Sepsis: Making Leading Practice Common Practice The Evolving Science

Transcription

1 Sepsis: Making Leading Practice Common Practice The Evolving Science Ed Septimus, MD, FACP, FIDSA, FSHEA Medical Director Infection Prevention and Epidemiology Professor Internal Medicine Texas A&M Professor, Distinguished Senior Fellow, School of Public Health, George Mason University

2 Sepsisalliance.org

3 Objectives After completing this continuing medical education activity, the physician should be able to: Recognize the early signs and symptoms of severe sepsis and septic shock Identify appropriate timely treatments for early severe sepsis that have been proven to improve patient outcome Cite the key elements of an effective hospital based sepsis management program

4 Patient Safety vs. Quality Patient Safety Absence of bad things, things that are under your control, happening to patients. 1 Infection Prevention Antimicrobial Stewardship Quality Presence of the right things happening to patients evidencebased care in the right quantity at the right time. 1 Sepsis Bundle There is inherent overlap between the Patient Safety and Quality initiatives Solovy, 2004.

5 Proposed Wedges Model for US Health Care, With Theoretical Spending Reduction Targets for 6 Categories of Waste HAIs Sepsis Antibiotics Berwick, D. M. et al. JAMA 2012;307:

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7 Case History: This is a 26-year-old Hispanic male admitted to a Houston hospital with left leg and knee swelling after falling off a ladder 4 days PTA. He has no underlying medical problems, NKDA, no prior surgical history, on no meds, denies IVDA PE: initial BP 120/75 which quickly increased with fluids, P-80, RR 18 ; lungs CTA, gr 1/6 murmur; abdomen minimal mid-abdominal tenderness; left leg erythema, swelling with 8/10 pain level in his leg, left knee effusion, neuro intact

8 Case continued Lab: WBC 9300, 56% bands; creat 1.0; CO 2 24; ABG ph 7.25, pco 2 60, po (on vent); ALT 25; alk phos 85; lactate 2.7; alb 3.7 Initial hospital course: while in observation waiting for a bed, he suddenly drops his BP to 80/50, P 140. He is initially started on ceftriaxone, IV fluids are administered but he remains hypotensive admitted to ICU and norepinephrine is started. Imaging: CXR clear; left leg diffuse swelling

9 Questions: 1. How would you classify this case a) Severe sepsis b) Septic shock 2. Is this patient a candidate for EGDT? 3. What do you think the most likely source of infection and what antibiotic(s) would you order or change? 4. What other interventions or studies should we consider?

10 Agenda Introduction to sepsis Importance of early recognition and tools for screening Role of antimicrobial therapy Review literature on hemodynamic resuscitation / early goal directed therapy Discuss the role of lactate monitoring Review the pharmacology of vasopressors and literature on outcomes Describe evidence based steroid use Review literature describing outcomes of effective sepsis programs Describe the keys of a successful sepsis program

11 The great tragedy of science the slaying of a beautiful hypothesis by an ugly fact Thomas Huxley

12 INTRODUCTION

13 Severe Sepsis: A Growing Healthcare Challenge #1 cause of death in non-coronary ICU 11 th leading cause of death overall 28-day mortality: 30-50% >750,000 US cases annually Incidence growing faster than overall population $17.0 billion cost of treatment in the US(30 billion) Source: Sands KE, et al. JAMA 1997; Murphy, NVSR; Angus DC et al. Crit Care Med. 2001

14 Cases/100,000 Annual Deaths (000) Severe Sepsis vs Other Major Diseases Incidence Mortality AIDS* Colon Breast CHF Cancer Severe Sepsis AIDS* Breast Cancer AMI Severe sepsis is more common than other major diseases and comparable in mortality to AMI. Severe Sepsis National Center for Health Statistics, American Cancer Society, *American Heart Association Angus DC et al. Crit Care Med

