SEPSIS Y SHOCK SEPTICO

DEFINICIONES
CAMPAÑA PARA SOBREVIVIR A LA SEPSIS

DR.JESUS JAUREGUI BERNAOLA

MEDICO INTENSIVISTA
DEFINICIÓN DE
SEPSIS
La sepsis es una disfunción orgánica
potencialmente mortal causada por
una respuesta desregulada del
huésped a la infección.
 Fisiopatología en Sepsis
Sepsis

 Coagulación Injuria
 Fibrinolisis Endotelial
 Inflamación

Falla Orgánica

Muerte
ENDOTOXINA Ó LPS
A COAGULACIÓN (ESTADO
MEDIADORES INFLAMATORIOS C
T PROCOAGULANTE Y
(CITOQUINAS) I
V ANTIFIBRINOLÍTICO)
A

EXPRESIÓN DEL FACTOR TISULAR (SUPERFICIE DE

CÉLULAS ENDOTELIALES Y MONOCITOS)

EXPRESIÓN DEL RECEPTOR DE PROTEINA C (CÉLULA

ENDOTELIAL)
EXPRESIÓN DE TROMBOMODULINA

EXPRESIÓN DEL TPA

LIBERAN EL INHIBIDOR DEL TPA (PAI-1)
 NO: efecto vascular en sepsis 3.14b

Estimulo
Ej:. Acetilcolina o shear stress)

Vasodilatacion/
regulacion del
ecNOS
flujo sanguíneo
Oxido
nítrico
iNOS

Excesiva vasodilatacion
Sobre-expresion
de iNOS Sepsis hipotension refractaria

Estímulo
(ej. LPS, IL-1, TNF, PAF)
SHOCK SEPTICO

ecNOS: endothelial constitutive nitric oxide synthase, iNOS: inducible nitric oxide synthase
LPS: lipopolysaccharide, IL: interleukina, PAF: platelet activating factor, TNF: tumour necrosis factor
 The Third International
Consensus Definitions for
Sepsis and Septic Shock
El grupo de trabajo formado por expertos en sepsis de la European Society of Intensive Care
Medicine y de la Society of Critical Care Medicine, han definido la sepsis como “la disfunción
orgánica causada por una respuesta anómala del huésped a la infección que supone una
amenaza para la supervivencia”.
Esta nueva definición comporta la búsqueda de una nueva herramienta clínica que
sustituya a los criterios de síndrome de respuesta inflamatoria sistémica (SIRS) en la
identificación de los pacientes con sepsis, ya que estos criterios no están presentes en
todos los pacientes con infección, y no necesariamente reflejan una respuesta anómala
por parte del huésped que condicione una amenaza para la supervivencia, y, por lo
tanto, resultan inespecíficos.
• Para la identificación de la disfunción orgánica, el grupo de trabajo
recomienda emplear una variación de 2 ó más puntos en la escala
SOFA (Sequential [Sepsis-Related] Organ Failure Assessment),
considerando una puntuación basal de 0 a menos que se conozca que
el paciente tuviera una disfunción orgánica previamente a la aparición
de la infección. Una puntuación de SOFA ≥ 2 refleja un riesgo de
mortalidad global de aproximadamente un 10% en la población
general.
SOFA RESPIRATORIO COAGULACIÓN HEPÁTICO CARDIOVASCULAR NEUROLÓGICO RENAL

PA(mmHg) o
PUNTAJE PaO2/FiO2 Plaquetas Bilirrubina Inotrópicos- Creatinina (mg/dl)
Glasgow
 (mmHg) (x103/mm3) (mg/dl) Vasopresores o Diuresis 24 horas
(ug/kg/min)

> 400 Sin hipotensión

0 > 150 < 1,2 15 < 1,2
Con o sin VM (PAM  70)

