SEPSIS & SEPTIC SHOCK

SEPSIS & SEPTIC SHOCK

DISCLOSURE Relevant relationships with commercial entities none Potential for conflicts of interest within this presentation none Steps taken to review and mitigate potential bias N/A

LEARNING OBJECTIVES This lecture is designed to meet the following end-of-week learning objective: 1. To describe sepsis and septic shock and understand the implications of patients presenting with either syndrome

MODULE OBJECTIVES By the end of this module, you should be able to: 1. Define, according to the 2016 consensus definitions, sepsis and septic shock 2. Understand how the host response to infection results in sepsis 3. Identify key principles of management for sepsis and septic shock

YOUR PATIENT A 63-year-old woman with a history of recurrent urinary tract infections She presents with: Burning with urination followed by pain in the right back/flank 1 episode of vomiting You diagnose a kidney infection (pyelonephritis) The case presented here is fictitious and used for illustrative purposes only. Any resemblance to a real person, living or dead, is purely coincidental.

YOUR PATIENT As you are assessing your patient, her vital signs change: T = 38.9 o C T = 37 o C HR 110 bpm HR = 90 bpm RR of 18/min RR = 24/min BP 110/70 mmhg BP = 98/64 mmhg She is drowsy and harder to rouse The case presented here is fictitious and used for illustrative purposes only. Any resemblance to a real person, living or dead, is purely coincidental.

SEPSIS Life-threatening organ dysfunction caused by a dysregulated host response to infection Organ dysfunction is identified by a change in baseline SOFA score 2 points In-hospital mortality > 10% Bone RC, et al. Chest. 1992; 101: 1644-1655. Munford RS, Suffredini AF. Chapter 70: Sepsis, Severe Sepsis, and Septic Shock. in Principles and Practices of Infectious Diseases. 7 th ed. 2010. Singer M, et al. JAMA. 2016;315(8):801-810.

SOFA (SEQUENTIAL ORGAN FAILURE ASSESSMENT) SCORE 1. Respiratory failure 2. Cardiovascular failure 3. Liver dysfunction 4. Renal dysfunction 5. Thrombotic dysfunction 6. Neurologic abnormalities Singer M, et al. JAMA. 2016;315(8):801-810. Vincent JL, et al. Crit Care Med. Nov;26(11):1793-800. 1998.

SEPTIC SHOCK Profound circulatory, cellular, and metabolic abnormalities associated with a greater risk of mortality than with sepsis alone Serum lactate is elevated (organ hypoperfusion) despite IV fluids, and Medications to support blood pressure ( vasopressors ) are required In-hospital mortality > 40% Singer M, et al. JAMA. 2016;315(8):801-810. Shankar-Hari M, et al. JAMA. 2016;315(8):775-787.

KEY CONCEPT #1: Infection to septic shock is a continuum of disease severity Infection Sepsis Septic Shock Bone RC, et al. Chest. 1992; 101: 1644-1655. Graphic copyright Dr. A. Page.

KEY CONCEPT #2: Recognizing patients at risk for sepsis can be life-saving

QUICK SOFA (qsofa) SCORE Out-of-hospital, ED and ward patients Poor outcome likely if 2 of 3 is present: Investigate for organ dysfunction, advance therapy, and/or consider ICU Singer M, et al. JAMA. 2016;315(8):801-810.

YOUR PATIENT As you are assessing your patient, her vital signs change: T = 38.9 o C T = 37 o C HR 110 bpm HR = 90 bpm RR of 18/min RR = 24/min BP 110/70 mmhg BP = 98/64 mmhg She is drowsy and harder to rouse The case presented here is fictitious and used for illustrative purposes only. Any resemblance to a real person, living or dead, is purely coincidental.

Singer M, et al. JAMA. 2016;315(8):801-810.

KEY CONCEPT #3: Sepsis involves exaggerated proand anti- inflammatory responses (as well as changes in many nonimmune pathways) Singer M, et al. JAMA. 2016;315(8):801-810.

