Current concept of pathophysiology of sepsis Manutham Manavathongchai MD

ACCP/SCCM Consensus definitions Systemic inflammatory response syndrome ( SIRS) Tachycardia, HR >2 SD, <1yr bradycardia Mean RR >2 SD WBC elevate or depressed for age Core temp >38.5 °C or <36 °C one of two have to be abn Temp or WBC

ACCP/SCCM Consensus definitions Infection Inflammatory response to microorganisms, or Invasion of normally sterile tissues

ACCP/SCCM Consensus definitions Sepsis Infection plus SIRS criteria

ACCP/SCCM Consensus definitions Severe Sepsis Sepsis plus Cardiovascular dysfunction or Acute respiratory distress syndrome (ARDS) or Other 2 organs dysfunction

Organ dysfunction Cardiovacular pulmonologic Neurologic Hematologic Renal Hepatic

ACCP/SCCM Consensus definitions Septic shock Sepsis plus Hypotension despite fluid resuscitation or Need vasoactive drugs or 2 organs dysfunction

Sepsis This conceptual framework shows the interrelationships between infection, non-infectious disorders, SIRS, sepsis, and severe sepsis. Components of the process not discussed on the following slides include: Infection: a microbial phenomenon characterized by an inflammatory response to the presence of microorganisms or the invasion of normally sterile host tissue by those organisms Bacteremia: the presence of viable bacteria in the blood stream Septic shock: sepsis-induced hypotension despite adequate fluid resuscitation along with the presence of perfusion abnormalities that may include, but are not limited to, lactic acidosis, oliguria, or an acute alteration in mental status Multiple organ dysfunction syndrome (MODS): presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention Inflammation and hemostasis are tightly linked. Therefore, although not shown on this slide, sepsis and severe sepsis lie on a background of disturbed hemostasis. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101:1644-55. Opal SM, Thijs L, Cavaillon JM, et al. Relationships between coagulation and inflammatory processes. Crit Care Med. 2000;28:S81-2. Adapted from: Bone RC et al. Chest. 1992;101:1644-55. Opal SM et al. Crit Care Med. 2000;28:S81-2.

ACCP/SCCM Consensus definitions Multiple Organ Dysfunction Syndrome (MODS) Altered organ function in an acutely ill patient Homeostasis cannot be maintained without intervention

Early sepsis Innate system (non specific) Adaptive system (specific)

Innate system (non specific) Cell adhesion molecules Procoagulants and anticoagulants Nitric oxide synthase

Russel JA. N Engl J Med 2006;355:1699-713

Russel JA. N Engl J Med 2006;355:1699-713

Ann Emerg Med. 2006;48:28-54

Depletion of platelets and coagulation factors SYSTEMIC ACTIVATION OF COAGULATION Intravascular deposition of fibrin Depletion of platelets and coagulation factors Bleeding Thrombosis of small and midsize vessels Organ failure DEATH

Septic shock Role of NO Infection induce NOS expression High level Help eradicate infection but Also cause vasodilation/ Massive hypotension Samjot S et al Chest 2005;128:1706

Activated protein c in Pediatric septic shock P<0.01, n=30 60 50 40 Activated protein C activity 30 20 10 Survivors Non-Survivors Samransamruajkit et al ATS 2005

Adaptive system (specific) Cell-mediated response (T-cells) Humoral response (B-cells)

Organ dysfunction Circulatory dysfunction: redistribution of bl flow : vascular resistance : myocardial contraction Acute lung injury : microvascular permeability Liver, kidney , CNS dysfunction

Septic shock stage/Course Early resuscitation Aggressive Rx Paliative Rx “Early Warm Shock” “Reversible Phase” “Irreversible Phase”

Septic shock General principle summary Early Recognition Immediate Resuscitation **Prevention Stabilization Prevention Prophylactic Abx P Iatrogenic Vaccine Early Recognition Warm Shock Reversible signs of hypo Perfusion Wide PP UO Immediate Resuscitation 1 st HR Resuscitation ABC Volume Inotrope Steroids Stabilization Hemodynamic support Appropriate Inotrope use Close monitoring Nutrition