NovasNovas diretrizesdiretrizes da Surviving Sepsis da Surviving Sepsis CampaignCampaignCampaignCampaign

2012 – o que foi atualizado?2012 o que foi atualizado?

Os pacotes da sepseOs pacotes da sepse

6-horas24 horas

Coleta de lactatoH lt CorticosteróidesHemoculturasAntibióticos

CorticosteróidesProteína C ativdadaC l li ê iFluidos/vasopressores

Otimização de PVC

Controle glicêmicoPressão de platô < 30 cmH2O

Otimização de SvO2

Os pacotes da sepseOs pacotes da sepse

6 – horas 3-horas

VasopressoresM s ã d PVC

Coleta de lactatoHemoculturas

Mensuração de PVCMensuração de SvO2

AntibióticosFluidosFluidos

Alvos são PVC > 8 mmHg, SvcO2 > 700% e normalização do lactato

Screening for sepsis and performance improvement

We recommend routine screening of potentially infectedWe recommend routine screening of potentially infectedseriously ill patients for severe sepsis to increase theearly identification of sepsis and allow implementation ofearly identification of sepsis and allow implementation ofearly evidence-based sepsis therapy (1C). New!!!

STRONG RECOMMENDATION

Performance improvement efforts in severe sepsisshould be used to improve patient outcomes (UG).

DiagnosisDiagnosis

We recommend obtaining appropriate cultures beforeantimicrobial therapy is initiated if such cultures do not causesignificant delay (> 45 minutes) in the start of antimicrobial(s)administration (grade 1C).

STRONG RECOMMENDATIONS O G CO O

DiagnosisDiagnosis

We suggest the use of the 1,3 β-d-glucan assay (grade 2B),mannan and anti-mannan antibody assays (grade 2C) wheninvasive candidiasis is in the differential diagnosis of infection.

WEAK RECOMMENDATIONCO O

Antimicrobial therapy

The administration of effective intravenous antimicrobials withinthe first hour of recognition of septic shock (grade 1B) and severesepsis without septic shock (grade 1C) should be the goal oftherapy.t e apy

STRONG RECOMMENDATIONSTRONG RECOMMENDATION

Reworded

CoorteN 261N= 261

Subanálise de Jones et alN = 2913 t3 centros

Subanálise de Jones et alN = 2913 t3 centros

Antimicrobial therapy

We recommend that initial empiric anti-infective therapy includeone or more drugs that have activity against all likely pathogens(bacterial and/or fungal or viral) and that penetrate in adequateconcentrations into the tissues presumed to be the source ofco ce t at o s to t e t ssues p esu ed to be t e sou ce osepsis (grade 1B).

STRONG RECOMMENDATIONSTRONG RECOMMENDATION

Reworded

Antimicrobial therapy

2c. Given the high risk of mortality from sepsis, empiric therapyshould cover all the likely pathogens based on the clinicalcircumstances and local susceptibility patterns. In light of theincreasing frequency of resistance to antimicrobial agents inc eas g eque cy o es sta ce to a t c ob a age tsmany parts of the world, such broad-spectrum coverage generallyrequires initial use of combinations of antimicrobial agents (grade2B)2B).

WEAK RECOMMENDATIONWEAK RECOMMENDATION

New!!!

Antimicrobial therapy

2d. We suggest combination empirical therapy for neutropenicpatients with severe sepsis (2B) and for patients with difficult totreat, multidrug- resistant bacterial pathogens such astreat, multidrug resistant bacterial pathogens such asAcinetobacter and Pseudomonas spp. (grade 2B).

WEAK RECOMMENDATION

Changed from2D to 2B

WEAK RECOMMENDATION

For selected patients with severe infections associated withi t f il d ti h k bi ti th ithrespiratory failure and septic shock, combination therapy with an

extended spectrum beta-lactam and either an aminoglycoside or afluoroquinolone is suggested for P. aeruginosa bacteremia (grade2B). Similarly, a more complex combination of beta-lactam and amacrolide is suggested for patients with septic shock frombacteremic Streptococcus pneumoniae infections (grade 2B).p p (g )

STRONG RECOMMENDATION New!!!

Antimicrobial therapy

We suggest that combination therapy, when used empirically inpatients with severe sepsis, should not be administered for longerpatients with severe sepsis, should not be administered for longerthan 3 to 5 days.

