iv corso sepsi in ostetricia m. franchi & co · lo shock settico è la forma più grave di...

Azienda Ospedaliera Universitaria Integrata di Verona

Ginecologia e Ostetricia

IV°Corso

Sepsi in Ostetricia

M. Franchi & Co



Introduzione e Metodologica Storica

Fisiopatologia

Valutazione clinica specifica

Definizioni attuali e quadri clinici

Sepsi associata alla gravidanza

Post parto/aborto

In Gravidanza TSS

Indirizzi Operativi Regionali e Nazionali

Conclusioni

Casi Clinici

Casi Clinici

Linee Guida e «Bundle»

Nessuna disclosure

Gestione di 36 000 parti circa

2003-2017

(2 casi in Altra Sede/1 Caso in Consulenza Esterna)

SEPSI Intervento esito

Post TC 21 gg Isterectomia Totale Guarita

Post Ematoma da TC

18° gg Isterectomia Totale Guarita

Post TC e relaparotomia

per sospetta fascite 6gg

Laparotomia 11° gg

Isterectomia Totale Necrosectomia

Addominale

Guarita

Ricostruzione parete

addominale

Post TC per MEF

reintervento in 3 gg per

peritonite

16 gg fistola entero

uterina

Isterectomia Sub Totale

Necrosectomia

Addominale Ileostomia

Guarita*

Post Tc reintervento

14gg Isterectomia Totale

Reintervento per

ascesso sottofasciale

Fistola vescico-

vaginale*

Shock Settico Intervento esito

Post aborto criminale

oltre 20a sett Revisione Strumentale

DECEDUTA

MOF/DIC

Emorragia Cerebrale

TTS alla 36 a sett Isterectomia Totale DECEDUTA

MOF/DIC**

Azienda Ospedaliera Universitaria Integrata di Verona Ginecologia e Ostetricia



Edwin Smith Papyrus NY Academy of Medicine

Luxor Egypt 1980: 3000-2500 BC

The word Infection mentined for the first time in hystory

Prevention and Curing Infection with honey



The term “sepsis” dates back

to at least the time of Hippocrates (460-370BC),

who considered it the process by

which flesh rots and wounds fester.

More recently, it has been defined

as life-threatening organ

dysfunction resulting from infection.

Greek word:spsis= make rotten

History of Sepsis



Herrman Boerhave

(1668-1738)

A Dutch Botanist, Chemist, Christian Humanist,

and Physician of European fame in Leyden.

He tought that toxic substances in the air

were the cause of sepsis



"Sepsis is present if a focus has developed

from which pathogenic bacteria, constantly

or periodically, invade the blood stream in

such a way that this causes subjective and

objective symptoms."

"A therapy should not be directed against

bacteria in the blood but against the released

bacterial toxins (...)."

Modern definition of Sepsis

(1914)

Hugo Schottmuller

(1867-1936) Eppendorf Hospital

Germany



In 1989 R Bone offered a sepsis

definition that is still valid

until today

"Sepsis is defined as an invasion of

microorganisms and/or their toxins into the

bloodstream, along with the organism's

reaction against this invasion."

Roger C. Bone

(1941-1997)



A 1991 consensus conference developed initial definitions

that focused on the then-prevailing view that sepsis resulted from

a host’s systemic inflammatory response syndrome (SIRS) to

infection

Adapted from: Bone RC et al Crit Care Med 1992;20:864-74

Angus DC, Van der Poll T NEJM 2013;369:840-51




Presence of

Organ Dysfunction

Ospite Pathogen

Factors

Host Factors

Age,Sex,Race,Genetic,

Pregnancy,

Comorbidities,

Environment

Evolve

over the time

Aberrant/dysregulated

host response

(not present in infection)

In a patient with (or suspected) infection.



