L’USO DELLA RISORSA ALBUMINA LA PROSPETTIVA DEL …...AISF-SIMTI POSITION PAPER - L’USO...
Transcript of L’USO DELLA RISORSA ALBUMINA LA PROSPETTIVA DEL …...AISF-SIMTI POSITION PAPER - L’USO...
AISF-SIMTI POSITION PAPER - L’USO APPROPRIATO DELL’ALBUMINA Roma, 29 marzo 2016
L’USO DELLA RISORSA ALBUMINA
LA PROSPETTIVA DEL CLINICO
Mauro Bernardi
Semeiotica Medica Dipartimento di Scienze Mediche e Chirurgiche Alma Mater Studiorum - Università di Bologna
DISCLOSURES
• CLS Behring GmbH consultant
speaker
• PPTA Europe speaker
• Baxter Healthcare SA consultant
speaker
• Gilead Sciences speaker
ALBUMIN CONSUMPTION WORLDWIDE YEAR 2012
ISTISAN Report 12-53
601
514
416
305
303
299
245
238
194
148
118
110
87
82
81
73
71
33
9
1
0 100 200 300 400 500 600 700
Italy
Belgium
USA
Australia
Spain
Japan
Canada
France
Sweden
Germany
Iran
Cina
Egypt
UK
Argentina
Turkey
Mexico
Russia
India
Brasil
0
3000
6000
9000
0 100 200 300 400 500 600 700
Albumin consumption (g / 1000 pop) *
He
alt
h E
xp
en
d /
po
p (
US
$)
**
R = 0.66; P = 0.0014
* ISTISAN Report 12-53
** The World Bank - 2010
ALBUMIN CONSUMPTION WORLDWIDE RELATIONSHIP WITH HEALTH EXPENDITURE
ALBUMIN CONSUMPTION IN ITALY YEAR 2011
ISTISAN Report 12-53
1222
920
742
729
705
665
604
599
598
581
580
556
513
509
499
411
372
365
275
231
601
0 200 400 600 800 1000 1200 1400
Sardegna
Puglia
Campania
Calabria
Lazio
Toscana
Basilicata
ITALIA
Molise
Abruzzo
V. d'Aosta
Sicilia
Lombardia
Umbria
Emilia-Romagna
Liguria
Veneto
Piemonte
Marche
Friuli V. Giulia
Trento / Bolzano
INAPPROPRIATE USE OF ALBUMIN
22 public hospital in Spain (3 non consecutive days – 5 mo period)
Use of albumin deemed inappropriate in 76% of cases
Main reasons for inappropriate use:
nutritional intervention
hypoalbuminemia
cardiac surgery
abdominal surgery
nephrotic syndrome
Remohì et al, Ann Pharmacother 2000
$ 140,891 expenditure (77% of total) for inappropriate use
RESTRAINTS FOR ALBUMIN USE
•Lack of solid scientific evidence
•Availability of cheaper alternatives
•High cost
•Limited availability
•Fear of transmission of viral infection
•Lack of solid scientific evidence
•Availability of cheaper alternatives
•High cost
•Limited availability
•Fear of transmission of viral infection
USE OF ALBUMIN IN LIVER DISEASE INDICATIONS EMERGING FROM EBM
• Prevention of post-paracentesis circulatory
dysfunction (> 4-5 L of tapped ascites)
• Prevention of renal failure induced by
spontaneous bacterial peritonitis
• Hepatorenal syndrome, associated with
vasopressors [terlipressin; midodrine +
octreotide; noradrenalin])
8 g / L of tapped ascites
1.5 g / Kg bw at diagnosis
1 g / Kg bw on day 3
EASL – CPGs on Tx of ascites, SBP & hepatorenal syndrome, J Hepatol 2010
1 g / Kg bw at diagnosis
20-40 g / day thereafter
• Albumin + vasoconstrictors in HRS 1: 84%
• Albumin + vasoconstrictors in HRS 2: 72%
• Mean daily albumin dose: 27 ± 2 g
• Complete response: 30%
• Partial response: 20%
Salerno et al, J Hepatol 2011
USE OF ALBUMIN IN HRS THE ITALIAN EXPERIENCE
HRS 1: 76 patients
HRS 2: 40 patients
Bajaj et al, Hepatology 2015
ALBUMIN USE IN PATIENTS WITH CIRRHOSIS AASLD MEMBERS SURVEY
ALBUMIN USE ACCORDING TO GUIDELINES THE CANONIC STUDY1
1Moreau et al, Gastroenterology 2013
Arroyo V – Use of Albumin in the CANONIC Study
*There were patients with more than one complication associated
to albumin administration.
Patients Patients receiving (N = 1343) albumin N (%) N (%)
Included with follow-up* 699 (52) 425 (61)
Infection (SBP 26%) 398 (57) 152 (38)
Paracentesis 291 (42) 225 (77)
HRS 179 (26) 75 (42)
RESTRAINTS FOR ALBUMIN USE
•Lack of solid scientific evidence
•Availability of cheaper alternatives
•High cost
•Limited availability
•Fear of transmission of viral infection
Bernardi et al, Hepatology 2012
PREVENTION OF PICD META-ANALYSIS: MORTALITY
USE OF ALBUMIN IN HEPATOLOGY ARE THEY CHEAPER ALTERNATIVES ?