>300 y 400
1  150 1,2 - 1,9 PAM < 70 13 – 14 1,2 – 1,9
Con o sin VM

>200 y 300con o sin VM. Dopa 5 ó Dobu

2 100 2,0 – 5,9 10 – 12 2,0 – 3,4
200 sin VM cualquier dosis

Dopa >5, Epi 0,1, 3,5 – 4,9 ó

3  200 y VM  50 6,0 – 11,9 6–9
Norepi 0,1 Diur<500cc

Dopa>15, Epi>0,1 ó > 5,0 ó

4  100 y VM  20 > 12 <6
Norepi>0,1 Diur<200cc
DEFINICIÓN DE SEPSIS

UNA PUNTUACIÓN SOFA DE 2 O MAYOR IDENTIFICA UN AUMENTO DE 2 A 25 VECES

MAYOR RIESGO DE MORIR EN COMPARACIÓN CON LOS PACIENTES CON UN SOFA
PUNTUACIÓN INFERIOR A 2
• Además, se desarrolla una nueva escala, denominada qSOFA (quick
SOFA), que incluye exclusivamente criterios clínicos fácil y
rápidamente mensurables a pie de cama.
• Los criterios del qSOFA son:
• • Alteración del nivel de conciencia, definido como una puntuación en
la escala de Glasgow ≤ 13
• • Tensión arterial sistólica ≤ 100 mmHg
• • Frecuencia respiratoria ≥ 22 rpm
Apenas hace unas horas que JAMA publicaba la Tercera Conferencia Internacional para las definiciones
• Cuando al menos 2 de los 3 criterios están presentes presenta una
validez predictiva similar al SOFA para la detección de aquellos
pacientes con sospecha de infección y probabilidad de presentar una
evolución desfavorable. Por lo tanto, resultaría útil en la identificación
de pacientes que pudieran precisar de un nivel de vigilancia más
estrecho y un estudio más específico en busca de la posibilidad de
presentar disfunción orgánica. La medición del lactato no aumentó su
validez predictiva, pero podría ayudar a identificar a los pacientes con
un riesgo intermedio.
• Por último, el grupo de trabajo define shock séptico como aquella
situación en el que las anormalidades de la circulación, celulares y del
metabolismo subyacentes son lo suficientemente profundas como
para aumentar sustancialmente la mortalidad. Se identifica
clínicamente por la necesidad de vasopresores para mantener una
tensión arterial media ≥ 65 mmHg y por presentar un láctato sérico ≥
2 mmol/l (18 mg/dl) en ausencia de hipovolemia. Esta situación
refleja tasas de mortalidad superiores al 40 %.
Timeline of the SSC Guidelines

• First edition in 2004

• Previous Revisions in 2008 and 2012

• Current revision started in 2014

• Jointly sponsored by ESICM and SCCM
SSC Guidelines Panel Members
• Andrew Rhodes, MB BS, MD • Craig J. French, MBBS • Osamu Nishida, MD, PhD

• Laura E. Evans, MD, MSc, FCCM • Seitaro Fujishima, MD • Tiffany M. Osborn, MD, MPH, FCCM

• Waleed Alhazzani, MD, MSc, FRCPC • Herwig Gerlach, MBA, MD, PhD • Anders Perner, MD

• Mitchell M. Levy, MD, MCCM • Jorge Luis Hidalgo, MD, MACP, MCCM • Colleen M. Plunkett

• Massimo Antonelli, MD • Steven M. Hollenberg, MD, FCCM • Marco Ranieri, MD

• Ricard Ferrer, MD, PhD • Alan E. Jones, MD • Christa A. Schorr, MSN, RN, FCCM

• Anand Kumar, MD, FCCM • Dilip R. Karnad, MD, FACP • Maureen A. Seckel, CCRN, CNS, MSN, FCCM

• Jonathan E. Sevransky, MD, FCCM • Ruth M. Kleinpell, PhD, RN-CS, FCCM • Christopher W. Seymour, MD

• Charles L. Sprung, MD, JD, MCCM • Younsuk Koh, MD, PhD, FCCM • Lisa Shieh, MD, PhD

• Mark E. Nunnally, MD, FCCM • Thiago Costa Lisboa, MD • Khalid A. Shukri, MD

• Bram Rochwerg, MD, MSc • Flavia R. Machado, MD, PhD • Steven Q. Simpson, MD

• Gordon D. Rubenfeld, MD, MSc • John J. Marini, MD • Mervyn Singer, MD

• Derek C. Angus, MD, MPH, MCCM • John C. Marshall, MD, FRCSC • B. Taylor Thompson, MD

• Djillali Annane, MD • John E. Mazuski, MD, PhD, FCCM • Sean R. Townsend, MD

• Richard J. Beale, MD, MB BS • Lauralyn A. McIntyre, MD, MSc, FRCPC • Thomas Van der Poll, MD

• Geoffrey J. Bellinghan, MRCP • Anthony S. McLean, MBChB, MD, FRACP, FJFICM • Jean-Louis Vincent, MD, PhD, FCCM

• Gordon R. Bernard, MD • Sangeeta Mehta, MD • W. Joost Wiersinga, MD, PhD

• Jean-Daniel Chiche, MD • Rui P. Moreno, MD, PhD • Janice L. Zimmerman, MD, MACP, MCCM

• Craig Coopersmith, MD, FACS, FCCM • John Myburgh, MB ChB, MD, PhD, FANZCA, FCICM, FAICD • R. Phillip Dellinger, MD, MCCM

• Daniel P. De Backer, MD, PhD • Paolo Navalesi, MD

Prose GRADE descriptions

2016 Descriptor 2012 Descriptor

Strength GRADO,FUERZA Strong FUERTE 1
Weak DEBIL 2
Quality CALIDAD High ALTA A
Moderate MODERADA B
Low BAJA C
Very Low MUY BAJA D

Ungraded Strong Best Practice Statement Ungraded Strong

Recommendation MEJOR PRACTICA DECLARADA Recommendation
RECOMENDACION FUERTE SIN
CLASIFICAR
Practice recommendations
TREATMENT INITIATION
3 hour bundle
6 Hour Bundle
 A. Resucitación inicial
1. Sepsis y shock séptico son emergencias médicas y el tratamiento y la resucitación deben comienzar
inmediatamente.(BPS)