De-escalation to the most appropriate single-agent therapyDe-escalation to the most appropriate single-agent therapyshould be performed as soon as the susceptibility profile isknown (grade 2B).

Exceptions would include aminoglycoside monotherapy, whichshould be generally avoided, particularly for P. aeruginosa sepsis,

d f l t d f f d diti h l dand for selected forms of endocarditis, where prolonged coursesof combinations of antibiotics are warranted.

WEAK RECOMMENDATIONNew!!!

Antimicrobial therapy

We suggest that the duration of therapy typically be 7 to 10 days ifclinically indicated; longer courses may be appropriate in patientswho have a slow clinical response undrainable foci of infectionwho have a slow clinical response, undrainable foci of infection,bacteremia with S. aureus; some fungal and viral infections, orimmunologic deficiencies, including neutropenia (grade 2C).

WEAK RECOMMENDATION

Antimicrobial therapyAntimicrobial therapy

We suggest the use of low procalcitonin levels or similarbiomarkers to assist the clinician in the discontinuation of empiricantibiotics in patients who appeared septic, but have nosubsequent evidence of infection (grade 2C)

WEAK RECOMMENDATION

New!!!

Antimicrobial therapyAntimicrobial therapy

W t th t ti i l th b i iti t d l iblWe suggest that antiviral therapy be initiated as early as possiblein patients with severe sepsis or septic shock of viral origin, whenavailable, such as for severe influenza infection (2C).

New!!!

WEAK RECOMMENDATION

Infection preventionInfection prevention

We suggest that SOD and SDD should be introduced andinvestigated as a method to reduce the incidence of ventilator-associated pneumonia; this infection control measure can then ininstituted in health care settings in regions where thisinstituted in health care settings in regions where thismethodology has been found to be effective (2B).

New!!!

We suggest oral CHG be used as a form of oropharyngealdecontamination to reduce the risk of ventilator-associatedpneumonia in ICU patients with severe sepsis (2B)pneumonia in ICU patients with severe sepsis (2B)

WEAK RECOMMENDATIONS

New!!!

WEAK RECOMMENDATIONS

Initial resuscitationInitial resuscitation

We recommend the protocolized, quantitative resuscitation of apatient with sepsis-induced shock, defined as tissue hypoperfusion(h t i i ti ft i iti l fl id h ll bl d l t t(hypotension persisting after initial fluid challenge or blood lactateconcentration ≥ 4 mmol/L).

During the first 6 hrs of resuscitation, the goals of initialresuscitation of sepsis-induced hypoperfusion should include all ofthe following as one part of a treatment protocol:g p p

Central venous pressure 8–12 mm HgMean arterial pressure (MAP) ≥65 mm HgMean arterial pressure (MAP) ≥65 mm HgUrine output ≥ 0.5 mL·kg-1·hr-1

Central venous (superior vena cava) or mixed venous oxygensaturation 70% or 65% respectivelysaturation 70% or 65%, respectively.

STRONG RECOMMENDATION

N 203 481N = 203.4811998 - 2009

12,6 para 78 por 100.000

Redução de mortalidade: - 4.2 (-3.2, - 4.2)

vs– 2.9 (-2.3, -3,5)

p-= 0.016

Initial resuscitationInitial resuscitation

We suggest targeting resuscitation to normalize lactate inpatients with elevated lactate levels as a marker of tissuehypoperfusion (grade 2C).

WEAK RECOMMENDATION

New!!!

WEAK RECOMMENDATION

Near future answers???Near future answers???

N=1600

N=1260

N=1935

Fluid therapyFluid therapy

1. We recommend crystalloids be used as the initial fluid ofchoice in the resuscitation of severe sepsis and septic shock(Grade 1B).

STRONG RECOMMENDATIONNew!!!

2. We recommend against the use of hydroxyethyl ethyl starchesfor fluid resuscitation of severe sepsis and septic shock.(Grade 1B)(Grade 1B).

STRONG RECOMMENDATIONNew!!!

3. We suggest the use of albumin in the fluid resuscitation ofsevere sepsis and septic shock when patients require

b t ti l t f t ll id (G d 2C) N !!!substantial amounts of crystalloids (Grade 2C).

WEAK RECOMMENDATION

New!!!