• Albumin is superior to any other alternative tool (artificial plasma
expanders, crystalloids, vasoconstrictors) in preventing PPCD
and paracentesis-induced hyponatremia and mortality
Bernardi et al, Hepatology 2012
• Albumin is superior to hydroxyethyl starch in improving effective
volemia in patients with SBP
Fernandez et al, Hepatology 2005
• Terlipressin plus albumin is superior to terlipressin alone in
achieving a complete response to treatment in HRS
Ortega et al, Hepatology 2002
•Lack of solid scientific evidences
•Availability of cheaper alternatives
•High cost
•Limited availability
•Fear of transmission of viral infection
RESTRAINTS FOR ALBUMIN USE
FIGHTING THE SCARCITY OF RESOURCES
JAMA 2013; February 27, 2013
FIGHTING THE SCARCITY OF RESOURCES THE ST. ORSOLA-MALPIGHI HOSPITAL EXPERIENCE
0
10000
20000
30000
40000
50000
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
ALB
UM
IN V
IALS
YEAR
Mirici-Cappa et al., World J Gastroent 2011
• 7 departments
• 91 units
• 1,758 beds
• 72,000 admissions / y
• OLT program
Albumin not recommended
• cerebral ischemia
• would healing
• nutritional purposes
• neprotic syndrome
Albumin as 2nd line tx
• hypovolemic shock
• major surgery
• burns
• malabsorption syndrome
FIGHTING THE SCARCITY OF RESOURCES THE ST. ORSOLA-MALPIGHI HOSPITAL EXPERIENCE
Mirici-Cappa et al., World J Gastroent 2011
0
10000
20000
30000
40000
50000
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
ALB
UM
IN V
IALS
Enforcement of guidelines
FIGHTING THE SCARCITY OF RESOURCES THE ST. ORSOLA-MALPIGHI HOSPITAL EXPERIENCE
Mirici-Cappa et al., World J Gastroent 2011
0
20
40
60
80
100
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
Liver Units Other Units Intensive care
AL
BU
MIN
: %
OF
TO
TA
L C
ON
SU
MP
TIO
N
YEAR
Enforcement of guidelines
FIGHTING THE SCARCITY OF RESOURCES MAXIMIZING BENEFITS
“ Choose interventions and care settings that maximize
benefits, minimize arms, and reduce costs (using
comparative effectiveness and cost-effectiveness data)”
Smith et al, Ann Int Med 2012
• Identify features (clinical, lab, biomarkers) allowing to
select patients who would mostly receive benefit from
albumin administration
• Identify the lowest effective albumin dosages and
treatment durations in different settings
• Assess cheaper alternatives or combined treatments
with (at least) equal efficacy through reliable studies
• Promote controlled clinical trials assessing albumin
use in new indications
FIGHTING THE SCARCITY OF RESOURCES MAXIMIZING BENEFITS
FIGHTING THE SCARCITY OF RESOURCES APPROPRIATE COST ASSESSMENT
“ Choose interventions and care settings that maximize
benefits, minimize arms, and reduce costs (using
comparative effectiveness and cost-effectiveness data)”
Smith et al, Ann Int Med 2012
- 4,6% according to the
SAFE study
Guidet et al, J Crit Care 2007
Cost /life saved: € 6,037
Cost /y life saved: € 617
COST-EFFECTIVENESS OF ALBUMIN USE SEVERE SEPSIS & SEPTIC SHOCK
SALINE vs ALBUMIN
Prevention programs in which the cost per year of
gained life is less than twice the per capita GNP (€ 50,000 in
France) should be systematically adopted
10 high risk SBP pts (4 with RI)
10 high risk SBP pts (4 with RI)
Total cost € 52,151
Albumin infusion 1,750 g = € 4,655
Days in hospital 125 d = € 37,500
Days in hospital 135 d = € 40,500
Total cost € 57,916
assumptions:
1 g Albumin = € 2.66
1 mg Terlipressin = € 37.86
1 hospital day = € 300
No RI: discharge after 10 d
RI: discharge after 15 days + 1 RI
(3 HRS)
No RI: discharge after 10 d
RI: discharge after 15 days + 3 RI
(5 HRS)
Potential
deaths 1
Potential
deaths 3
PREVENTION OF RENAL FAILURE IN SBP COST ANALYSIS
Albumin infusion 1,110 g = € 2,953
Terlipressin 186 mg = € 7,043
Albumin infusion 1,850 g = € 4,921
Terlipressin 330 mg = € 12,495
ALBUMIN vs POLYGELINE IN CIRRHOSIS EFFICACY & COST ANALYSIS
Moreau et al, Liver Int 2006
Cirrhosis with ascites
30 albumin group
38 polygeline group
Follow-up 6 months
RISK FOR DEVELOPING LIVER RELATED COMPLICATIONS*
Polygeline vs Albumin: HR 1.95; 95% CI [1.323.37], P < 0.016
* adjustment for baseline
history of portal hypertensive bleeding
creatinine clearance
serum albumin
MEDIAN COST ADJUSTED TO A 30-DAY PERIOD
Polygeline: € 4,612 vs Albumin: € 1,915; P < 0.004
Inclusion criteria
therapeutic paracentesis
renal impairment
severe hyponatremia
• The use of albumin for the current indications given by
guidelines is variable and often sub-optimal
• Continuing education is still needed
• In order to avoid and oppose uncritical rationing of albumin
use by health Authorities it would be essential:
- avoid inappropriate use
- refine indications and dosages
- perform appropriate cost analysis
- support new indications or alternative treatments with
reliable studies
CONCLUSIONS