2. Por lo menos 30 cc/kpc IV de cristaloides dentro de las primeras tres horas.

3. Continuando con líquidos adicionales guiados por la evaluación frecuente del estado
hemodinámico.

5. Recomendamos variables dinámicas, sobre las estáticas para predecir la respuesta a líquidos.

6. Recomendamos una PAM de 65 mmHg como meta, en pacientes con choque séptico que requieren
vasopresores.

7. Recomendamos guiar la resucitación para normalizar el lactato en pacientes con niveles elevados
como marcador de hipoperfusión tisular.
 2012 Recommendation for Initial
Resuscitation.
We recommend the protocolized, quantitative resuscitation of patients
with sepsis- induced tissue hypoperfusion. During the first 6 hours of
resuscitation, the goals of initial resuscitation should include all of the
following as a part of a treatment protocol:
a) CVP 8–12 mm Hg
b) MAP ≥ 65 mm Hg
c) Urine output ≥ 0.5 mL/kg/hr
d) Scvo2 ≥ 70%.
Rivers Protocol Early insertion of ScvO2
catheter

Therapy titrated to
CVP, MAP and ScvO2

Potential for RBC and

Inotropes
Early goal Directed therapy
• Single Center (Henry Ford)
• 263 Patients
• Severe Sepsis/Septic Shock
• Reduction in mortality of 12.6%
• NNT of 8

• Concerns
• Difficult to parse out the individual impact of each intervention
• Use of invasive central venous monitoring difficult to demonstrate benefit

Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001
Nov 8;345(19):1368-77.
Current literature

ProMISE
(April 2015)

ARISE
(October 2014)

ProCESS
(May 2014)
 PROCESS trial

31 Academic Centers
United States
 Arise trial

51 Hospitals
Varied Settings
5 Countries
 Promise trial

56 Sites
United Kingdom
Intravenous Fluids Intravenous Antibiotics
EGDT 2.8 L EGDT 97.5%
Usual Care 2.3 L Usual Care 96.9%
Sepsis and septic shock are medical
emergencies and we recommend that
treatment and resuscitation begin
immediately.
Best Practice Statement
B. Detección para sepsis y mejora del
rendimiento
• 1. Recomendamos que los
hospitales y los sistemas
hospitalarios, tengan un programa
de mejora del rendimiento para
sepsis, incluyendo detección de
sepsis para pacientes enfermos de
alto riesgo.
C. Diagnóstico
• 1. Recomendamos que cultivos
microbiológicos apropiados deben
ser tomados de rutina, antes de
comenzar la terapia antimicrobiana
en pacientes con sospecha de
sepsis, o choque séptico si estos no
demoran sustancialmente el inicio
los antibióticos.
 D. Terapia antimicrobiana

1. Recomendamos  la administración de los antibióticos tan pronto como sea posible, dentro de la primera
hora después de reconocer la sepsis o el choque séptico.

2. Recomendamos terapia empírica de amplio espectro, con uno o más antimicrobianos para pacientes que se
presentan con sepsis o choque séptico, para cubrir patógenos conocidos.

4. No se recomienda el uso de antibiótico como terapia sistémica profiláctica, en pacientes con estados
inflamatorios severos de origen No-infeccioso (ejemplo Pancreatitis severa o quemaduras)
 D. Terapia antimicrobiana
5. Recomendamos que la estrategia de dosificación de antimicrobianos, se
optimice basada en la farmacocinética y farmacodinámica de cada
medicamento en pacientes con sepsis o choque séptico.

6. Sugerimos una terapia combinada empírica (usando por lo menos 2

antibióticos de diferente clase antimicrobiana), relacionada con las
bacterias más frecuentes para el manejo inicial del choque séptico.
10. Sugerimos que una duración de tratamiento antibiótico de 7 a 10 días,
es adecuada para la mayoría de las infecciones serias asociadas con sepsis
y choque séptico.
 D. Terapia antimicrobiana

11.  tratamientos largos,  en pacientes que tienen baja

respuesta clínica, foco de infección no drenable,
bacteriemia con S aureus, algunas infecciones virales o
fungicas, o deficiencias inmunológicas incluyendo
neutropenia.

12. Sugerimos que tratamientos cortos son apropiados en

algunos pacientes, particularmente aquellos con rápida
resolución clínica, seguida de control adecuado de la
fuente.
 Retardo en el inicio de una terapia..puede constituir una
terapia inadecuada
En NAV, una terapia temprana apropiada, antes de que se
conozcan datos bacteriológicos… mejoró el pronóstico

p<0.01
100
p=NS

80 91% Adequate ATB therapy

% Mortality

60 71% 70% Inadequate ATB therapy

40
38%
20

0
Pre-BAL (n=68) Post-BAL (n=65)

Adapted from Luna CM et al. Chest 1997;111:676-685.

Mortalidad asociada con antibioticoterapia inicial inadecuada en
pacientes con NIH o Sepsis
16.2%
Alvarez-Lerma, 1996** 24.7% Initial adequate
38% therapy
Luna, 1997 91%
Initial inadequate
15.6%
Rello, 1997 therapy
37%
33.3%
Kollef, 1998 60.8%

28.4%
Ibrahim, 2000*** 61.9%
24%
Harbarth, 2003*** 39%
31%
Valles, 2003*** 63%

Mortality
0% 20% 40% 60% 80% 100%

*Mortality refers to crude or infection-related mortality. **Includes patients with HAP.

