colloids versus crystalloids: do we have an answer … versus crystalloids: do we have an answer...
TRANSCRIPT
Colloids versus Crystalloids: Do we have an answer yet??
Lauralyn McIntyre MD, FRCP(C), MHScScientist, Ottawa Hospital Research Institute
Assistant Professor, University of OttawaDepartment of Epidemiology and Community Medicine
Center for Transfusion and Critical Care Research
Conflicts of Interest
• Unrestricted funds CSL Behring
The Colloid Crystalloid Question……
• Is one of the oldest• Basic yet fundamental question
• The first intervention given • To every patient • Often several litres • Since fluids critical for achievement of
hemodynamic stability, there is a potential for impact on clinically important outcomes
Main categories of usual care resuscitation fluids
Crystalloid FluidNormal SalineRingers Lactate
Colloid FluidAlbuminHydroxyethyl starch
Main categories of usual care resuscitation fluids
Crystalloid FluidNormal SalineRingers Lactate
Colloid FluidAlbuminHydroxyethyl starch
Other Colloids:GelatinsDextrans
Components of Normal Saline and Ringers Lactate
28
0
Lactatemmol/L
272
308
Osmo-larity
2.7
0
Ca++mmol/L
4
0
K+mmol/L
109130Ringers Lactate
154154Normal Saline
Cl-mmol/L
Na+mmol/L
• Most common human plasma protein (60%)• Synthesized in the liver• Molecular weight of 66 Kd• Responsible for 80% osmotic pressure
• Available:• Iso – oncotic (4 – 5%)• Hyper – oncotic (20 – 25%)
Quinlan et al, Hepatology, 2005
Albumin
What are hydroxyethyl starch (HES) fluids?
• Amylopectin starch (branched chain glucose molecules)
Hydroxyethylation at C2 and C6 carbon units (substitution)
Vary in size (130 – 200 kD)Vary in the amount of substitution and ratio of substitution
ISS10 L
IC30 L
Plasma3 L
Blood Cells2 L
Rationale for Resuscitating with Colloids compared to Crystalloids
ISS10 L
IC30 L
Plasma3 L
Blood Cells2 L
Rationale for Resuscitating with Colloids compared to Crystalloids
Plasma3 L
Blood Cells2 L
Iso-oncotic colloid
ISS10 L
IC30 L
Plasma3 L
Blood Cells2 L
Rationale for Resuscitating with Colloids compared to Crystalloids
Plasma3 L
Blood Cells2 L
Iso-oncotic colloidHyper-oncotic colloid
ISS10 L
IC30 L
Plasma3 L
Blood Cells2 L
Rationale for Resuscitating with Colloids compared to Crystalloids
Plasma3 L
Blood Cells2 L
Iso-oncotic colloidHyper-oncotic colloid
ISS10 L
IC30 L
ISS10 L
IC30 L
Plasma3 L
Blood Cells2 L
Rationale for Resuscitating with Colloids compared to Crystalloids
Plasma3 L
Blood Cells2 L
Iso-oncotic colloidHyper-oncotic colloid
ISS10 L
IC30 L
Optimization of the microcirculation?Impact on microcirculatory dysfunction?Modulation of inflammatory response
The Colloid Crystalloid Question…
• Research on this question for several decades
• And yes, there have been many studies and many systematic reviews
Cochrane Systematic Reviews
Author/Year Fluids compared # StudiesPerel, 2011 Colloids vs Crystalloids 56Bunn, 2011 Colloid vs Colloid 72Alderson 2009 Albumin vs no albumin 37Dart 2010 HES vs other fluid 34
Cochrane Systematic Reviews
Author/Year Fluids compared # StudiesPerel, 2011 Colloids vs Crystalloids 56Bunn, 2011 Colloid vs Colloid 72Alderson 2009 Albumin vs no albumin 37Dart 2010 HES vs other fluid 34
So why are we still studying this question?
