SEPSE

Lucas Kolotelo Veltrini

@intensiva.ro
Médico Intensivista titulado pela AMIB
Médico diarista da UTI do Hospital 9 de Julho
de Rondônia
PG Ciências militares
Pós graduando Cardiointensivismo

DEFINIÇÕES
• Sepsis: uma síndrome caracterizada por disfunção orgânica que
ameaça a vida, causada por uma resposta desregulada a infecção
(não homeostática).

• Disfunção orgânica: SOFA maior ou igual a 2.

(SOFA > 2 representa RR 2-25x de óbito em comparação com SOFA 0)

• Choque séptico: necessidade de vasopressor para manter PAM

maior ou igual 65 mmHg OU lactato > 18mg/dL (2mmol/L).
“Anormalidades circulatórias, celulares e metabólicas subjacentes.”
• Fora da UTI: SIRS; MEWS; NEWS.

• Infecção não complicada X Sepse X Choque séptico.

• A presença de uma nova disfunção orgânica com etiologia não
determinada deve nos alertar a possibilidade de sepse.
• O fenótipo clínico e biológico da sepse pode ser modificado por
doença aguda preexistente, comorbidades de longa data,
medicamentos e intervenções.
 • Vasopressor + lactato > 4 49,7%
• Vasopressor + lactato > 2 42,3%
• Hiperlactatemia isolada > 2 25,7%
• Hiperlactatemia isolada > 4 29,9%
• Vasopressor com lactato normal 30,1%

MEWS
ModifiedEarlyWarningScore(MEWS)

Score 3 2 1 1 2 3
Respiratoryrate <9 9-14 15-20 |21.30 >30
Saturationrate(withtherapy) <90
Heartfrequency <40 40-50 51-100 101-110 111-130 >130
Systolicbloodpressure <70 70-80 81•100 101-200
Temperature <35.1 35.1-36.536.5-37.5 >37.5
Consdousness A V U
Urineproduction <75mlinthelast4hours
Nursebeingworried 1point

A=Alert V=Responsetoverbalstimulation P=Responsetopainfulstimulation U=Unresponsive

RITprotocol
1.DetermineMEWS->MEWS≥3contactclinicianonduty
2.Clinicianondutyassesspatient<30minanddraftaplanfortreatment
3.Effectoftreatmentisanalyzed<60min
4.Ifnoeffectoftreatment-›clinicianondutycontactsRIT
5.Ifnotcompledwith2,3,4->dinicanondutyornursecontactsRIT
6.Documentaberrantparametersinthepatientcharts
 NationalEarlyWarningScore2(NEWS2)-versãobrasileira

Parâmetros Pontuação

Fisiológicos 1 2 3
Frequênciarespiratória
58 9.11 12-20 21-24 ≥25
(porminuto)

Sp02%-Escala1 591 92-93 94-95 296

88.92
93-94com 95.96com 297com
Sp02%-Escala2 <83 84-85 86-87 >93emar oxigênio oxigênio
ambiente oxigênio

Arambienteou
oxigênio? Oxigênio ArAmbiente

Pressãoarterial
<90 91-100 101-110 111-219 ≥220
sistólica(mmHg)

Pulso(porminuto) ≤40 41-50 51-90 91-110 111-130 ≥131

Confusão
aguda
Consciência Alerta Respostaa
vozoudor
Irresposivo

Temperatura(°C) 535.0 35.1-36.0 36.1-38.0 38.1-39.0 ≥39.1

NationalFarIywarningscore?EWSaRovaollegeOPaysicians?O?Adaptaçãotranscultura.p gues.Brasil.2018

DEFINIÇÕES PRESTE ATENÇÃO, isso é

importante !

LEGAL, recomendação
mudou para melhor!

NÃO ESTÁ LEGAL, essa

recomendação precisa
melhorar !
 SCREENINGFORPATIENTSWITHSEPSISANDSEPTICSHOCK

1Forhospitalsandhealthsystems,werecommendusingaperformance
improvementprogrammeforsepsis,includingsepsisscreeningforacutelyill,
high-riskpatientsandstandardoperatingproceduresfortreatment.

Screening
MODERATE

Standardoperatingprocedures
VERYLOW

2016STATEMENT
©
"Werecommendthathospitalsandhospitalsystemshaveaperformanceimprovement
programmeforsepsisincludingsepsisscreeningforacutelyill,highriskpatients."

