Revised Sepsis Guidelines and the Impact on Practice

Objectives Consider the impact of sepsis, emphasizing the importance of early recognition & treatment Review the current sepsis definitions and discuss the proposed changes Examine key elements of the Surviving Sepsis Guidelines

Cleveland Clinic—Fairview Hospital Cleveland, Ohio

Disclosures I have no financial disclosures http://www.sepsisalliance.org/

https://www.polleverywhere.com/multiple_choice_polls/B8GfqgeYfmJIDxH

Sepsis Sepein Septikos Septicus Greek, to rot Greek, characterized by putrefaction Septicus Latin, of or pertaining to putrefaction

http://www. montereybayaquarium http://www.montereybayaquarium.org/animal-guide/octopuses-and-kin/common-cuttlefish

https://www.polleverywhere.com/multiple_choice_polls/7T7BFADPxTNyJik

What percentage of the general public has even heard of sepsis? 19% 31% 43% 55% 67% However, most people could not place the correct context Poll Everywhere Correct answer is D. 55%

Sepsis “Septicemia is a state of microbial invasion from a portal of entry into the bloodstream which causes signs of illness.“ Schottmueller, 1914

Sepsis Admissions for sepsis in 2000 621,000 Mortality rate of 28-50% http://www.cdc.gov/sepsis/basic/qa.html

Sepsis Contributed to 1 in every 2 to 3 hospital deaths, and most of these patients were admitted with sepsis JAMA July 2, 2014 Volume 312, Number 1, Page 90 The most expensive hospital condition, costing over $24 billion per year Statistical Brief #204, May, 2016 Healthcare Cost and Utilization Project

Sepsis 40% of total ICU expenditure Davies, et al. 14th Annual Congress of the European Society of Intensive Care Medicine 2001 The number of sepsis patients is projected to increase by 1.5% per year Angus, et al. Crit Care Med 2001

Hospital Readmissions Patients who survived sepsis to be discharged from the hospital More than 40% were readmitted within 90 days Half of these readmissions were deemed possibly preventable JAMA March 10, 2015 Volume 313, Number 10

Hospital Readmissions Patients who survived sepsis to be discharged from the hospital The majority of unplanned hospital readmissions after sepsis are due to an infection and identified that many rehospitalized survivors present through the ED with recurrent sepsis Crit Care Med March 2016 • Volume 44 • Number 3 Sepsis is a leading contributor to excess healthcare costs due to hospital readmissions Crit Care Med October 2015 • Volume 43 • Number 10

Hospital Readmissions Index admission for heart failure Pneumonia & sepsis are frequent reasons for readmission Index admission for acute myocardial infarction Pneumonia & sepsis Index admission for pneumonia Recurrent pneumonia, sepsis, C. diff infection JAMA January 23/30, 2013—Vol 309, No. 4

Mortality MI ~610,000 deaths/year All cancers combined ~600,000 Sepsis ~300,000 Stroke ~140,000 COPD ~135,000 Alzheimer’s ~85,000 Motor vehicle crashes ~35,000 Prescription drug overdose ~35,000 Firearm deaths ~35,000

https://www.polleverywhere.com/multiple_choice_polls/4GAW9tIwPr1xn5c

How many deaths could be prevented each year if optimal care is provided to every septic patient? A. 22,000 B. 37,000 C. 62,000 D. 77,000 E. 92,000 Crit Care Med 2007;35(5):1257 Poll Everywhere Correct answer: E

Definitions Systemic inflammatory response syndrome (SIRS) Two or more of the following variables: Temperature greater than 38°C or less than 36°C Heart rate greater than 90 beats per minute Respiratory rate greater than 20 breaths per minute or a PaCO2 level of less than 32 mm Hg Abnormal white blood cell count (>12,000/mL or <4,000/mL or >10% bands)

Definitions Sepsis Severe sepsis ICD-10-CM A41.9 SIRS + infection Severe sepsis ICD-10-CM A41.9 SIRS + infection + new organ dysfunction Septic shock ICD-10-CM R65.21 Impaired perfusion despite adequate fluid resuscitation

Organ Dysfunction Increased thrombosis & decreased fibrinolysis Microvascular thrombosis Decreased microvascular flow Ischemia

Organ Dysfunction Capillary leak Increased interstitial fluid Hypovolemia Edema Decreased cardiac output Acute lung injury Hypovolemic shock Decreased cardiac compliance

