 2, SUPPORTIVE (organ support) a, Haemodynamic support (fluids, vasopressors, inotropes) b, Ventilatory support 3, ADDITIONAL SUPPORT 9/9/2020 7

ADDITIONAL ADVANCED SUPPORT n Adrenal hormone replacement n 9/9/2020 n Tight glycaemic control n

ADDITIONAL ADVANCED SUPPORT n Adrenal hormone replacement n 9/9/2020 n Tight glycaemic control n Renal replacement n Blood purification 8

GLYCAEMIC CONTROL n Hypoglycaemia n Stringent n n 9/9/2020 n Normal n Intermediate n

GLYCAEMIC CONTROL n Hypoglycaemia n Stringent n n 9/9/2020 n Normal n Intermediate n Liberal n Hyperglycaemia n n <80 80— 100 111— 144 145 ---180 181 ---200 >201 9

SURVIVING SEPSIS COMPAIGN 2002, survey conducted by; ESICM, SCCM to have views on; “sepsis”

SURVIVING SEPSIS COMPAIGN 2002, survey conducted by; ESICM, SCCM to have views on; “sepsis” “current definitions” “routes to dignosis” “treatment options” “ They revealed that most physcians find sepsis challeging & frustrating to diagnose & treat”. 9/9/2020 10

THE RESPONSE; to SSC n 9/9/2020 SCCM +ESICM +ISF 3 Phase SSC First phase.

THE RESPONSE; to SSC n 9/9/2020 SCCM +ESICM +ISF 3 Phase SSC First phase. 6 point action plan Second phase. Guide lines for sepsis management Third phase. Translating the guidelines into clinical practice 11

IDENTIFYING PATIENTS n n SEPSIS DEFINITIONS 1, General variables; FEVER > 38. 3 Hypothermia

IDENTIFYING PATIENTS n n SEPSIS DEFINITIONS 1, General variables; FEVER > 38. 3 Hypothermia < 36. 0 Heart rate >90/min Tachypnea Altered mental status Significant odema Hyperglycaemia >120 mg/dl no diabetes 9/9/2020 12

SEPSIS DEFINITION n 2, Inflamatory variables Leukocytosis ( WBC > 12000) Leukopenia (WBC <

SEPSIS DEFINITION n 2, Inflamatory variables Leukocytosis ( WBC > 12000) Leukopenia (WBC < 4000) Normal WBC with > 10% immature forms Plasma c-reactive proteins > 2 SD Above N Plasma procalcitonin > 2 SD above normal 9/9/2020 13

SEPSIS DEFINITION n Severe sepsis; organ dysfunction+ hypoperfusion or hypotension ORGAN DYSFUNCTION variables; Arterial

SEPSIS DEFINITION n Severe sepsis; organ dysfunction+ hypoperfusion or hypotension ORGAN DYSFUNCTION variables; Arterial hypoxaemia ( Pao 2/FIO 2 < 300) Acute oligurea Creatinine > 2. 0 mg/dl Coagulation abnormality (INR > 1. 5 or APTT > 60 s Platelet count < 100, 000 Bilirubin > 35 mmol/L OR > 2. 0 mg/dl 9/9/2020 14

SEPSIS DEFINITIONS TISSUE PERFUSION VARIABLES; Hyperlactataemia ( > 2 mmol/L ) Haemodynamic Variables; Arterial

SEPSIS DEFINITIONS TISSUE PERFUSION VARIABLES; Hyperlactataemia ( > 2 mmol/L ) Haemodynamic Variables; Arterial hypotension SBP <90 MAP < 65 “Septic shock is acute circulatory failure unexplained by other causes. (persistant hypotension despite volume resuscitatation)”. 9/9/2020 15

GUIDELINES by SSC 2003 11 International organizations laid criteria; 1, Initial Resuscitation 11, Sedation/anal.

GUIDELINES by SSC 2003 11 International organizations laid criteria; 1, Initial Resuscitation 11, Sedation/anal. 2, Diagnosis 12, Glucose control 3, Antibiotic therapy 14, Renal. R. T. 4, Source control 15, D. V. T. 5, Fluid therapy 16, HCO 3 therapy 6, Vasopressors 17, Stress ulcer 7, Inotropic therapy Prophylaxis 8, Steroids 9, Blood products administration 10, Mechanical ventilation 9/9/2020 16

SEVERE SEPSIS BUNDLES n 1, Sepsis resuscitation Bundle Over first 6 hours 2, Sepsis

SEVERE SEPSIS BUNDLES n 1, Sepsis resuscitation Bundle Over first 6 hours 2, Sepsis management Bundle as soon as possible scored over first 24 hours 9/9/2020 17

1. Sepsis resuscitation Bundle n Seven tasks within first 6 hours. 1, measure serum

1. Sepsis resuscitation Bundle n Seven tasks within first 6 hours. 1, measure serum lactate. 2, Obtain blood culture. 3, Administer antibiotic, ED 3 h, Non ED. 1 h. 4, Hypotension and/or Lactate > 4 mmol/L a, fluids 20 ml/Kg b, Vasopressors (MAP > 65) 5, Persistant hypotension +or Lactate >4 a, achieve CVP > 8 b, achieve Scv. O 2 >70% 9/9/2020 18

2. Sepsis management Bundle n 4 goals within 24 hours. 1, administer low dose

2. Sepsis management Bundle n 4 goals within 24 hours. 1, administer low dose steroids/ policy 2, administer drotecorgin alfa ( activated) 3, maintain glucose control > lower limit < 8. 3 mmol/l 4, maitain inspiratory plateau pressure < 30 cm of H 2 O 9/9/2020 19

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