Early Management Saves Lives SURVIVING SEPSIS: Early Management Saves Lives Pat Posa RN, BSN, MSA System Performance Improvement Leader St. Joseph Mercy Health System Ann Arbor, MI Patricia.posa@stjoeshealth.org

Objectives a. Understand the incidence of sepsis b. Discuss the difference between sepsis, severe sepsis and septic shock c. Define an early recognition process for severe sepsis d. Discuss the evidence based interventions for severe sepsis

Severe Sepsis: A Significant Healthcare Challenge Sixth most common reason for hospitalization Most costly reason for hospitalization in 2009** 15.4 billion in aggregate hospital cost 1 out of 23 patients in hospital had septicemia** Major cause of morbidity and mortality worldwide Leading cause of death in noncoronary ICU (US)1 10th leading cause of death overall (US)2* In the US, more than 500 patients die of severe sepsis daily (1.6 million new cases per year) Sepsis is a major worldwide cause of morbidity and mortality. Sands et al described the epidemiology of sepsis in eight academic medical centers in the United States. They reported that sepsis is the leading cause of death in patients admitted to noncoronary intensive care units. The National Vital Statistics Report indicates that sepsis is the 11th leading cause of death in the United States, based on data for septicemia. Angus et al studied the age-specific incidence and outcomes of severe sepsis in the United States. Their investigation indicates that there are more than 750,000 cases of severe sepsis (sepsis with acute organ dysfunction) each year in the United States. Based on data from Angus et al, more than 500 Americans die of severe sepsis daily. Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome and associated costs of care. Crit Care Med 2001;29:1303-10. Murphy SL. Deaths: final data for 1998. National Vital Statistics Reports Web site. Available at: http://www.cdc.gov/nchs/data/mvs48_11.pdf. Accessed January 2001. Sands KE, Bates DW, Lanken PN, et al. Epidemiology of sepsis syndrome in 8 academic medical centers. JAMA 1997;278:234-40. * Based on data for septicemia †Reflects hospital-wide cases of severe sepsis as defined by infection in the presence of organ dysfunction 1 Sands KE, et al. JAMA 1997;278:234-40. 2 National Vital Statistics Reports. 2005. 3 Angus DC, et al. Crit Care Med 2001;29:1303-10. **AHRQ Healthcare cost & Utilization Project October 2011 3

Polling Question Do you send residents to the hospital for infections? Yes No

Time Sensitive Diseases Changing the Paradigm of Practice AMI Stroke Trauma < 10% <10% < 5% 5

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°C or < 36°C Heart Rate: > 90 beats/min Respirations: > 20/min WBC count: > 12,000/mm3, or < 4,000/mm3, or > 10% immature neutrophils Sepsis with 1 sign of organ dysfunction, hypoperfusion or hypotension. Examples: Cardiovascular (refractory hypotension) Renal Respiratory Hepatic Hematologic CNS Unexplained metabolic acidosis SIRS with a presumed or confirmed infectious process Beyond the basic definition, it is helpful to think of sepsis as a continuum: Beginning with a localized infection that triggers a systemic response, called SIRS. SIRS due to infection is sepsis. Once the patient experiences organ dysfunction due to sepsis, that patient has the clinical diagnosis of severe sepsis. Any acute organ dysfunction qualifies the patient for the diagnosis of severe sepsis. Several examples of potential organ systems are listed on the slide. If the cardiovascular organ dysfunction deteriorates into shock, then this is commonly referred to as septic shock. Septic shock is a form (subgroup) of severe sepsis. Infection + SIRS + Organ Dysfunction = Severe Sepsis Shock SIRS = Systemic Inflammatory Response Syndrome Bone et al. Chest. 1992;101:1644-1654.