Vascular permeability Platelet adherence Vasodilation Antiinflammatory mediators Adaptive Delivery of white blood cells, etc Wall off site of infection Local blood flow Limits inflammation Infection resolves Maladaptive Low blood pressure, fluid leak into tissues Excess clotting Tissue hypoxia at other sites, serum lactate Net state of immunosuppression Sepsis Munford RS, Suffredini AF. Chapter 70: Sepsis, Severe Sepsis, and Septic Shock. in Principles and Practices of Infectious Diseases. 7 th ed. 2010. Graphic copyright Dr. A. Page.

WHY DID YOUR PATIENT DEVELOP SEPSIS? Bacteria ascend in the urinary tract A systemic inflammatory response occurs to control the infection The systemic inflammatory response becomes dysregulated Bladder infection with burning on urination (cystitis) Bacteria ascend to the kidney and cause back/flank pain (pyelonephritis) Vasodilation, vascular leak, excess clotting, etc occur Your patient feels unwell, but not enough to seek medical attention The local inflammatory response became insufficient Sepsis, and possibly, septic shock Initial, local inflammatory response occurs in the bladder The local inflammatory response is adaptive and limited Resolution of Infection The case presented here is fictitious and used for illustrative purposes only. Any resemblance to a real person, living or dead, is purely coincidental.

KEY CONCEPT #4: The pathogenesis of sepsis guides the treatment of sepsis Since sepsis results from an inciting infection and the resulting dysregulated immune response: 1. Treat the inciting infection 2. Provide supportive care to address immune dysregulation and the organ dysfunction it causes Dellinger RP, et al. Intensive Care Med. Feb;39(2):165-228. 2013.

1. Treat the inciting infection Broad-spectrum antimicrobial agents that can treat many types of bacteria Narrow once a pathogen is identified Source Control Remove sources of infection where possible E.g., repair bowel leaks and drain abscesses (pockets of pus) Dellinger RP, et al. Intensive Care Med. Feb;39(2):165-228. 2013.

The Importance of the Correct Empiric Antimicrobial Therapy Kumar A, et al. Crit Care Med. Jun;34(6):1589-96. 2006.

KEY CONCEPT #5: Delays in appropriate empiric antimicrobial therapy increase mortality.

2. Address the effects of the dysregulated immune response Early Goal-directed Therapy Objective: Ensure adequate organ perfusion Early : Treatment begins in the ED, within 3 hours of presentation Goal-directed : Specific targets for near-normal physiologic function Rivers E, et al. New Engl J Med. Nov 8;345(19):1368-77.2001. Dellinger RP, et al. Intensive Care Med. Feb;39(2):165-228. 2013.

2. Address the effects of the dysregulated immune response Early Goal-directed Therapy 1. Measure serum lactate 2. Administer intravenous fluids to target normal/near-normal serum lactate and blood pressure (BP) 3. Use medications to support BP ( vasopressors ) in septic shock 4. Be aware: Treatment for sepsis/septic shock is evolving! Rivers E, et al. New Engl J Med. Nov 8;345(19):1368-77.2001. Dellinger RP, et al. Intensive Care Med. Feb;39(2):165-228. 2013. ProCESS Investigators. Yealy DM et al. N Engl J Med. 2014 May 1;370(18):1683-93.

YOUR PATIENT She has a positive qsofa score After performing additional lab tests, you determine that she also has a SOFA score 2 points above baseline After making the diagnosis of sepsis, you: Prescribe broad spectrum antimicrobials Administer intravenous fluids to support her BP Monitor lactate and BP closely The case presented here is fictitious and used for illustrative purposes only. Any resemblance to a real person, living or dead, is purely coincidental.

KEY MESSAGES 1. Sepsis is on a continuum from infection to septic shock 2. Sepsis involves exaggerated pro- and antiinflammatory responses and non-immune pathways 3. Sepsis and septic shock are medical emergencies that require prompt therapy Early appropriate empiric antimicrobial agents Early goal-directed therapy

MODULE OBJECTIVES By now you should be able to: 1. Define, according to the 2016 consensus definitions, sepsis and septic shock 2. Understand how the host response to infection results in sepsis 3. Identify key principles of management for sepsis and septic shock