Albumin in sepsisAlbumin in sepsis

Albumin in sepsis

N 196N=196

Fluid therapyFluid therapy

6. We recommend an initial fluid challenge in patients with sepsis-inducedtissue hypoperfusion with suspicion of hypovolemia to achieve a minimum oftissue hypoperfusion with suspicion of hypovolemia to achieve a minimum of30 ml/kg of crystalloids (a portion of this may be albumin equivalent.). Morerapid administration and greater amounts of fluid may be needed in somepatients (see Initial Resuscitation recommendations) (grade 1C). Slightpatients (see Initial Resuscitation recommendations) (grade 1C).

STRONG RECOMMENDATIONS

Slight changed

7. We recommend that a fluid challenge technique be applied wherein fluidadministration is continued as long as there is hemodynamic improvementeither based on d namic (eg change in p lse press re stroke ol meeither based on dynamic (eg, change in pulse pressure, stroke volumevariation) or static (eg, arterial pressure, heart rate) variablescontinues (UG).

New!!!

VasopressorsVasopressors

We recommend norepinephrine as the first choice vasopressor (Grade 1B)

STRONG RECOMMENDATION New!!!STRONG RECOMMENDATION

We suggest epinephrine (added to and potentially substituted forgg p p ( p ynorepinephrine) when an additional agent is needed to maintain adequateblood pressure (Grade 2B).

STRONG RECOMMENDATION

VasopressorsVasopressors

Vasopressin (up to 0.03 U/min) can be added to norepinephrine with the intent of raising MAP to target or decreasing norepinephrine dosage (UG).

Low-dose vasopressin is not recommended as the single initial vasopressor for treatment of sepsis-induced hypotension, and vasopressin doses higher than 0 03–0 04 U/min should be reservedvasopressin doses higher than 0.03–0.04 U/min should be reserved for salvage therapy (failure to achieve an adequate MAP with other vasopressor agents) (UG).

UNGRADED RECOMMENDATIONNew!!!New!!!

VasopressorsVasopressors

We suggest dopamine as an alternative vasopressor agent tonorepinephrine only in highly selected patients (eg, patients with low risk

f h h h i d b l l i b d di ) ( d 2C)of tachyarrhythmias and absolute or relative bradycardia) (grade 2C).

WEAK RECOMMENDATION New!!!

Phenylephrine is not recommended in the treatment of septic shockexcept in the following circumstances: (a) norepinephrine is associatedexcept in the following circumstances: (a) norepinephrine is associatedwith serious arrhythmias, (b) cardiac output is known to be high andblood pressure persistently low, or (c) as salvage therapy whencombined inotrope/ vasopressor drugs and low-dose vasopressin havecombined inotrope/ vasopressor drugs and low-dose vasopressin havefailed to achieve the MAP target (grade 1C).

STRONG RECOMMENDATIONSTRONG RECOMMENDATIONNew!!!

CorticosteroidesCorticosteroides

1. We suggest not using intravenous hydrocortisone in adult septic shockpatients if adequate fluid resuscitation and vasopressor therapy are able topatients if adequate fluid resuscitation and vasopressor therapy are able torestore hemodynamic stability (see recommendations for initialresuscitation). In case this is not achievable, we suggest intravenoushydrocortisone at a dose of 200 mg per day (grade 2C)hydrocortisone at a dose of 200 mg per day (grade 2C).

WEAK RECOMMENDATIONReworded

WEAK RECOMMENDATION

CorticosteroidesCorticosteroides

N=16N=16

ImmunoglobulinImmunoglobulin

We suggest not using intravenous immunoglobulin inWe suggest not using intravenous immunoglobulin in adult patients with severe sepsis and septic shock (2B)

N !!!WEAK RECOMMENDATION New!!!

SeleniumSelenium

We suggest not using intravenous selenium to treatWe suggest not using intravenous selenium to treat severe sepsis

N !!!WEAK RECOMMENDATION New!!!

Redução da pneumonia...

Mechanical Ventilation (ARDS)Mechanical Ventilation (ARDS)

We recommend that clinicians target a tidal volume of 6 mL/kg predictedWe recommend that clinicians target a tidal volume of 6 mL/kg predictedbody weight in patients with sepsis induced acute respiratory distresssyndrome (ARDS) (grade 1A vs. 12 mL/kg).

We recommend that plateau pressures be measured in patients withp p pARDS and that the initial upper limit goal for plateau pressures in apassively inflated lung be ≤ 30 cm H2O (grade 1B).

