ICN Victoria: Robertson on "The Case For Albumin"

Albumin - YES
The Great Debate
Dr Megan Robertson
MBBS FRACP FANZCA FCICM AFRACMA
Director of Research
St Vincent’s Hospital Melbourne
9 July 2014

Day/Month/Year Footnote to go here Page 2
Outline
• Albumin – the Australian product
• History
• Current status
• Albumin safety
• Albumin as a colloid for fluid replacement
• Fluid alternatives
• Albumin in specific clinical cases
• When not to use Albumin

Albumin History in Australia
• SPPS – Stable Plasma Protein Solution
• 86% albumin, 14% α and β globulins
• 14% protein content in aggregates
• Significant batch-to-batch variability in content, aggregates and PKA levels
• NSA – Normal Serum Albumin
• > 96% albumin
• 5% protein in aggregates
• Hyperoncotic 20% albumin introduced
• Albumex 5% (1VI)
• Double purification process – Cohn and chromatography
• Albumex 4% (2VI)
• Pure chromatography

Australian Albumin Timeline

Albumex Production - CSL
CSL Behring, formerly CSL
Biotherapies, fractionates
(manufactures) plasma-derived
therapies at its unique, purpose built
plasma fractionation facility located in
Broadmeadows, Australia.
More than AUD$500 million has been
invested in this facility to create one of
the most sophisticated plasma
fractionation facilities in the world.
Commissioned in 1994, it remains the
only commercial scale facility of its
type, and was the first commercial
plant to use chromatography – a
technology that is now in widespread
use in plasma fractionation.

Current status - Albumex 4
• 4% albumin, 40g protein/L
• Saline base
• Na 140 mmol/L
• Cl 128 mmol/L
• Iso-oncotic fluid
• Produced a by-product of packed red cell
concentrates
• Provided free-of-charge to hospitals by
Australian Red Cross Blood Bank
• In vivo albumin half life 19 days
• Approx 15g turnover/day
• Exchanged between intra- and extra-vascular
space (40% intra, 60% extra )
• In healthy subjects, 10% loss from vascular
space over 2 hours

Current status - Albumex 20
• 20% albumin, 200gprotein/L
• Hyper-oncotic fluid
• Saline base
• Na 48-100 mmol/L
• Cl 19 mmol/L
• Low sodium resusctiation fluid
• Only other commonly utilised hyper-oncotic
resusctiation fluid is packed red blood cells
• Infrequently used in ICU setting
• Limited evidence for improved diuretic action
in fluid overload

BMJ 1998;317:235-240

SAFE Study
(Saline v Albumin Fluid Evaluation)
Aim: to compare the effects of two resuscitation fluids
(4% human albumin or saline) on 28 day all cause
mortality in critically ill patients requiring intravascular
volume resuscitation
Hypothesis: no difference in mortality at 28 days

Fluid administration
• The treating clinicians decided the amount and rate of
fluid administration according to each patient’s
clinical status and response to treatment
• The allocated study treatment was used for all fluid
resuscitation in the ICU until death or discharge or
until 28 days following randomization.
• Administration of intravenous fluids outside the ICU
was not controlled.

Primary Outcome - All patients
• Albumin 726 deaths in 3473 patients (20.9%)
• Saline 729 deaths in 3460 patients (21.1%)
• Absolute difference 0.17%, (-2.08% to +1.75%)
• Relative risk 0.99, (0.91 - 1.09)
• P = 0.866

Secondary outcomes
• Days of mechanical ventilation
•Albumin 4.5 ± 6.1
•Saline 4.3 ± 5.7 P = 0.744
• Days renal replacement therapy
•Albumin 0.48 ± 2.28
•Saline 0.39 ± 2.0 P = 0.411

Conclusions from SAFE
• In this population, in this setting,
albumin and saline are clinically equivalent treatments
• Use of either results in:
•Similar mortality
•Similar time to death in those who die
•Similar use of mechanical ventilation and renal replacement therapy
•Similar incidence of new organ failures
•Similar ICU and hospital length of stay

Albumin
Colloid for fluid resuscitation

Study details
• Multicentre, randomised clinical trial
• Open label fluid administration but blinded outcome assessment
• No prior resuscitation fluid and now hypovolaemic
• Stratified for sepsis, trauma, hypovolaemic shock ± sepsis/trauma
• Colloids – gelatins, dextrans, hydroxyethyl starches, albumin
• Crystalloids –Saline or Ringers lactate solution
• Managed exclusively with one category of fluid until ICU discharge
• EXCEPT maintenance fluid crystalloid, and albumin to treat hypoalbuminaemia
• Participants 2857 – colloids 1414, crystalloids 1443
• End points – Death at 28 days, 90 days
Days alive not on mechanical ventilation, renal replacement
therapy and inotropes

Results
• Median cumulative fluid excluding maintenance for first 7 days
• Colloid group 2000 mL
• Crystalloid group 3000 mL P<0.001

Conservative fluid
management
• SAFE study
• Reduced fluid volume in albumin group (1:1.4 in first 4 days)

Other options:
Colloid for fluid resuscitation

HES associated with increased acute renal failure and RRT

Preventing Hepatorenal syndrome
in patients with SBP
Image caption here Image caption here Image caption here

Hepatorenal syndrome

Comparison of Treatment Effects
With vs. without severe sepsis
Relative risk of death for patients assigned albumin versus saline:
With severe sepsis 0.87, without severe sepsis 1.05
P=0.059 (Test for common relative risk)

Mortality in patients
with and without severe sepsis
0
10
20
30
40
Albumin
Saline185/603
p=0.088
518/2734 492/2720
217/615
Mortality(%)
Sepsis Without sepsis

• 1218 pts: 603 albumin, 615 N Saline (a priori subgroup)
• Day 1-3 albumin group received significantly less study fluid
• No difference in renal failure, RRT or other organ function
• Unadjusted relative risk of death albumin v saline 0.87 (0.74-1.02)
• Adjusted relative risk of death albumin v saline 0.71 (0.52-0.97)
• “Administration of albumin compared to saline …may have
decreased the risk of death”

Study Details
• 1818 patients with severe sepsis
• 20% albumin and crystalloid OR crystalloid alone
• Initial resuscitation according to physiological endpoints
• Target serum albumin 30 g/L or more
• Then albumin 20% 300 mL/day in intervention group
• No difference in death rates at 28 or 90 days
• Reduced net daily fluid balance in albumin group
• Reduced time to suspension of vasopressor or inotropic agents
52

Albumin
Specific cases not to use

Title

Conclusions
• Australia has a uniquely homogenous high quality supply
• Safe to use, no increased mortality
• Cheap – no cost to the user v high cost alternative colloids
• Associated with reduced total volume in resuscitation to clinical
end points
• Good evidence in SBP and hepatorenal syndrome
• Should not be used in TBI
• Albumex 20% associated with reduced chloride load

Albumin should remain part of
fluid armentarium available
to intensivists in Australia
Day/Month/YearFootnote to go here Page 63

ICN Victoria: Robertson on "The Case For Albumin"

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