The ESPEN Initiative for Diagnostic Criteria for ... · Weight as predictor of COPD mortality...

Tommy Cederholm

Professor, Klinisk nutrition och metabolism, Folkhälso-och vårdvetenskap, Uppsala Universitet

Överläkare, Geriatriska kliniken, Akademiska sjukhuset, Uppsala

Sjukdoms- vs. svältrelaterad undernäring- malnutrition ur etiologiskt perspektiv

http://upload.wikimedia.org/wikipedia/commons/6/64/UppsalaUniversitetsSigill.png

http://upload.wikimedia.org/wikipedia/commons/6/64/UppsalaUniversitetsSigill.png

Catabolic trajectories leading to disability & death

Robust

&

Healthy

Cachexia, sarcopenia and frailty are risk

factors for disability and death

†

Kakexi = Sjukdoms-relaterad malnutrition (DRM) med inflammation

- Sjukdom

- Viktförlust >5% s. 12 m

eller

- BMI<20

+ ≥3 av

- Minskad muskelstyrka

- Minskad muskelmassa

- Trötthet

- Anorexi

- CRP/albumin/anemi

Evans et al. Clin Nutr 2008

- Sjukdom

- Viktförlust >5% 3m/10%

och

- BMI<20/22 (<70/>70 år)

eller

- Minskad muskelmassa

- CRP/albumin

ESPEN Consensus. Clin Nutr 2015

Current challenges

The nutrition community needs

- clinically relevant aetiology-baseddiagnoses of malnutrition

(to be used for the ICD and other classificationsystems)

- diagnostic criteria for malnutrition

Etiology-based defintionsGeneral mechanisms underlying

malnutrition/undernutrition

• Food deprivation/starvation

– due to poverty, natural disaster; floodings, droughts

• Catabolic disease with inflammation and anorexia

• Disease with non-inflammatory reasons for reducedfood intake or absorption

Todays diagnostic procedures of malnutrition don’ttake aetiology into consideration

Malnutrition diagnoses tree

ESPEN Consensus Statement 2016

At risk for malnutrition

Malnutrition/Undernutrition

Disease-related malnutrition (DRM) with inflammation

Acute disease- or injury-related malnutrition

Chronic DRM with inflammation

Cancer cachexia and other disease-specific cachexia

Disease-related malnutrition (DRM) without inflammation

Malnutrition/Undernutrition without disease

Socioeconomic or psychologic related

malnutrition

Hunger-related malnutrition

Risk screening

Basic diagnosis

Etiology-based

diagnoses

ESPEN Guidelines on Definitions and Terminology

Cederholm et al. Clin Nutr 2016;e-pub

ESPEN membership ballot >300 votes:

53% malnutrition

47% undernutrition

More consideration is needed

Malnutrition or undernutrition?











malnutrition


Risk screening

Basic diagnosis

Etiology-based

diagnoses

Malnutrition related to- Cancer- COPD- Congestive heart failue- Infections- Trauma- ICU




0

10

20

30

40

50

60

70

COPD/PEM COPD Controls

S-T

NF

(p

g/m

l)

Di Francia Am J Respir Crit Care Med 1994;150:1453-5

(16)

(14)

p<0.05

Inflammation och kakexi/KOL

Inflammation

Insulin resistenceNeuropeptid Y↓

Leptin↑Ubiquitin-proteasom↑

Lipoprotein lipase

Anorexia Proteolysis Lipolysis

Hormon sensitive lipase↑

Cathepsin↑

Disease/trauma/aging

Cachexia → Sarcopenia

http://www.gotlandsfoto.se/butiken/images/butiksbilder/farg/farg_35x50/glodbadd.jpg

http://www.gotlandsfoto.se/butiken/images/butiksbilder/farg/farg_35x50/glodbadd.jpg

nucleus

proteasome

protein

ubiquitine

Amino acids

- alanine

- glutamine

insulin

+-

TNFa

IL-1b

+

gluconeogenesis

gut

immune system

Inflammation och muskelnedbrytning

Oliff 1987

Insulin

resistance

Sarkopeni

Muskel...

• ~40% av kroppsvikten

• ~20% av muskeln är protein

• 50-75% av kroppens protein

• Rörlighet

• Styrka

• Aminosyrapool

• Glukosreglering

• Energiomsättning

• Endokrina funktioner

• ....