***Patients had blood stream infections rather than pneumonia as in the other studies.
Alvarez-Lerma F et al. Intensive Care Med 1996;22:387-394.
Luna CM et al. Chest 1997;111:676-685.
Rello J et al. Am J Respir Crit Care Med 1997;156:196-200.
Kollef MH et al. Chest 1998;113:412-420.
Ibrahim EH at al. Chest 2000;118:146-155.
Harbarth S et al. Am J Med 2003;115:529-535.
Valles J et al. Chest 2003;123:1615-1624.
 E. Control de la fuente
2. Recomendamos una remoción
temprana de dispositivos de
1. Recomendamos un diagnóstico acceso intravascular, que son una
anatómico específico de la posible fuente de sepsis o
 infección y control de la fuente.  choque séptico después que
otros accesos vasculares han sido
establecidos
F. Terapia de Fluidos.
1. Recomendamos que la fluidoterapia sea aplicada, hasta tanto los
factores hemodinámicos, continúen mejorando

2. Recomendamos que los cristaloides son los líquidos de elección

para la resucitación inicial .

3. Sugerimos usar albúmina en adición a   cristaloides, cuando se a

requerido una gran cantidad de cristaloides.

4. Recomendamos en contra del uso de HESs

5. Nosotros sugerimos usar cristaloides sobre gelatinas

 G. Medicamentos
vasoactivos
1. Recomendamos Norepinefrina como el vasopresor de elección.

2. Sugerimos añadir Vasopresina o Epinefrina a la NE, para lograr  PAM meta o vasopresina
para disminuir la dosis de noradrenalina.

3. Sugerimos Dopamina, en pacientes con bajo riesgo de taquiarritmias y bradicardia

4. No Recomendamos bajas dosis de dopamina para protección renal.

5. Sugerimos Dobutamina en evidencia de hipoperfusión persistente, a pesar de líquidos y

agente vasopresores.
6. Sugerimos que los pacientes que requieren vasopresor tengan un catéter arterial insertado
cuando sea posible.
We recommend an initial target mean arterial pressure of 65 mmHg
in patients with septic shock requiring vasopressors.
(Strong recommendation; moderate quality of evidence)
Lactate can help guide resuscitation
• We suggest guiding resuscitation to normalize lactate in patients
with elevated lactate levels as a marker of tissue hypoperfusion.
(Weak recommendation; low quality of evidence)
 H. Corticoides
• 1. Recomendación en contra del uso de
hidrocortisona IV,  para tratar el choque
séptico si el reemplazo con líquidos y el
vasopresor restauran la estabilidad
hemodinámica.
• Si falla, dar Hidrocortisona 200 mg día.
I. Productos sanguíneos.
• 1. Se recomienda transfusión de glóbulos
rojos sólo cuando le hemoglobina es
menor a 7g por litro en adultos, y en
ausencia de circunstancias especiales.
• 2. Se recomienda en contra del uso de
eritropoyetina.
• 3. Se recomienda en contra del uso de
plasma fresco congelado (PFC) de rutina.
• 4. Nosotros sugerimos transfusión
profiláctica de plaquetas cuando el
conteo es menor a 10,000 en ausencia de
sangrado aparente, o cuando el conteo es
menor a 20,000 con riesgo de sangrado.
 K. Purificación
J. Inmunoglobulinas L. Anticoagulantes.
sanguínea.
• 1. Recomiendacion • 1. No sé da • 1. Recomendación
en contra del uso de recomendación con en contra del uso de
inmunoglobulinas respecto al uso de antitrombina III.
venosas,  en técnicas de • 2. No se recomienda
pacientes con sepsis purificación el uso de
o choque séptico. sanguínea trombomodulina o
(Hemofiltración, heparina.
hemoadsorción-
hemoperfusión)
M. Ventilación mecánica.
2. Se recomiendo un
3. Se sugiere usar alto
1. Se recomienda un límite superior de
PEEP frente a  bajo PEEP,
volumen corriente meta presión meseta de 30 cm
en adultos con SDRA
de 6cc/kg de agua en SDRA x
inducido x sepsis.
sepsis.

4. Se sugiere usar
5. Se recomienda usar 6. Se recomienda en
maniobras de
Prono versus posición contra del uso de
reclutamiento en
Supina en pacientes con ventilación de alta
pacientes adultos con
ARDS con pafi<150.. frecuencia.
SDRA inducido x sepsis.