Increase in nitric oxide production Organ Dysfunction Increase in nitric oxide production Vasodilation Hypotension Distributive shock Oxidative injury Direct cellular damage Impaired mitochondrial function

Organ Dysfunction Damaged cell membranes Impaired cardiac output Hypovolemic Distributive Cardiogenic Blockage of microvascular flow Disordered oxygen metabolism

Organ Dysfunction Altered mental status Acute kidney injury Acute lung injury Decreased cardiac output Insulin resistance Acid-base derangement Thrombocytopenia Ileus Coagulopathy Adrenal insufficiency

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Sepsis can be diagnosed by: Positive blood cultures Elevated C-reactive protein Elevated lactic acid Elevated procalcitonin All of the above None of the above Poll Everywhere Correct answer is F. None of the above

Surviving Sepsis Surviving Sepsis Campaign (2002) Society of Critical Care Medicine European Society of Intensive Care Medicine International Sepsis Forum Surviving Sepsis Guidelines http://www.survivingsepsis.org/

Surviving Sepsis Routine screening of at-risk patients Obtain appropriate cultures & imaging The administration of effective intravenous antimicrobials within the first hour of recognition Source Control Initial Resuscitation

Lactate “Measuring lactate levels can risk stratify patients with suspected sepsis, to prompt aggressive early treatment, and help monitor the impact of therapy” Chee C et al. Crit Care Med 2015

Lactate “The prognostic value of lactate levels exceeds that of blood pressure.” “Many studies have confirmed the association between initial serum lactate level and mortality independently of clinical signs of organ dysfunction” Cecconi M, et al. Intensive Care Med 2014;40:1795 “In this multicenter, open-label randomized controlled study, lactate monitoring during the first 8 hours of ICU admission, aimed at reducing lactate levels by at least 20% per 2 hours, significantly reduced ICU length of stay and also ICU and hospital mortality” Jansen TC, et al. Am J Respir Crit Care Med 2010;182:752

Initial Resuscitation “We recommend the protocolized, quantitative resuscitation of patients with sepsis-induced tissue hypoperfusion” Surviving Sepsis Guidelines

Initial Resuscitation “We suggest targeting resuscitation to normalize lactate in patients with elevated lactate levels as a marker of tissue hypoperfusion” Surviving Sepsis Guidelines

Surviving Sepsis TIME SENSITIVE! Identify patients early in their course Administer antibiotics promptly Fluid resuscitation—fast & furious

https://www.polleverywhere.com/multiple_choice_polls/hOtgZQS7kQpqdVh

The minimum volume of the initial fluid resuscitation for the septic patient is: 250 ml 500 ml 1000 ml 10 ml/kg 30 ml/kg Poll Everywhere Correct answer is E

Surviving Sepsis Measure lactate level Draw blood cultures 3-hour bundle 6-hour bundle Measure lactate level Draw blood cultures Administer broad spectrum antibiotics Administer 30 ml/kg crystalloid fluid bolus If persistent hypotension after initial fluid resuscitation, then: Add vasopressors Measure CVP, SvO2 Remeasure lactate

Surviving Sepsis Compliance with the Surviving Sepsis Campaign bundles is associated with improved mortality Levy MM, et al. Crit Care Med 2015;43:3 Levy MM et al. Intensive Care Med 2010;36:222

National Inpatient Quality Measures Within 3 hours of identification of severe sepsis: Initial lactate level measurement Broad spectrum or other antibiotics administered Blood cultures drawn prior to antibiotics Within 6 hours: Repeat lactate measurement if initially elevated

National Inpatient Quality Measures Within 3 hours of identification of septic shock: Initial lactate level measurement Broad spectrum or other antibiotics administered Blood cultures drawn prior to antibiotics Within 6 hours: Repeat lactate measurement if initially elevated Resuscitation with 30 ml/kg crystalloid fluids Vasopressors if hypotension persists after fluid administration

National Inpatient Quality Measures Reassessment to include OR A focused exam including: Vital signs, AND Cardiopulmonary exam, AND Capillary refill evaluation, AND Peripheral pulse evaluation, AND Skin examination Any 2 of the following: Central venous pressure measurement Central venous oxygen measurement Bedside Cardiovascular Ultrasound Passive Leg Raise or Fluid Challenge

Challenges Can we screen patients effectively? Can we measure the lactate quickly? Can fluids be administered rapidly? Can the patient be frequently re-assessed?

