Le sang artificiel Espoirs et limites - JFSPH
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Dr Patrick Schoettker, PD Service d’Anesthésiologie Centre Hospitalier Universitaire 1011 Lausanne-CHUV Suisse Le sang artificiel Espoirs et limites [email protected]
Transcript of Le sang artificiel Espoirs et limites - JFSPH
Dr Patrick Schoettker, PD
Service d’Anesthésiologie
Centre Hospitalier Universitaire
1011 Lausanne-CHUV
Suisse
Le sang artificiel
Espoirs et limites
Cause of early mortality in trauma
Shapiro MB et al. JTrauma 2000;49:969-78
Sauaia A et al. JTrauma 1995;38:185-193
Murphy G. J. et al. Circulation (2007) 116: 2544
8598 patients cardiac surgery - UK
1996 - 2003
Pre-specified adverse infectious,
ischemic (MI, stroke, renal failure) and
cost outcomes
RBC transfusion and mortality
Murphy G. J. et al. Circulation (2007) 116: 2544
Koch C.G. et al. New Engl J Med (2008) 358: 1229
„Old“ RBC - Serious adverse outcome
RBC < 14 d RBC > 14 d
In-hospital mortality 1.7 % 2.8 %
1 year mortality 7.4% 11.0 %
Intubation > 72 h 5.6 % 9.7 %
Renal failure 1.6 % 2.7 %
Sepsis 2.8 % 4.0 %
Koch C.G. et al. New Engl J Med (2008) 358: 1229
Produit Prix (CHF)
CE adulte 217.60
CP 5U 780.20
CP 5U inactivés 1016.00
PFC 150.00
Total estimated cost of blood 2013
Total estimated cost of blood
$ 760.82 $ 293.74
$ 1183.32 - $ 726.05 - $ 611.44 – $ 522.45
Total costs of blood 2007
Transfusion in
Rapports annuels SRTSVD et Swissmedic
2006 2007 2008 2009 2006-2009
CE 12’435 13’559 15’351 15’867 +27%
CP 1’893 2’062 2’353 2’330 +23%
PFC 6’895 5’619 4’860 5’785 -16%
TOTAL 21’223 21’240 21’240 23’982 +13%
Total estimated blood transfusion in CH
2007 2008 2009
CE 308’470 313’587 311’521
CP 22’937 27’669 29’654
PFC 69’822 65’823 70’353
total 401’229 407’079 411’528
Rapports annuels SRTSVD et Swissmedic
Elective surgery
Patient Blood Management
Early individual goal directed coagulation
algorithm
It’s bleeding?
Restoration of oxygen delivery to organs
Support of intravascular volume
Restoration of oxygen delivery
Universally compatible
Loads, Transports, Unloads O2
Long shelf life (years)
Virtualy sterile
Restoration of oxygen delivery
Cell free Hb (1933)
Dimerization and renal failure
Dissociated Dimers undergo renal clearance
• short serum ½ life
• renal tubular toxicity
• acute renal failure
Free Hemoglobin
Rapid reaction with NO
Nitrosylated compounds
Methemoglobin
NO autoregulates systemic / pulmonary
vascular tone
elimination leads to vasoconstriction
Systemic and pulmonary HTA
Decreased cardiac output
It’s bleeding?
Restoration of oxygen delivery to organs
Cell free Hb (1933)
Perfluorocarbon emulsion
Recombinant Hb
Liposome-encapsulated Hb
Heme containing nanoparticles
Hb-based O2 carriers (HBOC) 1st and 2nd generation
Perfluorocarbon-based O2 carriers
PFBOC
Achieve O2 delivery by using organic
chemicals with high gas solubility
Oil-like fluid
Must be mixed with fluid (Albumin,
emulsifying agents)
Dimerization and renal failure
No dissociation
No glomerular filtration
First generation HBOCs
DCLHb (HemAssist, 1992) diaspirin-cross linked low O2 affinity to maximize tissue oxygen delivery small size low viscosity
HemAssist
Animal models: survival up to Ht 1.2% improved O2 delivery to anoxic brain tissue
HemAssist
Human trials: Trauma: HemAssist vs. Saline. Terminated early after 28 days
Mortality 56% vs. 17% (p=0.003)
Ischemic stroke Cardiac / non cardiac surgery STOP in 2003
Crosslinking and polymerization
No dissociation
No glomerular filtration
Biopure (HBOC-201) 2000-2003
Glutaraldehyde to catalyze intermolecular
polymerization
Phase II: reduced the need for allogenic blood
transfusion in op. patients
Phase III: orthopedic patients, increased risk of AE
Biopure (HBOC-201) 2000-2003
2001: RSA approval for ttt surgical anemia
US Navy: $14 million phase III
RESUS (Restore Effective Survival in Shock)
www.biopure.com
« Oxyglobin »
2004
Jesus Manzano
Tour de France
PolyHeme
Start in 1969
Northfield laboratory
Bigger molecule (160 Kda)
Does not penetrate subendothelium
Little vasoconstriction
Longer half life (24h vs. 12h)
PolyHeme
Volume 500ml
Hb concentration 10g/L
Tetramer conc. < 1%
9th May 2009
PolyHeme
> 200 millions $
Characteristics of HBOCs
MP4OX (Hemospan)
90 millions $
Chemical modifications and SAE
The future ?
Dendrimers
Current US military funding to date
Biopure (Hemopure) 22.5 million $
Northfield (Polyheme) 5.0
Sangart 1.3
Dendritech 0.75
Hemostatic resuscitation
Cost
Problems Availability Strategy
Bleeding and coagulation in trauma
BIG changes in the last 5 years
Brohi K et al. AnnSurg 2007;245:812
