Fluids in Sepsis

Septic Shock: Fluid
Resuscitation
Ashraf Al Tarifi,MD,FCCP
King Faisal Specialist Hospital and Research CenterRiyadh
Amman-Jordan
Oct 22,2014
Questions About Fluids
•
•
•
•
•
Why Fluids
What Type
How Much
How Fast
End Points
Why Fluids in septic shock
Cardiovascular management of septic shock. Crit Care Med 2003;31:946-955.
Shock Definition
Inadequate organ perfusion to meet the
tissue’s oxygenation demand leading to
Anaerobic metabolism and lactic
acidosis
“Hypoperfusion can be present
in the absence of significant
hypotension.”
Arterial Oxygen Delivery
DO2
DO2 = (1.34 x Hgb x SaO2) x COP + (PaO2 x
0.0031)
DO2 = (1.34 x Hgb x SaO2) x (SV x HR)
Volume expansion will increase stroke volume
only if ventricles are preload-dependent
preload-independent
Stroke Volume
preload-dependent
Ventricular preload
What Type of Fluids : The
Great Debate
Choices of fluids
• Crystalloids
– Unbalanced fluids : “normal Saline”
– Balanced fluids : “Ringer’s Lactate, Plasmalyte”
• Colloids
– Albumin
– Hydroxyethylstarch (HES)
• Blood
Early Goal-Directed Protocol
Rivers E, et al. N Eng J Med
2001;345:1366
Patients
randomized N=263
Early Goal
Directed Therapy
N=130
Standard
Therapy N=133
Antibiotics given at
discretion of treating
clinicians
CVP > 8-12 mm Hg
MAP > 65 mm Hg
Urine Output > 0.5 ml/kg/hr
ScvO2 > 70%
SaO2 > 93%
Hct > 30%
At least 6 hours
of EGDT
Mean 8hrs
Transfer to ICU
ICU MDs blinded to
study treatment
CVP > 8-12 mm Hg
MAP > 65 mm Hg
Urine Output > 0.5 ml/kg/hr
As soon as
possible Mean
6.2hrs
NEJM 2001;345:1368-77.
Early Goal Directed Therapy -results
50
45
40
35
30
% 25
20
15
10
5
0
P=0.009
NNT 7
46.5
30.5
In-Hospital Mortality
Standard
Goal-Directed
Rivers E, et al. N Eng J Med 2001;345:1366
The Importance of Early Goal-Directed
Therapy for Sepsis Induced Hypoperfusion
Mortality (%)
60
50
Standard therapy
EGDT
P=0.009
NNT 7 (to
prevent one
death)
40
30
20
10
0
In-hospital
mortality
(all patients)
28-day
mortality
60-day
mortality
Rivers et al. N Engl J Med 2001; 345:1368-1377
Early Goal-Directed Therapy
p = 0.73
Fluids
( crystalloids/colloids)
[litres]
14
** p = 0.01
12
10
13.4
* p < 0.001
8
13.5
**
10.6
8.6
6
Stand T
EGDT
*
4
2
0
3.5
5
0-6 hours
7-72 hours
0-72 hours
Rivers et al, NEJM 2001; 345 : 1368-1377.
Crystalloids Vs Colloids
Safe Study :Probability of Survival
The SAFE Study Investigators, N Engl J Med 2004;350:2247
Relative Risk of Death from Any Cause
among All the Patients :SAFE study
The SAFE Study Investigators, N Engl J Med
2004;350:2247-2256
Favors
Albumin
Favors
Others
Critical Care Medicine2011Critical Care Medicine:
February 2011 - Volume 39 - Issue 2 - pp 386-391;39:386-391
Albumin Supplementation in hypoalbuminemic
patients with Sepsis (ALBIOS Study)
N Engl J Med 2014; 370:1412-1421
Hopefully the final word on Albumin in Sepsis
Perner et al ,NEJM, N Engl J Med 2012; 367:124-134
Meta-analysis: HES versus Other
Fluids- Mortality
Zarychanski R. JAMA.RR,
2013;309:678-688.
1.06; 95% CI, 1.00 to 1.13
Meta-analysis: HES versus Other
Fluids - Renal Replacement Therapy
Zarychanski R. JAMA. 2013;309:678-688.
