Sepsis Guidelines PDF

# Sepsis ## VETM 5291 ## Objectives 1. Define sepsis and septic shock 2. List and describe the homeostatic mechanisms that are disrupted in sepsis. 3. Describe the concepts of cryptic shock and cytopathic hypoxia. 4. Describe how inflammation and coagulation interact and contribute to sepsis 5. L...

# Sepsis ## VETM 5291 ## Objectives 1. Define sepsis and septic shock 2. List and describe the homeostatic mechanisms that are disrupted in sepsis. 3. Describe the concepts of cryptic shock and cytopathic hypoxia. 4. Describe how inflammation and coagulation interact and contribute to sepsis 5. List the clinical signs and basic treatment for sepsis ## Consensus Terminology - Surviving Sepsis Campaign: International Guidelines for Management Of Sepsis and Septic Shock - Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) ## Terminology - **Systemic Inflammatory Response Syndrome (SIRS):** - Clinical presentation associated with systemic response to infection, trauma - HR, RR, temperature, WBC - **Multiple Organ Dysfunction Syndrome (MODS):** Abnormal organ function associated with SIRS ## SIRS criteria |Parameter |Dog|Cat|Horse| |:---:|:---:|:---:|:---:| |Heart Rate (beats/ min)|>120|<140 or >225|Tachycardia| |Respiratory Rate (resps/min)|>40 or PaCO2 <30 mmHg| >40 |Tachypnea| |Temperature|<100.4°F or >104.0°F|<100°F or >104°F|Pyrexia or hypothermia| |Leukogram|>18,000 or <5000 WBC/uL|>19,000 or <5000 WBC/uL|Leukocytosis or leukopenia, >10% bands| ## Current Definitions: Sepsis - Life-threatening organ dysfunction caused by a dysregulated host response to infection - Organ dysfunction assessed as Sequential (or Sepsis-related) Organ Failure Assessment (SOFA) score of ≥ 2 points in people, MEWS/NEWS scores, ≥ 2 SIRS criteria ## SOFA score | | 0 | 1 | 2 | 3 | 4 | |:-------------|:-------------|:----------|:----------|:----------|:-------------| | Respirationa | >400 | <400 | <300 | <200 | <100 | | PaO2/FIO2 (mm Hg) | | | | | | | SaO2/FIO2 | 221-301 | 142-220 | 67-141 | <67 | | | Coagulation | >150 | <150 | <100 | <50 | <20 | | Platelets 103/mm³ | | | | | | | Liver | <1.2 | 1.2-1.9 | 2.0-5.9 | 6.0-11.9 | >12.0 | | Bilirubin (mg/dL) | | | | | | | Cardiovascular^b | No hypotension | MAP <70 | Dopamine </=5 or dobutamine (any) | Dopamine >5 or norepinephrine </=0.1 | Dopamine >15 or norepinephrine >0.1 | | Hypotension | | | | | | | CNS | 15 | 13-14 | 10-12 | 6-9 | <6 | | Glasgow Coma Score | | | | | | | Renal | <1.2 | 1.2-1.9 | 2.0-3.4 | 3.5-4.9 or <500 | >5.0 or <200 | | Creatinine (mg/dL) | | | | | | | or urine output (mL/d) | | | | | | ## Current Definition: Septic Shock - A subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality - Pressor requirement ## Sepsis ≠ Bacteremia ## Organisms of Sepsis - Gram-negative bacteria - Gram-positive bacteria - Aerobes / anaerobes - Fungi - Protozoa ## Conditions associated with Sepsis - **Thoracic** - Pyothorax - Pneumonia/pleuropneumonia - Endocarditis - Traumatic reticulopericarditis - Neoplasia - **Abdominal** - Perforated bowel (FB, ulcer) - Translocation - Hepatitis, cholangiohepatitis - Pyelonephritis - Pyometra - **Tissue injury** - Surgery, trauma, burns - **Cutaneous** - Bite wounds - Pyoderma - **Hypotension/Ischemia** - Especially GI - **Immunocompromise** - Chemo / immunosuppression - DM, Cushings - Immune system dysfunction - Failure of passive transfer ## Infection - Lipotechoic acid, peptidoglycan - bacterial DNA •exotoxins - fungal cell walls - Flagellin - LPS - PAMPS (Pathogen-associated Molecular Patterns) - DAMPS (Damage-associated Molecular Patterns) - TNF-a IFN-Y - IL-1 IL-6 IL-8 - TGF-B IL-4 - IL-10 IL-13 - Release of cytokines - Pro-inflammatory - Anti-inflammatory ## Host responses to infection - Cytokines and chemokines - Neutrophils and other inflammatory cells - enzymes, reactive oxygen species, TNF-a, IL-1 platelet activating factor - Activation of coagulation cascade ## Disrupted homeostatic mechanisms - Vasomotor tone - Inflammatory and coagulation cascades - Microvascular changes - Endothelial function - Microvascular bloodflow - > cryptic shock - Mitochondrial functions - > cytopathic hypoxia ## Vasomotor tone in sepsis - Normal tone is a balance between vasoconstriction & vasodilation - Vasodilation is hallmark of sepsis - Cytokines -> iNOS -> NO ## Inflammation and Coagulation - Anticoagulant and fibrinolytic pathways - Consumption of anticoagulant proteins - Thrombin receptor - Thrombin - Assembly of tenase and prothrombinase complex - Platelet activation - Fibrin deposition - Activated protein C - Protease-activated receptors - Activated coagulation proteases - Protein C receptor - Thrombo-modulin - Proinflammatory cytokines - Tissue factor expression - P-selectin - Thrombosis - Toll-like receptor 4 - TAFI - Fibrinolytic activators and inhibitors - u-PA/PAI-1 - U-PAR - Inflammatory cells - Inflammation - Plasminogen activation/inhibition - Factor VII - Inhibition of anticoagulant and fibrinolytic paths via decreased ΤΡΑ, ΑΤ, TFPI ## Inflammation and coagulation - End result is pro-coagulant state - Microthrombi formation - Decreased oxygen delivery to tissues - MODS and MOFS - Progression to a hypocoagulable DIC can also occur ## Microvascular changes - Loss of vascular muscle autoregulation - Microthrombosis - Leukocyte activation - Changes in RBC rheologic properties - Endothelial cell dysfunction - Disruption of endothelial glycocalyx - Changes in capillary permeability ## Cryptic shock - Decreased microcirculatory perfusion despite normal hemodynamic values - Edema from increased capillary permeability - Heterogenous microvascular blood flow - Arteriovenous shunting - Decreased functional capillary density - Increased diffusional distance to mitochondria ## Clinical Signs of Sepsis ## Signs of Early Sepsis - Red mucous membranes - Vasodilation - Increased heart rate - Response to hypoxia, vasodilation - Brisk capillary refill time - Increased cardiac output - Bounding pulses - Decreased vascular resistance, lower diastolic pressure, increased cardiac output ## Signs of Early Sepsis - Depression - Fever - Hyper- or hypoglycemia - Stress (early) - Decreased production, increased consumption ## Cats are not small dogs! - Do not manifest a hyperdynamic phase - will not have red membranes in sepsis! - Pale membranes (100%) - Bradycardia (66%) - Hypothermia (60%) - Abdominal pain (95%) ## Signs of Late Sepsis - Thready pulses - Prolonged capillary refill time - Pale/"muddy” mucous membranes - Hypothermia - Hypoglycemia - Stupor/coma - Organ failure ## Progression of sepsis to MODS/MOFS - Cardiovascular system - Respiratory - Gastrointestinal - Renal - Liver - Brain - Coagulation ## General treatment for Sepsis - Resuscitate - Fluids - Pressors/inotropes - Antimicrobial therapy - Cytology - Broad spectrum - Treat the underlying cause/ source control - Support function of organ systems ## Fluid Resuscitation and management of Hypotension - Resuscitation first - Then rehydration, losses, maintenance - Crystalloids - Synthetic Colloids - Increase oncotic pressure - Plug leaky vessels? - Plasma - Coagulation abnormalities ## Refractory Hypotension: Indications for Pharmacologic management - Hypotensive AFTER adequate volume replacement - Norepinephrine - Vasopressin - Dopamine - Dobutamine ## Antimicrobial therapy - Culture if possible - Empirical therapy - Site dependent - 4 quadrant ## Effect of delayed Abs on mortality > Kumar. Crit Care Med 2006; 34(6):1589–96 ## Source Control - Debridement or repair - After resuscitation ## Additional medical therapy - Electrolyte supplementation - Glucose infusions - Nutrition - Blood products - Antiemetics - Antacids and sucralfate - Nebulization, coupage - Pain management - Good nursing care - Bandage and catheter maintenance - Clean, dry, repositioned - Body temperature ## Monitoring - Risk of decompensation - Early recognition and treatment = better outcome? - Temperature, HR, RR, RE - Pulse rate and quality, mucous membrane color, CRT - Urine output, Urine sg. - Mentation - ECG, blood pressure - Pulse oximetry, blood gases, - Routine CBC, chemistry, coagulation profile - Glucose ## Prognosis - > 50% mortality - Septic shock - Multiple organ failures