Weight as predictor of COPD mortality

Survival (%)

0

20

40

60

80

100

12 24 36 48

Months

BMI>29

BMI 24-29

BMI 20-24

BMI <20

400 COPD-patients, >65 y

4 y follow-up

Independent mortality predictors;

• BMI <24 (obesity paradox)

• Age

• PaO2

• PaCO2, FEV1, sex

Schols et al. Am J Respir Crit Care Med 1998;157:1791-7

Kardiell kakexi

Definition: >6% viktförlust s. 6 mån

Prevalens: 12-15% (NYHA II-IV)

Incidens: 10%/år

Anker et al. Clin Nutr 2006;25:311

Myrianthefs et al. Cytokine 2007

Anker et al. Lancet 2003;361:1077-83

Kardiell kakexi - mortalitet












malnutrition


Risk screening

Basic diagnosis

Etiology-based

diagnoses

Malnutrition related to- Stroke, Parkinson- Dementia- Anorexia nervosa- Depression- Malabsorption

- Coeliac disease- Short bowel syndrome













malnutrition


Risk screening

Basic diagnosis

Etiology-based

diagnoses




Kroppsviktens relation till funktion och överlevnad hos hemmaboende äldre

~13.000 >65 år

7 års uppföljning

Optimal funktion vid BMI ~25

Högst överlevnad vid BMI ~25-30

Sämst överlevnad vid BMI <22

Al Snih S et al. Arch Intern Med 2007;167:774-80

Bra funktion

Överlevnad

”Obesity paradox”

!

BMI<22

MAIDS –malnutrition associated immune deficiency syndrome

Infections

Cell mediated immunity↓

– T lymphocytopenia

– CD4/CD8 ratio↓

• Humoral immunity↓

– Ig-prod↓→Vaccination↓

• Granulocyte dysfunction

– Chemotaxis↓

– Oxygen radicalproduction↓

Mentala effekter av svält

• Depression

• Apati

• Irritabilitet

• Social tillbakadragenhet

0

50

100

0 6 9 15

Mån

Dep

ress

ions

skala

Svält 0-6 Refeeding 6-15

Keys A. The Biology of Human Starvation 1950

34 unga män, 1500 kcal/dag 6 mån,

förlorade 25% av kv

The nutrition care process needs to assure a diagnostic procedure• Screening/risk evaluationnutritional risk• Assessment for treatment• Treatment• Monitoring

Next challenge: Define diagnostic criteriafor malnutrition/undernutrition

Next challenge: Define diagnostic criteria for malnutrition/undernutrition

The nutrition care process needs to assure a diagnostic procedure• Screening/risk evaluationnutritional risk• Assessment for diagnosis and treatment• Diagnosis• Treatment• Monitoring

”…elements important in operationalism of malnutrition were involuntary weight loss, body mass index, and no nutritional intake”

Conclusion: This study shows that there is no full agreement among experts on the elements defining malnutrition. The results of this study may fuel the discussion within the nutritional societies, which will most ideally lead to an international consensus on a definition and operationalism of malnutrition.

ESPEN initiative 2012-2015 Diagnostic criteria for malnutrition

to be

• used by physicians in daily clinical practice;

• simple; i.e. minimum no. of items

– compare Obesity = BMI >30 kg/m2

• adopted by the International Classificationof Diseases (ICD-10/11)

Cederholm et al. Clin Nutr 2015;34:335-40.

• Weight loss

• Reduced food intake

• Reduced appetite

• Low BMI

• Reduced lean mass

• Reduced fat mass

• Inflammation

• Subjective evaluation

• Functional measures

ESPEN initiative 2012-2015What is the core of malnutrition?Nutrition indicators considered

ESPEN Working Group:Tommy Cederholm, Ingvar Bosaeus, Rocco Barazzoni, Juergen Bauer, Andre Van Gossum, Stanislaw Klek, Maurizio Muscaritoli, Ibolya Nyulasi, Johann Ochenga, Stéphane Schneider, Marian de van der Schueren, Pierre Singer

ESPEN suggestion for diagnostic criteria for malnutrition

Step 2. Diagnosis is confirmed by

• BMI <18.5 kg/m2

or

• Weight loss >10% (indefinite time)/>5% last 3 mo

combined with either

• BMI <20 (<70 y)/<22 (>70 y) or

• FFMI <15 and 17 kg/m2 in women and men, respect.