Blood
Remember To Diurese all that
fluids that you just gave
Critical Care Medicine
2011;39:259-265
Critical Care Medicine 2013;41:580
If you were sleepy during my lecture!!!!
2013 International Sepsis Guidelines
•
•
•
•
•
Crystalloids as the initial fluid of choice in the
resuscitation of severe sepsis and septic shock (grade
1B).
Against the use of hydroxyethyl starches for fluid
resuscitation of severe sepsis and septic shock (grade
1B).
Consider Albumin in the fluid resuscitation of severe
sepsis and septic shock when patients require
substantial amounts of crystalloids (grade 2C).
Initial fluid challenge in patients with sepsis-induced
tissue hypoperfusion with suspicion of hypovolemia to
achieve a minimum of 30 mL/kg of crystalloids (a
portion of this may be albumin equivalent). More rapid
administration and greater amounts of fluid may be
needed in some patients (grade 1C).
Fluid challenge as long as there is hemodynamic
improvement either based on dynamic (eg, change in
pulse pressure, stroke volume variation) or static (eg,
arterial pressure, heart rate) variables (UG).
This is how fluid overload feels like for
the patient
Resuscitation of Sepsis Induced
Tissue Hypoperfusion
• Recommend MAP 65 mm Hg
• Recommend urine output .5 ml/kg/hr
Grade 1C
SVO2
• Low SVO2 Means increased consumption by tissues
and indicates need to increase Oxygen delivery
• Reflects decreased COP relative to demand
• Improving SVO2 means improved balance between
supply and demand
• However, SVO2 can be high in sepsis indicating
shunting of blood away from tissues and poor tissue
utilization
Fluid Therapy - Kidney injury
•
Three multicenter randomized trials showed a significant
increase in the risk of acute kidney injury with
hydroxyethyl starch as compared with crystalloids.
Brunkhorst F. N Engl J Med. 2008;358:125-139.
Perner A. N Engl J Med. 2012;367:124-134.
Myburgh JA. N Engl J Med. 2012;367:1901-1911.
•
One multicenter randomized trial did not find an increase
in the risk of acute kidney injury with hydroxyethyl starch
as compared with crystalloids.
Guidet B. Crit Care. 2012;16:R94.
SSC 2012 Guidelines
Initial Resuscitation
Hemodynamic Support
D. Annane
•
•
•
•
Initial Resuscitation
Fluid Therapy
Vasopressor Therapy
Inotropic Therapy
Initial Resuscitation
• We recommend the protocolized, quantitative
resuscitation of patients with sepsis-induced
tissue hypoperfusion (defined as hypotension
persisting after initial fluid challenge or lactate ≥4
mmol/L). This protocol should be initiated as soon
as hypoperfusion is recognized and should not be
delayed pending ICU admission.
Initial Resuscitation
• During the first 6 hours, the goals of initial
resuscitation of sepsis-induced hypoperfusion
should include all of the following as a part of a
treatment protocol (Grade 1C):
– Central venous pressure 8-12 mm Hg
– Mean arterial pressure ≥65 mm Hg
– Urine output ≥0.5 mL/kg/h
– Central venous (superior vena cava) or mixed
venous oxygen saturation 70% or 65%,
respectively
Initial Resuscitation
•
One randomized single-center trial demonstrated reduced
mortality with early quantitative resuscitation for
emergency department patients presenting with septic
shock.
Rivers E. N Engl J Med. 2001;345:1368-1377.
•
Second multicenter randomized trial of 314 patients with
severe sepsis in 8 Chinese centers reported a 17.7%
absolute reduction in 28-day mortality (survival rates,
75.2% vs. 57.5%, P=0.001).
EGDT Collaborative Group of Zhejiang Province.
Zhongguo Wei Zhong Bing Ji Jiu Yi
Xue. 2010;6:331-334.
Early Goal-Directed Therapy in the Treatment
of Severe Sepsis and Septic Shock
Control
EGDT
Relative Risk
(95% Confidence
Interval)
In-Hospital
46.5
30.5
0.58
(0.38-0.87)
0.009
28-day Mortality
49.2
33.3
0.58
(0.39 – 0.87)
0.01
44.3
0.67
(0.46-0.96)
0.03
60-day Mortality
56.9
P
Rivers E. N Engl J Med. 2001;345: 1368-1377.