15 The most expensive reason for hospitalization-15.4 B annually

16 Nationwide trend of Severe Sepsis in the 21 st Century ( ) Chest 2011; 140:1223

17 What is Severe Sepsis? Inflammation + Infection + Organ Dysfunction Crit Care Med 2000;28:S81

18 Severe Sepsis: Defining a Disease Continuum Infection SIRS Sepsis Severe Sepsis Adult Criteria A clinical response arising from a nonspecific insult, including 2 of the following: Temperature:> 38.3 C or < 36 C Heart Rate: > 90 beats/min Respiration: > 20/min WBC count: > 12,000/mm 3, or < 4,000/mm 3, or > 10% immature neutrophils SIRS with a presumed or confirmed infectious process Sepsis with 1 sign of organ dysfunction, hypoperfusion or hypotension. Examples: Cardiovascular (refractory hypotension) Renal Respiratory Hepatic Hematologic Shock CNS Unexplained metabolic acidosis SIRS = Systemic Inflammatory Response Syndrome Bone et al. Chest.1992;101: modifed

19 Severe Sepsis-Associated Mortality Increases with Number of Organ Dysfunctions Mortality (%) Organ Dysfunctions Angus DC, et al. Crit Care Med. 2001;29: Vincent JL, et al. Crit Care Med. 1998;26:

20 Summary #1 cause of death in non-coronary ICUs The incidence of severe sepsis has increased in the last decade Historically there is a 45% mortality associated with septic shock

21 Goals for Treatment of Severe Sepsis and Septic Shock Early identification Treat infection with appropriate antibiotics in a timely manner Source control Resuscitation with IV fluids and vasopressors if necessary(resuscitation bundle) Emergency supportive care for acute organ dysfunction

22 Sepsis Guideline Update In February 2013, the initial Surviving Sepsis Campaign Guidelines (2008) were updated. The guidelines include recommendations for early quantitative resuscitation of the septic patient during the first 6 hours after recognition. Dellinger, R.P. et al. (2013, February). Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock. Critical Care Medicine: 41(2)

23 Why Do You Need to Have a Screening Process? TIME IS TISSUE!! Similar to trauma, AMI, or stroke, the speed and appropriateness of therapy administered in the initial hours after severe sepsis develops are likely to influence outcomes. 1 To screen effectively, it must be part of the nurses daily routines i.e., part of admission and shift assessment Must define a process for what to do with the results of the screen If you don t screen you will miss patients that may have benefited from the interventions Crit Care Med. 2008;36:

24 Clin Chest Med 2008; 29:689 Occult Tissue Hypoxia Tissue hypoxia is often occult, reaches an advanced and lethal stage before its presence is known and resuscitation is attempted. Vital signs are inadequate for detecting global tissue hypoxia and not adequate as a resuscitation end point. Up to 50% of patients resuscitated from shock may have continued global tissue hypoxia (elevated lactate and decreased ScvO 2 ) despite normalized vital signs and central venous pressure.

25 Timely Screening for early identification! SEVERE SEPSIS (2) SIRS (1) Organ dysfunction (1)Infection Start EGDT

26 (%) Mortality Mortality Escalates along the Sepsis Continuum: A Clear Trend Exists Sepsis Mortality Continuum The Best Opportunity for Safe, and Effective Intervention is Here! SIRS SEPSIS SEVERE SEPSIS SEPTIC SHOCK Sepsis Category N Engl J Med 2003:348, 1546

27 Screening: SIRS and Sepsis SIRS Temp > 38 o C(>100.4 o F) or < 36 o C(<96.8 o F) HR >90 RR > 20 or PaCO 2 <32 or mechanical ventilation WBC > 12,000 or < 4,000 or > 10% bands SEPSIS 2 of 4 SIRS criteria and suspected or confirmed infection

28 Screening: Severe Sepsis and Septic Shock Sepsis and one or more organ dysfunction o Cardiovascular BP <90 or MAP <70 o Respiratory P/F ratio <250 o Renal UO <0.5ml/kg/hr or increased creat >50% from baseline o Hepatic liver enzymes >2x upper limit normal o Hematologic platelet < 100,000 or PT/PTT > upper limit of normal o Metabolic ph < 7.3 or lactate level >1.5 upper limit of normal o CNS altered mental status or reduced GCS Septic Shock o Patient with severe sepsis and hypotension BP <90 or MAP<70 despite fluids or on pressors

29 Identifying Acute Organ Dysfunction as a Marker of Severe Sepsis Altered Consciousness Reduced GCS Tachypnea PaO 2 /FiO Mechanical Ventilation PEEP >7.5 Liver Enzymes >2x ULN Low ph with high lactate (eg, ph, 7.3 & lactate>1.5uln) Tachycardia Systolic BP 90, or MAP 70 despite fluids & Vasopressors Urine Output <0.5 ml/kg/hr despite fluids Creatinine >50% from baseline Acute dialysis Platelets <100,000/mm 3 PT/aPTT D-dimer Crit Care Nurs NAM. 2003;15:27.