2WerecommendagainstusingqSOFAcomparedtoSIRS,NEWS,or
MODERATE MEWSasasinglescreeningtoolforsepsisorsepticshock.

3
Foradultssuspectedofhavingsepsis,wesuggestmeasuringblood
VERYLOW lactate.
 INFECTION

A 11
Foradultswithsuspectedsepsisorsepticshockbutunconfirmed
BESTPRACTICE infection,werecommendcontinuouslyre-evaluatingandsearchingfor
alternativediagnosesanddiscontinuingempiricantimicrobialsifanalternative
causeofillnessisdemonstratedorstronglysuspected.

12Foradultswithpossiblesepticshockorahighlikelihoodforsepsis,we
recommendadministeringantimicrobialsimmediately,ideallywithinonehour
ofrecognition.

Septicshock
LOW

Sepsiswithoutshock
VERYLOW

2016STATEMENT
"Werecommendthatadministrationofintravenousantimicrobialsshouldbeinitiated
assoonaspossibleafterrecognitionandwithinonehourforbotha)septicshockand
b)sepsiswithoutshock."

13Foradultswithpossiblesepsiswithoutshock,werecommendrapid
BESTPRACTICE assessmentofthelikelihoodofinfectiousversusnon-infectiouscausesof
acuteillness.

14Foradultswithpossiblesepsiswithoutshock,wesuggestatime-
VERYLOW limitedcourseofrapidinvestigationandifconcernforinfectionpersists,the
administrationofantimicrobialswithin3hoursfromthetimewhensepsiswas
firstrecognized.

2016STATEMENT

"Werecommendthatadministrationofintravenousantimicrobialsshouldbeinitiated
assoonaspossibleafterrecognitionandwithinonehourforbotha)septicshockana
Ib)sepsiswithoutshock."

(15Foradultswithalowlikelihoodofinfectionandwithoutshock,we
VERYLOW suggestdeferringantimicrobialswhilecontinuingtocloselymonitorthe
patient.
 patient.

2016STATEMENT

"Werecommendthatadministrationofintravenousantimicrobialsshouldbeinitiated
assoonaspossibleafterrecognitionandwithinonehourforbotha)septicshockand
b)sepsiswithoutshock."

16
Foradultswithsuspectedsepsisorsepticshock,wesuggest
VERYLOW againstusingprocalcitoninplusclinicalevaluationtodecidewhentostart
antimicrobials,ascomparedtoclinicalevaluationalone.
 22Foradultswithsepsisorsepticshockathighriskoffungalinfection,we
LOW suggestusingempiricantifungaltherapyovernoantifungaltherapy.

2016STATEMENT

"Werecommendempiricbroad-spectrumtherapywithoneormoreantimicrobialsfor
patientspresentingwithsepsisorsepticshocktocoveralllikelypathogens(including
bacterialandpotentiallyfungalorviralcoverage."

23Foradultswithsepsisorsepticshockatlowriskoffungalinfection,we
LOW suggestagainstempiricuseofantifungaltherapy.

2016STATEMENT

"Werecommendempiricbroad-spectrumtherapywithoneormoreantimicrobialsfor
patientspresentingwithsepsisorsepticshocktocoveralllikelypathogens(including
bacterialandpotentiallyfungalorviralcoverage."

24Wemakenorecommendationontheuseofantiviralagents.

25Foradultswithsepsisorsepticshock,wesuggestusingprolonged
MODERATE infusionofbeta-lactamsformaintenance(afteraninitialbolus)over
conventionalbolusinfusion.

26Foradultswithsepsisorsepticshock,werecommendoptimising
BESTPRACTICE dosingstrategiesofantimicrobialsbasedonacceptedpharmacokinetic/
pharmacodynamic(PK/PD)principlesandspecificdrugproperties.
 VENTILATION

46Thereisinsufficientevidencetomakearecommendationontheuse
ofconservativeoxygentargetsinadultswithsepsis-inducedhypoxemic
respiratoryfailure.

47Foradultswithsepsis-inducedhypoxemicrespiratoryfailure,we
LOW suggesttheuseofhighflownasaloxygenovernon-invasiveventilation.

48Thereisinsufficientevidencetomakearecommendationontheuseof
non-invasiveventilationincomparisontoinvasiveventilationforadultswith
sepsis-inducedhypoxemicrespiratoryfailure.

