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