30 Validation of a Screening Tool for the Early Identification of Sepsis* J Trauma 2009;66: *The screening tool yielded a sensitivity of 96.5%, specificity of 96.7%, a positive predictive value of 80.2%, and a negative predictive value of 99.5%. In addition, sepsis-related mortality decreased from 35.1% to 23.3%.

31 Mortality Severe Sepsis/Septic Shock Mortality by ICU 40% 30% 20% 10% 0% SICU CVICU MICU % 21% 38% % 24% 37%

32 Summary: Early recognition Recognizing early signs and symptoms of severe sepsis and septic shock can greatly improve survival rates Effective sepsis screening must be part of the nurses daily routines Early quantitative resuscitation of the septic patient must occur during the first 6 hours after recognition There must be a defined process for timely response to screening results

33 ANTIMICROBIAL THERAPY Mortality is increased if initial antimicrobial therapy is incorrect and not given in a timely manner

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35 Kollef et al. Chest 1998;113: Ibrahim et al. Chest 2000;118: Luna et al. Chest 1997;111: Rello et al. Am J Respir Crit Care Med 1997;156: Mortality associated with initial inappropriate therapy in patients with serious infections Rello et al Infection-related mortality Initial appropriate therapy Initial inappropriate therapy Kollef et al Crude mortality Ibrahim et al Infection-related mortality Luna et al Crude mortality Mortality (%)

36 Impact of Previous Therapy on Outcome of Gram-Negative Severe Sepsis Crit Care Med 2011; 39:1859

37 Crit Care Med 2011; 39:1859

38 Duration of hypotension before initiation of effective antimicrobial therapy Crit Care Med 2006; 34:1589

39 Summary: 2012 Guidelines Antibiotic therapy Blood cultures should be obtained prior to the first dose of antibiotics Administration of broad spectrum antibiotics within one hour of recognition of septic shock and sever sepsis without shock (1B) Assess to de-escalate antibiotics daily Antimicrobial de-escalation(1b) Infection source control Assess the risks and benefits of chosen method within 12 hours of diagnosis Crit Care Med :580

40 HEMODYNAMIC RESUSCITATION Early Goal Directed Therapy EGDT

41 Initial resuscitation for hypotension Begin resuscitation for Arterial Hypotension and positive Sepsis screen: SBP < 90 mm hg MAP < 70 mm hg SBP decrease > 40 mm Hg in adults Initial fluid resuscitation with crystalloid (1B) Initial fluid challenge for patients with sepsis-induced hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 ml/kg* of crystalloids More rapid administration and greater amounts of fluid may be needed in some patients Continue fluid challenge as long as improvement *change from 2008

42 Early Goal-Directed Therapy for Severe Sepsis and Septic Shock Randomized, non-blinded trial of traditional vs. early goal-directed therapy (EGT) Septic shock unresponsive to 20 ml/kg crystalloids, or Lactate 4 mmol/l Standard CVP 8-12 mm Hg Vasopressors for SBP 90 mm Hg Maintain UOP 0.5 ml/kg/hr MAP 65 mm Hg Goal-directed Above, plus monitor CVP and SVO 2 If SVO 2 <70% RBCs until Hct 30% If SVO 2 still <70%, add dobutamine to dose of 20 μg/kg/min N Engl J Med 2001;345:1368

43 ScvO2 and Central Venous Catheter ScvO2 can be monitored via minimally invasive sensor or central venous catheter. Invasive ScvO2 continuously monitors central venous oxygen saturation and central venous pressure

44 EGDT for Severe Sepsis and Septic Shock Mortality (%) EGDT* in patients with severe sepsis produced the following: 42% in relative risk of in-hospital and 28-day mortality (P=0.009, P=0.01) 33% in relative risk of death at 60 days (P=0.03) NNT to prevent 1 event (death) = 6-8 *Aggressive resuscitation begun in emergency department. N Engl J Med 2001;345:1368

45 TRANSFUSION OF PACKED RED BLOOD CELLS IS NOT ASSOCIATED WITH IMPROVED CENTRAL VENOUS OXYGEN SATURATION OR ORGAN FUNCTION IN PATIENTS WITH SEPTIC SHOCK J Emerg Med 2012;43:593 Conclusions: In this study, the transfusion of PRBC was not associated with improved cellular oxygenation, as demonstrated by a lack of improved achievement of ScvO2> 70%. Also, the transfusion of PRBC was not associated with improved organ function or improved achievement of the other goals of EGDT.