49Foradultswithsepsis-inducedARDS,werecommendusingalowtidal
HIGH volumeventilationstrategy(6mL/kg),overahightidalvolumestrategy(>10
mL/kg).

50Foradultswithsepsis-inducedsevereARDS,werecommendusing
MODERATE anupperlimitgoalforplateaupressuresof30cmH20,overhigherplateau
pressures.
 AntibioticTiming

Shockispresent Shockisabsent

Sepsisisdefinite Administerantimicrobialsimmediately,ideallywithin1hourof
orprobable recognition

Administerantimicrobials Rapidassessment*of
Sepsisispossible immediately,ideallywithin infectiousvsnoninfectious
1hourofrecognition causesofacuteillness

Administerantimicrobials
within3hoursifconcern
forinfectionpersists

*Rapidassessmentincludeshistoryandclinicalexamination,testsforbothinfectiousandnon-infectiouscausesofacuteillness
andimmediatetreatmentforacuteconditionsthatcanmimicsepsis.Wheneverpossiblethisshouldbecompletedwithin3hours
ofpresentationsothatadecisioncanbemadeastothelikelihoodofaninfectiouscauseofthepatient'spresentationandtimely
antimicrobialtherapyprovidedifthelikelihoodisthoughttobehigh.

Fig.1Recommendationsontimingofantibioticadministration

SÍTIO DA PAI
VASOPRESSORES

VASOPRESSORES

Figure2.Kaplan-MeierSurvivalCurves

0.5-

Usualcare
Permissivehypotension
0.4

Allrandomizedpatientsareincluded
whencalculatingsurvival,excluding
0.3
Mortality

8patientsinthepermissive
hypotensiongroupand7intheusual
caregroupwhodidnotconsentto
0.2
thetrialandrefusedpermissionfor
datause.Othersurvivingpatients
werecensoredatthelastknowndate
0.1
aliveoratdateofwithdrawalor
UnadjustedHR,0.96(95%CI,0.86-1.07) refusalofconsent(fromwhomtrial
AdiustedHR,0.94(95%CI,0.84-1.05)
consentwasnotobtained).The
0•
1 45 6 89101112 medianfollow-uptime(usingthe
Months reverseKaplan-Meiermethod)was
14.3months(interquartilerange
No.atrisk
Permissivehypotension1283794743721699667631596545509480442409 [IQR],8.8-19.3)forthepermissive
1300772727697677642 604569 525489 459 435 395 hypotensiongroupand14.2months
(IQR,8.5-19.4)fortheusualcare
group.HRindicateshazardratio.
VASOPRESSORES

VASOPRESSORES
 SepticShock

FluidResponder? No StartVasopressorImmediately

Yes CVCorPVC?
r
sso
opre
s+vas n t Norepinephrine Vasopressin
fluid
e
FluidTolerant? No om (SecondOption)
ving yfirstm (Firstoption)
s i dergi v e r Initialdose0.01mcg/kg/min Initialdose0.01U/min
Con e

Keepnorepinephrinedose
eth

Addsecondvasopressor
sinc
Reasses

Yes
Needdose Needdose
20.25-0.5mcg/kg/min 20.04U/min

GiveIVFluid No tomaintain tomaintain

300-500ml MAP≥65mmHg? MAP≥65mmHg?

Keepmonitoring
(5-10ml/kg)
over10-15min Corticosteroid
Hydrocortisone Ye No Yes
200mgIV/day

HypotensionPersist? No

Continue
Lookfor
alternativediagnosis
No seyousure?
Areyousure

samedose,
Yes
Keepmonitoring
ActiveProtocolforRefractorySepticShock Yes

1.Rationalapproachandmanagementofsepticshockwithintravenousfluidsandearlyvasopressorsbasedoncur-
evidence.IV:Intravenous,CV:CentralVenousCatheter,PVC:PeripheralVenousCatheter.

