What is Sepsis?New and Old Definitions, How Do They Match Reality?

Magnus Brink M.D. Ph.D.

Departement of Infectious Diseases

Sahlgrenska University Hospital

Gothenburg, Sweden

Vadhar sepsis och fotbollgemensamt?

ση̃ψιζrot, foul smell

Hippokrates(460-370 f.kr.)

“A local lesion, heated by humor afflux, makes the whole body become feverish. One can die because of this, especially on odd numbered days”

Hippocrates

Robert Koch (1843-1910)

Louis Pasteur (1822-1895)

Germ theory

penicillin 1928

Alexander Flemming (1881-1951)

multiorgan failure

39°“The time has come to close the book on infectious diseases. We have basically wipedout infection in the United States.”

the Surgeon General of the United States of America,William Stewart, 1967

ANTI-

BIOTIC

multiorgan failure

HOST THEORY39°

Exterminate the Beast

Dr. Roger C. Bone, 1941–1997Specialist in Pulmonary Medicine

Published some 1,000 scientific articles and wrote or edited 56 books.

bacteremia ≠ sepsis

positive blood-culture

sepsis

International Classification of Diseases

≥ 2 of• BT > 38° or < 36• WBC > 12 or < 4 • HR > 90• RR > 20 or PaCO2 < 4 kPa

Infection+

SIRS

Sepsis with organ dysfunction, hypoperfusion(lactacidosis, oliguria, altered mental status),

or hypotension (SBP < 90 mmHg or SBP >40 mmHg below baseline)

Severe sepsis with hypotension despite adequate fluid resuscitation

SEPSIS

SEVERESEPSIS

SEPTICSHOCK

SIRSSystemic Inflammatory Response Syndrome

Sepsis-1

1992

≥ 2 of• BT > 38° or < 36• WBC > 12 or < 4 • HR > 90• RR > 20 or PaCO2 < 4 kPa

Sepsis with organ dysfunction

Severe sepsis with hypotension (SBT < 90 mmHg or MAP < 60 mmHg or > 40 mmHg below baseline despite adequate fluid resuscitation)

“Because of the limitations of SIRSdiscussed above, we included a list of

possible signs of systemic inflammationin response to infection (Table 1)”.

SEPSIS

SEVERESEPSIS

SEPTICSHOCK

SIRSSystemic Inflammatory Response Syndrome

Sepsis-2

2001

PIRO(predisposition,

infection, response, organ dysfunction)

SIRS= Systemic Inflammatory Response Syndrome

>2 av: ● Temp > 38° el. <36° ● LPK >12 el. <4

● HF >90/min ● AF >20/min el. PaCO2 <4kPa

SEPSISmisstänkt el. verifierad infektion

+ SIRS

SEPTISK

CHOCK

SVÅR SEPSISSEPSIS + endera

hypotension/

hypoperfusion/organdysfunktion

Hypotension= SBT<90 MAP<70

Hypoperfusion=

P-laktat > 3 mmol

el. BE <-5 mmol/l

Organdysfunktion=

● oliguri <0,5 ml/kg/tim

el. krea >45 mmol/l

● PaO2/FiO2 <33 (27)

SaO2 ≈ 86% (78%)

● TPK <100,

INR >1,5

● RLS

● Bil >70

Septisk hypotensionsom inte svarar

på adekvat

mängd

vätska

tillsammans med

hypoperfusion

o/el. organ-

dysfunktion

12 % of patients in ICU with infection and organ failure did not have SIRS Kaukonen 2015

Of all patients with SIRS in EDonly 38 % had infection Liao 2014

> 2 av: ● Temp > 38° el. <36° ● LPK >12 el. <4

● HF >90/min ● AF >20/min el. PaCO2 <4kPa

GÅR DET ATT FÅ ORDNING PÅ ELÄNDET?

SEPSIS-3

DEFINITIONER

ANGER VAD VI UTIFRÅN VÅR NUVARANDE

KUNSKAPSHORISONT ANSER ATT SEPSIS ÄR

SVAR PÅ FRÅGAN:VAD ÄR SEPSIS?

DIAGNOSTISKA KRITERIER

ANGER KRITERIER FÖR ATT FASTSTÄLLA SEPSISDIAGNOS HOS ENSKILDA PATIENTER

SVAR PÅ FRÅGAN:VEM HAR (HAFT)

SEPSIS?

SCREENING

VERKTYG FÖR TIDIG KLINISK

IDENTIFIERING AV PATIENTER SOM KAN HA SEPSIS

SVAR PÅ FRÅGAN:VEM KAN HA

SEPSIS?

Sepsis 3: tre nivåer

SIRS

SEPSIS

SEPTIC

SHOCK

SEVERE SEPSISSEPSIS

Sepsis-3

2016

definition SEPSIS

life-threatening organ dysfunction caused by a dysregulated host

response to infection.

INFEKTIONDYSREGULATEDHOST RESPONSE

ORGANDYSFUNCTION

LIFE-THREATENING

Sepsis is life threatening

organ dysfunction caused

by a dysregulated host

response to infection.

This is Sepsis!

Ok, Plato I get your point, but is this

guy septic?