Sepsis is not a specific illness but rather a syndrome

encompassing

a still-uncertain pathobiology

It can be identified by a

constellation of clinical signs and symptoms

Singer M et al JAMA 2016;315:801-10

Sepsis is a life-threatening condition that arises when

the body’s response to infection injures its own

tissues

ICD-9 Sepsi = 995.92

La disfunzione d’organo va identificata dalla variazione acuta

del SOFA Score da 0 a ≥ 2 (VN: 0)

SOFA ≥ 2

Nella popolazione ospedaliera con infezione

sospetta la mortalità è circa del 10%

con possibile rapido peggioramento e

deterioramento delle condizioni generali

Si definisce Sepsi una disfunzione d’organo

pericolosa per la vita

causata da un alterata risposta all’infezione*

che va sempre provata o fortemente sospettata



*in puerpere/ pazienti sottoposte a chirurgia O&G diagnosi differenziale

tra disfunzione d’organo non da causa infettiva

ICD-10 Sepsi = R 65.20

Si definisce shock settico la

Sepsi con persistente ipotensione

per cui è necessario l’impiego di vasopressori

per mantenere una MAP ≥ 65mmHg

e con concentrazioni nel sangue arterioso

di lattati >2 mmol/Lin

In appropriato ripristino volemico



ICD-9 Shock Settico = 785.52

Lo shock settico è la forma più grave di sepsi in cui

le alterazioni circolatorie e del metabolismo cellulare

sono così gravi da incrementare sostanzialmente il rischio di morte

In tali condizioni la mortalità

è superiore al 40%

ICD-10 Shock Settico = R 65.21



Vincent JL et al Int Care Med 1996;22:707-10

Vincent JL et al Crit Care Med 1998;261793-1800


SOFA Score

Sepsis-related Organ Failure Assessment



Quando due delle tre variabili sono presenti nella paziente

con sospetta/accertata infezione

il loro potere predittivo simile a quello del SOFA

AUROC 0.81(CI, 0.80-0.82)

Ipotensione (PASistolica<100mmHg)

Alterazione dello stato mentale

(Glasgow Coma Scale<13)

Tachipnea (>22 atti respiratori/minuto)

Seymour CW et al JAMA 2016; 315:762-74



Teasdale G, Jennet B Lancet 1974;13(7872):81-4

http://www.universitystory.gla.ac.uk/images/UGSP01022.jpg



Pressione arteriosa media

(MAP)

Pdiastolica+(Psistolica-Pdiastolica/3)

La pressione arteriosa media esprime

l'andamento medio della pressione arteriosa

nell'intervallo di tempo di un ciclo cardiaco

È il miglior indice di perfusione degli organi

Si differenzia dalla pressione

differenziale/pulsazione

(pulse pressure Psistolica-Pdiastolica)



SV02 = 60-80%

Saturazione venosa dell’Ossigeno

Lactate and Shock ipoperfusion

Global tissue hypoxia

Anaerobic

metabolism

Shock cellular

metabolic failure

Decrease clearance

by the liver

Stressed/no tissue hypoxia

Lactate<2 mm/L*

Lactic acidosis

Lactate >4 mm/L

*Normal Value: 0.5-1 mm/L



Iskander KM et al Physiol Rev 2013;93:1247–88

*An episode of hypotension represented the initial onset of SS

Hypotension: mean 65 mmHg; systolic 90; decrease in systolic 40

Persistent hypotension

Persitent hypotension despite 2 L of saline or equivalent

Recurrent hypotension

Only transiently improved (hypotension resolution for 1 hr) with fluid resuscitation

14 ICU-10 Hosp

1989-2004

2,731 SS*

Kumar A et al Crit Care Med 2006;34:1589-96


Over the first 6 hrs after recurrent/persistenthypotension

each hour of delay in antimicrobial therapy

mean decrease in survival of 7.6%

(range 3.6 –9.9%)

Hrs

http://images.google.ca/imgres?imgurl=http://ec.europa.eu/education/img/flags/usa.gif&imgrefurl=http://ec.europa.eu/education/programmes/eu-usa/index_en.html&h=329&w=492&sz=6&hl=en&start=1&tbnid=Rk5l56U0QzbEqM:&tbnh=87&tbnw=130&prev=/images?q%3DUSA%2BFLAGS%26gbv%3D2%26svnum%3D10%26hl%3Den%26sa%3DG



*Same very low quality of the evidence

for </>2;3;4;5;6 hours intervals

*

Studies comparing the effectiveness of early (up to 12h)

antimicrobial therapies versus delayed administration

as initial treatment of sepis/septic shock

20 Cohort Studies no RCT:

NICE guideline N 51 july 2016

http://www.nhsdirect.nhs.uk/index.asp

Rivers E et al N Engl J Med 2001;345:1368-77

RCT: 263 pts enrolled

130 Six hours of early goal-directed therapy*

133 Standard therapy (controls)*

1997-2000

*before admission to the ICU


Angus DC et al Int Care Med 2015;411549-60




Patterns of ICU utilization are un inappropriate proxy

for study of the burden of severe maternal-morbidity or

near miss events in high-resource health care

environment with high supply of ICU beds

Oud L Infect Dis Ther 2014;3:175-89

Oud L J Clin Med 2017;9-143-53

Many existing terms (eg, sepsis,

severe sepsis) are used interchangeably, whereas

others areredundant (eg, sepsis syndrome)

or overly narrow (eg, septicemia,SIRS).

