Sepsis: Definitions, Objectives, and Treatment PDF

Sepsis / SIRS and MOF Objectives The Definitions of Sepsis and the Sepsis Syndromes. The Factors that precipitate and perpetuate the Sepsis Cascade. The Pathogenesis of Multiple Organ Dysfunction in Sepsis. Treatment options in Sepsis What is Sepsis? Definitions...

Sepsis / SIRS and MOF Objectives The Definitions of Sepsis and the Sepsis Syndromes. The Factors that precipitate and perpetuate the Sepsis Cascade. The Pathogenesis of Multiple Organ Dysfunction in Sepsis. Treatment options in Sepsis What is Sepsis? Definitions Systemic Inflamatory Response Syndrome (SIRS): The systemic inflammatory response to a variety of severe clinical insults (For example, infection). SIRS is the body’s response to infection, inflammation, stress. Sepsis: The systemic inflammatory response to infection. SIRS is manifested by two or more of the following conditions: Temperature >38 degrees Celsius or 90 beats per minute. Respiratory rate>20 breaths per minute or PaCO2 12,000/cu mm, 2 SIRS Criteria. Severe Sepsis: Sepsis plus >1 organ dysfunction. MODS. Septic Shock.  Septic Shock: Sepsis induced with hypotension despite adequate resuscitation along with the presence of perfusion abnormalities which may include, but are not limited to lactic acidosis, oliguria, or an acute alteration in mental status.  Multiple Organ Dysfunction Syndrome (MODS): The presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention.  Sepsis - SIRS + Infection Severe Sepsis - Sepsis + Organ dysfunction Septic shock – Sepsis + Hypotension despite fluid resuscitation High Risk Patients For Sepsis and Dying Middle-aged, elderly Post op / post trauma Post splenectomy Transplant immune supressed Alcoholic / Malnourished Genetic predisposition Delayed appropriate antibiotics Comorbidities : AIDS, renal or liver failure, neoplasms Clinical Signs of Sepsis Fever. Leukocytosis. Tachypnea. Tachycardia. Reduced Vascular Tone. Organ Dysfunction.  Organ System Involvement Circulation Hypotension, increases in microvascular permeability Shock Lung Pulmonary Edema, hypoxemia, ARDS Hematologic DIC, coagulopathy (DVT)  Organ System Involvement GI tract stress ulcer Translocation of bacteria, Liver Failure, Gastroparesis and ileus, Cholestasis ► Kidney Acute tubular necrosis, Renal Failure  Organ System Involvement Nervous System Encephalopathy ► Skeletal Muscle Rhabdomyolysis Endocrine Adrenal insufficiency Sources of Sepsis The International Cohort Study Severe Septic Sepsis Shock Respiratory 66 53 Abdomen 9 20 Bacteremia 14 16 Urinary 11 11 Multiple - - 35% mortality Clinical Signs of Septic Shock Hemodynamic Alterations Hyperdynamic State (“Warm Shock”) Tachycardia. Elevated or normal cardiac output. Decreased systemic vascular resistance. Hypodynamic State (“Cold Shock”) Low cardiac output. Clinical Signs of Septic Shock Myocardial Depression. Altered Vasculature. Altered Organ Perfusion. Imbalance of O2 delivery and Consumption. Metabolic (Lactic) Acidosis. Levels of Clinical Infection Level I Locally Controlled. Level II Locally Controlled, Leukocytosis. Level III Systemic Hyperdynamic Response. Level IV Oxygen metabolism becomes uncoupled. Level V Shock, Organ Failure. Stages In the Development of SIRS (Bone, 1996) Stage 1. In response to injury / infection, the local environment produces cytokines. Stage 2. Small amounts of cytokines are released into the circulation: Recruitment of inflammatory cells. Acute Phase Response. Normally kept in check by endogenous anti- inflammatory mediators (IL-10, PGE2, Antibodies, Cytokine receptor antagonists). Stages In the Development of SIRS Stage 3. Failure to control inflammatory cascade: Loss of capillary integrity. Stimulation of Nitric Oxide Production. Maldistribution of microvascular blood flow. Organ injury and dysfunction. Why is Sepsis Important? Severe Sepsis Major cause of morbidity and mortality worldwide. Leading cause of death in noncoronary ICU. 11th leading