7. No se hace 8. Se sugiero usar

9. Se recomienda una
recomendación con agentes bloqueadores
estrategia conservadora
respecto al uso de neuromusculares las
de fluidos.
ventilación no invasiva primeras 48 hrs
 M. Ventilación mecánica.
10. Se recomienda en contra
del uso y de Beta2 agonistas,
para el tratamiento de
pacientes con SDRA.
13. Cabeza de la cama elevada
entre 30 y 45°, para prevenir
aspiración y evitar la neumonía
asociada el ventilador
11. No se recomienda el uso
12. Se sugiere usar bajos
de catéter de PA en pacientes
volúmenes corrientes.
con SDRA
14. Uso de ensayos de ventilación 15. Se recomienda uso de
espontánea en pacientes con
protocolo de despertar y
ventilación mecánica y sepsis que
están listos para extubar. extubar (weaning)
 N. Sedación y analgesia
• 1. Se recomienda que la sedación
continua o intermitente, sea
minimizada en el paciente
mecánicamente ventilados.
O. Control de glucosa
• 1. Seguir protocolo con insulina
cuando la glucosa es mayor de
180mg/dl en 2 tomas consecutivas .
• 2. Se recomienda que los valores de
glicemia se monitoricen cada una o
dos horas.
• 3. Se recomienda tener precaución
con los valores tomados por
glucometría x punción de sangre
capilar.
• 4. Se recomienda toma de muestra
arterial en los pacientes que tienen
catéter arterial.
 P. Terapia de reemplazo renal.
• 1. No se recomienda terapia de
reemplazo renal
intermitente(RRT) o continuo
(CRRT), en pacientes con sepsis
y falla renal aguda de rutina sin
otras indicaciones definitivas de
hemodialisis .
• 2. Se recomienda el uso de
CRRT, para facilitar el manejo y
balance de líquidos en un
paciente séptico inestable
Q. Terapia con bicarbonato
• 1. Se recomienda en contra del
bicarbonato de sodio, para
mejorar la hemodinámica o
reducir el requerimiento de
vasopresores en pacientes con
acidosis láctica inducido por
hipoperfusión con pH>7,15.
 R. Profilaxis del
Tromboembolismo Venoso.
• 1. Se recomienda Heparina
fraccionada o de Bajo Peso
molecular, para prevenir el TEV,
en ausencia de
contraindicaciones
• 2. Se recomienda combinar
profilaxis mecánica y
farmacológica en pacientes de
alto riesgo.
S. Profilaxis de úlceras de estrés
• 1. Se recomienda el uso de la
profilaxis de úlceras x estrés en
pacientes, que tiene factores de
riesgo para sangrado
Gastrointestinal.
• 2. Se sugiere usar: inhibidor de
bomba de protones o
bloqueadores H2
 T. NUTRICIÓN
Sugerimos el inicio precoz de la alimentación enteral en lugar de una glucosa iv.

Recomendamos tambien la dieta temprana / hipocalórica a la alimentación enteral total en pacientes

críticamente enfermos con sepsis o shock séptico para una mejor tolerancia.

Sugerimos medición de los residuos gástricos en pacientes con intolerancia a la alimentación o que son
considerados como de alto riesgo de aspiracion.

Sugerimos el uso de agentes procinéticos en pacientes críticamente enfermos y con intolerancia a la