Inconsistent strategies in selecting

International Classification of

Diseases, Ninth Revision (ICD-9), and ICD-10 codes

have compounded the problem

As it provided us a construct on how to understand

resuscitation:

Start early- (give antibiotics)

Correct hypovolaemia

Restore perfusion pressure

And in some cases a little more may be required..!

These concepts are as important today as they ever were


90%

of scottish consultant/senior trainer

obstetricians have personal experience of

postpartum hysterectomy

whereas

only 40% have such experience of internal

iliac ligation


19:00 - 20:30

Taglio cesareo secondo Stark modificato Prolungamento II stadio (37+5)

Laparotomia secono Pfannestiel, isterotomia trasversale segmentaria. LA chiaro,

estrazione per il vertice di feto di sesso maschile vivo che risulta estremamente difficoltosa

per il notevole spessore della parete addominale. Viene affidato alle cure del pediatra

presente in sala. Secondamento spontaneo completo. Isterorrafia difficoltosa per

prolungamento della breccia uterina verso la vagina. Posizionamento di drenaggio

tubolare in addome a caduta. Utero contratto dopo uterotonici. Controllo integrità

vescicale (blu di metilene) negativa. Annessi nella norma. Chiusura a strati della parete

senza peritoneizzazione, drenaggio easy flow sottocutaneo, sutura cutanea a punti staccati

riassorbibile.

Perdita ematica: leggermente superiore alla norma.

Neonato: Sesso M, Peso 3730 g, APGAR 4 - 7 - 9, pH 7.2



Versamento imbibisce le fasce pararenali sia anteriore che posteriore di destra, e lo spazio

lateroconale omolaterale. Utero post-gravidico, globoso, latero-deviato a sinistra da grossolana

formazione espansiva iperdensa in fase precontrastografica, con significato di ematoma di

recente insorgenza, esso divarica i foglietti del legamento largo con maggior asse sagittale e

trasversale di 10 cm. In fase arteriosa un vaso di piccolo calibro che decorre lungo il miometrio

della porzione laterale destra dell’utero, si dispone a contornare ventralmente l’ematoma

(possibile rifornimento); versamento ematico si dispone anche lungo la faccia mesorettale destra

e nella fossetta ischiorettale omolaterale contornando il retto.


Ia giornata anemizzazione

7a giornata

(Trasfuse 3 GRC)

Dimissione, in buone condizioni generali, stazionarietà

della raccolta confermata da una seconda TAC

14-15a giornata

Febbre domiciliare trattata con paracetamolo

18a giornata: Metrorragia imponenente

Viene condotta in PS di altro

ospedale : Hb 5.0 g/dL trasfusa

con 4 U GRC

Ns osservazione

Tachipnea 18/20 atti/min

PA 90/60, FC 110 bpm, SpO2 99%


Massa ascessuale

con bolle gassose

Utero infarcito

con bolle gassose


Quadro laparotomico iniziale


Emoperitoneo

Raccolta ascessuale emipelvi dx


Ematoma emipelvi dx


Deiscenza precedente sutura uterina


Isterectomia

DX

SX


Isterectomia


Parete Ascessuale


Rimozione Completa Ascesso

Cupola vaginale

Uretere

destro


Annesso di

destra

Collo uterino


Precedente sutura

uterina Ovaio destro

Tuba destra

Ovaio e tuba uterina con marcato edema

stromale, periviscerite talora a carattere

ascessuale e presenza di trombi fibrino-

granulocitari nel lume dei vasi.


2500 cc Cristalloidi

1000 cc Colloidi

4U GRC

1200 cc Plasma

Dimessa in 11° giornata



Toxic Shock Syndrome (TTS)

Is a toxin mediate acute life – threatening illness

Fever, headache, mental confusion

diffuse macular erythematous

rash, subcutaneous edema, nausea, vomiting, watery diarrhea,

and marked hemoconcentration.