Life-threateninghypotension

and/orIDAP$40mmH

and/orHR/DAP≥3

and/orHighriskoffluidoverload

NO YES

Completefluidresuscitation StartNErapidly
(individualized)beforestartingNE+fluidresuscitation(individualized)
Fig.1Howtooptimizetimingofintroductionofnorepinephrine.Suggestedflowchartfordecidingwhentointroducenorepinephrine.DAP:
Diastolicarterialpressure,HR/DAP:ratiobetweenheartrateandDAP
SVO2 / SCVO2

Normalstate Shock

ScvO,<SvO2 ScvO2>Svo2
SVO2 / SCVO2

LACTATO
• Marcador de gravidade e mortalidade.
• Mas INSUFICIENTE / INEXATO para usar sua cinética como
alvo de ressuscitação de maneira isolada.
• Hoje visto como um Shuttle, substrato energético celular
 Nonhypoperfusion Hypoperfusion
• GLICÓLISE AERÓBICA context • GLICÓLISE ANAERÓBIA
context
induzida pela resposta em território hipoperfundido
adrenérgica relacionadaSystemicinflammation
ao Tissueswithlowflow
Sympatheticresponse
estresse

Increasedaerobicglycolysis Increasedanaerobicglycolysis
Epinephrine
B2 Glycogen Glucose

(T
ADP
IADP
,G-6-P Glycolysis
›2ATP y y
›2ATPH+H+
Pyruvate Pyruvate H+

Lactate Lactate

Stress-related Flowsensitive
hyperlactatemia hyperlactatemia
 catecholamines†->glycolysis†
glycogenolysis

Na/KATPase|| glucose

ATP+

pyruvate' lactate lactateclearance]

POHI
Krebs
cycle
02|4 -critical02delivery

oxidative
phosphorylation

mitochodrialfailure

“The correlation between lactate and CO is, therefore, weaker. Improving CO initially causes a
rapid drop in lactate, followed by persistent only slowly decreasing lactate levels despite the already
normalized perfusion. Therefore, trying to normalize lactate could lead to harmful over-
resuscitation by fuid and inotropes [8].” Normalization of PCO2 gap and PCO2 gap/ Ca–vO2 ratio
(faster reacting markers of anaerobic metabolism) would suggest that perfusion is normalized and
lactate level is elevated for other reasons.”

“Normalization of PCO2 gap and PCO2 gap/ Ca–vO2 ratio

(faster reacting markers of anaerobic metabolism) would
suggest that perfusion is normalized and lactate level is
elevated for other reasons.”
MOTLING
SCORE
“The concept of lactate as merely a metabolic waste product has now evolved
toward lactate being viewed as an energetic shuttle. Thus, in most clinical critical
care situations, hyperlactatemia must be mainly perceived as an adaptive response
to a shock state and not as a marker of tissue hypoxia.”
P(A-V)CO2
 5%
Produção de CO2
(VCO2) é
influenciada por:
Produção 90%
aeróbica
5%
Taxa
metabólica
Quociente
Respiratório

Apesar de haver REDUÇÃO

ASSIMÉTRICA de VCO2 e
VO2 (por queda da produção
aeróbica de CO2), ocorre
aumento da relação
VCO2/VO2 (MAS POR
ACUMULAÇÃO TECIDUAL
DO CO2 ESTAGNADO por
condições de baixo fluxo! NÃO
 Pinsky M.R.
Hemodynamic Monitoring

DC NORMAL

Microcirculaçã
o Normal
 DC
Normal
48mLCO,/100mLblood
10mmHgPaCO;

CUCO.
PICO,'
APCO,

DC Lo macroflow/heterogeneousmicroflow
BG

Heterogeneidade
da
Microcirculação

e Increasedmacroflow/heterogeneous
microflow
ag
DC NORMAL

1PCO,
Heterogeneidade
da
Microcirculação

DC

Heterogeneidade
da
Microcirculação
A MICROCIRCULAÇÃO NA
SEPSE

A MICROCIRCULAÇÃO NA
SEPSE
A MICROCIRCULAÇÃO NA
SEPSE

P(A-V)CO2/C(A-
V)O2
 ÍNDICE DE CHOQUE
DIASTÓLICO

PAS Cardiogênico,
hemorrágico, componente
hipovolêmico.
PAD Sepse
PAD por sua vez é
influenciado por:
• Tônus vascular
• Duração do clíclo
cardíaco
• Volume de sangue
ejetado
• Complacência
arterial
CORTICÓIDE
CORTICÓIDE

• Dias livres de vasopressor (1,25 dias)

• Sem diferença de mortalidade, superinfecção, hiperglicemia, HDA.
• Aumento risco de HiperNa e fraqueza muscular.

BICARBONAT
O
AZUL DE METILENO

• Descontinuidade de vasopressor (69 vs 94h); 1 dia a menos

• Internação UTI 1,5 dias a menos e hospitalar 2,7 dias.
• Dias de VM e mortalidade similares.