alimentación.
Appendix 1
Recommendations and best practice statements
A. INITIAL RESUSCITATION
1. Sepsis and sepc shock are medical emergencies, and we recommend that treatment and resuscitaon begin
immediately (BPS).
2. We recommend that, in the resuscitaon from sepsis-induced hypoperfusion, at least 30 mL/kg of IV crystalloid fluid
be given within the first 3 hours (strong recommendaon, low quality of evidence).
3. We recommend that, following inial fluid resuscitaon, addional fluids be guided by frequent reassessment of
hemodynamic status (BPS).
Remarks: Reassessment should include a thorough clinical examinaon and evaluaon of available physiologic
variables (heart rate, blood pressure, arterial oxygen saturaon, respiratory rate, temperature, urine output, and
others, as available) as well as other noninvasive or invasive monitoring, as available.
4. We recommend further hemodynamic assessment (such as assessing cardiac function) to determine the type of shock
if the clinical examinaon does not lead to a clear diagnosis (BPS).
5. We suggest that dynamic over stac variables be used to predict fluid responsiveness, where available (weak
recommendaon, low quality of evidence).
6. We recommend an inial target mean arterial pressure of 65 mm Hg in paents with sepc shock requiring
vasopressors (strong recommendaon, moderate quality of evidence).
7. We suggest guiding resuscitaon to normalize lactate in paents with elevated lactate levels as a marker of ssue
hypoperfusion (weak recommendaon, low quality of evidence).
B. SCREENING FOR SEPSIS AND PERFORMANCE IMPROVEMENT
1. We recommend that hospitals and hospital systems have a performance improvement program for sepsis, including
sepsis screening for acutely ill, high risk paents (BPS).
C. DIAGNOSIS
1. We recommend that appropriate roune microbiologic cultures (including blood) be obtained before starng
anmicrobial therapy in paents with suspected sepsis or sepc shock if doing so results in no substanal delay in the
start of anmicrobials (BPS).
Remarks: Appropriate roune microbiologic cultures always include at least two sets of blood cultures (aerobic and
anaerobic).
D. ANTIMICROBIAL THERAPY
1. We recommend that administraon of IV anmicrobials should be iniated as soon as possible aer recognion and
within one hour for both sepsis and sepc shock (strong recommendaon, moderate quality of evidence).
2. We recommend empiric broad-spectrum therapy with one or more anmicrobials for paents presenng with sepsis
or sepc shock to cover all likely pathogens (including bacterial and potenally fungal or viral coverage) (strong
recommendaon, moderate quality of evidence).
3. We recommend that empiric anmicrobial therapy be narrowed once pathogen idenficaon and sensivies are
established and/or adequate clinical improvement is noted (BPS).
4. We recommend against sustained systemic anmicrobial prophylaxis in paents with severe inflammatory states of
noninfecous origin (e.g., severe pancreas, burn injury) (BPS).
5. We recommend that dosing strategies of anmicrobials be opmized based on accepted
pharmacokinec/pharmacodynamic principles and specific drug properes in paents with sepsis or sepc shock
(BPS).
6. We suggest empiric combinaon therapy (using at least two anbiocs of different anmicrobial classes) aimed at the
most likely bacterial pathogen(s) for the inial management of sepc shock (weak recommendaon, low quality of
evidence).
Remarks: Readers should review Table 6 for definions of empiric, targeted/definive, broad-spectrum, combinaon,
and muldrug therapy before reading this secon.
7. We suggest that combinaon therapy not be rounely used for ongoing treatment of most other serious infecons,
including bacteremia and sepsis without shock (weak recommendaon, low quality of evidence).
Remarks: This does not preclude the use of muldrug therapy to broaden anmicrobial acvity.
8. We recommend against combinaon therapy for the roune treatment of neutropenic sepsis/bacteremia (strong
recommendaon, moderate quality of evidence).
Remarks: This does not preclude the use of muldrug therapy to broaden anmicrobial acvity.
9. If combinaon therapy is used for sepc shock, we recommend de-escalaon with disconnuaon of combinaon
therapy within the first few days in response to clinical improvement and/or evidence of infecon resoluon. This
applies to both targeted (for culture-positive infecons) and empiric (for culture-negave infecons) combinaon
therapy (BPS).
10. We suggest that an anmicrobial treatment duraon of 7 to 10 days is adequate for most serious infecons
associated with sepsis and sepc shock (weak recommendaon, low quality of evidence).
11. We suggest that longer courses are appropriate in paents who have a slow clinical response, undrainable foci of
infecon, bacteremia with Staphylococcus aureus, some fungal and viral infecons, or immunologic deficiencies,
including neutropenia (weak recommendaon, low quality of evidence).
12. We suggest that shorter courses are appropriate in some paents, parcularly those with rapid clinical resoluon
following effecve source control of intra-abdominal or urinary sepsis and those with anatomically uncomplicated
pyelonephris (weak recommendaon, low quality of evidence).
(BPS).
14. We suggest that measurement of procalcitonin levels can be used to support shortening the duraon of anmicrobial
therapy in sepsis paents (weak recommendaon, low quality of evidence).
15. We suggest that procalcitonin levels can be used to support the disconnuaon of empiric anbiocs in paents who
inially appeared to have sepsis, but subsequently have limited clinical evidence of infecon (weak recommendaon,
low quality of evidence).
E. SOURCE CONTROL
1. We recommend that a specific anatomic diagnosis of infecon requiring emergent source control should be idenfied
or excluded as rapidly as possible in paents with sepsis or sepc shock, and that any required source control
intervenon should be implemented as soon as medically and logiscally praccal aer the diagnosis is made (BPS).
2. We recommend prompt removal of intravascular access devices that are a possible source of sepsis or sepc shock
aer other vascular access has been established (BPS).
F. FLUID THERAPY
1. We recommend that a fluid challenge technique be applied where fluid administraon is connued as long as
hemodynamic factors connue to improve (BPS).
2. We recommend crystalloids as the fluid of choice for inial resuscitaon and subsequent intravascular volume
replacement in paents with sepsis and sepc shock (strong recommendaon, moderate quality of evidence).
3. We suggest using either balanced crystalloids or saline for fluid resuscitaon of paents with sepsis or sepc shock
