severe sepsis/ septic shock - mums.ac.ir · with the confirmation of germ theory by semmelweis,...
TRANSCRIPT
Severe Sepsis/
Septic Shock
Fereshte Sheybani, MD.
Assistant Professor in Infectious Diseases
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.
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.
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.
Thus, researchers suggested that it was the host,
not the germ, that drove the pathogenesis of sepsis
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
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.
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.
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), 1644–1655.
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.
Pneumonia is the most common cause, accounting for about half of
all cases, followed by intraabdominal and urinary tract
infections.
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.
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), 1644–1655.
TWO out of four criteria
acute change from baseline
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
Guidelines for the Treatment of Severe
Sepsis and Septic Shock from the
Surviving Sepsis Campaign
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
6 Hour Resuscitation Bundle
• Early Identification
• Early Antibiotics and
Cultures
• Early Goal Directed
Therapy
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 20-40 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 ScvO2 measured.
– CVP maintained >8 mmHg.
– MAP maintain > 65 mmHg.
• ScvO2<70%with CVP > 8 mmHg, MAP > 65 mmHg:
– PRBCs if hematocrit < 30%.
– Inotropes.
System-based Approaches to sepsis
Early-Goal Directed Therapy INCLUSION = SEPSIS AND [BP < 90 after fluid OR Lactate > 4]
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), 1368–1377.
Control Intervention EGDT
System-based Approaches to sepsis
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), 1368–1377.
Used to promote:
1. CVP > 8 as an initial target
2. Use of Svo2 monitoring and
use of blood/dobutamine
Control EGDT
49% mortality 33% mortality
...treated at the clinicians’
discretion according to a protocol
for hemodynamic support, with
critical-care consultation, and
were admitted for inpatient care as
soon as possible...
...treated in the emergency
department (by ER attending, 2
residents, 3 nurses) according to a
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), 1368–1377.
Do whatever you normally do. Use a rigid protocol with multiple
dedicated team members
Antibiotics
No randomized-controlled data
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):1045–53.
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):1589–96.
Time from EDGT qualification to ABX
Time from hypotension to appropriate ABX
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.
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
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.
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.
Source Control
No randomized-controlled data
Moss RL, Musemeche CA, Kosloske AM. Necrotizing fasciitis in children: Prompt recognition and aggressive therapy improve survival. J Pediatr Surg 1996;31:1142-6.
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
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):661–5.
Freischlag JA, Ajalat G, Busuttil RW: Treatment of necrotizing soft tissue infections: The need for a new approach. Am J Surg 149:751-755, 1985
In necrotizing fasciitis, multiple case series have shown improvement with an
aggressive operative approach.
Expert opinion supports identifying the source of infection and aggressively managing
it when possible.
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.
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
Lactate
Jansen TC, van Bommel J, Schoonderbeek FJ, et al. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-
label, randomized controlled trial. American Journal of Respiratory and Critical Care Medicine 2010;182(6):752–61.
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):739–46.
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):2734-2739, October 2008.
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.
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
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.
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
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
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
Somewhere, something incredible is waiting to be known -Carl Sagan
Thanks for your attention