cause of death overall. More than 750,000 cases of severe sepsis in US annually. In the US, more than 500 patients die of severe sepsis daily. Pathophysiology Excessive anti-inflammatory response Sepsis: auto-destructive process allowing normal responses to infection/injury to involve normal tissues Severe Sepsis: The Final Common Pathway Endothelial Dysfunction and Microvascular Thrombosis Hypoperfusion/Ischemia Acute Organ Dysfunction (Severe Sepsis) Death  Identification of septic focus history physical examination imaging cultures Blood cultures, urine culture, sputum culture, abscess culture.  Investigations Basic Specific ?Source WBC Platelets Urine Coags CxR Renal function Blood Cultures Glucose Biopsy Albumin LFT ABG May all be normal early on! Differentiate sepsis from noninfectious SIRS Procalcitonin C-reactive protein (CRP) IL-6 protein complement C3a Leptin test is not yet readily available for clinical practice  Treatment of Sepsis Antibiotics Steroid therapy (adrenal insufficiency) Early aggressive fluid resuscitation Activated protein C Inotropes for BP support Ventilatory Strategies (Dopamine, vasopressin, norepinephrine) Glycemic control Source control Newer therapies.  I.V. antibiotics Initiated as soon as cultures are drawn. Severe sepsis should receive broadspectrum antibiotic. Empiric antifungal drug; Neutropenic patients, DM, chronic steroids.  Antibiotics Abx within 1 hr hypotension: 79.9% survival Survival decreased 7.6% with each hour of delay Mortality increased by 2nd hour post hypotension Time to initiation of Antibiotics was the single strongest predictor of outcome Antibiotics dosing Dosage for intravenous administration (normal renal function). Imipenem-cilastin Meropenem Piperacillin-tazobactam Cefepime Ceftriaxone Levofloxacin  Source control Early recognition of the Sepsis syndrome. Surgical intervention when indicated. Aggressive supportive care in intensive care units.  Surgery pus out Get the abscesses or foci of infection should be drained Early definitive care ; e,.g; ruptured appendix, cholecystitis Supportive Oxygenate / Ventilate Electrolyte homeostasis Inotropes (DVT) and stress ulcer prophylaxis ARDS causes respiratory failure in patients with severe Sepsis Assess the airway, respiration, and perfusion Supplemental oxygenation, Ventilator for respiratory failure Sepsis-induced hypotension systolic less than 90 mm Hg or a reduction of more than 40 mm Hg from baseline in the absence of other causes of hypotension." 1. A loss of plasma volume into the interstitial space, 1. Decreases in vascular tone, 2. Myocardial depression.  Treatment of Hypotension Intravenous fluids : Crystalloids vs. Colloids. need more than ‘maintenance’ + replace losses  Fluid Therapy No mortality difference between; colloid vs. crystalloid  Goals for initial resuscitation Central venous pressure 8 to 12 mmHg. Mean arterial pressure 65 mmHg. Urine output 0.5 mL per kg per hr. Pulmonary capillary wedge pressure exceeds 18 mmHg  Steroids For Non-responders; Improved refractory hypotension Reduced mortality 10% 50mg of hydrocortisone iv 6hrs With fludrocortisone 50mcg for 7 days  Stress hyperglycemia in critically ill patients Due to; 1. A decreased release of insulin 2. increased release of hormones with effects countering insulin 3. increased insulin resistance 4. Hyperglycemia diminishes the ability of neutrophils and macrophages to combat infections.  Tight Glycemic control Continuous insulin infusion Maintaining serum glucose levels between 80 and 110 mg/dl Decreased mortality development of renal failure Failed therapies Corticosteroids— high dose methylprednisolone Anti-endotoxin antibodies TNF antagonists—soluble TNF receptor Ibuprofen  Mortality Sepsis: 30% - 50% Septic Shock: 50% - 60%  KEY TAKE HOME POINTS Recongnize Sepsis EARLY and determine SEVERITY EARLY Antibiotics are critical to resolution of shock RESUSCITATE severe sepsis and septic shock EARLY GOAL DIRECTED THERAPY Questions ?