(weak recommendaon, low quality of evidence).
4. We suggest using albumin in addion to crystalloids for inial resuscitaon and subsequent intravascular volume
replacement in paents with sepsis and sepc shock, when paents require substanal amounts of crystalloids (weak
recommendaon, low quality of evidence).
5. We recommend against using hydroxyethyl starches for intravascular volume replacement in paents with sepsis or
sepc shock (strong recommendaon, high quality of evidence).
6. We suggest using crystalloids over gelans when resuscitang paents with sepsis or sepc shock (weak
recommendaon, low quality of evidence).
G.
G. VASOACTIVE MEDICATIONS
1. We recommend norepinephrine as the first-choice vasopressor (strong recommendaon, moderate quality of
evidence).
2. We suggest adding either vasopressin (up to 0.03 U/min) (weak recommendaon, moderate quality of evidence) or
epinephrine (weak recommendaon, low quality of evidence) to norepinephrine with the intent of raising mean
arterial pressure to target, or adding vasopressin (up to 0.03 U/min) (weak recommendaon, moderate quality of
evidence) to decrease norepinephrine dosage.
3. We suggest using dopamine as an alternave vasopressor agent to norepinephrine only in highly selected paents
(e.g., paents with low risk of tachyarrhythmias and absolute or relave bradycardia) (weak recommendaon, low
quality of evidence).
4. We recommend against using low-dose dopamine for renal protecon (strong recommendaon, high quality of
evidence).
5. We suggest using dobutamine in paents who show evidence of persistent hypoperfusion despite adequate fluid
loading and the use of vasopressor agents (weak recommendaon, low quality of evidence).
Remarks: If iniated, dosing should be trated to an end point reflecng perfusion, and the agent reduced or
disconnued in the face of worsening hypotension or arrhythmias.
6. We suggest that all paents requiring vasopressors have an arterial catheter placed as soon as praccal if resources
are available (weak recommendaon, very low quality of evidence).
H. CORTICOSTEROIDS
1. We suggest against using IV hydrocorsone to treat sepc shock paents if adequate fluid resuscitaon and
vasopressor therapy are able to restore hemodynamic stability. If this is not achievable, we suggest IV hydrocorsone
at a dose of 200 mg per day (weak recommendaon, low quality of evidence).
I. BLOOD PRODUCTS
1. We recommend that RBC transfusion occur only when hemoglobin concentraon decreases to < 7.0 g/dL in adults in
the absence of extenuang circumstances, such as myocardial ischemia, severe hypoxemia, or acute hemorrhage
(strong recommendaon, high quality of evidence).
2. We recommend against the use of erythropoien for treatment of anemia associated with sepsis (strong
recommendaon, moderate quality of evidence).
3. We suggest against the use of fresh frozen plasma to correct clo.ng abnormalies in the absence of bleeding or
planned invasive procedures (weak recommendaon, very low quality of evidence).
4. We suggest prophylacc platelet transfusion when counts are < 10,000/mm3 (10 × 109/L) in the absence of apparent
bleeding and when counts are < 20,000/mm3 (20 × 109/L) if the paent has a significant risk of bleeding. Higher
platelet counts ( 50,000/mm3 [50 x 109/L]) are advised for acve bleeding, surgery, or invasive procedures (weak
recommendaon, very low quality of evidence).
J. IMMUNOGLOBULINS
1. We suggest against the use of IV immunoglobulins in paents with sepsis or sepc shock (weak recommendaon, low
quality of evidence).
K. BLOOD PURIFICATION
1. We make no recommendaon regarding the use of blood purificaon techniques.
L. ANTICOAGULANTS
1. We recommend against the use of anthrombin for the treatment of sepsis and sepc shock (strong recommendaon,
moderate quality of evidence).
2. We make no recommendaon regarding the use of thrombomodulin or heparin for the treatment of sepsis or sepc
shock.
M. MECHANICAL VENTILATION
1. We recommend using a target dal volume of 6 mL/kg predicted body weight compared with 12 mL/kg in adult
paents with sepsis-induced acute respiratory distress syndrome (ARDS) (strong recommendaon, high quality of
evidence).
2. We recommend using an upper limit goal for plateau pressures of 30 cm H2O over higher plateau pressures in adult
paents with sepsis-induced severe ARDS (strong recommendaon, moderate quality of evidence).
3. We suggest using higher posive end-expiratory pressure (PEEP) over lower PEEP in adult paents with sepsis-induced
moderate to severe ARDS (weak recommendaon, moderate quality of evidence).
4. We suggest using recruitment maneuvers in adult paents with sepsis-induced, severe ARDS (weak recommendaon,
moderate quality of evidence).
5. We recommend using prone over supine posion in adult paents with sepsis-induced ARDS and a PaO2/FIO2 rao <
150 (strong recommendaon, moderate quality of evidence).
6. We recommend against using high-frequency oscillatory venlaon in adult paents with sepsis-induced ARDS (strong
recommendaon, moderate quality of evidence).
7. We make no recommendaon regarding the use of noninvasive venlaon for paents with sepsis-induced ARDS.
8. We suggest using neuromuscular blocking agents for 48 hours in adult paents with sepsis-induced ARDS and a
PaO2/FIO2 rao < 150 mm Hg (weak recommendaon, moderate quality of evidence).
9. We recommend a conservave fluid strategy for paents with established sepsis-induced ARDS who do not have
evidence of ssue hypoperfusion (strong recommendaon, moderate quality of evidence).
10. We recommend against the use of ß-2 agonists for the treatment of paents with sepsis-induced ARDS without
bronchospasm (strong recommendaon, moderate quality of evidence).
11. We recommend against the roune use of the pulmonary artery catheter for paents with sepsis-induced ARDS
(strong recommendaon, high quality of evidence).
12. We suggest using lower dal volumes over higher dal volumes in adult paents with sepsis-induced respiratory
failure without ARDS (weak recommendaon, low quality of evidence).
13. We recommend that mechanically venlated sepsis paents be maintained with the head of the bed elevated
between 30 and 45 degrees to limit aspiraon risk and to prevent the development of venlator-associated
pneumonia (strong recommendaon, low quality of evidence).
14. We recommend using spontaneous breathing trials in mechanically venlated paents with sepsis who are ready for
weaning (strong recommendaon, high quality of evidence).
15. We recommend using a weaning protocol in mechanically venlated paents with sepsis-induced respiratory failure
who can tolerate weaning (strong recommendaon, moderate quality of evidence).
N. SEDATION AND ANALGESIA