Cochrane Systematic Reviews
Author/Year Fluids compared # StudiesPerel, 2011 Colloids vs Crystalloids 56Bunn, 2011 Colloid vs Colloid 72Alderson 2009 Albumin vs no albumin 37Dart 2010 HES vs other fluid 34
So why are we still studying this question?
• Small sample size• Single centre• Dated resuscitation protocols• Insufficient dose• Surrogate outcomes• Few studies in the critically ill• Low methodological rigor (risk of bias high)
SAFE TRIPS II: International cross sectional study 391 ICUs and 25 countries
Finfer et al, Critical Care, 2010; 14:R185
SAFE TRIPS II: International cross sectional study 391 ICUs and 25 countries
Finfer et al, Critical Care, 2010; 14:R185
SAFE TRIPS II: International cross sectional study 391 ICUs and 25 countries
Finfer et al, Critical Care, 2010; 14:R185
SAFE TRIPS II: International cross sectional study 391 ICUs and 25 countries
Finfer et al, Critical Care, 2010; 14:R185
SAFE TRIPS II: International cross sectional study 391 ICUs and 25 countries
Finfer et al, Critical Care, 2010; 14:R185
Are colloid fluids better maintained in the intravascular space as compared to
RCT/Yr Population Fluid Comparators RatioCrystalloid/Colloid
SAFE/04 Critically illN = 6997
4% albumin vs normal saline
1.4
VISEP/08 Severe Sepsis/Septic Shock
N = 537
10% HES vs ringers lactate
1.4
McIntyre/08 Septic ShockN = 40
10% HES vsnormal saline
1.1
Hartog et al, Anesth and Anal 2011, 112:635-645
RCT/Yr Population Fluid Comparators RatioCrystalloid/Colloid
SAFE/04 Critically illN = 6997
4% albumin vs normal saline
1.4
VISEP/08 Severe Sepsis/Septic Shock
N = 537
10% HES vs ringers lactate
1.4
McIntyre/08 Septic ShockN = 40
10% HES vsnormal saline
1.1
Hartog et al, Anesth and Anal 2011, 112:635-645
RCT/Yr Population Fluid Comparators RatioCrystalloid/Colloid
SAFE/04 Critically illN = 6997
4% albumin vs normal saline
1.4
VISEP/08 Severe Sepsis/Septic Shock
N = 537
10% HES vs ringers lactate
1.4
McIntyre/08 Septic ShockN = 40
10% HES vsnormal saline
1.1
Hartog et al, Anesth and Anal 2011, 112:635-645
RCT/Yr Population Fluid Comparators RatioCrystalloid/Colloid
SAFE/04 Critically illN = 6997
4% albumin vs normal saline
1.4
VISEP/08 Severe Sepsis/Septic Shock
N = 537
10% HES vs ringers lactate
1.4
McIntyre/08 Septic ShockN = 40
10% HES vsnormal saline
1.1
Hartog et al, Anesth and Anal 2011, 112:635-645
? Endothelial Cell Leak
Are there potential harms associated with the use of colloid fluid in the
Hydroxyethyl starches Albumin
Coagulopathy yes yes
Transmission viral infection no yes
Anaphylaxis yes(<0.006%)
yes(<0.1%)
Pruritis yes no
Renal Failure yes ?
Grocott, M, Anesthesia and Analgesia, 2005
Hydroxyethyl starches Albumin
Coagulopathy yes yes
Transmission viral infection no yes
Anaphylaxis yes(<0.006%)
yes(<0.1%)
Pruritis yes no
Renal Failure yes ?
Grocott, M, Anesthesia and Analgesia, 2005
Brunkhorst et al, NEJM, 2008
Baseline CharacteristicsMean (SD)
Ringers LactateN=275
HESN=262
P value
Age 64.9 ±4.1 64.4 ± 13.3
Sex (male) (%) 59.6 60.3
APACHE II Score 20.3 ± 6.7 20.1 ± 6.7
Results (%) *RRT 18.8% 31% 0.001
Acute renal failure 22.8 34.9 0.001
28 day Mortality 24.1% 26.7% 0.484
90 day Mortality 33.9% 41% 0.092
Brunkhorst et al, NEJM, 2008*RRT = renal replacement therapy
VISEP trial: HES dose and RRT
Brunkhorst et al, NEJM, 2008
VISEP trial: HES dose and RRT
Brunkhorst et al, NEJM, 2008
Limitations of the VISEP Trial
• Fluid protocol violations • No criteria for dialysis
• Un-blinded study
What evidence related to HES is forthcoming?