Initial Resuscitation
• We suggest, in patients with elevated lactate
levels as a marker of tissue hypoperfusion,
targeting resuscitation to normalize lactate as
rapidly as possible. (Grade 2C)
Initial Resuscitation
•
•
One multicenter randomized trial demonstrated that early
quantitative resuscitation based on lactate clearance (decrease
by at least 10%) was non-inferior to resuscitation based on
achieving ScvO2 of 70% or more.
Jones A. JAMA. 2010;303:739–746.
A second multicenter randomized trial demonstrated that a
strategy based on >20% decrease in lactate levels per 2 hours of
the first 8 hours, in addition to achievement of an ScvO2 target,
was associated with a 9.6% absolute reduction in mortality.
Jansen TC. Am J Respir Crit Care Med. 2010;182:752–761.
Lactate Clearance vs Central Venous
Oxygen Saturation as Goals of Early
Sepsis Therapy: Mortality
25
20
15
Lactate group
10
ScvO2 group
5
0
Intent to treat
Per protocol
Jones A. JAMA. 2010;303:739–746.
Early Lactate-Guided Therapy in
Intensive Care Unit Patients
adjusted HR= 0.61;
95% CI, 0.43-0.87; P= 0.006
Jansen TC. Am J Respir Crit Care Med. 2010;182:752–761.
Fluid Therapy
• We recommend crystalloids be used as the initial
fluid of choice in the resuscitation of severe sepsis
and septic shock. (Grade 1B)
• We recommend against the use of hydroxy- ethyl
starches for fluid resuscitation of severe sepsis and
septic shock. (Grade 1B)
Fluid Therapy - Mortality
•
Three multicenter randomized trials showed no significant
difference in mortality between crystalloids and
hydroxyethyl starches.
Brunkhorst F. N Engl J Med .2008;358:125-139.
Guidet B. Crit Care. 2012;16:R94.
Myburgh JA. N Engl J Med. 2012;367:1901-1911.
•
One multicenter randomized trial demonstrated increased
mortality rates with HES 130/0.42 fluid resuscitation
compared to Ringer acetate (51% vs 43%. P=0.03).
Perner A. N Engl J Med. 2012;367:124-134.
Fluid Therapy
• We suggest the use of albumin in the fluid
resuscitation of severe sepsis and septic shock
when patients require repeated boluses of
crystalloids. (Grade 2C)
Meta-analysis: Albumin versus Other
Fluids
Short-term mortality
(albumin vs crystalloids)
Illustrative comparative
Relative
No. Of
risks (95% CI)
effect
participants
(studies)
Assumed Corresponding risk (95% CI)
risk
Control Other fluids (may
be crystalloid or
colloid)
RR 0.84
1683
Study population
(0.73 to 0.97) (11 studies)
342 per 287 per 1000
1000
(249 to 332)
RR 0.85
1402
444 per 377 per 1000
(0.73 to 0.98) (4 studies)
1000
(324 to 440)
Short-term mortality
(albumin vs other colloids)
342 per
1000
Outcomes
Short-term mortality
195 per 1000
(249 to 396)
RR 0.81
(0.57 to 1.16)
281
(7 studies)
Quality of
the
evidence
(GRADE)
⊕⊕⊕⊝
moderate
⊕⊕⊕⊝
moderate1
⊕⊕⊕⊝
moderate1
Fluid Therapy
• We recommend an initial fluid challenge in
patients with sepsis-induced tissue hypoperfusion
with suspicion of hypovolemia to achieve a
minimum of 30 mL/kg of crystalloids (a portion of
this may be albumin equivalent). More rapid
administration and greater amounts of fluid may
be needed in some patients. (Grade 1C)
Fluid Therapy
• We recommend that a fluid challenge technique be
applied wherein fluid administration is continued as
long as there is hemodynamic improvement either
based on dynamic (eg, change in pulse pressure,
stroke volume variation) or static (eg, arterial
pressure, heart rate) variables (Ungraded).