46 Efficacy of red blood cell transfusion in the critically ill Crit Care Med 2008; 36:2667 Risk of Infectious Complications

47 Crit Care Med 2012; 40:3308

48 Blood Product Administration Once tissue hypoperfusion has resolved and in the absence of extenuating circumstances, such as myocardial ischemia, severe hypoxemia, acute hemorrhage, or ischemic coronary artery disease, we recommend that red blood cell transfusion occur when hemoglobin concentration decreases to <7.0 g/dl to target a hemoglobin concentration of g/dl in adults (grade 1B). Crit Care Med :580

49 Summary: 2012 Guidelines Hemodynamic resuscitation Complete within 3 hours: Complete within 6 hours: Measure lactate level Obtain blood cultures prior to administration of antibiotics Administer broad spectrum antibiotics Administer 30 ml / kg crystalloid IV fluid for hypotension or lactate > 4 mmol/l Vasopressors for hypotension not responsive to fluid resuscitation For persistent hypotension or initial lactate > 4 mmol/l Measure CVP Target is > 8 mm Hg Measure Scvo2 Target of > 70% Remeasure lactate if initial lactate was elevated Crit Care Med :580

50 LACTATE Global tissue hypoxia (elevated lactate and decreased ScvO 2 ) can occur despite normalized vital signs and central venous pressure.

51 Early Lactate Clearance is Associated with Improved Outcome in Severe Sepsis and Septic Shock Crit Care Med 2004; 32:1637

52 Lactate Clearance vs. Central Oxygen Saturation as Goals of Early Sepsis Therapy* Lactate clearance=[lactate initial -lactate delayed/ lactate initial ]X100%. JAMA 2010;303:739

53 Hospital Mortality and Length of Stay CVP goal was 8-12 in both groups JAMA 2010;303:

54 Summary: Lactate Comment: Many prefer to target an Scv0 2 70% because it has been more extensively studied (1C)*, but lactate clearance 10% appears to be a reasonable alternative if Scv0 2 is not readily available. (2C)* *Crit Care Med :580 Chest 2011; 140:1406

55 VASOPRESSORS

56 Norepinephrine or Dopamine for the treatment of hyperdynamic shock? Chest 1993; 103: 1826 Norepinephrine was more effective and reliable than dopamine to reverse septic shock

57 Effect of Norepinehrine on the Outcome of Septic Shock Crit Care Med 2000; 28: 2758 * *dopamine, epinephrine,

58 Comparison of Dopamine and Norepinephrine in the Treatment of Shock In this comparative-effectiveness trial, there was no significant difference in the overall survival rate between patients with shock who were treated with dopamine and those who were treated with norepinephrine However, dopamine was associated with more cardiac arrhythmias and with a higher mortality rate among patients with cardiogenic shock N Engl J Med 2010; 362:779

59 Dopamine vs. NE in Treatment of Septic Shock: meta-analysis Crit Care Med 2012; 40:725

60 Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomized trial Lancet 2000; 356:2139 Do not use low-dose dopamine for renal protection (1A) Crit Care Med 2008; 36:296

61 Summary: Vasopressors Recommend that vasopressor therapy initially target a mean arterial pressure (MAP) of 65 mm Hg (grade 1C). Recommend norepinephrine as the first choice vasopressor (grade 1B). Suggest epinephrine (added to and potentially substituted for norepinephrine) when an additional agent is needed to maintain adequate blood pressure (grade 2B). Vasopressin up to 0.03 units/minute can be added to norepinephrine (NE) with the intent of raising MAP to target or decreasing NE dosage (UG) Recommend that low-dose dopamine not be used for renal protection (grade 1A). *Crit Care Med :580

62 Inotropic Therapy Recommend that a trial of dobutamine infusion up to 20 μg/kg/min be administered or added to vasopressor (if in use) in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion, despite achieving adequate intravascular volume and adequate mean arterial pressure (grade 1C). *Crit Care Med :580

