SEPSIS

Fluid resuscitation and initial management

Mihai Popescu MD PhD

UMF Carol Davila Bucuresti
ATI III, Institutul Clinic Fundeni
 What would you do?
• 55 y.o. with h/o HTN and smoking admitted
with fever/chills, productive cough.
• CXR RLL infiltrate; WBC 22 (11% bands)

• BP 120/80; HR 115; Temp 39.1

• CVP 4; ScvO2 66%; Lactate 1.9

• Should antibiotics be ordered? If so what type?

• Should fluid be ordered? If so what type?

JAMA. 2016;315(8):801-
Pathophysiology

Clària et al. J Immunol

2016
Glycocalyx and
Sepsis
Pinsky. Annals Intensive Care 2016; 4:38
Pathophysiology
 Septic
shock
critical
DO2
(mL/min/m2)

(mg/dL)
Lactate
VO2

Tissue hypoxia

DO2
(mL/min/m2)
 Treatment
Infection
Systemic inflammation Sepsis

Hemodynamic
resuscitation
Specific
To ensure adequate 2O
treatmen
supply to the
t ATB
tissues
in order to maintain a
Source normal cellular
control function
cellular dysoxia

SH
OC
K
Organ
Antibiotics versus cardiovascular support in
a canine model of human septic shock

Survival:
-No TTM= 0%
-ABX= 13%
-CV support= 13%
-Both= 43%

Natanson C. AJP
SSC 2016 Guidelines

Sepsis is time dependent: TEMPUS

FUGIT

Unlikely to be tested
or challenged
Hard to audit: time 0
Prioritazing sepsis ahead
other emergencies
Treatment strategies: balanced DO2/VO2
 Treatments: ↑ DO2
Restore an adequate tissue
VO2
perfusion
1 Septic Shock 2 Resuscitated Shock
Restored VO2

Sepsis
1

Lactate

DO2
 Treatments: ↑
DO2
How? Optimizing global oxygen delivery
(DO2)

iDO2 = CI x
Fluids CaO2
Inotropes
Vasopressor
s
CI = HR x O2
SV PRBC
CaO 2 = (1.34 x Hb x SaO2) + (0.003 x
PaO2)
SSC 2016 Guidelines

Fluids and Tools for guiding

Resuscitation:
Initial Fluid
Administration
↑ contractility
SV
normal
contractility
left
ventricular
performance
↓ contractility

preload (venous return)

ARISE, ProCESS, ProMISe RCT’s: Fluid
resuscitation ProCESS ARISE ProMISe Rivers
(EGDT group) (EGDT group) (EGDT group) (EGDT group)
Mortality (%) 21 18.6 24.8 33.3
(60-day mortality) (90-day mortality) (28-day mortality) (28-day mortality)

Time to 197 ± 116 168 (130, 230) 162 ± 78 -

randomization (min)

Fluids pre- 2254 ± 1472 2515 ± 1244 1600 -

randomization (1000, 2500)
(mL)
Lactate 4.8 ± 3.1 6.7 ± 3.3 7 ± 3.5 7.7 ± 4.7
(mmol/L) at
inclusion
ScvO2(%) at 71 ± 13 73 ± 11 70 ± 12 49 ± 12
inclusion
ScvO2< 70% - 20-30 % 30-35 % -
at inclusion
ScvO2(%) after 6 - 76 ± 8 74 ± 10 77 ± 10
hours
ScvO2< 70% - < 20 % < 20 % 5%
after 6 hours
212 patients in Zambia
Initial 2 L of isotonic crystalloid within 1H + 2 L in 4H. vs Control
Group
SSC 2016 Guidelines

Tools for guiding additional fluid

Resuscitation:
Hemodynamic
resuscitation Tools
Cardiac output
manipulation

Preload-
dependency
(static parameters)

Oxygen
delivery Preload-dependecy
(dynamic parameters)
optimizatio
n

CO
monitoring

Safety limits /
Risk assessment

EARLY PHASE of
shock
 Fluid Responsiveness: Static
variables
ICM 2015
Fluid Responsiveness: Dynamic
variables