Renal failure followed by hepatic failure, disseminated intravascular

coagulation, and circulatory collapse may follow in rapid sequence.

TTST-1/SEB

(Staphilococcus)

Pyrogenic exotoxin A

(Streptococcus M1/M3)

Vascular damage, with extremities

edema leading to compartment

Syndrome frequent necessity of amputations

Clinical symptoms

LT-HT-α Toxin

(Clostridi)

The side effects of Misoprostol

(Vomiting,Diarrhea, abdominal cramping)

May be similar to initial symptoms of TTS


Fatal TTS Post Medical Abortion

Clostridium Sordellii/Perfrigens/Bifermentans)

Afetr delivery/after surgical

Medical Abortion

Endometritis

Myometrial vasculitis

Tachycardia,ipotension,edema,hemoconcentration

(Capillary Leak Toxin)

Absence of Fever, No of gas production, No skin rush

No Positive Blood culture, Marked leucicytosis (>50,000)

Fischer M FD et al NEJM 2005;353:2352-60

Ho SC et al AJOG 2009;201:459e1-7

Hale A et al OFID 2017doi: 10.1093/ofid/ofw095


The intracellular environment protects

staphylococci from host defense mechanisms

as well as the bactericidal effects of antibiotics

Lowy FD NEJM 1998;339:520-32

Komuro H et al IDCases 2017;10:12-4


Postoperative TTS focal sign of surgical sites infection were minimal/absent

(apurulent) in 85% cases

Most strains produce small quantities of alpha-hemolysin

but large amounts of toxin TSST-1

37° postop day fever 38 °C

rigidity and pain in the surgical scar

2 days later

Fever 39 °C

Pressure 84/45 mmHg

HR 143 beats

Rash on the trunk/arms

WBC 17,700

AST/ALT/LDH 221/136/408 U/L

Suprafascial Debridement

Growth of MRSA

sensitive to vancomycin

(administred from 3° day

of antibacterial therapy)


Calderon L al Biomed Res Int 2014 ID203639

Haemotoxins are

likely to act in a synergistic manner to perturbhaemostasis.

by causing ischaemic or haemorrhagic

events or shock due to systemic hypotension


Slagboom J al Br J Haematol 2017;177:947-59



VIDEO

https://www.youtube.com/watch?v=vidQ_t--uWo

Irani M et al J Obste Gynaecol Res 2017 doi.10.111/jog13418


29-year-old primigravid 36 weeks'

prenatal care had been uneventful

She worked as a day care teacher

Patient denied vaginal bleeding

At home

watery diarrhea

mild abdominal

pain

12

Hours

Persistent

bleeding E/Norepinephrine

pip-tbactam/vanco

Bakri Baloon


ADMISSION

Watery diarrhea

severe

diffuse abdominal pain.

Uterine tenderness

38.5°C HR:130 b.p.m

i.v line+O2

FHR 70-80

Bedside

US confrmed

7’ 5’

Emergency CS

general anesthesia

Placental Abrubtio

Uterine atony EBL

2200ml

Male 2625 g

Apgar 0 0 2 2 2

intubated/epinephrine.

Resuscitation:15’;120bpm.

NCU ampi/grnta/Ctxime

Total body cooling

Cefazolin 1 g/iv

deteriorate 4 day

Died

Hb 12.5 g/dL Htc 36.8%

WBC16.2 k/UL plt 107 k/UL,

PPT 83.7 sec

fibrinogen 97 mg/dL,


Laparotomy

2000 mL Blood

Uterus atonic,

actively bleeding,

Supracervical

Hysterectomy abdomen open to prevent the

recurrence ACS

DIC/MOF

The output from the Bakri balloon 550 mL/h blood

Unsucessful partial embolisation

200 ml vaginal bleeding 800 mL suctioned from her mouth

8 U PRBC, 8 U FFP, 1 unit of plt, 2 units of cryoprecipitate.

Hb 6.5 g/dL; htc18.8 pH of 7.125, BD19.6 mEq/L

Lactate12.9 mmol/ AST, 230 IU/L; ALT, 175 IU/L Creat 1.8 mg/dL.