DIAGNOSTIC CRITERIA for SEPSIS

INFECTIONDYSREGULATEDHOST RESPONSE

ORGANDYSFUNCTION

LIFE-THREATENING

INFECTIONDYSREGULATEDHOST RESPONSE

ORGANDYSFUNCTION

LIFE-THREATENING

DIAGNOSTIC CRITERIA for SEPSIS

0-24

Diagnostic criteriera for SEPSIS

infection

+an acuet increase

of≥ 2 SOFA-points

definition SEPTIC SHOCK

a subset of sepsis in which underlying

circulatory and cellular metabolism

abnormalities are profound enough

to substantially increase mortality

Persisting hypotension requiring

vasopressors to maintain MAP 65 mmHg

and having a serum lactate level

>2 mmol/L (18mg/dL) despite adequate

volume resuscitation

Diagnostic criteriera for

SEPTIC SHOCK

≈ 1 milion patients with infection

Singer 2016

Diagnostic criteria

for SEPSIS

42,3% 30,1%

Singer 2016

Diagnostic criteria for SEPTIC SHOCK

mortality rates

SEPSIS-3

mortality risk

alla with INFECTION 5%

SEPSIS 10%

SEPTIC SHOCK 40%

quick SOFA

confirmed/suspected infection + qSOFA > 2

WARNING! It can be sepsis!

RR

> 22

SBP

< 100GSC

< 15

Nya koder

R65.2 Sepsis

R65.21 Septic chock

SEPSIS-2

How Do They Match Reality?

SEPSIS-1

SEPSIS-3

Sepsis 2 vs. 3

in the ICU

Shankar-Hari, BJA, 2017

Sepsis 2 vs. 3

in the ICU

Shankar-Hari, BJA, 2017

Shock Sepsis-3

Shock Sepsis-2

2. Fewer patients in the ICU with septic chock criteria,

but higher case fatality rate

1. Same number of patients the ICU with sepsisas previously with severe sepsis, unchanged case fatality rate

What shall we expect in the ICU when

changing from Sepsis-2 to Sepsis-3

SEPSIS

SEPTICSHOCK

SEPTICSHOCK

• Sepsis: same incidence, same CFR

• Septic shock: lower incidence, higher CFR

SEPSIS-2 → SEPSIS-3

SEPSISSEPSISSEPTIC

SHOCK

SEPTICSHOCK

SEPSIS SEPTIC SHOCK:Lower incidence, higher CFR

SEPSIS:Higher incidence, higher CFR

BUT, HOW ARE WE CODING?

SEPSIS OR SEPTIC SHOCK

Sepsis på Svenska IVA 2017–2018

Svenska intensivvårdsregistret

ICU

hospitalwards

Sepsis in one Swedish Centre

Ljungström 2017

Men hur skall vi ha det?

SILFMagnus BrinkJonas Cronqvist

SWESEMLisa KurlandMantas Okas

SFAIAnneli FagerbergMiklos Lipcsey

SIRJohan PeterssonPär Lindgren

SEPSIS-3 i Sverige

Definition:Livshotande organdysfunktion som

orsakas av ett stört systemiskt svar på infektion

Diagnostiska kriterier:infektionsutlöst akut ökning≥ 2 SOFA-poäng

Screening utanför IVA:infektion med≥ 2 qSOFA

ICD-10: R65.2

Definition:En undergrupp av sepsis där bakom-liggande cirkulatoriska och cellulära / metabola störningar är tillräckligt uttalade för att avsevärt öka dödligheten

Diagnostiska kriterier:Kvarstående hypotension som kräver vasopressor för att upprätthålla MAP ≥65 mmHg tillsammans med laktat >2 mmol/L trots adekvat vätske-rescusitering

ICD-10: R65.21

SEPSIS SEPTISK CHOCK

✔ ✔

✔

✔

✗

✗ ✗

National Early Warning Score 2 (NEWS-2)

KoderDe föreslagna koderna (R65.2, R65.21) kan bara användas I USA

Lösning: Återanvändning av de gamla sepsiskoderna:

R65.1 Sepsis

R57.2 Septisk chock

Inga fastställda tidsgränser

Maximalt tidsintervall för SOFA-poäng?

Vårt beslut: max 36 timmar

The main SOFA-problem outside ICU

Grading of respiratorydysfunction

PaO2/FiO2PaO2: partial pressure of O2 i arterial bloodFiO2: O2-fraction i inspired gas (0,21-1,0)

Simplification Aproximation

Breathing room air (FiO2=0,21)

SpO2 92-95% – 1 SOFA-pointSpO2 < 92% – 2 SOFA-points

Clinical care

Sepsis CriteriaWhat Reality Shall They Match?

Researchbasic

clinical

Epidemiologyand

surveillance

Quality improvement

and audit

an exercise in pragmatism

How has Sepsis-3 been received?

Parts of SEPSIS-3 that were not so good

Process

• Some key specialities (e.g. Emergency Medicine) were not involved

• Underrepresentation from resource poor settings

Content

• Suggested codes (R 65.2, R 65.21) not universally accept by WHO

• No timeframe for SOFA-scoring

• SOFA is not an optimal tool for grading of organ failure outside ICU

• The calibration of SOFA (≥2 for sepsis) can be questioned

EXTRA

Sepsis-3

Nu även

i Sverige

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