The ESPEN Initiative for Diagnostic Criteria for Undernutrition

Sjukdoms- vs. svältrelaterad undernäring
- malnutrition ur etiologiskt perspektiv
Tommy Cederholm
Professor, Klinisk nutrition och metabolism, Folkhälsooch vårdvetenskap, Uppsala Universitet
Överläkare, Geriatriska kliniken, Akademiska
sjukhuset, Uppsala
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-based
diagnoses of malnutrition
(to be used for the ICD and other classification
systems)
- diagnostic criteria for malnutrition
Etiology-based defintions
General 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 reduced
food intake or absorption
Todays diagnostic procedures of malnutrition don’t
take aetiology into consideration
ESPEN Guidelines on Definitions and Terminology
Malnutrition diagnoses tree
Risk screening
Basic diagnosis
Etiology-based
diagnoses
At risk for
malnutrition
Malnutrition/Undernutrition
Disease-related malnutrition
(DRM) with inflammation
Acute disease- or
injury-related
malnutrition
Disease-related malnutrition
(DRM) without inflammation
Chronic DRM with
inflammation
Malnutrition/Undernutrition
without disease
Socioeconomic or
psychologic related
malnutrition
Hunger-related
malnutrition
Cancer cachexia and other
disease-specific cachexia
ESPENCederholm
Consensus
2016
et al. Statement
Clin Nutr 2016;e-pub
ESPEN Guidelines on Definitions and Terminology
Malnutrition diagnoses tree
Risk screening
Basic diagnosis
Etiology-based
diagnoses
At risk for
malnutrition
Malnutrition/Undernutrition
Disease-related malnutrition
(DRM) with inflammation
Acute disease- or
injury-related
malnutrition
Disease-related malnutrition
(DRM) without inflammation
Chronic DRM with
inflammation
Malnutrition/Undernutrition
without disease
Socioeconomic or
psychologic related
malnutrition
Hunger-related
malnutrition
Cancer cachexia and other
disease-specific cachexia
ESPENCederholm
Consensus
2016
et al. Statement
Clin Nutr 2016;e-pub
Malnutrition or undernutrition?
ESPEN membership ballot >300 votes:
53% malnutrition
47% undernutrition
More consideration is needed
ESPEN Guidelines on Definitions and Terminology
Malnutrition diagnoses tree
Risk screening
Basic diagnosis
Etiology-based
diagnoses
At risk for
malnutrition
Malnutrition/Undernutrition
Disease-related malnutrition
(DRM) with inflammation
Acute disease- or
injury-related
malnutrition
Malnutrition/Undernutrition
Disease-related malnutrition
Malnutrition
related
to without disease
(DRM) without inflammation
Chronic DRM with
inflammation
Cancer cachexia and other
disease-specific cachexia
-
Cancer
Socioeconomic or
COPD
psychologic related
Congestive heart failue
malnutrition
Infections
Trauma
ICU
Hunger-related
malnutrition
ESPENCederholm
Consensus
2016
et al. Statement
Clin Nutr 2016;e-pub
Inflammation och kakexi/KOL
70
S-TNF (pg/ml)
60
50
(16)
40
30
p<0.05
20
10
(14)
0
COPD/PEM
COPD
Controls
Di Francia Am J Respir Crit Care Med 1994;150:1453-5
Disease/trauma/aging
Inflammation
Neuropeptid Y↓
Leptin↑
Anorexia
Insulin resistence Hormon sensitive lipase↑
Cathepsin↑
Ubiquitin-proteasom↑
Proteolysis
Lipoprotein lipase
Lipolysis
Cachexia → Sarcopenia
Inflammation och muskelnedbrytning
insulin
TNFa
IL-1b
protein
Insulin
resistance
+
Sarkopeni
+
ubiquitine
nucleus
proteasome
Amino acids
- alanine
- glutamine
Oliff 1987
gluconeogenesis
gut
immune system
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 (%)
100
400 COPD-patients, >65 y
4 y follow-up
80
Independent mortality predictors;
• BMI <24 (obesity paradox)
60
40
20
• Age
• PaO2
• PaCO2, FEV1, sex
BMI>29
BMI 24-29
BMI 20-24
BMI <20
0
12
24
36
48
Months
