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

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

Vad har sepsis och fotboll gemensamt?

σ ηψιζ Hippokrates (460-370 f.kr.) rot, foul smell

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

Germ theory Louis Pasteur (1822-1895) Robert Koch (1843-1910)

penicillin 1928 Alexander Flemming (1881-1951)

39 The time has come to close the book on infectious diseases. We have basically wiped out infection in the United States. the Surgeon General of the United States of America, William Stewart, 1967 ANTI- BIOTIC multiorgan failure

39 HOST THEORY multiorgan failure

Exterminate the Beast

Dr. Roger C. Bone, 1941 1997 Specialist in Pulmonary Medicine Published some 1,000 scientific articles and wrote or edited 56 books.

bacteremia sepsis International Classification of Diseases positive bloodculture sepsis

Sepsis-1 1992 SEPTIC SHOCK SEVERE SEPSIS SEPSIS Severe sepsis with hypotension despite adequate fluid resuscitation Sepsis with organ dysfunction, hypoperfusion (lactacidosis, oliguria, altered mental status), or hypotension (SBP < 90 mmhg or SBP >40 mmhg below baseline) Infection + SIRS SIRS Systemic Inflammatory Response Syndrome 2 of BT > 38 or < 36 WBC > 12 or < 4 HR > 90 RR > 20 or PaCO 2 < 4 kpa

Sepsis-2 2001 SEPTIC SHOCK Severe sepsis with hypotension (SBT < 90 mmhg or MAP < 60 mmhg or > 40 mmhg below baseline despite adequate fluid resuscitation) SEVERE SEPSIS SEPSIS SIRS Systemic Inflammatory Response Syndrome Sepsis with organ dysfunction PIRO Because of the limitations of SIRS discussed above, we included a list of possible signs (predisposition, of systemic inflammation in response to infection (Table 1). infection, response, organ dysfunction) 2 of BT > 38 or < 36 WBC > 12 or < 4 HR > 90 RR > 20 or PaCO 2 < 4 kpa

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 PaO 2 /FiO 2 <33 (27) SaO 2 86% (78%) TPK <100, INR >1,5 Bil >70 RLS SEPSIS misstänkt el. verifierad infektion SIRS= Systemic Inflammatory Response Syndrome >2 av: Temp > 38 el. <36 LPK >12 el. <4 HF >90/min SEPTISK CHOCK SVÅR SEPSIS SEPSIS + endera hypotension/ hypoperfusion/organdysfunktion + SIRS Septisk hypotension som inte svarar på adekvat mängd vätska AF >20/min el. PaCO 2 <4kPa tillsammans med hypoperfusion o/el. organdysfunktion

Of all patients with SIRS in ED only 38 % had infection Liao 2014 > 2 av: Temp > 38 el. <36 LPK >12 el. <4 HF >90/min AF >20/min el. PaCO 2 <4kPa 12 % of patients in ICU with infection and organ failure did not have SIRS Kaukonen 2015

GÅR DET ATT FÅ ORDNING PÅ ELÄNDET?

SEPSIS-3

Sepsis 3: tre nivåer 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 2016 SEPTIC SHOCK SEVERE SEPSIS SEPSIS SIRS

definition SEPSIS life-threatening organ dysfunction caused by a dysregulated host response to infection. INFEKTION DYSREGULATED HOST RESPONSE ORGAN DYSFUNCTION LIFE- THREATENING

Sepsis is life threatening organ dysfunction caused by a dysregulated host response to infection. Ok, Plato I get your point, but is this guy septic? This is Sepsis!

DIAGNOSTIC CRITERIA for SEPSIS INFECTION DYSREGULATED HOST RESPONSE ORGAN DYSFUNCTION LIFE- THREATENING

DIAGNOSTIC CRITERIA for SEPSIS INFECTION DYSREGULATED HOST RESPONSE ORGAN DYSFUNCTION LIFE- THREATENING

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

Diagnostic criteriera for SEPTIC SHOCK 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 criteria for SEPSIS 1 milion patients with infection Singer 2016

Diagnostic criteria for SEPTIC SHOCK mortality rates 42,3% 30,1% Singer 2016

SEPSIS-3 mortality risk alla with INFECTION 5% SEPSIS 10% SEPTIC SHOCK 40%

quick SOFA RR > 22 SBP < 100 GSC < 15 confirmed/suspected infection + qsofa > 2 WARNING! It can be sepsis!

Nya koder R65.2 Sepsis R65.21 Septic chock

How Do They Match Reality? SEPSIS-1 SEPSIS-2 SEPSIS-3

Sepsis 2 vs. 3 in the ICU Shankar-Hari, BJA, 2017

Sepsis 2 vs. 3 in the ICU Shock Sepsis-2 Shock Sepsis-3 Shankar-Hari, BJA, 2017

What shall we expect in the ICU when changing from Sepsis-2 to Sepsis-3 1. Same number of patients the ICU with sepsis as previously with severe sepsis, unchanged case fatality rate 2. Fewer patients in the ICU with septic chock criteria, but higher case fatality rate

SEPSIS-2 SEPSIS-3 SEPSIS SEPTIC SHOCK Sepsis: same incidence, same CFR Septic shock: lower incidence, higher CFR

BUT, HOW ARE WE CODING? SEPSIS OR SEPTIC SHOCK SEPTIC SEPSIS SHOCK SEPTIC SHOCK SEPTIC SEPSIS SHOCK: Lower incidence, higher CFR SEPSIS: Higher incidence, higher CFR

Sepsis på Svenska IVA 2017 2018 Svenska intensivvårdsregistret

ICU hospital wards

Sepsis in one Swedish Centre Ljungström 2017

Men hur skall vi ha det? SILF Magnus Brink Jonas Cronqvist SWESEM Lisa Kurland Mantas Okas SFAI Anneli Fagerberg Miklos Lipcsey SIR Johan Petersson Pär 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 SEPSIS SEPTISK CHOCK Definition: En undergrupp av sepsis där bakomliggande 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 vätskerescusitering ICD-10: R65.2 ICD-10: R65.21

National Early Warning Score 2 (NEWS-2)

Koder De 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 respiratory dysfunction PaO 2 /FiO 2 PaO 2 : partial pressure of O 2 i arterial blood FiO 2 : O 2 -fraction i inspired gas (0,21-1,0)

Simplification Aproximation Breathing room air (FiO 2 =0,21) SpO 2 92-95% 1 SOFA-point SpO 2 < 92% 2 SOFA-points

Sepsis Criteria What Reality Shall They Match? Clinical care Research basic clinical Epidemiology and 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 Va ska det vara bra för? Hmm ganska bra tror jag