Disclosures Sepsis: Diagnosis and Treatment Allergan research - PDF document

Disclosures Sepsis: Diagnosis and Treatment • Allergan – research grant • Genentech – research grant Henry F. Chambers, MD Scope of the problem In theory • 2-3 cases per 100 admissions there is no difference • A leading cause of death in the US between theory and practice. • Leading immediate cause of death in ICUs In practice, there is. • 1,000,000 cases annually and increasing • 20-40% mortality 1

Case 1 Case 1 • 77 y/o female, h/o prior stroke, lives in LTCF • What is the appropriate next step(s)? • Exam • Likely source(s) of infection? – T = 38.1, P=105, BP=89/60, RR=20 • Potential pathogen(s)? – HEENT: limited ROM of neck, poor dentition, PERL • What antibiotic(s) would you prescribe? – Heart: 2/6 sem, irreg rhythm – Lungs: poorly cooperative, shallow breathing – Abd: guarding, diffusely – GU: foley, cloudy urine in foley bag – Neuro: altered, nonverbal, R hemiparesis with hand contracture, L gaze preference Systemic Inflammatory Response Syndrome (SIRS) What is Sepsis? • At least two of the following –Temp > 38 o C or < 36 o C –RR > 20 per min or PaCO 2 < 32 torr –HR > 90 per min –WBC > 12,000 or < 4000 per mm 3 or 10% bands 2

SIRS ≠ Infection !!! Pop Quiz! • More general term than “ sepsis ” • Infection may or may not be present (e.g. SIRS criteria were developed to identify pancreatitis, trauma, burns, liver disease, etc) patients who have an infection. – Note: SIRS may be absent and infection still present • Described by Dr. William R. Nelson in 1983 as 1. True definition which dealt with the multiple etiologies 2. False associated with organ dysfunction and failure following circulatory shock. • Implies systemic inflammation, remote tissue injury Partial List: Non-infectious Infection ≠ SIRS Causes of SIRS • Mesenteric ischemia • Erythema multiforme • Adrenal insufficiency • Hemorrhagic shock • Autoimmune disorders • Heme malignancy • Burns (all types) • MI • Chemical aspiration • Pancreatitis • Vascilitis • Seizure • Dehydration • Sybstance abuse • Drug reaction • TEN • Pulmonary embolism • UGI bleed • Trauma • Transfusion • Surgery Seymour, et al. JAMA 315:762, 2016 3

SIRS ≠ Infection: Utility of SIRS criteria in SIRS ≠ Infection !!! the ED for Identifying Infection Sensitivity = 0.69 Specificity = 0.35 +LR = Sens/(1-Spec) = 1.06 -LR = (1- Sens)/Spec) = 0.89 + LR PCT - LR PCT Jamies, et al. Intensive Care Medicine 29: 1368, 2003 Churpeck, et al. Am J Respir Crit Care Med 192:958, 2105 Assessment of Clinical Criteria for Predicting New Sepsis Terminology Sepsis-Related In-Hospital Mortality Seymour, et al. JAMA 315:762, 2016 1991 and 2001 2015 Term Definitions Definition Clinical Criteria AUROC* (95% CI) Sepsis Suspected or Life-threatening Suspected or Setting SIRS SOFA LODS qSOFA documented organ dysfx from documented infection + SIRS dysregulated host infection + acute ICU 0.64 (0.62- 0.74 (0.73- 0.75 (0.73- 0.66 (0.64- > 2 points response to increase in 0.66) 0.76) 0.76) 0.68) infection SOFA > 2 points Non-ICU 0.76 (0.75- 0.79 (0.78- 0.81 (0.80- 0.81 (0.80- Severe sepsis Sepsis + hypotension, N/A N/A 0.77) 0.80) 0.82) 0.82) hypoperfusion, organ dysfx *Area under the Receiver Operating Characteristic Curve Septic shock Severe sepsis + Sepsis + major Sepsis + pressor SOFA = Sequential Organ Function Assessment; hypotension circulatory/metab to keep MAP > LODS = Logistic Organ Dysfunction System unresponsive to olic/cellular 65 + lactate > 2 NOTE: NONE USEFUL FOR PREDICTING INFECTION fluids abnormalities mmol/L after AS ALL ASSUMED TO BE INFECTED fluids 4

Glasgow Coma Score SOFA Scorecard Behavior Response Score Eyes Spontaneous 4 Score Opens to verbal command 3 Opens to pain 2 System 0 1 2 None 1 Resp:PaO2/FiO2 > 400 <400 <300 Verbal Oriented 5 Coag: Platelets > 150 <150 <100 Confused conversation 4 Inappropriate 3 Liver: Bilirubin <1.2 1.2-1.9 2.0-5.9 Incomprehensable 2 Cardiovascular: MAP > 70 < 70 Any pressor None 1 CNS: GCS 15 13-14 10-12 Motor Obeys commands 6 Purposeful movement to pain 5 Renal: Creatinine < 1.2 1.2 - 1.9 2.0 – 3.4 Withdraws from pain 4 Urine output > 500 >500 > 500 Decortcate posture to pain 3 Decerebrate posture to pain 2 None 1 qSOFA SOFA Calculator • Criteria (1 point for each) – Altered mental status – Respiratory rate > 22 per minute http://clincalc.com/IcuMortality/SOFA.aspx – Systolic BP < 100 mm Hg • Score > 2 associated with 3-14 fold increase in-hospital mortality for patients with suspected infection 5