ACS Abd Pressure 20 mmHg

Total

21 U RBC, 19 U FFP, 5 U platelets,

7 U cryoprecipitate,

1 U Fct IX,

1 g tranexamic ac


3 hours



Postop day 6, abdomen was closed

tracheostomy was performed

hematologic indices stabilized, DIC resolved

MOF

acute respiratory distress syndrome (ARDS),

acute epatic and renal failure /temporary hemodialysis

Postop day 28 extubated

liver and kidney function recovered fully

Ischemia

Amputation bilateral below-the-knee

of the lower extremities

Amputation of the right hand fingertips

Right buttock necrosis

related to the right hypogastric embolization,

tissue debridement and a

rotational flap to cover the defect.

After a 3-month hospital stay, the patient was

discharged to a rehabilitation facility



Postop day 6, abdomen was closed

tracheostomy was performed

hematologic indices stabilized, DIC resolved

MOF

acute respiratory distress syndrome (ARDS),

acute epatic and renal failure /temporary hemodialysis

Postop day 28 extubated

liver and kidney function recovered fully

Ischemia

Amputation bilateral below-the-knee

of the lower extremities

Amputation of the right hand fingertips

Right buttock necrosis

related to the right hypogastric embolization,

tissue debridement and a

rotational flap to cover the defect.

After a 3-month hospital stay, the patient was

discharged to a rehabilitation facility


GAS

positive

placental culture

Hypotension

MOF-DIC-ARDS

Decesso

Neonato 7h dalla nascita


Decesso

Materno

12 h dai

primi sintomi

Publication of papers, conference

presentations, expert opinions cannot

achieve reliable change inbedside clinical

practice without conversion of these

recommendations

into a practical working plan

Thomas KW Crit Care Med 2007; 35:1210–2

Rhodes A Evans LE et al Crit Care Med 2017 45:486-552

Rhodes A Evans LE et al IntensiveCare Med 2017;43:304-377

2017


http://www.nhsdirect.nhs.uk/index.asp

Mukherjee V, Evans L Curr Opin Crit Care 2017;23:412–6



Sepsis 6: iPhone.iPad

SSC official app

iPhone,Android


Reinhart K et al NEJM 2017;377:414-7


Necessità di introduzione PDTA

Regionali /Aziendali

Ruolo

Organizzativo



Timpanic temperature less than 36 °C Temperatura auricolare inferiore a 36°C Barton JR et al

Obs Gyn 2012;120:689-706

a-b

https://www.google.it/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiV_-3_y93JAhUBOxQKHXwCARwQjRwIBw&url=https://www.rcog.org.uk/&psig=AFQjCNEwY9Z537lGzaAuXehLSxpHXD8HDQ&ust=1450259382409201

http://www.rcog.org.uk/home.asp?PageID=3


Trigger Morbidity

More Sensitivity

Less False Negative

Less Specificity

More False Positive*

More Specificity

Less False Positive

Less Sensitivity

More False Negative


Trigger Morbidity

More Sensitivity

Less False Negative

Less Specificity

More False Positive*

More Specificity

Less False Positive

Less Sensitivity

More False Negative

*A number of False Positive where due to a single triggers that were not reproduced

Need that the Midwifes ensure tha parameters are measured accurately

Single unexplained trigger repeated before callout


Take attention/ICU


Cabana D et al JAMA 1999;282:1458-65

Studies on improving physician guideline adherence

may not be generalizable,

since barriers in one setting may not be present in another

Matrice delle Responsabilità

R:Responsabilità – C:Collaborazione – I:Informazione

Conclusioni

Instaurare nella UO specifico «bundle» condiviso Ostetrici/Anestesisti

prontamente disponibile in Sala Parto/Reparto/PS

Applicare una a matrice di responsabilità

Confidenza con segni/sintomi non della routine O&G

Conoscenza della complessità concettuale della Sepsi

Conoscenza della patogenesi della Sepsi/MOF

Conoscenza del razionale della attuale classificazione

Gestione preordinata nella sospetta TTS con immediato intervento

dell’Anestesista possibilmente dedicato/esperto

Intervento di Chirurgo Ostetrico esperto

nei casi post partum

Monitoraggio clinico dei parametri vitali con procedura validata

Conclusioni


iv corso sepsi in ostetricia m. franchi & co · lo shock settico è la forma più grave di...

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