Presentation on theme: "Rogers Kyle, MD Medical University of South Carolina 5/21/13"— Presentation transcript:
1Rogers Kyle, MD Medical University of South Carolina 5/21/13 SepsisRogers Kyle, MDMedical University of South Carolina5/21/13
2Objectives Examine the epidemiology of sepsis in the US. Review the definitions of SIRS, sepsis, severe sepsis, septic shock.Understand the elements of early goal directed therapy in the non-ICU setting.Review the Surviving Sepsis Campaign Bundles
3Key MessagesEpidemiologic studies suggest that the incidence of sepsis is increasing as well as the co-morbidities of patients admitted to the ICU with sepsis.The mortality from sepsis is declining, suggesting improvements in recognition and care.Rapid recognition of sepsis is essential in its treatment.Early goal directed therapy - including rapid fluid resuscitation, measurement of tissue perfusion, cultures and diagnostic studies, and broad spectrum antibiotic coverage - is imperative.
4Epidemiology of Sepsis Steady increase in frequencyNEJM 031970’s ~ 164,000 cases/yearNow > 1.6 millionEstimated cost > $50,000/pt>$17 billion/yearMortality remains 20-50%Second leading cause of death among patients in non-coronary ICU’s.10th leading overall
5Epidemiology of Sepsis Consensus definitionCombination of pathologic infection and systemic inflammatory response syndromePatients with acute organ dysfunction are considered to have severe sepsisHowever, there remains a fair amount of contention over the use of these definitions
8Epidemiology of Sepsis Increasing comorbiditiesSignificant disparities among races and between men and womenMen more likely to have sepsis although there are more women in the U.S.Men are more likely to be enrolled in trialsAlmost double risk for sepsis in non-white, especially black men (youngest and highest mortality)
11Epidemiology of Sepsis Increasing comorbiditiesSignificant disparities among races and between men and womenMen more likely to have sepsis although there are more women in the U.S.Men are more likely to be enrolled in trialsAlmost double risk for sepsis in non-white, especially black men (youngest and highest mortality)Increasing incidence
13Epidemiology of Sepsis Increasing comorbiditiesSignificant disparities among races and between men and womenMen more likely to have sepsis although there are more women in the U.S.Men are more likely to be enrolled in trialsAlmost double risk for sepsis in non-white, especially black men (youngest and highest mortality)Increasing incidenceDecreasing mortality
15Epidemiology of Sepsis Decline in mortalityIncreased fungal infectionsIncrease in organ failureIncreased ageIncreased severity of illnessIncreased discharge to subacute facilitiesAll of which point to continued growth in the need for care of this population
16Epidemiology of Sepsis What else has increased?Invasive proceduresImmunosuppressive drugsChemotherapyTransplantationHIVMicrobial resistanceCoding
17Epidemiology of Sepsis Predicted that the rate of sepsis will continue to increase at 1.5% per year due to aging of the population
18Surviving Sepsis Campaign: 2012 Crit Care Med 2013; 41:580–637
19Surviving Sepsis Campaign: 2012 Update from 200868 international experts representing 30 international organizationsLiterature reviewedUse GRADE (Grading of Recommendations Assessment, Development and Evaluation)Quality of evidence: A-DStrength 1 (strong) or 2 (weak)UG (ungraded)
23Definitions Definitions Systemic Inflammatory Response Syndrome, sepsis, severe sepsis, septic shock from 1992 (ACCP, SCCM)Continuum of severity from SIRS to septic shock and multiple organ dysfunction syndrome (MODS)
24DefinitionsDiagnostic criteria for sepsis, severe sepsis
27Therapeutic Priorities Early supportive care to correct physiologic abnormalitiesHypoxemia, hypotensionDistinguish SIRS from sepsisMost of the guidelines are directed towards severe sepsis or septic shockStabilize respirationO2 to intubationAssess perfusionSBP < 90, MAP < 70, drop in BP > 40Note difference in threshold vs. definition
28Therapeutic Priorities May need arterial lineTissue hypoperfusion can occur in the absence of hypotensionCool, mottled extremities, lactate > 1 (> 4 is consistent with severe sepsis)CVC should be inserted with severe sepsis or septic shock (not pulm art catheter)CVP, ScvO2
29Early Goal Directed Therapy Early resuscitation prevents or limits multiple organ dysfunction and reduces mortalityGoals for fluid resuscitation in the first 6 hoursProtocolized, quantitative resuscitation of patients with sepsis- induced tissue hypoperfusion (defined in this document as hypotension persisting after initial fluid challenge or blood lactate concentration ≥ 4 mmol/L). Goals during the first 6 hrs of resuscitation:a) Central venous pressure 8–12 mm Hgb) Mean arterial pressure (MAP) ≥ 65 mm Hgc) Urine output ≥ 0.5 mL/kg/hrd) Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectivelyIn patients with elevated lactate levels targeting resuscitation to normalize lactate
30Early Goal Directed Therapy ScvO2Same CVP, MAP, urine output. Lower mortality in group targeting ScvO2 > 70 (31 vs. 47%) (NEJM 01)LactateLactate clearance may be a substitute for ScvO2 (JAMA 10)
31Early Goal Directed Therapy Restoring perfusionFluids – crystalloid vs. albumin (no HES)Crystalloid…at least initially30 ml/kg minimum earlyAs long as there is hemodynamic improvement (change in pulse pressure, stroke volume, HR, sys BP)Dobutamine up to 20mcg/kg/min if adequate volume resuscitation with persistent low BP
32Early Goal Directed Therapy Fluid ResuscitationCrystalloids as the initial fluid of choice in the resuscitation of severe sepsis and septic shock.Against the use of hydroxyethyl starches for fluid resuscitation of severe sepsis and septic shock.Albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids.Initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (a portion of this may be albumin equivalent). More rapid administration and greater amounts of fluid may be needed in some patients.Fluid challenge technique be applied wherein fluid administration is continued as long as there is hemodynamic improvement either based on dynamic (eg, change in pulse pressure, stroke volume variation) or static (eg, arterial pressure, heart rate) variables.