63 STEROIDS

64 28-day Mortality Steroids Low-Dose Steroids: 28-day Mortality Patients with Relative Adrenal Insufficiency (ACTH Test Nonresponders) (77%) P=0.04 Patients Without Relative Adrenal Insufficiency (ACTH Test Responders) (23%) P=0.96 N=114 N=115 N=36 N=34 Low-dose Steroids Placebo JAMA 2002; 288:862

65 Hydrocortisone Therapy for Patients with Septic Shock Charles L. Sprung, M.D., Djillali Annane, M.D., Ph.D., Didier Keh, M.D., Rui Moreno, M.D., Ph.D., Mervyn Singer, M.D., F.R.C.P., Klaus Freivogel, Ph.D., Yoram G. Weiss, M.D., Julie Benbenishty, R.N., Armin Kalenka, M.D., Helmuth Forst, M.D., Ph.D., Pierre-Francois Laterre, M.D., Konrad Reinhart, M.D., Brian H. Cuthbertson, M.D., Didier Payen, M.D., Ph.D., Josef Briegel, M.D., Ph.D., for the CORTICUS Study Group Mortality was lower than expected Therefore, inadequately powered to detect a clinically important effect Corticotropin stimulation test did not identify patients who would benefit from corticosteroids Steroids improved shock reversal N Engl J Med Volume 358(2): January 10, 2008

66 Kaplan-Meier Curves for the Time to Reversal of Shock N Engl J Med 2008;358:

67 Corticosteroids Summary Suggest not using intravenous hydrocortisone as a treatment of adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability. In case this is not achievable, we suggest intravenous hydrocortisone alone at a dose of 200 mg per day (grade 2C). Suggest not using the ACTH stimulation test to identify the subset of adults with septic shock who should receive hydrocortisone (grade 2B). *Crit Care Med :580

68 GLYCEMIC CONTROL

69 HYPERGLYCEMIA IMPAIRS IMMUNITY Inactivates IgG Decreases Complement Activation Increases Collagenase Activity Impairs Leukocyte Function - impairs chemotaxis - decreases phagocytosis - decreases bactericidal activity

70 In-Hospital Survival (%) The Role of Intensive Insulin Therapy in a SICU PRCT, N = 1548 Titrate glucose to vs mg/dl At 12 months, intensive insulin therapy reduced mortality by 3.4% (P<0.04) Intensive insulin therapy also resulted in: 34% in-hospital mortality Intensive treatment Conventional treatment 46% bloodstream infections 41% ARF requiring RRT 50% median RBC transfusions Days after Admission N Engl J Med 2001;345:1359

71 Effect of an Intensive Glucose Management Protocol on the Mortality of Critically Ill Adult Patients Mayo Clin Proc 2004; 79:992 Treatment to maintain glucose levels < 140 mg/dl CII was used if glucose values exceeded 200 mg/dl on 2 successive occasions The protocol resulted in significantly improved glycemic control and was associated with decreased mortality ( 29.3%), organ dysfunction, and LOS in the ICU

72 Intensive Insulin Therapy in the MICU N Engl J Med 2006; 354: P 0.40 P 0.02

73 Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis N Engl J Med 2008; 358:125 In the conventional-therapy group, a continuous insulin infusion in 50 ml of 0.9% saline solution was delivered through a perfusion pump when the blood glucose level exceeded 200 mg per deciliter ; the insulin level was then adjusted to maintain a blood glucose level of 180 mg per deciliter to 200 mg per deciliter. In the intensive-therapy group, infusion of insulin was started when blood glucose levels exceeded 110 mg per deciliter; the insulin level was then adjusted to maintain euglycemia (80 to 110 mg per deciliter).

74 Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis N Engl J Med 2008; 358:125 There was no benefit in the intensive-therapy group with respect to either 28-day survival or organ function; there was more severe hypoglycemia in the intensive-therapy group

75 Intensive versus Conventional Glucose Control in Critically Ill Patients The NICE-SUGAR Study Investigators In this study, adults who were expected to require treatment in the intensive care unit on 3 or more consecutive days were randomly assigned to undergo intensive blood glucose control (target range, 81 to 108 mg per deciliter [4.5 to 6.0 mmol per liter]) or conventional blood glucose control (180 mg per deciliter [10.0 mmol per liter]) The primary end point was death from any cause within 90 days after randomization Intensive glucose control increased mortality among the patients N Eng J Med 2009; 360:1283

76 Summary Glucose Control Recommend a protocolized approach to blood glucose management in ICU patients with severe sepsis commencing insulin dosing when 2 consecutive blood glucose levels are >180 mg/dl. This protocolized approach should target an upper blood glucose <= 180 mg/dl rather than an upper target blood glucose <= 110 mg/dl (grade 1A). Recommend blood glucose values be monitored every 1 2 hrs until glucose values and insulin infusion rates are stable and then every 4 hrs thereafter (grade 1C).