STRONG RECOMMENDATIONslightly changed

Mechanical Ventilation (ARDS)Mechanical Ventilation (ARDS)

We recommend PEEP be applied to avoid alveolar collapse at endexpiration (atelectotrauma) (Grade 1B).

STRONG RECOMMENDATIONSTRONG RECOMMENDATION

We suggest strategies based on higher rather than lower levels of PEEPfor patients with sepsis induced moderate to severe ARDS (grade 2C).

WEAK RECOMMENDATION New!!!

PEEP alta vx PEEP baixaPEEP alta vx PEEP baixaMortalidade- 34.1% vs 39.1%; RR, 0.90; 95% CI, 0.81-1.00;P=.049)

Desmame OR 1.16; 95% CI, 1.03-1.30; P=.01

Mechanical Ventilation (ARDS)Mechanical Ventilation (ARDS)

W t it t i i ti t ithWe suggest recruitment maneuvers in sepsis patients withsevere refractory hypoxemia due to ARDS (Grade 2C).

N !!!WEAK RECOMMENDATION

New!!!

We suggest prone positioning in sepsis-induced ARDSpatients with a PaO2/FiO2 ratio ≤ 100 mm Hg in facilitiesthat have experience with such practices (grade 2B).

WEAK RECOMMENDATIONWEAK RECOMMENDATION

Sedation, Analgesia, and Neuromuscular gBlockade

1. We suggest a short course of NMBA (< 48 hours) forpatients with early, severe sepsis-induced ARDS andpatients with early, severe sepsis induced ARDS andpO2/FiO2 < 150 mmHg ( grade 2C).

New!!!

WEAK RECOMMENDATION

New!!!

N=340

Adj t d t lit

N=340Use for 24 hours

Adjusted mortalityOR - 0.68 (0.48 to 0.98) P = 0.04

Longer MV free daysLonger MV free daysLonger ICU free daysBarotrauma reduction

Glucose control

1. We recommend a protocolized approach to bloodglucose management in ICU patients with severe sepsisg ucose a age e t CU pat e ts t se e e seps scommencing insulin dosing when two consecutive bloodglucose levels are >180 mg/dL. This approach should targetan pper blood gl cose < 180 mg/dL rather than an pperan upper blood glucose < 180 mg/dL rather than an uppertarget blood glucose < 110 mg/dL (grade 1A).

STRONG RECOMMENDATION

New!!!

STRONG RECOMMENDATION

The literatureThe literature....

Renal replacementRenal replacement

We suggest that continuous renal replacement therapiesand intermittent hemodialysis are equivalent in patientsand intermittent hemodialysis are equivalent in patientswith severe sepsis and acute renal failure because theyachieve similar short-term survival rates (grade 2B).

We suggest the use of continuous therapies to facilitateWe suggest the use of continuous therapies to facilitatemanagement of fluid balance in hemodynamically unstableseptic patients (grade 2D).

WEAK RECOMMENDATIONSWEAK RECOMMENDATIONS

Nutrition NEW TOPIC!!!Nutrition TOPIC!!!

We suggest administering oral or enteral (if necessary)feedings as tolerated rather than either complete fasting orfeedings, as tolerated, rather than either complete fasting orprovision of only intravenous glucose within the first 48hours after a diagnosis of severe sepsis/septic shock.(Grade 2C).

We suggest avoiding mandatory full caloric feeding in thefirst week but rather suggest low dose feeding (eg, up to

) (G )500 cal per day), advancing only as tolerated (Grade 2B).

WEAK RECOMMENDATIONS

Nutrition in SSC NEW TOPIC!!!Nutrition in SSC TOPIC!!!

We suggest using intravenous glucose and enteralnutrition rather than total parenteral nutrition (TPN)nutrition rather than total parenteral nutrition (TPN)alone or parenteral nutrition in conjunction with enteralfeeding in the first 7 days after a diagnosis of severefeeding in the first 7 days after a diagnosis of severesepsis/septic shock (Grade 2B)

WEAK RECOMMENDATIONWEAK RECOMMENDATION

Nutrition in SSC NEW TOPIC!!!Nutrition in SSC TOPIC!!!

W t i t iti ith ifiWe suggest using nutrition with no specificimmunomodulating supplementation in patients withsevere sepsis (grade 2C)severe sepsis (grade 2C).

WEAK RECOMMENDATION

ConclusõesConclusões

SOBREVIDASOBREVIDA

=RECONHECIMENTO PRECOCE

+

TRATAMENTO ADEQUADO