33Early Goal Directed Therapy Diagnosing InfectionCultures as clinically appropriate before antimicrobial therapy if no significant delay (> 45 mins) in the start of antimicrobial(s). At least 2 sets of blood cultures (both aerobic and anaerobic bottles) be obtained before antimicrobial therapy with at least 1 drawn percutaneously and 1 drawn through each vascular access device, unless the device was recently (<48 hrs) inserted.Use of the 1,3 beta-D-glucan assay, mannan and anti-mannan antibody assays, if available and invasive candidiasis is in differential diagnosis of cause of infection.Imaging studies performed promptly to confirm a potential source of infection.
34Early Goal Directed Therapy AntibioticsAdministration of effective intravenous antimicrobials within the first hour of recognition of septic shock and severe sepsis without septic shock as the goal of therapy.Initial empiric anti-infective therapy of one or more drugs that have activity against all likely pathogens (bacterial and/or fungal or viral) and that penetrate in adequate concentrations into tissues presumed to be the source of sepsis.Antimicrobial regimen should be reassessed daily for potential deescalation.Use of low procalcitonin levels or similar biomarkers to assist the clinician in the discontinuation of empiric antibiotics in patients who initially appeared septic, but have no subsequent evidence of infection .Combination empirical therapy for neutropenic patients with severe sepsis and for patients with difficult-to-treat, multidrug resistant bacterial pathogens such as Acinetobacter and Pseudomonas. For patients with severe infections associated with respiratory failure and septic shock, combination therapy with an extended spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone is for P. aeruginosa bacteremia . A combination of beta-lactam and macrolide for patients with septic shock from bacteremic Streptococcus pneumoniae infections.Empiric combination therapy should not be administered for more than 3–5 days. De-escalation to the most appropriate single therapy should be performed as soon as the susceptibility profile is known.Duration of therapy typically 7–10 days; longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection, bacteremia with S. aureus; some fungal and viral infections or immunologic deficiencies, including neutropenia.Antiviral therapy initiated as early as possible in patients with severe sepsis or septic shock of viral origin.Antimicrobial agents should not be used in patients with severe inflammatory states determined to be of noninfectious cause.
35Early Goal Directed Therapy Early is important - Larger meta-analysis of trials with therapy initiated more than 24 hrs after onset of sepsis did not show the same mortality benefit.
36Vasopressor TherapyRecommended when required to sustain life and maintain perfusion in the face of life-threatening hypotension, even when hypovolemia has not yet been resolvedMAP > 65Norepinephrine firstEpinephrine addedVasopressin 0.03 U/min may be substituted for epi, not to be used aloneDopamine instead of norepi only in selected patientsPhenylephrine only if arrhythmias with norepi, high CO with low BP, salvage
37Many additional recommendations in the Surviving Sepsis Campaign Mostly in the ICU settingSteroidsHgb targetARDSNeuromuscular blockadeGlycemic controlDVT prophylaxisNutritionGoals of care
39References1. Dellinger et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: Crit Care Med 2013; 41:2. Rivers et al. Early Goal Directed Therapy in the Treatment of Severe Sepsis and Septic Shock. N Engl J Med 2001;345:3. Martin et al. The Epidemiology of Sepsis in the United States from 1979 through N Engl J Med 2003;348:4. Annane et al. Septic Shock. Lancet 2005; 365: 63–78.5. Jones et al. The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: A meta-analysis. Crit Care Med 2008; 36:2734–2739.6. Jones et al. Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy. JAMA 2010;303(8):