Identifying Acute Organ Dysfunction as a Marker of Severe Sepsis Cardiovascular Respiratory Increased O2 requirements SaO2 < 90% Tachycardia SBP<90mmHg Renal UO <0.5 ml/kg per hr (despite fluid) Metabolic Following identification of a patient with sepsis, the clinician must assess the patient for the presence of acute organ dysfunction (severe sepsis). The presence of acute organ dysfunction is often recognized clinically by the patient’s presenting signs and symptoms. However, in some instances laboratory data or results of invasive monitoring will confirm the diagnosis of organ dysfunction. The illustration of the patient on this slide has arrows pointing to various organs that might provide clues to the presence of organ dysfunction. Indications of organ dysfunction include: Central nervous system: altered consciousness, confusion, psychosis, delirium Respiratory system: tachypnea, hypoxemia, oxygen saturation <90%, decreased ratio of arterial oxygen vs inspired oxygen Liver: jaundice, increased liver enzymes, hypoalbuminemia, increased prothrombin time Cardiovascular: tachycardia, hypotension, altered central venous pressure, altered pulmonary artery occlusive pressure Kidney: oliguria, anuria, increased creatinine Hematological: thrombocytopenia, abnormal coagulation tests, decreased levels of Protein C, increased D-dimers Neurological Unexplained metabolic acidosis pH<7.30 or Base deficit > 5.0 mEq/l Lactate > 4 Altered level of consciousness (unrelated to primary neuro pathology)

Except on few occasions, the patient appears to die from the body's response to infection rather than from it." Sir William Osler – 1904 The Evolution of Modern Medicine

Homeostasis Is Unbalanced in Severe Sepsis Coagulation Inflammation In simplified terms, sepsis can be conceptualized as a dysfunction of opposing mechanisms of coagulation/inflammation and fibrinolysis. In normal patients homeostasis is maintained because these mechanisms balance each other. Patients with severe sepsis have increased coagulation and increased inflammation. Manifestations of these include: Circulating proinflammatory mediators Endothelial injury Expression of tissue factor by monocytes and possibly a subset of endothelial cells Thrombin generation Patients with severe sepsis also have decreased fibrinolysis. Manifestations of these include: Increased levels of PAI-1 Increased levels of TAFI Carvalho AC, Freeman NJ. How coagulation defects alter outcome in sepsis: survival may depend on reversing procoagulant conditions. J Crit Illness. 1994;9:51-75. Kidokoro A, Iba T, Fukunaga M, et al. Alterations in coagulation and fibrinolysis during sepsis. Shock. 1996;5:223-8. Vervloet MG, Thijs LG, Hack CE. Derangements of coagulation and fibrinolysis in critically ill patients with sepsis and septic shock. Semin Thromb Hemost. 1998;24: 33-44. Fibrinolysis Carvalho AC, Freeman NJ. J Crit Illness. 1994;9:51-75; Kidokoro A et al. Shock. 1996;5:223-8; Vervloet MG et al. Semin Thromb Hemost. 1998;24:33-44.

Inflammation, Coagulation and Impaired Fibrinolysis In Severe Sepsis Factor VIIIa Tissue Factor COAGULATION CASCADE Factor Va THROMBIN Fibrin Fibrin clot Endothelium Neutrophil Monocyte IL-6 IL-1 TNF- TAFI PAI-1 Suppressed fibrinolysis Cytokines may induce the endothelial cell to shift from an antithrombotic to a prothrombotic phenotype. Expression of tissue factor by monocytes, and perhaps a subset of endothelial cells, initiates coagulation through the extrinsic system in patients with severe sepsis. At the same time, fibrinolysis is inhibited through the following mechanisms: Release of thrombin activatable fibrinolysis inhibitor (TAFI) Release of plasminogen-activator inhibitor-1 (PAI-1) Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699-709. Inflammatory Response to Infection Thrombotic Response to Infection Fibrinolytic Response to Infection Reprinted with permission from the National Initiative in Sepsis Education (NISE).

Microcirculation of Septic Patient: Othogonal Polarization Spectral Imaging BP: 120/80 Hg SaO2: 98% We’ve discussed clinical indications of organ dysfunction and some of the external, visible signs of severe sepsis (purpura fulminans), but now I would like to show you what is happening beneath the signs and symptoms, in the microvasculature. First, let’s look at the microvascular circulation of a healthy volunteer as detected by OPS imaging. Orthogonal Polarization Spectral (OPS) imaging is a special technique that allows us to visualize blood flow in the microcirculation in vivo. OPS imaging allows for direct visualization of human microcirculation in a noninvasive manner. Sublingual imagery may be reflective of the blood flow in the microcirculatory beds in the GI tract. 1. www.opsimaging.net. Accessed April 2004. 2. Spronk PE, Ince C, Gardien MJ, et al. Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet. 2002; 360:1395-1396.

