Everything You Need to Know About Sepsis Sam Antonios, MD, MMM, FACP, SFHM, CPE, CCDS Chief Medical Officer Via Christi Hospitals This is the Full Title of a Session Wichita, Kansas 1
Learning Objectives At the completion of this educational activity, the learner will be able to: Understand basic scientific concepts of prediction, definitions, manifestations and phenotyping. Review history of sepsis definitions and treatment Understand the changes in definitions that occurred with Sepsis 3 Understand the rationale behind the new definitions Understand the response in medical literature and practice since 2016, following the publication of the new sepsis definitions 2
Basic Concepts to Understand What is a definition? How is prediction used in definitions? What is a manifestation? What is the gold standard in sepsis definition? EGDT Surviving Sepsis Campaign SEP 1 New Sepsis Definitions Future for Sepsis 3
What is a Definition? A: a statement of the meaning of a word or word group or a sign or symbol B: a statement expressing the essential nature of something C: the action or the power of describing, explaining, or making definite and clear 4
In the End A word may have meaning because people create that meaning and agree on the criteria that define it: an inning = 3 outs by each team a kilogram = weight of a bar of platinum A word may have meaning because data derived from the scientific process establish a plausible constraint: a year = time required for the earth to revolve around the sun cancer = disease characterized by the abnormal proliferation of transformed cells A definition delimits what something is and what it is not. A crow = bird because of consensus on what makes a living organism a bird; it is not a flying insect for the same reason 5
What is a manifestation, a phenotype? 6
Medical Definitions Medical definitions describe populations of patients whose clinical trajectory is shaped by a common process and who might, therefore, benefit from interventions that target that process. The validation of a medical definition, however, requires more than consensus: it requires that the definition reliably inform one or more treatment approaches that can be shown to alter clinical outcomes, that it converts a syndrome to a disease. John C. Marshall, MD 7
σῆψις 8
Predictions in Establishing Medical Definitions 9
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Price = Square footage + ZIP code + number of beds + age + zone + number of baths insects taxes annoying neighbors + pool (Y/N) + etc. 21
The history of science shows that theories are perishable. With every new truth that is revealed we get a better understanding of nature and our conceptions and views are modified. Nicola Tesla 22
Things in this box mean that they are a reference that you can review later. 23
1992 For simplicity, the systemic inflammatory response syndrome (SIRS) was defined by four variables: 1. Temperature 2. Heart rate 3. Respiratory rate 4. White blood cell count These simple clinical criteria allowed researchers to identify patients to enroll in sepsis trials and were rapidly adopted. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992; 20:864. 24
2001 2 nd consensus conference attempted to revisit the SIRS criteria but did not come up with an easy to use list of variables to define sepsis. Sepsis to be the clinical syndrome defined by the presence of both infection and a systemic inflammatory response Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31:1250. 25
It is important to emphasize that none of the findings is specific for sepsis 26
PIRO 27
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2012 Critical hypoperfusion can also occur in the absence of hypotension 29
Early Goal Directed Therapy in the Treatment of Severe Sepsis and Septic Shock Control EGDT In Hospital 46.5 30.5 28 day Mortality 49.2 33.3 60 day Mortality 56.9 44.3 Relative Risk (95% Confidence Interval) 0.58 (0.38 0.87) 0.58 (0.39 0.87) 0.67 (0.46 0.96) P 0.009 0.01 0.03 Rivers E, Nguyen B, Havstad S, et al. Early goal directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368 1377 30
SSC Guidelines 1. Initial Resuscitation 2. Fluid Therapy 3. Vasopressor Therapy 4. Inotropic Therapy Campaign by the Society of Critical Care Medicine, European Society of Intensive Care Medicine, and the International Sepsis Forum and launched at the ESICM Annual Meeting in Barcelona in Fall 2002 with presentation of plan to develop guidelines. Dellinger RP, Carlet JM, Masur H, Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004 Mar;32(3):858 73. (1 st guidelines) Dellinger RP, Vincent. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med. 2008 Jan; 34(1): 17 60 (2 nd guidelines) Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013; 41:580. (3d guidelines) Dellinger, R.P., Schorr, C.A.&Levy, M.M. Intensive Care Med (2017) 43: 299. (4th guidelines) 31
Consensus definitions of sepsis Second consensus meeting Surviving Sepsis 3 nd Guidelines SEP 1 Measure Rivers trial Surviving Sepsis 1 st Guidelines Xigris pulled off the market PROCESS Trial 1992 2001 2002 2004 2008 2012 2014 2015 Barcelona Declaration: Surviving Sepsis early work Surviving Sepsis 2 nd Guidelines ARISE Trial ProMISE Trial 32
Push for Change Vincent JL, Opal SM, Marshall JC, Tracey KJ. Sepsis definitions: time for change. Lancet 2013; 381:774. 33
High Sensitivity, Low specificity SIRS criteria are so sensitive that up to 90% of patients admitted to an intensive care unit (ICU) meet the criteria. Sprung CL, Sakr Y, Vincent JL, et al. An evaluation of systemic inflammatory response syndrome signs in the Sepsis Occurrence In Acutely Ill Patients (SOAP) study. Intensive Care Med. 2006;32:421 27. Lai NA, Kruger P. The predictive ability of a weighted systemic inflammatory response syndrome score for microbiologically confirmed infection in hospitalised patients with suspected sepsis. Crit Care Resusc. 2011;13:146 50. 34