Background - Basic Definitions
• Sepsis = known or suspected infection plus
systemic manifestations of infection (SIRS
and others)
• Severe Sepsis = Sepsis + either
– Acute organ dysfunction thought to be due to
sepsis
– Acute tissue hypoperfusion thought to be due to
sepsis
•
•
•
•
Hypotension
Elevated lactate
Oliguria
(Altered mental status)
Kumar A, et al. Crit Care Med 2006; 34:1589-1596
JAMA. 2013;310(17):1809-1817
JAMA. 2013;310(17):1809-1817
Fluid Therapy
•
Recommend fluid resuscitation may
consist of natural or artificial colloids or
crystalloids.
Grade 1B
Lactate
Evidence is clear that Lactate levels are predictive of death and MODS
Clearance of lactate is associated with improved survival
Algorithms of care based on lactate clearance appear to work as well or better than other
approaches.
Jones AE, Shapiro NI, Trzeciak S, et al. Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy: A Randomized
Clinical Trial. JAMA: The Journal of the American Medical Association 2010;303(8):739–46.
Jansen TC, van Bommel J, Schoonderbeek FJ, et al. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized
controlled trial. American Journal of Respiratory and Critical Care Medicine 2010;182(6):752–61.
Goals in resuscitation
Early, quantitative resuscitation goals vs.
standard care have resulted in improved
mortality
The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: A meta-analysis *.
Jones, Alan E. MD; Brown, Michael D. MD, MSc; Trzeciak, Stephen MD, MPH; Shapiro, Nathan I. MD, MPH; Garrett, John S. MD; Heffner, Alan C. MD; Kline, Jeffrey A.
MD; on behalf of the Emergency Medicine Shock Research Network investigators
Critical Care Medicine. 36(10):2734-2739, October 2008.
Resuscitation
Crystalloids are favored as the initial fluid
Hydroxyethyl starches are likely harmful
Albumin may have a role, particularly if alot
of fluid is given
A lower Hb target (~7) is generally accepted
Summary
System-based strategies are effective for improving sepsis care
Processes should aim to:
Identify patients early and identify the severity of sepsis
Quickly administer appropriate antibiotics and source control
Establish institutional goals for physiologic resuscitation
Multidisciplinary chronic phase of care to ensure compliance
Sepsis Induced Hypotension
• Fluid challenge
– Minimum of 20 ml/kg crystalloid or colloid
equivalent
Sepsis Induced Tissue
Hypoperfusion
Requirement for Vasopressors after
initial fluid challenge
Lactate ≥ 4 mg/dL
During Septic Shock
Diastole
Systole
10 Days Post Shock
Diastole
Systole
Images used with permission from Joseph E. Parrillo, MD
Initial Resuscitation of Persistent
Hypotension or Lactate >4
Recommend
Insertion central venous catheter
Recommended goals :
• Central venous pressure: 8–12 mm Hg
• Higher with altered ventricular compliance or
increased intrathoracic pressure
• ScvO2 saturation (SVC)  70%
Grade 1C
Trials of Late Hemodynamic Optimization
with Control Group Mortality > 20%
After onset of organ failure
Alia et al. 1999
Favors
Optimization
Favors
Control
Yu et al. 1998
Yu et al. 1998
Gattinoni et al. 1995
Hayes et al. 1994
Yu et al. 1993
OVERALL RESULT
-0.4
Kern and Shoemaker Crit Care Med 2002
0.0
0.4
Jones AE, Shapiro NI, Trzeciak S, et al. Lactate
clearance vs central venous oxygen saturation as
goals of early sepsis therapy: a randomized
clinical trial. JAMA. 2010;303(8):739-46.
Hospital Mortality
and Length of Stay
Jones, A. E. et al. JAMA 2010;303:739-746.
Copyright restrictions may apply.
Guidelines Are Not Enough
• Protocols
• Performance Improvement Programs
Severe Sepsis Resuscitation Bundle
Complete tasks within 6 hours of identifying severe sepsis.
1. Measure serum lactate.
2. Obtain blood cultures prior to antibiotic administration.
3. Administer broad-spectrum antibiotic within 3 hours of ED admission
and within 1 hour of non-ED admission.
