Severe Sepsis/ Septic Shock. Fereshte Sheybani, MD. Assistant Professor in Infectious Diseases

Transcription

1 Severe Sepsis/ Septic Shock Fereshte Sheybani, MD. Assistant Professor in Infectious Diseases

2 Sepsis is one of the oldest and most elusive syndromes in medicine. Hippocrates claimed that sepsis (σήψις) was the process by which flesh rots, swamps generate foul airs, and wounds fester.

3 With the confirmation of germ theory by Semmelweis, Pasteur, and others, sepsis was recast as a systemic infection, often described as blood poisoning, and assumed to be the result of the host's invasion by pathogenic organisms that then spread in the bloodstream.

4 However, with the advent of modern antibiotics, germ theory did not fully explain the pathogenesis of sepsis: many patients with sepsis died despite successful eradication of the inciting pathogen.

5 Thus, researchers suggested that it was the host, not the germ, that drove the pathogenesis of sepsis

6 In 1992, an international consensus panel defined sepsis as a systemic inflammatory response to infection, noting that sepsis could arise in response to multiple infectious causes and that septicemia was neither a necessary condition nor a helpful term

7 Instead, the panel proposed the term severe sepsis to describe instances in which sepsis is complicated by acute organ dysfunction, and they codified septic shock as sepsis complicated by either hypotension that is refractory to fluid resuscitation or by hyperlactatemia.

8 In 2003, a second consensus panel endorsed most of these concepts, with the caveat that signs of a systemic inflammatory response, such as tachycardia or an elevated white-cell count, occur in many infectious and noninfectious conditions and therefore are not helpful in distinguishing sepsis from other conditions.

9 Infection, SIRS, Sepsis Bone, R., Balk, R., Cerra, F., Dellinger, R., Fein, A., Knaus, W., Schein, R., et al. (1992). Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest, 101(6),

10 Thus, severe sepsis and sepsis are sometimes used interchangeably to describe the syndrome of infection complicated by acute organ dysfunction. Severe sepsis occurs as a result of both community-acquired and health care associated infections.

11 Pneumonia is the most common cause, accounting for about half of all cases, followed by intraabdominal and urinary tract infections.

12 Systemic Inflammatory Response Syndrome (SIRS) Temp > 38 or < 36 HR > 90 RR > 20 or PaCO2 < 32 WBC > 12 or < 4 or Bands > 10% Sepsis The systemic inflammatory response to infection. TWO out of four criteria acute change from baseline Severe Sepsis Organ dysfunction secondary to Sepsis. e.g. hypoperfusion, hypotension, acute lung injury, encephalopathy, acute kidney injury, coagulopathy. Septic Shock Hypotension secondary to Sepsis that is resistant to adequate fluid administration and associated with hypoperfusion. Bone, R., Balk, R., Cerra, F., Dellinger, R., Fein, A., Knaus, W., Schein, R., et al. (1992). Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest, 101(6),

13 The signs of both infection and organ dysfunction may be subtle, and thus the most recent international consensus guidelines provide a long list of warning signs of incipient sepsis

14 Guidelines for the Treatment of Severe Sepsis and Septic Shock from the Surviving Sepsis Campaign

15 The most important elements of the guidelines are organized into two bundles of care: an initial management bundle to be accomplished within 6 hours after the patient's presentation and a management bundle to be accomplished in the ICU. Implementation of the bundles is associated with an improved outcome

16 6 Hour Resuscitation Bundle Early Identification Early Antibiotics and Cultures Early Goal Directed Therapy

17 6 - hour Severe Sepsis/ Septic Shock Bundle Early Detection: Obtain serum lactate level. Early Blood Cx/Antibiotics: within 3 hours of presentation. Early EGDT: Hypotension (SBP < 90, MAP < 65) or lactate > 4 mmol/l: initial fluid bolus ml of crystalloid (or colloid equivalent) per kg of body weight. Vasopressors: Hypotension not responding to fluid Titrate to MAP > 65 mmhg. Septic shock or lactate > 4 mmol/l: CVP and ScvO 2 measured. CVP maintained >8 mmhg. MAP maintain > 65 mmhg. ScvO2<70%with CVP > 8 mmhg, MAP > 65 mmhg: PRBCs if hematocrit < 30%. Inotropes.

18 System-based Approaches to sepsis Early-Goal Directed Therapy INCLUSION = SEPSIS AND [BP < 90 after fluid OR Lactate > 4] Control Intervention EGDT CVP 8-12 Fluids CVP 8-12 MAP > 65 Vasopressors MAP > 65 Transfusions Dobutamine ScvO2 > 70% 49% mortality 33% mortality Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin, A., Knoblich, B., Peterson, E., et al. (2001). Early goal-directed therapy in the treatment of severe sepsis and septic shock. New England Journal of Medicine, 345(19),

19 System-based Approaches to sepsis Used to promote: 1. CVP > 8 as an initial target 2. Use of Svo2 monitoring and use of blood/dobutamine Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin, A., Knoblich, B., Peterson, E., et al. (2001). Early goal-directed therapy in the treatment of severe sepsis and septic shock. New England Journal of Medicine, 345(19),

20 Control EGDT 49% mortality 33% mortality...treated at the clinicians discretion according to a protocol for hemodynamic support, with Do whatever you normally do. critical-care consultation, and were admitted for inpatient care as soon as possible......treated in the emergency department (by ER attending, 2 Use a rigid protocol with multiple residents, 3 nurses) according to a dedicated team members protocol for early goal-directed therapy...for at least six hours... They did not control for the system of care. Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin, A., Knoblich, B., Peterson, E., et al. (2001). Early goal-directed therapy in the treatment of severe sepsis and septic shock. New England Journal of Medicine, 345(19),

21 Antibiotics No randomized-controlled data Time from EDGT qualification to ABX Time from hypotension to appropriate ABX Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department*. Critical Care Medicine 2010;38(4): Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock*. Critical Care Medicine 2006;34(6):

22 Antibiotics Multiple large, observational studies have shown the time to administration of antibiotics to be strongly associated with improve survival. I m not aware of a single physician that recommends withholding or slowing down the time to antibiotics in a patient with severe sepsis.