Positive Predictive Value Low But Also, May Miss 1 in 8 Patients Kaukonen KM 1, Bailey M, Pilcher D, Cooper DJ, Bellomo R. Systemic inflammatory response syndrome criteria in defining severe sepsis. N Engl J Med. 2015 Apr 23;372(17):1629 38. 35
N Engl J Med. 2014 May 1; 370(18): 1673 1676 36
2010 2015 Sepsis and Coding Chanu Rhee, Michael V. Murphy, Lingling Li, Richard Platt, Michael Klompas. Comparison of Trends in Sepsis Incidence and Coding Using Administrative Claims Versus Objective Clinical Data, Clinical Infectious Diseases, Volume 60, Issue 1, 1 January 2015, Pages 88 95 Chanu Rhee, Michael V. Murphy. Improving documentation and coding for acute organ dysfunction biases estimates of changing sepsis severity and burden: a retrospective study. Critical Care2015, 19:338 Shruti K. Gohil,, Chenghua Cao,, Michael Phelan,, Thomas Tjoa,,Chanu Rhee,, Richard Platt,, Susan S. Huang. Impact of Policies on the Rise in Sepsis Incidence, 2000 2010,Clinical Infectious Diseases, Volume 62, Issue 6, 15 March 2016, Pages 695 703 Chanu Rhee, Sameer S. Kadri, Robert L. Danner. Diagnosing sepsis is subjective and highly variable: a survey of intensivists using case vignettes. Critical Care 2016 20:89 Chanu Rhee, Michael V. Murphy, Lingling Li, Richard Platt, Michael Klompas. Improving Documentation and Coding for Acute Organ Dysfunction Biases Severe Sepsis Surveillance Over Time, Open Forum Infectious Diseases, Volume 2, Issue suppl_1, 1 December 2015, 633, 37
Sepsis 3 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%. 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. Singer M, Deutschman CS, Seymour CW, Shankar Hari M, Annane D, Bauer M,Bellomo R, Bernard GR, Chiche J, Coopersmith CM, Hotchkiss RS, Levy MM,Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, VincentJ, Angus DC. The Third International Consensus Definitions for Sepsisand Septic Shock (Sepsis 3).JAMA.2016;315(8):801 810. doi:10.1001/jama.2016.0287 38
Sepsis 3 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 quick SOFA (qsofa): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. 39
How Is Sepsis 3 Performing? 57% of patients meeting old definition for septic shock did not meet Sepsis 3 criteria. Although Sepsis 3 criteria identified a group of patients with increased organ failure and higher mortality, those patients who met the old criteria and not Sepsis 3 criteria still demonstrated significant organ failure and 14% mortality rate. Sarah A. Sterling, Michael A. Puskarich, Andrew F. Glass, Faheem Guirgis, Alan E. Jones. The Impact of the Sepsis 3 Septic Shock Definition on Previously Defined Septic Shock Patients. Crit Care Med 2017; 45:1436 1442 40
How Is Sepsis 3 Performing? Sepsis 3 diagnostic criteria narrow the sepsis population at the expense of sensitivity, and the resulting false negatives may delay disease diagnosis. It may be inappropriate to compare the prediction performance of SIRS and SOFA criteria when Sepsis 3 is defined. Xueling Fang, MM; Zhenzhen Wang, BM; Jun Yang, PhD; Hongliu Cai, MM; Zhengjie Yao, BE; Kun Li, MM; and Qiang Fang, MM. Clinical Evaluation of Sepsis 1 and Sepsis 3 in the ICU. chest. 2017. 06.037 41
How Is Sepsis 3 Performing? Although qsofa may be valuable in predicting sepsisrelated mortality, it performed poorly as a screening tool for identifying sepsis in the ED. As the time to meet qsofa criteria was significantly longer than for SIRS, relying on qsofa alone may delay initiation of evidence based interventions known to improve sepsis related outcomes. Haydar, Spanier, Weems, Wood, Strout. Comparison of QSOFA score and SIRS criteria as screening mechanisms for emergency department sepsis. Am J of Emergency Medicine. Volume 35, Issue 11, November 2017, Pages 1730 1733 42
How Is Sepsis 3 Performing? A qsofa score 2 showed high specificity, but poor sensitivity may limit utility as a bedside screening method. Although mortality for organ dysfunction was comparable between Sepsis 2 and Sepsis 3, more prognostic and clinical information is conveyed using Sepsis 2 regarding number and type of organ dysfunctions. The SOFA score may require recalibration. Williams J. Lipman J. Systemic Inflammatory Response Syndrome, Quick Sequential Organ Function Assessment, and Organ Dysfunction: Insights From a Prospective Database of ED Patients With Infection. Chest. Volume 151, Issue 3, March 2017, Pages 586 596 43
How Is Sepsis 3 Performing? Analysis positively validated the use of SOFA score to predict unfavorable outcome and to limit misclassification into lower severity. However, qsofa score had inadequate sensitivity for early risk assessment. Giamarellos Bourboulis. Validation of the new Sepsis 3 definitions: proposal for improvement in early risk identification. Clinical Microbiology and Infection. Volume 23, Issue 2, February 2017, Pages 104 109 44
Summary 2001 SIRS Suspected Infection Sepsis Sepsis Organ Dysfunction Severe Sepsis Severe Sepsis Refractory Hypotension Septic Shock 45
Summary 2016 SIRS Suspected Infection Sepsis Sepsis Organ Dysfunction Severe Sepsis Suspected Infection SOFA qsofa Severe Sepsis 46
Sepsis 3 Sepsis 3 is not a tool to facilitate the early diagnosis of infection but rather a framework to identify, among patients with suspected or documented infection, those at greatest risk of imminent deterioration. 47
Future Machine learning? Algorithms? 48
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Thank you. Questions? Samer.antonios@viachristi.org In order to receive your continuing education certificate(s) for this program, you must complete the online evaluation. The link can be found in the continuing education section at the front of the program guide. 50