Arzu TOPELİ İSKİT

Hacettepe University Faculty of Medicine, Director of MICU

Council Memeber of WFSICCM

What is new after sepsis guideline?

Presentation Plan

• What is new in sepsis epidemiology?

• What is new in sepsis diagnosis?

• What is new in sepsis management?

What is new in sepsis epidemiology?

World Sepsis Declaration

• Sepsis is frequent but less known

in the world.

• Sepsis affects 20-30 million people

each year.

▫ 300->1000 / 100.000 people

• In the last decade incidence

increased bu 13%/yr.

• One person dies every 1-2 sec due

to sepsis.

Sepsis Mandates:  Improving Inpatient Care While Advancing Quality Improvement

• Mortality rate in acute myocadial infarction,

congestive heart failure and pneumonia

<10%.

• ½ deaths in the hospital are due to sepsis.

Cooke & Iwashyna. JAMA 2014;312(14):1397.

Sepsis is a public health problem !

Crit Care Med 2014; Sep.

Ani, et al. Crit Care Med 2014; Sep.

What is new in sepsis diagnosis?

Sepsis is a systemic inflammatory response to infection.

ACCP/SCCM 1992

Septic

shock +MO

F

SEPSIS

ACCP/SCCM 1992

2001 International Sepsis Conference

Zhao H, et al. Crit Care Med 2012;40:1700

Severe Sepsis

Refractory hypotension Septic shock

Sensitivity

0.77

Specificity

0.79

AUC 0.85

• Sepsis is the host’s deleterious and non-resolving

inflammatory response

to infection leading to organ dysfunction

▫ Cardiovascular

▫ Respiratory

▫ Renal

▫ Neurologic

▫ Hepatic

▫ Coagulation

▫ Gut

▫ Endocrine

«… we believe evidence of organ

dysfunction should be included in the

criteria for sepsis—ie, sepsis should be

defined as a systemic response to infection

with the presence of some degree of organ

dysfunction…»

What is new in sepsis management?

Sepsis Campaign: 2002

ISF(International Sepsis Forum)

IHI(Institute for

Healthcare

Improvement)

SCCM

ESICM

GUIDELINES

BUNDLES

Aim: Decrease in mortality RR by

25% in 5 yrs

Sepsis Campaign/Guidelines

2002 Barcelona

Declaration

2004Guideline

2008Guideline

2012 Guideline

AwarenessEarly diagnosis

Rapid appropriate treatmentEducation

Intervention beyond ICULocal and global guidelines

Similarities in 2004 – 2008 – 2012 Guidelines• EGDT – 6 hrs

• Antibiotics – 1 hr

• Infection management

• Prophylaxies and general management

• Use of blood product use

• Sedation management

• Mechanical ventilation management

• Renal replacement therapies

• …

Main Points Emphasized in the Last Guideline• Protocol based resuscitation targeting specific physiologic

targets

• Antibiotic treatment in 1 hr after clinical diagnosis

• Preferential use of crystalloids in volume resuscitation

• Preferential use of nor-epinephrine as vasopressor

• Not using corticosteroids routinely if shock state is

controlled with fluids and vasopressors

• Use of lactate and clearence for monitorization of tissue

hypoperfusion

Compliance to Bundles

•Around 20% (25 000 pt)

Levy, et al. Lancet Infect Dis 2012;12:919Levy, et al. Intensive Care Med 2014; Oct.

Recombinant human activated protein C for adults with septic shock: a randomized controlled trialAnnane D, et al. APROCCHSS Trial Investigators.

•No difference between placebo and

APC in mortality

Am J Respir Crit Care Med 2013 May 15;187:1091

Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial. Annane D, et al. JAMA 2013 Nov 6;310:1809

•Similar 28 d mortality; lower 90 d

mortality in the colloid group

•More ventilator and vasopressor free

days in the colloid group

•Protocol driven EGDT

▫Protocol of the first EGDT trial …

•Protocol driven standard therapy

▫Reaching goals in 6 hr: peripheral

catheter, hourly monitorization, SBP,

shock index

•Usual treatment

80-85 mmHg-

65-70 mmHg

•EGDT vs standard treatment

•More fluid, vasopressor, dobutamin

and blood product use in EGDT group

•No difference in mortality

• 80 mg Enteral Simvastatin 28 d vs placebo

• Similar mortality and ventilator free days

N Engl J Med 2014; 371:1695

Doig, et al. ANZICS CTG. JAMA 2013;309:2130

• Early EN vs PN

• Similar calories

• Less vomitting and hypoglycemia in PN

• Similar infection rates and mortality

For 96 hrs heart rate 80-94 bpm

Less fluid and norepi use and SVI in esmolol group

New Agents• A randomized, double-blind, placebo-controlled, Phase 2b study to

evaluate the safety and efficacy of recombinant human soluble

thrombomodulin, ART-123, in patients with sepsis and suspected

disseminated intravascular coagulation. Vincent JL, et al. Crit Care

Med 2013 Sep;41:2069

▫ Safe

• A phase 2 randomized, double-blind, placebo-controlled study of

the safety and efficacy of talactoferrin in patients with severe

sepsis. Guntupalli K, et al. TLF LF-0801 Investigator Group. Crit

Care Med 2013 Mar;41:706

▫ Decrease in 28 d and 6 mo mortality by use of Talactoferrin which is a

recombinant human laktoferrin

Ungoing Studies• A protocol for a multicentre randomised controlled trial of continuous beta-

lactam infusion compared with intermittent beta-lactam dosing in critically ill patients with severe sepsis: the BLING II study. ANZICS CTG

• The ADRENAL study protocol: adjunctive corticosteroid treatment in critically ill patients with septic shock. ANZICS CTG

• Enteral vs. intravenous ICU sedation management: study protocol for a randomized controlled trial. SedaEN investigators

• Medical education for sepsis source control and antibiotics: The MEDUSA study

• HEROICS study

• Sepsis pathophysiological & organisational timing: The SPOT(Light) study

• Placebo controlled trial of sodium selenite and procalcitonin guided antimicrobial therapy in severe sepsis (SISPCT)

>100 Phase III Studies with (-) Results• Corticosteroids

• Agents targeting LPS or TLR-

4

• Agents targeting TNF

• Agents targeting IL-1

• Agents targeting PAF

• Agents targeting coagulation

cascade

• Agents up-regulating immune

function

• Others

▫ NOS inhibitors

▫ Ibuprofen

▫ Pentoxifylline

▫ NAC

• …

SIRS

CARS

Hotchkiss, et al. Lancet Infect Dis 2013;13:260.

In Summary …• Sepsis is a public health problem with increasing incidence.

• More than 10 yrs ago sepsis campaign was established to

increase awareness and improve survival.

• 3 guidelines was published the last of which in February

2013.

• Although there is some decrease in mortality, compliance to

guidelines and bundles is still low.

• An advance in diagnosis and treatment has not been

observed so far.

Thank you …atopeli@hacettepe.edu.tr