Sepsis new definitions of sepsis and septic shock and Novelities in sepsis treatment

Transcription

1 Sepsis new definitions of sepsis and septic shock and Novelities in sepsis treatment

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3 What is sepsis? Life-threatening organ dysfunction caused by a dysregulated host response to infection

4 A 1991 consensus conference developed initial definitions that focused on the then-prevailing view that sepsis resulted from a host s systemic inflammatory response syndrome (SIRS) to infection. A 2001 task force, recognizing limitations with these definitions, expanded the list of diagnostic criteria but did not offer alternatives because of the lack of supporting evidence. In effect, the definitions of sepsis, septic shock, and organ dysfunction have remained largely unchanged for more than 2 decades.

5 Terminology Systemic Inflammatory Response Syndrome (SIRS) Temp > 38 or < 36 HR > 90 RR > 20 or PaCO2 < 32 WBC > 12 or < 4 or Bands > 10% Sepsis The systemic inflammatory response to infection. TWO out of four criteria acute change from baseline Severe Sepsis Organ dysfunction secondary to Sepsis. e.g. hypoperfusion, hypotension, acute lung injury, encephalopathy, acute kidney injury, coagulopathy. Septic Shock Hypotension secondary to Sepsis that is resistant to adequate fluid administration and associated with hypoperfusion. Bone, R., Balk, R., Cerra, F., Dellinger, R., Fein, A., Knaus, W., Schein, R., et al. (1992). Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest, 101(6),

6 Relationship Between Sepsis and SIRS BACTEREMIA TRAUMA INFECTION SEPSIS SEPSIS SIRS BURNS PANCREATITIS

7 IDENTIFYING ACUTE ORGAN DYSFUNCTION AS A MARKER OF SEVERE SEPSIS Altered Consciousness Confusion Psychosis Tachycardia Hypotension CVP Tachypnea PaO 2 < 70 mm Hg SaO 2 < 90% Oliguria Anuria Creatinine Jaundice Enzymes Albumin PT Platelets PT/APTT Protein C D-dimer

8 Sepsis The result of the body s over-response to infection Pathogen Infection Host response ++ Inflammation Coagulation / fibrinolysis Loss of homeostasis Other factors Endothelial dysfunction Organ dysfunction Death

9 Inflammatory response to infection Pathogen Infection Monocyte/ macrophage Anti-inflammatory mediators IL-4, IL-10, IL-11, IL-13, IL-1r Pro-inflammatory cytokines Tumor necrosis factor, IL-1, IL-6, IL-8 Neutrophil activation, aggregation, degranulation; release of oxygen free radicals and proteases Platelet activation aggregation T-cell IL-2, Interferon-, GM-CSF Endothelial damage

10 Therefore: classical features of sepsis (classical means advanced stages) Systemic inflammatory response Reduced systemic vascular resistance / vasodilatation Increased capillary permeability Coagulopathy and microvascular thrombosis Metabolic (lactic) acidosis Organ dysfunction

11 % Prevalence and hospital mortality associated with severe sepsis 70 Proportion (%) of admissions to ICU with severe sepsis in the first 24 hours Hospital mortality (%) Age group (years)

12 % The prognostic effect of organ dysfunction in severe sepsis 100 Proportion (%) of admissions to ICU with severe sepsis in the first 24 hours in ICU with (N) organ dysfunctions Hospital mortality (%) Number of organ dysfunctions

13 Pathogens involved in severe sepsis Gram negative Gram positive 45% 20% 3% 10% 3% 19% Fungal infection Mixed bacterial Other mixed Unconfirmed Only 60% of severe sepsis/septic shock cases are associated with confirmed infection Disease progression is similar regardless of causative organism

14 SIRS is dead long live qsofa! Respiratory rate > 22/minute Altered mentation Systolic blood pressure <100 mmhg Outside ICU this predicts those with a higher mortality qsofa, quick SOFA; SOFA: Sequential [Sepsis-related] Organ Failure Assessment.

15 Date of download: 5/9/2016 Copyright 2016 American Medical Association. All rights reserved.

16 Date of download: 5/9/2016 Copyright 2016 American Medical Association. All rights reserved.

17 Sepsis Six within the first hour 1. Oxygen to achieve target sats 2. IV access and blood cultures 3. ABG/VBG to measure lactate 4. Fluid challenges to treat high lactate or low BP 5. IV antibiotics within 1 hour 6. Monitor urine output (catheter/fluid balance)

18 Early antibiotics matter or do they?

19 Crit Care Med 2013;41: Guideline recommendations Administration of effective IV antimicrobials within the 1 st hour of recognition of septic shock (grade 1B) and severe sepsis without septic shock (grade 1C) Initial empiric anti-infective therapy of one or more drugs that have activity against all likely pathogens and that penetrate in adequate concentrations into tissues presumed to be the source of sepsis (grade 1B)