Trial Population Fluids compared Primary Outcome
6S Severe SepsisN = 800
Voluven vsRingers lactate
90 Day Mortality or Dialysis
CHEST Critically illN = 7000
Voluven vsNormal Saline
90 Day Mortality
Finfer et al, NEJM 2004; 350: 2247 - 2256
Survival 28 Days Survival 24 Months
Survival in SAFE TBI sub-group (n = 460)
20.4%
33.2%
Survival 28 Days Survival 24 Months
Survival in SAFE TBI sub-group (n = 460)
20.4%
33.2%
Severe TBI (N = 290)
RR and 95% CI: 1.88 (1.31 to 1.70)
SAFE TBI comments
• Post - hoc sub group analysis• Co-interventions for TBI not described• Biological mechanisms not clear
• Intracranial hypertension • 30% vs 34% albumin vs normal saline
Predefined sub-group with severe sepsis n = 1218
Finfer et al, Intensive Care Medicine, published on line, October 6, 2010
SAFE Severe Sepsis: Baseline Characteristics
Albumin SalineAge 60.5 ±17.2 61.0±17.1
Gender (male) 59.6% 57.1%
APACHE II 21.6±7.8 21.8±7.7
Septic Shock 34.8% 37.3%ARDS 6.5% 6.8%Ventilation 56.8% 59.4%
SAFE Severe Sepsis: 28 day mortality
Finfer et al, Intensive Care Medicine, published on line, October 6, 2010
SAFE Severe Sepsis: 28 day mortality
Finfer et al, Intensive Care Medicine, published on line, October 6, 2010
SAFE Severe Sepsis: 28 day mortality
Finfer et al, Intensive Care Medicine, published on line, October 6, 2010
No differences in renal injury between fluid groups
FEAST Trial
• 3141 African children with febrile illness and impaired perfusion
• Randomized to boluses of 5% albumin, normal saline, or no bolus
Maitland et al, NEJM, 2011
FEAST Trial
• 3141 African children with febrile illness and impaired perfusion
• Randomized to boluses of 5% albumin, normal saline, or no bolus
Maitland et al, NEJM, 2011
Bolus5% albumin
Bolus normal saline
Control
48 hour death 10.6% 10.5% 7.3%
4 week death 12.2% 12.0% 8.7%
Neurologic sequlae
2.2% 1.9% 2.0%
Increased ICP or pulmonary edema
2.6% 2.2% 1.7%
More evidence for albumin in sepsis is coming……
EARRS Trial ALBIOS Trial PRECISE Trial
Population
Septic shock within first 6 hours ICU
admission
Severe Sepsis/Septic Shock within 24 hours in
ICU
Early Septic shock from the ED
Sample Size
800 1800 1808
Intervention
Open label100 mls 20% albumin Q8H versus normal
saline for first 3 days in ICU
Open labelUp to 300 mls infused
20% albumin vs crystalloid fluid according to albumin levels in ICU
Double blindHead to Head 500 ml
boluses 5% albumin versus normal saline starting in ED
Primary Outcome
28 Day Mortality
28 Day Mortality 90 Day Mortality
Colloids versus Crystalloids for Fluid Resuscitation: Do we have the ANSWERS yet?
Populations Albumin Hydroxyethyl starch
Heterogeneous critically ill Yes Evidence coming
Septic shock Evidence coming Evidence coming
Trauma SG evidence SG evidence
ARDS SG evidence SG evidence
Traumatic Brain Injury SG evidence SG evidence
Sub Arachnoid Hemorrhage ? ?
SG = evidence from sub group