Challenges Can we screen patients effectively? Can we measure the lactate quickly? Can fluids be administered rapidly? Can the patient be frequently re-assessed? Who’s going to do all of this?

Definitions Sepsis Severe sepsis Septic shock SIRS + infection Severe sepsis SIRS + infection + new organ dysfunction Septic shock Impaired perfusion despite adequate fluid resuscitation Many patients with severe sepsis do not have SIRS Many patients with severe sepsis do not initially have any obvious organ dysfunction Infection + new organ dysfunction can occur in the absence of severe sepsis

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) Definitions of sepsis, severe sepsis, and septic shock revisited Fair sensitivity & poor specificity of SIRS Recognition of inflammation as a normal response to infection JAMA February 23, 2016 Volume 315, Number 8

Key Concepts Difficult to distinguish between “normal” and “dysregulated” inflammatory response Organ dysfunction may not be obvious Sepsis might not be the cause of organ dysfunction

Key Concepts No “gold standard” diagnostic test for sepsis Change in approach to screening patients for sepsis New infectionlook for organ dysfunction New or worsening organ dysfunctionlook for infection

Proposed Definitions Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection Organ dysfunction can be identified as an acute change in total SOFA score ≥2 points consequent to the infection JAMA 2016;315(8):801-810

Proposed Definitions Septic shock is defined as a subset of sepsis in which underlying circulatory and cellular metabolism abnormalities are profound enough to substantially increase mortality Hypotension requiring vasopressor therapy to maintain mean BP 65mmHg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation JAMA 2016;315(8):775-787

Logistic Organ Dysfunction System LODS Heart rate Systolic blood pressure pO2/fiO2 Glasgow Coma Score Serum creatinine Serum urea Bilirubin White blood cell count Prothrombin time Platelets JAMA 1996;276(10):802-810 http://statpages.info/lods.html

Sequential Organ Failure Assessment SOFA Crit Care Med 1998; 26:1793-1800

qSOFA 0-3 points 1 point each for: Respiratory rate ≥ 22 Glasgow Coma Score ≤ 13 Systolic blood pressure ≤100 JAMA February 23, 2016 Volume 315, Number 8

qSOFA The presence of 2 or more qSOFA points associated with a greater risk of death or prolonged intensive care unit stay Prompt to identify infected patients outside the ICU who are likely to be septic JAMA February 23, 2016 Volume 315, Number 8

https://www.polleverywhere.com/multiple_choice_polls/XQutCeCpdJZNgqT

Which are risks factors for sepsis? Age > 65 years Age < 1 year Immunocompromised Recent surgery Chronic disease Wounds Previous sepsis Invasive devices All are risk factors Poll Everywhere All are risk factors for sepsis

Keys to Surviving Sepsis Prevention

Prevention Central venous catheter maintenance bundle Hand hygiene Scrub the hub Aseptic access technique Daily review of line necessity Appropriate dressing changes https://www.jointcommission.org/assets/1/6/CLABSI_Toolkit_Tool_3-22_CVC_Maintenance_Bundles.pdf

Prevention Minimize the need to access a vascular catheter Minimize blood draws Batch blood draws Convert medications from parenteral to enteral as soon as practical

Prevention (maybe) Antimicrobial catheter Antithrombogenic catheter Antimicrobial patch Antimicrobial dressing Sutureless securement device Disinfecting port protector Antimicrobial lock Daily chlorhexidine bath

Keys to Surviving Sepsis Early recognition New organ dysfunction—look for infection New infection—look for organ dysfunction Check the lactate Antibiotics immediately Blood cultures prior to antibiotics Brisk fluid resuscitation 30 ml/kg

Sample Sepsis Screening Tool

Sample Sepsis Screening Tool

Sepsis Screening Look for trends Leukocytosis & fever Heart rate increasing Blood sugars increasing Platelets decreasing Monitor for signs of new organ dysfunction qSOFA

Keys to Surviving Sepsis It is even better to act quickly and err than to hesitate until the time of action is past Carl von Clausewitz

Keys to Surviving Sepsis Remember—this is a time-sensitive problem, just like MI Stroke Trauma

Thank You!