23 Intravenous antibiotic therapy should be started as early as possible and should cover all likely pathogens. Inappropriate or delayed antibiotic treatment is associated with increased mortality

24 The choice of empirical therapy depends on the suspected site of infection, the setting in which the infection developed (i.e., home, nursing home, or hospital), medical history, and local microbial-susceptibility patterns.

25 It has not been determined whether combination antimicrobial therapy produces better outcomes than adequate single-agent antibiotic therapy in patients with severe sepsis. Current guidelines recommend combination antimicrobial therapy only for neutropenic sepsis and sepsis caused by pseudomonas species.

26 Source Control No randomized-controlled data In necrotizing fasciitis, multiple case series have shown improvement with an aggressive operative approach. Sudarsky LA, Laschinger JC, Coppa GF, Spencer FC. Improved results from a standardized approach in treating patients with necrotizing fasciitis. Ann Surg 1987;206(5): Moss RL, Musemeche CA, Kosloske AM. Necrotizing fasciitis in children: Prompt recognition and aggressive therapy improve survival. J Pediatr Surg 1996;31: Freischlag JA, Ajalat G, Busuttil RW: Treatment of necrotizing soft tissue infections: The need for a new approach. Am J Surg 149: , 1985 Expert opinion supports identifying the source of infection and aggressively managing it when possible. Marshall JC, Maier RV, Jimenez M, et al. Source control in the management of severe sepsis and septic shock: an evidence-based review. Crit Care Med 2004;32:S513-26

27 Source Control Don t be satisfied with a diagnosis of sepsis and no source. If a source exists and is potentially removable, get the ball rolling.

28 Defining the severity of sepsis Importance of looking for organ failure is self evident. Identification of shock dramatically alters the treatment and mortality. Blood Pressure, Response to Fluid, LACTATE

29 Lactate Evidence is clear that Lactate levels are predictive of death and MODS. Clearance of lactate is associated with improved survival. Algorithms of care based on lactate clearance appear to work as well or better than other approaches. Jones AE, Shapiro NI, Trzeciak S, et al. Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy: A Randomized Clinical Trial. JAMA: The Journal of the American Medical Association 2010;303(8): Jansen TC, van Bommel J, Schoonderbeek FJ, et al. Early lactate-guided therapy in intensive care unit patients: a multicenter, openlabel, randomized controlled trial. American Journal of Respiratory and Critical Care Medicine 2010;182(6):

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31 Goals in resuscitation Early, quantitative resuscitation goals vs. standard care have resulted in improved mortality The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: A meta-analysis *. Jones, Alan E. MD; Brown, Michael D. MD, MSc; Trzeciak, Stephen MD, MPH; Shapiro, Nathan I. MD, MPH; Garrett, John S. MD; Heffner, Alan C. MD; Kline, Jeffrey A. MD; on behalf of the Emergency Medicine Shock Research Network investigators Critical Care Medicine. 36(10): , October 2008.

32 Goals in resuscitation Initial fluid resuscitation: CVP 8-12, MAP > 65, UOP 0.5 ml/kg/hr, ScVO2 70% and Lactate Clearance. Give enough volume to maximize stroke volume. Start with 20cc/kg in most patients. Goal? Give vasopressors to raise the MAP enough to maintain adequate end-organ perfusion. Assessment of Cardiac Function UOP and Lactate Clearance are nice global indicators of success.

33 Resuscitation Crystalloids are favored as the initial fluid Hydroxyethyl starches are likely harmful Albumin may have a role, particularly if alot of fluid is given A lower Hb target (~7) is generally accepted

34 Chronic Phase Monitor for and prevent recurrence of sepsis VAP, CLABSI, UTI. Infection Control Practices. Lung Protective Ventilator Strategies Protocolized Sedation, Daily Awakenings Nutritional Support Early Mobilization Success with these measures is most likely with a multi-disciplinary approach.

35 Summary System-based strategies are effective for improving sepsis care Processes should aim to: Identify patients early and identify the severity of sepsis Quickly administer appropriate antibiotics and source control Establish institutional goals for physiologic resuscitation Multidisciplinary chronic phase of care to ensure compliance

36 De-escalation of initial broad-spectrum therapy may prevent the emergence of resistant organisms, minimize the risk of drug toxicity, and reduce costs, and evidence from observational studies indicates that such an approach is safe

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43 As summarized by Young, Early clinical suspicion, rigorous diagnostic measures, aggressive initiation of appropriate antimicrobial therapy, comprehensive supportive care, and measures aimed at reversing predisposing causes are the cornerstones of successful management

44 Thanks for your attention Somewhere, something incredible is waiting to be known -Carl Sagan