77 Supportive Therapy of Severe Sepsis

78 Mechanical Ventilation of Sepsis-Induced Acute Lung Injury (ALI)/ARDS Mortality* - Low vs. Traditional Tidal Volume P=0.007 * death before discharge home and breathing without assistance Low Tidal Volume Traditional Tidal Volume N Engl J Med 2000; 342:1301

79 Mechanical Ventilation of Sepsis-Induced Respiratory Distress Syndrome (ARDS) Recommend that clinicians target a tidal volume of 6 ml/kg (versus 12 ml/kg). predicted body weight in patients with sepsis-induced ARDS (grade 1A). Recommend that plateau pressures be measured in patients with ARDS and that the initial upper limit goal for plateau pressures in a passively inflated lung be 30 cm H 2 O (grade 1B). Ann Intern Med 2009; 151: ; PLoS One 2011; 6:e14623 Recommend that positive end-expiratory pressure (PEEP) be applied to avoid alveolar collapse at end expiration (atelectotrauma) (grade 1B). *Crit Care Med :580

80 OUTCOMES

81 Jt Comm J Qual 2007; 33:559

82 VHA Transforming the ICU Sepsis Outcomes Improving Care of Patients with Sepsis Presentation at IHI National Quality Meeting, 2004.

83 Crit Care 2005;9:R764

84 Impact of the Surviving Sepsis Campaign protocols on hospital length of stay and mortality in septic shock patients Crit Care Med 2010; 8:1036 A total of 384 adult patients in septic shock were enrolled after the educational intervention (September 2005 August 2008) and 96 patients in the historical group (June 2004 May 2005). Hospital mortality was reduce from 57.3% in the historical group to 37.5% in the intervention group (p =.001) Compliance with six or more interventions of the 6-hr resuscitation bundle was an independent predictor of survival(p <.001). The only single intervention with impact on mortality was the achievement of ScvO2 >70% (p =.048)

85 after Crit Care Med 2006; 34:2707

86 Reduced mortality after the implementation of a protocol for the early detection of severe sepsis J Crit Care 2011; 26:76 Phase II screening protocol

87 Change in Compliance Over Time Crit Care Med 2010; 38(2):

88 Change in Mortality Over Time Crit Care Med (2): ,

89 The Determinants of Hospital Mortality Among Patients with Septic Shock Receiving Appropriate Initial Antibiotic Treatment Crit Care Med 2012; 40:2016 Patients with septic shock, a positive blood culture, and receiving appropriate initial antimicrobial therapy were evaluated Bloodstream infections were do to gram-negative bacteria (59%) and gram-positive bacteria (41%) Multivariate logistic regression demonstrated that infection acquired in the ICU(p=.011) and severity of illness(p<.001) appear to be the most important determinants of outcomes Preventing HAIs in ICU should result in better outcomes

90 Multicenter Implementation of a Severe Sepsis and Septic Shock Treatment Bundle Am J Respir Crit Care 2013; 188:77-82 Observational study of severe sepsis and septic shock bundle from 18 Intermountain ICUs Bundle designed for ED to ICU Absolute compliance with bundle increased by 68.5% from Compliance was associated with a 59% relative reduction in hospital mortality adjusted for severity of illness Lower rates of progression to more severe disease in the first 24 hours was associated when early bundle elements were performed

91 Business Case Treatment of Sepsis Variable Before Protocol After Protocol Sepsis Survivor Rate 51.7% 70.0% (p=0.04) 28 Day Mortality 48.3% 30.0% (p=0.04) Hospital LOS 13 days 8 days (p=.001) Median Cost Patient $21,985 $16,103 (p=0.008) Median Cost Survivors $21,926 $13,663 (p=0.002) There is no sustainable business model without quality Crit Care Med; 2007; 35(5): 1257