Microcirculation of Septic Shock Patient: Othogonal Polarization Spectral Imaging Resuscitated with fluids and dopamine HR: 82 BPM BP: 90/35 mm Hg SaO2: 98% CVP: 25 mm Hg In contrast to the healthy patient, let’s look at the microvascular circulation of a patient with septic shock. Again, this image was detected by OPS imaging. Orthogonal Polarization Spectral (OPS) imaging is a special technique that allows us to visualize blood flow in the microcirculation in vivo. It allows for direct visualization of human microcirculation in a noninvasive manner. This patient has been resuscitated with fluids and dopamine to a stable condition. The primary goal of all hemodynamic therapeutic intervention is to optimize cardiovascular function in order to ensure adequate tissue perfusion. However, impaired microcirculatory perfusion occurs in patients with septic shock, despite normal blood pressure attained after restoration of intravascular volume. Severe sepsis is characterized by increased oxygen consumption, decreased peripheral vascular resistance, maldistribution of tissue blood flow, and derangement of microcirculatory perfusion. In patients with septic shock, oxygen consumption is increased, but oxygen delivery and extraction is impaired, partly because of microcirculatory shutdown and shunting. The decrease in capillary perfusion is due to the increase in the number of capillaries with stagnant or intermittent flow. 1. www.opsimaging.net. Accessed April 2004. 2. Spronk PE, Ince C, Gardien MJ, et al. Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet. 2002; 360:1395-1396.

CORNERSTONES OF MULTIDISCIPLINARY MANAGEMENT OF SEVERE SEPSIS Prevention Screening and Early Identification Early Intervention: Source control, Blood cultures and broad spectrum antibiotics Initial Resuscitation Bundle Septic Shock Bundle 13

Prevention Handwashing Device related infections Pneumonia CLABSI CAUTI Pneumonia

CORNERSTONES OF MULTIDISCIPLINARY MANAGEMENT OF SEVERE SEPSIS Prevention Screening and Early Identification Early Intervention: Source control, Blood cultures and broad spectrum antibiotics Initial Resuscitation Bundle Septic Shock Bundle 15

Polling Question Do you have a screening process to identify patients with severe sepsis? Yes No Planning on putting one in place

Severe Sepsis Screening Tool 18

Link with current process

NQF/SSC Bundles To be completed within 3 hours of time of presentation* Measure lactate level Obtain blood cultures prior to antibiotic administration Administer broad spectrum antibiotics Administer 30ml/kg crystalloid for hypotension or lactate > 4 mmol/L * “time of presentation” is defined as the time of triage in the Emergency department or if presenting from another care venue, from the earliest chart annotation consistent with all elements of severe sepsis or septic shock ascertained through chart review

NQF/SSC Bundles To be completed within 6 hours of time of presentation 5. Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain a mean arterial pressure (MAP) of > 65mmHg 6. In the event of persistent arterial hypotension despite volume resuscitation(septic shock) or initial lactate >4mmol/L (36mg/dL): Measure central venous pressure (CVP)* Measure central venous oxygen saturation (ScvO2)* 7. Remeasure lactate if elevated* *Targets for quantitative resuscitation included in the guidelines are *CVP of >8mm Hg, ScvO2 of > 70% and lactate normalization 23

Clinical Scenario 1: Early identification and intervention 88 year old, 51.6kg,white, female admit from ED; resided in ECF History: CAD, COPD, dementia, Alzheimer disease, depression, SVT Chief Complaint: rib pain, chest congestion and SOB Awake, alert and oriented, slight combative (history of combative behavior)

Clinical Scenario 1: Early identification and intervention Initial VS: Temp: 101.6 F RR: 31 HR: 109, atrial fib with occasional SVT B/P: 79/51 2L of O2, O2 sat of 96% Does this patient screen positive for severe sepsis? Positive Screen for severe sepsis: SIRS: HR >90; RR> 20; Temp > 38 Organ dysfunction: SBP<90mmHg WHAT ARE THE NEXT STEPS? Call physician—follow SBAR Expected orders: Give fluid bolus of 20ml/kg bolus Labs drawn(lactate, CBC, ABG)

Next Steps for Early Recognition of sepsis at your ECF Is your staff knowledgeable about the importance of early recognition and management of sepsis? Do you have a sepsis screening process? Is the screening process done on a regular basis or linked with another process—IE: linked with the InterACT Early Warning Tool How can we help?

Sepsis Early Identification Action Plan Step Who? When? Status 1. Get team together to create early identification process   2. Develop screening tool/process 3.Get medical staff support for screening and early intervention 4. Develop and implement educational plan for sepsis and screening 5. Evaluate screening: define outcome and process metrics

QUESTIONS???