Step 1. Risk screening by a validated instrument , e.g. NRS-2002, MUST, MNA(-SF), SNAQ, ...i.e. BMI, Weight loss, Reduced food intake, Disease severity

Cederholm et al. Clin Nutr 2015;34:335-40.

ESPEN Poll - 304 ”votes”

Criteria

26%

Result: ~70% ≥ 8/10 agreementConclusion: ”Strong support”

1=strongly disagree,2-9= ....10=strongly agree

1

5

8

10

Problems and issues raised that should be considered

• Too restrictive cut-offs

– Low prevalence figures less reimbursement

• How to handle weight loss/malnutrition in obesepatients?

• Low access to body composition measurement techniques

• Lack of criteria indicating pathophysiology

• Ethnicity/adapted cut-offs

Potential solutions from on-going discussions within the ESPEN community

Introduction of a grading system?

– At risk for malnutrition (not for ICD)

For ICD

–Malnutrition stage 1

–Malnutrition stage 2

Grading of malnutrition

• At risk for malnutrition (by any validated screening tool)

– The diagnosis of malnutrition is only considered after screening positive

• Malnutrition stage 1– Weight loss (unintentional, 5/10%) and

– Any etiology; e.g. food intake↓, catabolic disease, malabsorption and

– BMI >20/22 kg/m2 or

– FFM > lower cutoff/culture relevant (FFMI >15/17); BC, muscle function

• Malnutrition stage 2 (similar to ESPEN Diagnostic Criteria 2015)

– Weight loss (unintentional, 5/10%) and

– Any etiology; e.g. food intake↓, catabolic disease, malabsorption and

– BMI < 20/22 kg/m2 or

– FFM < lower cutoff/culture relevant (FFMI >15/17); BC, muscle function

On-going process since 2016The Global Leadership Initiative on Malnutrition*

(GLIM)Diagnosis and diagnostic criteria of malnutrition

*Working Group created with 5-7 delegates from each continental PEN- society: ESPEN, ASPEN, FELANPE and PENSA- A CORE Working Group with 2 delegates each is also created

Energi- och proteintillägg halverade dödligheten hos utskrivna sjukhuspatienter – The Nourish Study

• 652 undernärda sjukhuspat, >65 år

• Hjärtsvikt, KOL, AMI, pneumoni

• RCT: 350 kcal, 20 g prot, 160 IU D-vitamin, 1,5 g HMB x2/placebo

• 90 dagars behandling

Slutsats:

Halverad dödlighet efter 3 månaders behandling med kosttillägg; från ~10% till ~5%

Deutz et al. Clin Nutr 2016;35:18-26

Metaanalys av proteinrika näringstillskott

• 36 RCT, 3790 patienter (1/3 gamla, 1/3 höftfrakturer)

• Observationstid 3 mån

• Högprotein-ONS (>20E%)

• Färre

• Komplikationer

• Återinläggningar

• Förbättrad

• Vikt

• Greppstyrka

Cawood. Aging Res Rev 2012

ONS and re-admission –a meta-analysis

• 6 studies (n=852) qualified to be part of the meta-analyses

• 23% re-adm by ONS vs 33% in controls (p<0.001)

Conclusion: ONS reducedre-admissions by ~40%

Stratton et al. Aging Res Rev 2013

Ghrelin-agonist, lungcancer och lean body mass

495 patienter med små-cellig lungcancer och anorexi-kakexi.

Ghrelin-agonist under 12 veckor. DXA/lean body mass (kg). Handgreppsstyrka.

• LBM↑

• HGS

• Symptom

Temel et al. Lancet Oncol 2016;17:519-31

Sammanfattning

• Sjukdomsrelaterad malnutrition med inflammation– Cancer, KOL, hjärtsvikt, ….

• Sjukdomsrelaterad malnutrition utan inflammation– Stroke, Parkinson, demens, depression, ….

• Diagnoskriterier för malnutrition?– ESPEN: Viktförlust, BMI, Fettfri massa/muskel, etiologi,

– GLIM: Viktförlust, …?

• DRM är behandlingsbart– Mat, träning, läkemedel

• Att behandla DRM är kostnadseffektivt

The ESPEN Initiative for Diagnostic Criteria for ... · Weight as predictor of COPD mortality...

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