92 Nationwide trends of Severe Sepsis in the 21 st Century ( ) Chest 2011; 140:1223

93 Nationwide trends of Severe Sepsis in the 21 st Century ( ) Chest 2011; 140:1223 Proportion that involved septic shock increased from 30.3% in 2000 to 41.7% in 2007 In-hospital mortality rate for severe sepsis declined from 39.6% to 27.3% In-hospital mortality rate for septic shock declined from 47.1% to 36.4% Survivors experienced a significant increase in the number of discharges to SNF and home healthcare

94 Cognitive Impairment Among Survivors of Severe Sepsis at Each Survey Time Point JAMA 2010;304:1787

95 Mortality and quality of life in the five years after severe sepsis Critical Care 2013, 17:R70 A cohort study using data from a prospective audit in 26 adult ICUs in Scotland. Mortality was measured using clinical databases and quality of life using short-form 36 (SF-36) at 3.5 and 5 years after severe sepsis. Patients with severe sepsis have a high ongoing mortality after severe sepsis. They also have a significantly lower physical QOL compared to population norms. Mental QOL scores were also below population norms up to five years after severe sepsis.

96 Keys to Success Team in place with key stakeholders overseeing implementation Agreed measures based on evidenced-based interventions Project coordinator with lead clinical staff on each unit Sepsis resource/coordinator rounds frequently on units Strong physician leadership on team Reminders to staff through use of bedside sepsis tools/checklist Empowerment of nursing staff Administrative support to help manage barriers Review data monthly to identify opportunities for improvement Celebrate success Leadership and Culture

97 SEVERE SEPSIS ROADMAP: HOW WILL WE GET THERE? AGGRESSIVE MANAGEMENT CLINICAL EXCELLENCE MUST BE A CORE VALUE Where Are We? Where Are We Going? How Will We Get There? Severe Sepsis is a Problem. Is it a Priority? Environment * Introduction * CEO Goals * CFO Goals * Quality Goals * ICU Goals Medical Staff goals Severe Sepsis * Definition * National Incidence * National Impact * Institutional Incidence Institutional Impact * Systematic Treatment Standards for Severe Sepsis New Treatment Standards * Evidence-based Interventions * Surviving Sepsis Campaign * Regional ICU Projects * Success Stories Aggressive Management of Severe Sepsis 4-Step Process 1 Identify Severe Sepsis as a Priority 2 Implement Early Screening Procedures 3 Implement Aggressive Treatment Standards 4 Measure, Track, Evaluate, and Report Outcomes

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99 Endorsed NQF Measures WITHIN THREE HOURS 1. Measure serum lactate 2. Appropriate cultures before antibiotics 3. Broad spectrum antibiotics 4. Fluid resuscitation (30 ml/kg crystalloids for hypotension or lactate>4) WITHIN 6 HOURS 1. Start vasopressors for hypotension that does not respond to fluid resuscitation to maintain MAP>65 mmhg) 2. In event of persistent hypotension or initial lactate >4 mmol/l (36 mg/dl) i. Measure CVP (8-12 mm Hg) ii. Measure ScvO 2 ( 70%)

100 Case Questions: 1. How would you classify this case a) Severe sepsis b) Septic shock 2. Is this patient a candidate for EGDT? 3. What do you think the most likely source of infection and what antibiotic(s) would you order or change? 4. What other interventions or studies should we consider?

101 And Now the Rest of The Story Repeat lactate was 8.1 ID was consulted who changed antibiotics to vancomycin and pip/tz Arthrocentesis was performed Surgery evaluated patient for possible compartment syndrome and took patient to surgery Joint and intraop cultures grew

102 Cultures grew GAS Case continued Vancomycin was discontinued On day 7 he was given prophylactic fluconazole until discharge Patient was continued on pip/tz until discharge(total ~11 days) and then sent home on PO cephalexin for 10 days

103 Case continued 2 weeks later the patient was readmitted with a 4 day history of increased pain and swelling in left calf and knee An arthrocentesis is done with a joint WBC of 46,000; 88S CT of left leg shows possible fluid collection in left calf and fluid around left knee joint Patient is taken back to surgery for I&D Cultures grew?

104 How would you evaluate the management of this case?

105 Sepsisalliance.org Faces of Sepsis

106 Thank you for your kind attention