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Sepsis in the Rural Setting: Early Recognition and Management . Mike Broyles, BSPharm, PD, PharmD Director of Pharmacy and Laboratory Services Five Rivers Medical Center Pocahontas, AR . No Disclosures. Objectives. Outline. Severe sepsis is costly and life-threatening.
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Sepsis in the Rural Setting: Early Recognition and Management Mike Broyles, BSPharm, PD, PharmD Director of Pharmacy and Laboratory Services Five Rivers Medical Center Pocahontas, AR
Severe sepsis is costly and life-threatening • Strikes more than 750,000 people each year in the United States • Mortality remains greater than 30% (1 person every 2.5 minutes) • Mortality rate has not improved in the last 20 years • Newborn, pediatric, adults, aged • Morbidity • Surgical sepsis rate is increasing • Clinicaldiagnosisremains challenging
Determinants of mortality from sepsis • Early intervention is critical • Appropriate antibiotic therapy within one hour of hypotension • Resuscitation / re-establish perfusion within six hours
Duration of hypotension before initiation of appropriate ABX therapy is the critical determinant of survival in septic shock
SIRS Criteria: Two or more of the following • Temperature > 100.4F (38C) or < 96.8F (36C) • Heart rate > 90 beats/minute • Respiratory rate > 20 breaths/minute or PaCO2 < 32 mm Hg • WBC • >12,000/mm3 • < 4000/mm3 • > 10% immature (band) forms
Making the Diagnosis • Tachycardia – 718 possibilities • Tachypnea - 371 possibilities • Increased/Decreased Temperature – 1380 possibilities • Increased/Decreased WBC – 350 possibilities www.diagnosispro.com
Sepsis: ACCP/SCCM Definitions • Sepsisis SIRS plus a known or suspected infection. • Severe Sepsis is sepsis associated with organ dysfunction, • hypoperfusion, or hypotension. • Septic Shock is sepsis-induced hypotension despite adequate fluid resuscitation along with the presence of perfusion abnormalities. • May include • Lactic acidosis • Oliguria • An Acute alteration in mental status • Others… Bone RC, et al. Chest 1992 Jun;101(6):1644-55.
Probability of a Sepsis Diagnosis > 90% PCT2.0 40% PCT0.3 < 10% Michael Meisner; Procalcitonin-Biochemistry and Clinical Diagnosis
Procalcitonin • PCT is an immunologically active protein • PCT is induced in systemic inflammatory reactions • Bacterial infections induce PCT • PCT induction is generally in direction proportion to the bacterial insult to the body • Viral infections, autoimmune diseases, transplant rejections, and allergic reactions generally do not induce PCT • PCT is therefore an “indirect marker” of a bacterial infection: PCT a measurement of the body’s inflammatory response to the bacteria
Highly specific induction – Produced all tissue In relevant bacterial infection, PCT is produced and released into circulation from the entire body Healthy Sepsis Calcitonin: Source of production in healthy people PCT: Source of Production in Septic Patients Müller B. et al., JCEM 2001
PCT Kinetics PCT Plasma Concentration 2 6 12 24 48 72 1 Time (Hours) 17 Rapid kinetics: detectable 3 hours after infection has begun, with a peak after 12 to 24 hours Peak values up to 1000 ng/ml Half-life: ~ to 24 hours Brunkhort FM et al., Intens. Care Med (1998) 24: 888-892
PCT values correlate directly with severity of bacterial load • In critically ill patients, PCT levels elevate in correlation to the severity of bacterial infection • Integrating PCT in sepsis management can lead to improved patient outcomes
PCT as a response to bacterial challenge Elevated or rising PCT values • Systemic response to bacterial infection • Progressing infection • Immune system is overwhelmed • Risk of significant disease progression Low PCT values in presence of clinical presentation • Self-limiting infection • Non-bacterial etiology • Early phase of infection
Procalcitonin release in the absence of infection • Primary inflammation syndrome following trauma: multiple trauma, extensive burns, major surgery (abdominal and transplant) • Severe pancreatitis or severe liver damage (1) • Prolonged circulatory failure: IE severe multiple organ dysfunction syndrome (MODS) (1.4) • Medullary C-cell cancers of the thyroid, pulmonary small-cell carcinoma and bronchial carcinoma • Newborn < 48hr - increased PCT values (physiological peak)
Newborns less than 48 hours PCT measurements Chiesa et al., Council & Institute of Ped (1998) 45: 89-97
C-Reactive Protein (CRP) Acute Phase Reactant synthesized by the liver Secretion triggered by cytokine (IL-6, IL-1, TNF-α) Produced in response to acute & chronic inflammation Bacterial, Viral, Fungal Rheumatic Inflammatory diseases Malignancy Tissue Injury, Necrosis Steroid Treatment Liver Failure Obesity • Advantages: • Rises in 4 to 6 hours • Disadvantages: • Non-specific • No correlation to SOFA Scores, • Slow Kinetics (peak 36-50h) Vingishi et al., J Clin Invest. 1993 Apr ; 91(4): 1351-7 Pepys et al., J of Clin Invest. 2003g 1807 col 2 para 2, pg 1808 col 1 para 1 Standage et al., Expert Rev Anti Infect Ther. 2011 Jan 9(1): 71-79
Interleukin-6 (IL-6) • Pro-inflammatory cytokine (messenger protein) • Blood, monocytes, and endothelial cells • Advantage • Quick rise – one hour • Decreases rapidly • Disadvantage • Any inflammatory process can increase IL-6 • Affected in immune-compromised patients • Sample must be cooled and spun immediately • Containers must be free of endotoxins since IL-6 can be formed by decomposed leukocytes in the blood sample Vingishi et al., J Clin Invest. 1993 Apr ; 91(4): 1351-7 Pepys et al., J of Clin Invest. 2003g 1807 col 2 para 2, pg 1808 col 1 para 1 Standage et al., Expert Rev Anti Infect Ther. 2011 Jan 9(1): 71-79
Lactate • Lactate (lactic acid) is produced due to inadequate tissue perfusion – a defining parameter of late sepsis. • Advantage • Rapid turn-around • Readily available • Reliable marker of perfusion and prognosis • Disadvantage • Late elevation in course of sepsis • Non-specific Reduction of lactate is advocated as a target for therapeutic interventions (2C) BlomkalnsAL www.emcreg.org 2007 PoezeM, et al. Crit Care Med 2005 Nov;33(11):2494-500 Muller B, et al. Crit Care Med 2000 Apr;28(4):977-83
Diagnostic accuracy of PCT compared to other biomarkers used in sepsis
Case Presentations Application of PCT use for Sepsis and Antibiotic Management
HW ED Treatment Plan: Dx of Sepsis due to UTI • Admit to ICU • Meropenem • Tobramycin • Cystalloids and dopamine
HW • Hospitalist orders PCT in ICU after admission • PCT 0.25 ng/ml • Fluid bolus and continued rehydration • DC dopamine • DC merpenem • DC tobramycin • Start piperacillin/tazobactam • Moved to Med-Surg • Cx: Proteus mirabilis sensitive to 1st generation cephalosporins and resistant to quinolones (day2) • Changed to cephalexin