L’USO DELLA RISORSA ALBUMINA LA PROSPETTIVA DEL …...AISF-SIMTI POSITION PAPER - L’USO...

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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

Transcript of L’USO DELLA RISORSA ALBUMINA LA PROSPETTIVA DEL …...AISF-SIMTI POSITION PAPER - L’USO...

Page 1: L’USO DELLA RISORSA ALBUMINA LA PROSPETTIVA DEL …...AISF-SIMTI POSITION PAPER - L’USO APPROPRIATO DELL’ALBUMINA Roma, 29 marzo 2016 L’USO DELLA RISORSA ALBUMINA LA PROSPETTIVA

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

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DISCLOSURES

• CLS Behring GmbH consultant

speaker

• PPTA Europe speaker

• Baxter Healthcare SA consultant

speaker

• Gilead Sciences speaker

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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

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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

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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

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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

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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

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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

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• 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

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Bajaj et al, Hepatology 2015

ALBUMIN USE IN PATIENTS WITH CIRRHOSIS AASLD MEMBERS SURVEY

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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)

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RESTRAINTS FOR ALBUMIN USE

•Lack of solid scientific evidence

•Availability of cheaper alternatives

•High cost

•Limited availability

•Fear of transmission of viral infection

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Bernardi et al, Hepatology 2012

PREVENTION OF PICD META-ANALYSIS: MORTALITY

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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

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•Lack of solid scientific evidences

•Availability of cheaper alternatives

•High cost

•Limited availability

•Fear of transmission of viral infection

RESTRAINTS FOR ALBUMIN USE

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FIGHTING THE SCARCITY OF RESOURCES

JAMA 2013; February 27, 2013

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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

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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

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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

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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

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• 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

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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

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- 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

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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

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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

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• 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

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