4. In the event of hypotension and/or serum lactate > 4 mmol/L:
a. Deliver an initial minimum of 20 mL/kg of crystalloid or equivalent.
b. Begin vasopressors for hypotension not responding to initial fluid
resuscitation to maintain MAP > 65 mm Hg.
5. In the event of persistent hypotension despite fluid resuscitation (septic
shock) and/or lactate > 4 mmol/L:
a. Achieve a central venous pressure (CVP) of > 8 mm Hg
b. Achieve a central venous oxygen saturation (ScvO2) > 70% or mixed
venous oxygen saturation (ScvO2) > 65%
Implement the 6-hour bundle. Available at: http://ssc.sccm.org/6hr_bundles.
Findings
• Primary outcome of SSC: behavior change
– 20% increase in bundle compliance over 24
months
• Secondary outcome - Mortality
-- 7.0% ARR, 19% RRR
-- 5.4% ARR after severity adjustment
THANK YOU
In rigor mortis
• Starch solutions
• Dopamine
• “TIGHT” glucose
Humpty Dumpties still on the wall
• Steroids for all shock
• CVP targets, ScVo2
New on the block
• Lactate clearance
• Biomarkers- procalcitonin, beta D mannan,
galactomannan
• Better indicators of fluid responsiveness
• Kumar A, Roberts D, Wood KE, et al. Crit Care
Med 2006;34(6):1589–96
Fluid therapy
1. Crystalloids as the initial fluid of choice in the resuscitation of severe sepsis and septic
shock (grade 1B).
2. Against the use of hydroxyethyl starches for fluid resuscitation of severe sepsis and
septic shock (grade 1B).
3. Albumin in the fluid resuscitation of severe sepsis and septic shock when patients
require substantial amounts of crystalloids (grade 2C).
4. Initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with
suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (a portion
of this may be albumin equivalent). More rapid administration and greater amounts of
fluid may be needed in some patients (grade 1C).
5. Fluid challenge technique be applied wherein fluid administration is continued as long
as there is hemodynamic improvement either based on dynamic (eg, change in pulse
pressure, stroke volume variation) or static (eg, arterial pressure, heart rate) variables
(UG).
The role of albumin as a resuscitation fluid for patients with sepsis: A systematic
review and meta-analysis*
Delaney, Anthony P. MD, FCICM; Dan, Arina MD, FCICM; McCaffrey, John MD,
FCICM; Finfer, Simon MD, FCICM
Seventeen studies that randomized 1977 participants were included in the
meta-analysis. There were eight studies that included only patients with
sepsis and nine where patients with sepsis were a subgroup of the study
population. There was no evidence of heterogeneity, I2 = 0%.
The use of albumin for resuscitation of patients with sepsis was associated
with a reduction in mortality with the pooled estimate of the odds ratio of
0.82 (95% confidence limits 0.67–1.0, p = .047).
Objective: To determine whether the early administration of albumin as an
expander and antioxidant would improve survival on the 28th day for
septic shock patients.
Design: Prospective, multicenter, randomized, controlled versus saline,
stratified on nosocomial infection and center.
Setting: 27 Intensive Care Units (ICU) in France
Coordinator: Pr J.P. Mira and Dr J. Charpentier - Cochin Hospital- Paris
CVP for FLUID RESUSCITATION
CVP should not be used to make clinical decisions regarding fluid man
CHEST.July 2008;134(1):172-178. doi:10.1378/chest.07-2331
Mitchel Levi in SCCM sepsis presentation Jan 2013
Flowrates
• 20 g : 40 ml / minute
• 18 g : 75 m l / minute
• 16 g : 150 ml / minute
• 14 g : 300 ml / minute
• 16 G CVC of 16 cm length : 50 mL / minute only !
Certain Drug infusions need central access
Management of sepsis in Indian ICUs: Indian data
from the MOSAICS study
J Divatia
• Prospective cohort study of 162 adult patients with severe
sepsis admitted to 17 ICUs in India in July 2009.
• Hospital mortality was 38.3% (62/162)
• Compliance rate for the entire resuscitation and management
bundle was 6.8% (11/162)
• Compliance with the resuscitation bundles was associated with
mortality rates of 18.2%, while mortality rates with
noncompliance was 39.7%