qSOFA Glasgow Coma Scoring Diagnosis of Sepsis Behavior Response Score • Clinical diagnosis • Blood cultures positive in 20-30% of cases Eyes Spontaneous 4 • Focus of infection never identified in a quarter of cases Verbal Oriented 5 Motor Obeys commands 6 Altered mentation unless all of above are present Sources of Sepsis Approach to the Patients with • Urinary tract: 33% Suspected Infection • Intraabdominal: 15% • Lung: 10% • Skin, soft tissue: 10% • Unknown: 30% 6

Work-up of Infection • History – Fever, chills, sweats, localizing symptoms, ROS – Exposures, occupations, surgeries Biomarkers for Sepsis: – Medications Procalcitonin as an Example • Physical Exam: Vital signs, focused at first • Labs – CBC: WBC >12,000 or <4,000, > 10% bands – As appropriate • CXR, urinalysis/culture • electrolytes, metabolic, liver panel, lactate • LP, other imaging • Blood and other cultures before antibiotics Meta-Analysis of Procalcitonin as ROC-AUCs for Prediction of Infection a Biomarker for Sepsis Sensitivity = 0.77 LBP = lipopolysaccharide (95% CI 0.72-0.81) binding protein Specificity = 0.79 0.51-0.63 PCT = procalcitonin (95% CI 0.74-0.84) CRP = C-reactive protein IPS = Infection probability + LR PCT score - LR PCT Ratzinger, et al. PlosOne 8:e82946, 2013 Wacker, et al. Lancet Infect Dis 13:426, 2013 7

Risk Factors for Poor Outcome Mortality with Shock • Age Underlying No Shock Shock Condition • Underlying disease • APACHE II score Rapidly fatal 20 66 • Shock vs. no shock Ultimately fatal 10 50 • Appropriate vs inappropriate antibiotics Non-fatal 3 33 Effect of Antibiotics on Effect of Antibiotics on Occurrence of Shock Mortality Underlying Right Wrong Underlying Right Wrong Condition antibiotic antibiotic Condition antibiotic antibiotic Rapidly fatal 28 66 Rapidly fatal 30 77 Ultimately fatal 24 50 Ultimately fatal 25 40 Non-fatal 10 40 Non-fatal 10 30 8

Effect of Early Antibiotics on Life-Saving Power of Antibiotics in Sepsis Shock Mortality NNT to prevent Intervention OR 1 death ASA for MI 1.30 41 Low MW heparin 1.16 63 Appropriate 1.6 10 antibiotics by 48h Retamar , et al. Antimicrob Agents Chemother 54:4851, 2010 Kumar, et al. Crit Care Med 2006; 34:1589–1596 Bacteria that Can Kill Quickly Factors to Consider in Antibiotic Selection Organism Drug(s) of Choice • Community vs. Hospital Onset Meningococcus Penicillin • Healthcare associated E. coli , gram-neg rods Beta-lactam or FQ* • Immune status, comorbidities Nafcillin or vanco S. aureus • Prior antibiotics • Neutropenia Group A strep Penicillin • Site of infection Pneumococcus Penicillin or ceftriaxone Rickettsia (RMSF) Doxycycline 9

Possible Empirical Regimens for Sepsis Microbiology of Sepsis Regimen Holes • Gram-negatives – E. coli , Klebsiella sp., enterics: 65% Ceftriaxone 1-2 g qd MRSA, enterococcus, pseudomonas, ESBL/carbapenemase producers, B. fragilis , – Resistant GNR: 20% atypicals – Mixed/anaerobic: 15% Cefepime 2g q8-12h MRSA, enterococcus, some ESBL producers, carbapenemase producers, B. fragilis , • Gram-positives atypicals – S. aureus : 50-75% Carbapenem MRSA, carbapenemase producers, atypicals – Streptococci: 25% Pip/tazo 4.5 g q8h MRSA, ESBL/carbapenemase producers, atypicals • Other: Candida, viral Vanco 1-2 g q12 + Anaerobes (Gram-neg), FQ-resistant GNRs cipro 400 mg q8-12 Add ons: vanco, clindamycin, metronidazole, FQ, aminoglycoside Empirical Therapy Therapy of Sepsis • Urosepsis: FQ; 3 rd gen cephalosporin, • Support breathing carbapenem; aminoglycoside • Support blood pressure (norepi is pressor • Intra-abdominal: pip/tazo; FQ or 3 rd gen ceph + of 1 st choice if needed) and perfusion metronidazole; carbapenem (crystalloid) • SSTI*: vancomycin + 3 rd gen ceph or pip/tazo or carbapenem or FQ + clindamycin • Administer antibiotics (goal of 1-3 h) • Anticipate and manage complications • Community-acquired pneumonia: ceftriaxone + macrolide or doxy, FQ (vancomycin?) • Source control * Gram-neg and anaerobic coverage for necrotizing infections, severe sepsis 10