20 Crit Care Clin 2011;27:53-76 Early, appropriate antibiotics Early = within 1 hour after recognition of potential septic shock Appropriate = in vitro activity against pathogen Route of administration Dose and frequency Penetration Cidality

21 Fraction of total patients Effect of timing on survival Time from hypotension onset (hours) Adapted with permission from:

22 Risk Factors MDR/Health-care associated pathogens broad spectrum antibiotics within 90 d hospitalization >5 d local high antibiotic resistance rates residence in LTCF chronic dialysis within 30 d home wound care family member with MDR infection mechanical ventilation 5 d immunosuppression structural lung disease IV drug use COPD (Pseudomonas spp.) Influenza infection (MRSA) Clin Infect Dis 2007;44:S27-72 Am J Respir Crit Care Med 2005;171: Fungemia broad-spectrum antibiotics central venous catheter parenteral nutrition renal replacement therapy in ICU neutropenia hematologic malignancy implantable prosthetic devices immunosuppression chemotherapy Clin Infect Dis 2009;49:1-45 Clin Infect Dis 2009;48:503-35

23 Crit Care Med 2013;41: Guideline recommendations Combination empirical therapy for the following patients (grade 2B): Neutropenic with severe sepsis and for patients with difficult-to-treat, multidrugresistant bacterial pathogens (Acinetobacter or Pseudomonas bacteremia) Severe infections associated with respiratory failure and septic shock (Pseudomonas bacteremia) Septic shock from bacteremic Streptococcus pneumoniae

24 Antibiotic review: Sepsis from pulmonary source Infection Example antibiotic regimens CAP β-lactam 1 + azithromycin β-lactam 1 + respiratory FQ 2 HCAP antipseudomonal β-lactam 3 + aminoglycoside 4 or antipseudomonal FQ 5 + vancomycin or linezolid 1 ceftriaxone, cefotaxime, ampicillin/sulbactam 2 levofloxacin, moxifloxacin 3 piperacillin/tazobactam, cefepime, meropenem, imipenem, doripenem 4 gentamicin, tobramycin, amikacin 5 levofloxacin, ciprofloxacin Clin Infect Dis 2007;44:S27-72

25 Clin Infect Dis 2009;49:1-45 Antibiotic review: Sepsis from catheterrelated bloodstream infection (CRBSI) Infection Example antibiotic regimens CRBSI vancomycin or daptomycin 1 + antipseudomonal β-lactam 2,3 +/- aminoglycoside 4 Fungemia risk factors + fluconazole or echinocandin 5 1 if high rates of vancomycin MIC 2 µg/ml 2 piperacillin/tazobactam, cefepime 3 meropenem, imipenem, doripenem 4 gentamicin, tobramycin, amikacin 5 caspofungin, micafungin, anidulafungin

26 Int J Urol 2013; Epub ahead of print. Antibiotic review: Sepsis from urinary source Infection Example antibiotic regimens Urosepsis 3 rd generation cephalosporin 1 +/- aminoglycoside 2 or FQ 3 Urological interventions or MDR risk factors 1 ceftriaxone, cefotaxime 2 gentamicin, tobramycin, amikacin 3 levofloxacin, ciprofloxacin 4 piperacillin/tazobactam, cefepime 5 meropenem, imipenem, doripenem antipseudomonal β-lactam 4,5

27 Clin Infect Dis 2009;48: Infection Antibiotic review: Sepsis from unknown source Example antibiotic regimens Unknown antipseudomonal β-lactam 1,2 + aminoglycoside or antipseudomonal FQ 3 + vancomycin Fungemia risk factors + fluconazole or echinocandin 4 1 piperacillin/tazobactam, cefepime 2 meropenem, imipenem, doripenem 3 levofloxacin, ciprofloxacin 4 caspofungin, micafungin, anidulafungin

28 Evolution of Sepsis care Established Core Rx: Source Control Antibiotics Resuscitation Supportive Care Steroids Established Core Rx: Source Control More Antibiotics Faster Resuscitation Better Supportive Care In general the process of care has improved No Steroids Endotoxin Antagonists LPS/LPS receptor antagonist anti-tnf NSAIDs Nitric Oxide Synthase Inhibitors Tissue Factor Pathway Inhibitors anti-tlr4 Xigris Tight Immunonutrition Glycemic Steroids Control Loose Immunonutrition??Not Glycemic Steroids Xigris Control?

29 Recommendations Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%.

30 Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/l (>18 mg/dl) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%.

31 In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quicksofa (qsofa): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less.