Monnet X, et al. Ann Intensive Care 2016;

Diagnostic Accuracy of methods to assess fluid
responsiveness
Fluid
Responsiveness

Monnet X, et al. Ann Intensive Care 2016;

FENICE study. M. Cecconi et al. ICM
SSC 2016 Guidelines
 Sepsis-Induced
Hypoperfusion
• SIH→ 30 ml/kg of crystalloid in 3 hours.
• Persistent SIH→
– Frequent reassessment of the hemodynamic
status, including cardiac function.
– Assess fluid responsiveness (dynamic variables).
↓
Additional fluid ± vaspressors and inotropes
• NO SIH→ No Fluids (despite fluid
responsiveness), specially if sepsis-induced
ARDS
SSC 2016 Guidelines

Goals of
Resuscitation:
 Hemodynamic
Goals resuscitation Tool
s
Assessment of tissue Cardiac output
hypoperfusion manipulation
(Endpoints of HMDC resuscitation)

Perfusion Preload-
pressure dependency
(MAP ≥ 65 (static parameters)
mmHg)
Oxygen
delivery Preload-dependecy
(dynamic parameters)
optimizatio
n

CO
monitoring

Safety limits /
Risk assessment

EARLY PHASE of
shock
NEJM 2014
 Hemodynamic
Goals resuscitation Tool
s
Assessment of tissue Cardiac output
hypoperfusion manipulation
(Endpoints of HMDC resuscitation)

Perfusion Preload-
pressure dependency
(MAP ≥ 65 (static parameters)
mmHg)
Oxygen
delivery Preload-dependecy
(dynamic parameters)
Tissue
optimizatio
hypoperfusion n
· lactate clearance
· SvO2 / ScvO2 CO
· CO 2 gap ? monitoring

Safety limits /
Risk assessment
Microcirculation
evaluation ?

EARLY PHASE of
shock
Guidelines: Normalize
lactate levels
What about
SvO2? Standard
EGD
T therapy

Mortalit
y
30.5 46.5
% %

Rivers E. et al.
NEJM 2001;345:1368-
77
Inclusion criteria: Not responding to initial fluid challenge (2000ml before inclusion)
 ARISE, ProCESS, ProMISe RCT’s: the end of
ScvO2 ?
ProCESS ARISE ProMISe Rivers
(EGDT group) (EGDT group) (EGDT group) (EGDT group)
Mortality (%) 21 18.6 24.8 33.3
(60-day mortality) (90-day mortality) (28-day mortality) (28-day mortality)

Time to 197 ± 116 168 (130, 230) 162 ± 78 -

randomization (min)

Fluids pre- 2254 ± 1472 2515 ± 1244 1600 -

randomization (1000, 2500)
(mL)
Lactate 4.8 ± 3.1 6.7 ± 3.3 7 ± 3.5 7.7 ± 4.7
(mmol/L) at
inclusion
ScvO2(%) at 71 ± 13 73 ± 11 70 ± 12 49 ± 12
inclusion
ScvO2< 70% - 20-30 % 30-35 % -
at inclusion
ScvO2(%) after 6 - 76 ± 8 74 ± 10 77 ± 10
hours
ScvO2< 70% - < 20 % < 20 % 5%
after 6 hours
SSC 2016 Guidelines
Fluid
Administration
Risk of AKI by subgroups
 Semler M et al. AJRCCM 2016

Major Adverse Kidney Events within 30

days
 Semler M et al. AJRCCM
2016

Major Adverse Kidney Events within 30

days
Mortality
Multifunctional Protein

HEPATOLOGY 2013;58:1836-1846
Subgroup
Analysis
 Conclusion
• Guidelines andsRecommendations for
early resuscitation of Sepsis are accurate.
• Most of the recommendations are BPS
or supported by low quality of
evidence.
• Largely based on basic physiological
principals.
• Lack of clinical trials validating the benefits
of some strategies, i.e. dynamic variables.