1. We recommend that connuous or intermi.ent sedaon be minimized in mechanically venlated sepsis paents,
targeng specific traon end points (BPS).
N. SEDATION AND ANALGESIA
1. We recommend that connuous or intermi.ent sedaon be minimized in mechanically venlated sepsis paents,
targeng specific traon end points (BPS).
O. GLUCOSE CONTROL
1. We recommend a protocolized approach to blood glucose management in ICU paents with sepsis, commencing
insulin dosing when two consecuve blood glucose levels are > 180 mg/dL. This approach should target an upper
blood glucose level . 180 mg/dL rather than an upper target blood glucose level . 110 mg/dL (strong
recommendaon, high quality of evidence).
2. We recommend that blood glucose values be monitored every 1 to 2 hours unl glucose values and insulin infusion
rates are stable, then every 4 hours therea.er in paents receiving insulin infusions (BPS).
3. We recommend that glucose levels obtained with point-of-care tesng of capillary blood be interpreted with cauon
because such measurements may not accurately esmate arterial blood or plasma glucose values (BPS).
4. We suggest the use of arterial blood rather than capillary blood for point-of-care tesng using glucose meters if
paents have arterial catheters (weak recommendaon, low quality of evidenc
P. RENAL REPLACEMENT THERAPY
1. We suggest that either connuous or intermi.ent renal replacement therapy (RRT) be used in paents with sepsis
and acute kidney injury (weak recommendaon, moderate quality of evidence).
2. We suggest using connuous therapies to facilitate management of fluid balance in hemodynamically unstable sepc
paents (weak recommendaon, very low quality of evidence).
3. We suggest against the use of RRT in paents with sepsis and acute kidney injury for increase in creanine or oliguria
without other definive indicaons for dialysis (weak recommendaon, low quality of evidence).
Q. BICARBONATE THERAPY
1. We suggest against the use of sodium bicarbonate therapy to improve hemodynamics or to reduce vasopressor
requirements in paents with hypoperfusion-induced lacc acidemia with pH . 7.15 (weak recommendaon,
moderate quality of evidence).
R. VENOUS THROMBOEMBOLISM PROPHYLAXIS
1. We recommend pharmacologic prophylaxis (unfraconated heparin [UFH] or low-molecular-weight heparin [LMWH])
against venous thromboembolism (VTE) in the absence of contraindicaons to the use of these agents (strong
recommendation, moderate quality of evidence).
2. We recommend LMWH rather than UFH for VTE prophylaxis in the absence of contraindicaons to the use of LMWH
(strong recommendaon, moderate quality of evidence).
3. We suggest combinaon pharmacologic VTE prophylaxis and mechanical prophylaxis, whenever possible (weak
recommendaon, low quality of evidence).
4. We suggest mechanical VTE prophylaxis when pharmacologic VTE is contraindicated (weak recommendaon, low
quality of evidence).
S. STRESS ULCER PROPHYLAXIS
1. We recommend that stress ulcer prophylaxis be given to paents with sepsis or sepc shock who have risk factors for
gastrointesnal (GI) bleeding (strong recommendaon, low quality of evidence).
2. We suggest using either proton pump inhibitors or histamine-2 receptor antagonists when stress ulcer prophylaxis is
indicated (weak recommendaon, low quality of evidence).
3. We recommend against stress ulcer prophylaxis in paents without risk factors for GI bleeding (BPS).
T. NUTRITION
1. We recommend against the administraon of early parenteral nutrion alone or parenteral nutrion in combinaon
with enteral feedings (but rather iniate early enteral nutrion) in crically ill paents with sepsis or sepc shock who
can be fed enterally (strong recommendaon, moderate quality of evidence).
2. We recommend against the administraon of parenteral nutrion alone or in combinaon with enteral feeds (but
rather to iniate IV glucose and advance enteral feeds as tolerated) over the first 7 days in crically ill paents with
sepsis or sepc shock for whom early enteral feeding is not feasible (strong recommendaon, moderate quality of
evidence).
3. We suggest the early iniaon of enteral feeding rather than a complete fast or only IV glucose in crically ill paents
with sepsis or sepc shock who can be fed enterally (weak recommendaon, low quality of evidence).
4. We suggest either early trophic/hypocaloric or early full enteral feeding in crically ill paents with sepsis or sepc
shock; if trophic/hypocaloric feeding is the inial strategy, then feeds should be advanced according to paent
tolerance (weak recommendaon, moderate quality of evidence).
5. We recommend against the use of omega-3 fay acids as an immune supplement in crically ill paents with sepsis or
sepc shock (strong recommendaon, low quality of evidence).
6. We suggest against rounely monitoring gastric residual volumes in crically ill paents with sepsis or sepc shock
(weak recommendaon, low quality of evidence). However, we suggest measurement of gastric residuals in paents
with feeding intolerance or who are considered to be at high risk of aspiraon (weak recommendaon, very low
quality of evidence).
Remarks: This recommendaon refers to nonsurgical crically ill paents with sepsis or sepc shock.
7. We suggest the use of prokinec agents in crically ill paents with sepsis or sepc shock and feeding intolerance
(weak recommendaon, low quality of evidence).
8. We suggest placement of post-pyloric feeding tubes in crically ill paents with sepsis or sepc shock with feeding
intolerance or who are considered to be at high risk of aspiraon (weak recommendaon, low quality of evidence).
9. We recommend against the use of IV selenium to treat sepsis and sepc shock (strong recommendaon, moderate
quality of evidence).
10. We suggest against the use of arginine to treat sepsis and sepc shock (weak recommendaon, low quality of
evidence).
11. We recommend against the use of glutamine to treat sepsis and sepc shock (strong recommendaon, moderate
quality of evidence).
12. We make no recommendaon about the use of carnine for sepsis and sepc shock.
U. SETTING GOALS OF CARE
1. We recommend that goals of care and prognosis be discussed with paents and families (BPS).
2. We r ecommend that goals of c are be i ncorporated into t reatment and end-of-life c are planning, ulizing palliave
care principles where appropriate (strong recommendaon, moderate quality of evidence).
3. We suggest that goals of care be addressed as early as feasible, but no later than within 72 hours of ICU admission
(weak recommendaon, low quality of evidence).
CONCLUSIONES
La identificación temprana y el manejo apropiado en las horas
iniciales después de la sepsis se desarrolla mejora los resultados.
Surviving Sepsis Campaign
Thank You!