Sepsis PDF

SHOCK STATES PERFUSION Delivery of oxygenated blood BP= CO x SVR CO: cardiac output SVR: systemic vascular resistance Target MAP = 65 mmHg Cvphysiology.com SHOCK 100% SvO2=75% 25% Aneskey.com Shock- cellular hypoxia due to imbalance of oxygen delivery (DO2) vs. oxygen consumption (VO2) Cellular hypo...

SHOCK STATES PERFUSION Delivery of oxygenated blood BP= CO x SVR CO: cardiac output SVR: systemic vascular resistance Target MAP = 65 mmHg Cvphysiology.com SHOCK 100% SvO2=75% 25% Aneskey.com Shock- cellular hypoxia due to imbalance of oxygen delivery (DO2) vs. oxygen consumption (VO2) Cellular hypoxia and tissue ischemia Left untreated, can result in organ dysfunction/death TYPES OF SHOCK -------------------------------------------------------------------Hypovolemic Distributive Cardiogenic Obstructive HYPOVOLEMIC Primary issue: Decreased volume status Treatment: Fluid resuscitation +/- vasopressors Examples: Hemorrhagic Severe burns Dehydration DISTRIBUTIVE Primary issue: Treatment: Examples: Loss of blood flow regulation Vasopressors +/- fluid resuscitation +/- inotropes Sepsis Anaphylaxis Neurogenic CARDIOGENIC Primary issue: decreased cardiac output Treatment: treat underlying issue +/-inotropes Examples: Acute coronary syndrome Pulmonary hypertension Heart failure OBSTRUCTIVE Primary issue: decreased venous return and/or cardiac output Treatment: Treat the underlying issue Examples: Pulmonary embolism Cardiac tamponade SUMMARY Shock Type Subtypes Hemodynamic Changes Hypovolemic Hemorrhagic, volume depletion/dehydration ↓CO ↑SVR Distributive Sepsis, anaphylactic ↓SVR Variable CO change ↑ HR Cardiogenic LV heart failure, MI ↓CO ↑SVR Obstructive Pulmonary embolism, cardiac tamponade ↓CO ↑SVR VASOPRESSORS VASOPRESSORS Vasopressor Vasoconstriction Catecholamines Inotropes Increases force of contraction of heart Increases cardiac output RECEPTOR OVERVIEW Receptor Location Effect α1 Arteries, arterioles, veins Constriction α2 Presynaptic sympathetic fibers, platelets, smooth muscle Constriction β1 Heart ↑HR, ↑force of contraction β2 Skeletal muscle blood vessels, coronary arteries, bronchial smooth muscle Dilation, relaxation Vasopressin Vascular smooth muscle, renal collecting duct ↑SVR Dopamine Vascular smooth muscle in coronary arterioles, mesentery, renal proximal tubular cells Dilation PHENYLEPHRINE Pure alpha 1 activity Potent arterial vasoconstrictor Effects: ↑BP, ↑MAP, ↑SVR, vasoconstriction Can cause reflex bradycardia NOREPINEPHRINE Main neurotransmitter in sympathetic nervous system Αlpha-1,Beta-1 agonist Effects: ↑MAP, ↑CO, ↑SVR, vasoconstriction Little effect on cardiac output/inotropic support EPINEPHRINE Synthesized from norepinephrine, neurotransmitter of sympathetic nervous system Dose dependent effects Low dose (0.01-0.05 mcg/kg/min) Beta-1 effects Increased CO, increased BP Beta-2 effects Vasodilation Bronchodilation Higher dose (0.05-3 mcg/kg/min) Alpha effects Vasoconstriction Effects: ↑MAP, ↑SVR, ↑HR, ↑CO Drug of choice for anaphylactic shock VASOPRESSIN Hormone released from pituitary Possibly catecholamine sparing No inotropic/chronotropic activity Vasopressin receptors V1a Vascular smooth muscle, adrenal gland V2 Renal collecting duct Increased water permeability Effect: ↑BP ,↑SVR DOBUTAMINE Primarily a selective beta-1 agonist Mild beta-2 and alpha-1 activity Effect: ↑BP ,↑HR, ↓SVR Beneficial in cardiogenic shock DOPAMINE Precursor of norepinephrine and epinephrine Dose dependent effects Low dose (1-3 mcg/kg/min) Dopamine receptors Dilation of arteries in kidney, abdomen, heart, brain Increased urine output Doses (3-10 mcg/kg/min) Beta-1, some alpha-1 Increased renal blood flow, HR, contractility Doses (>10 mcg/kg/min) Alpha-1, beta-1, some beta-2 Tachycardia, dysrhythmias ANGIOTENSIN II & ISOPROTERENOL Angiotensin II AT-1 and AT-2 receptors ↑SVR Isoproterenol Isopropylamine analog of epinephrine Used in bradyarrhythmias (also torsades) and brugada syndrome VASOPRESSOR OVERVIEW Drug Alpha-1 Alpha-2 Beta-1 Beta-2 Vasopressin Dopamine Angiotensin Norepinephrine +++ ++ ++ + - - - Epinephrine 0.01-0.05 mcg >0.05 mcg + +++ + ++ +++ ++ - - - Phenylephrine +++ - - - - - - - - - - + - - - - +++ +++ - Vasopressin Dopamine Low dose Medium High +++ +++ Angiotensin-II - - - - - - +++ Dobutamine + - +++ +/- - - - Sepsis Definitions Sepsis Definitions Sepsis-3 (2016) Life threatening organ dysfunction caused by dysregulated host response to an infection Septic Shock subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality septic patients who require vasopressors to maintain MAP > 65 and serum lactate level ≥ 2 mmol/L despite adequate volume resuscitation Systemic Inflammatory Response Syndrome (SIRS) 2 or more criteria plus clinical evidence of infection HR >90 RR >20 WBC < 4K or > 12K T < 36C or > 38C Singer M, et al. JAMA. 2016;315(8):801-810. Identifying a Septic Patient u SOFA u Organ dysfunction defined as SOFA ≥2 as a result of infection Identifying a Septic Patient u SOFA u Organ dysfunction defined as SOFA ≥2 as a result of infection Antimicrobials in Sepsis Pathophysiology Local immune response triggered by an infection or tissue injury Common pathogens in sepsis Gram positive bacteria Staphylococcus, streptococcus, enterococcus Gram negative bacteria E. coli, enterobacter, klebsiella, proteus, pseudomonas Antimicrobial Timing Broad spectrum Within 1 hour presentation Adequate coverage Obtain blood cultures PRIOR to administering abx Ferrer R et al. Crit Care Med. 2014; 42(8): 1749-55 Kumar et al. Crit Care Med.2006; 34(6): 1589-96 Antimicrobial Selection Consider source of infection Be aware of drug allergies! Broad spectrum beta-lactams Cefepime Piperacillin-Tazobactam Carbapenems Plus gram-positive coverage Vancomycin Linezolid Daptomycin cdc.org SEPSIS: Overall Approach Septic Patient Life-threatening organ dysfunction caused by a dysregulated host response to infection Risk factors Advanced age History of multi-drug resistant organism infection Immunocompromised Malnutrition SOFA, SIRS, qSOFA Fluid Management Vasopressors Antibiotics Corticosteroids Fluid Management 30 ml/kg IV crystalloid fluid within the first 3 hours Target goal: MAP > 65 mmHg Complications: heart failure, kidney failure Types of fluids 0.9% Sodium Chloride Lactated Ringers Albumin Hetastarch Fluid responsiveness Dynamic vs. static Vasopressors First line à Norepinephrine Second line Vasopressin Epinephrine Other options Phenylephrine, dopamine, dobutamine Administration preferably through central line due to extravasation Antibiotics Administer within 1 hour of presentation Obtain blood cultures PRIOR to administration Start with broad coverage, then de-escalate as appropriate Consider source of infection and most common pathogens Broad-spectrum Beta-lactams Cefepime Piperacillin/Tazobactam Carbapenems Resistant gram-positive infections Vancomycin Linezolid daptomycin Atypical coverage Macrolides Doxycycline Corticosteroid Use Hemodynamic effects Modulate vascular tone Inhibit vasodilating substances Up-regulation of adrenoreceptors Immunomodulation/Anti-inflammatory Risks Hyperglycemia Immunosuppression GI bleeding Annane et al (JAMA 2002) found that stress-dose steroids plus fludrocortisone may improve mortality and decrease vasopressor use CORTICUS (NEJM 2008) showed faster shock resolution but no mortality benefit Corticosteroid Use IV hydrocortisone for adult septic shock patients with hypotension, not responsive to fluids/vasopressors Taper steroids once vasopressors no longer required Max dose of 200mg daily Evans et al. Crit Care Med. 2021