Schols et al. Am J Respir Crit Care Med 1998;157:1791-7
Kardiell- kakexi
Kardiell kakexi
mortalitet
Definition: >6% viktförlust s. 6 mån
Prevalens: 12-15% (NYHA II-IV)
Incidens: 10%/år
Anker et al. Clin Nutr 2006;25:311
Anker et al. Lancet 2003;361:1077-83
Myrianthefs et al. Cytokine 2007
ESPEN Guidelines on Definitions and Terminology
Malnutrition diagnoses tree
Risk screening
Basic diagnosis
Etiology-based
diagnoses
At risk for
malnutrition
Malnutrition/Undernutrition
Disease-related malnutrition
(DRM) with inflammation
Acute disease- or
injury-related
malnutrition
Disease-related malnutrition
(DRM) without inflammation
Chronic DRM withMalnutrition related to
inflammation
Malnutrition/Undernutrition
without disease
Socioeconomic or
psychologic related
malnutrition
Hunger-related
malnutrition
- Stroke, Parkinson
- Dementia
Cancer cachexia and other
- Anorexia nervosa
disease-specific cachexia
- Depression
- Malabsorption
ESPEN Consensus Statement 2016
- Coeliac disease
-
Short bowel syndrome
Cederholm et al. Clin Nutr 2016;e-pub
ESPEN Guidelines on Definitions and Terminology
Malnutrition diagnoses tree
Risk screening
Basic diagnosis
Etiology-based
diagnoses
At risk for
malnutrition
Malnutrition/Undernutrition
Disease-related malnutrition
(DRM) with inflammation
Acute disease- or
injury-related
malnutrition
Disease-related malnutrition
(DRM) without inflammation
Chronic DRM with
inflammation
Malnutrition/Undernutrition
without disease
Socioeconomic or
psychologic related
malnutrition
Hunger-related
malnutrition
Cancer cachexia and other
disease-specific cachexia
ESPENCederholm
Consensus
2016
et al. Statement
Clin Nutr 2016;e-pub
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
Bra funktion
Al Snih S et al. Arch Intern Med 2007;167:774-80
”Obesity paradox”
!
BMI<22
Överlevnad
MAIDS –
malnutrition associated immune deficiency syndrome
Cell mediated immunity↓
–
–
•
Humoral immunity↓
–
•
T lymphocytopenia
CD4/CD8 ratio↓
Ig-prod↓→Vaccination↓
Granulocyte dysfunction
–
–
Chemotaxis↓
Oxygen radical
production↓
Infections
Mentala effekter av svält
34 unga män, 1500 kcal/dag 6 mån,
förlorade 25% av kv
• Depression
• Apati
• Irritabilitet
• Social tillbakadragenhet
Depressionsskala
100
50
Svält 0-6 Refeeding 6-15
0
0
6
9
15
Mån
Keys A. The Biology of Human Starvation 1950
Next challenge: Define diagnostic criteria
for malnutrition/undernutrition
The nutrition care process needs to assure a
diagnostic procedure
• Screening/risk evaluationnutritional risk
• Assessment for treatment
• Treatment
• Monitoring
Next challenge: Define diagnostic criteria
for malnutrition/undernutrition
The nutrition care process needs to assure a
diagnostic procedure
• Screening/risk evaluationnutritional 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 Classification
of Diseases (ICD-10/11)
ESPEN initiative 2012-2015
What is the core of malnutrition?
Nutrition indicators considered
•
•
•
•
•
•
•
•
•
Weight loss
Reduced food intake
Reduced appetite
Low BMI
Reduced lean mass
Reduced fat mass
Inflammation
Subjective evaluation
Functional measures
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
Cederholm et al. Clin Nutr 2015;34:335-40.
ESPEN suggestion for diagnostic criteria for malnutrition
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
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.
Cederholm et al. Clin Nutr 2015;34:335-40.
ESPEN Poll - 304 ”votes”
Criteria
1
5
10
1=strongly disagree,
2-9= ....
10=strongly agree
26%
8
Result: ~70% ≥ 8/10 agreement
Conclusion: ”Strong support”
Problems and issues raised that should be
considered
• Too restrictive cut-offs
– Low prevalence figures  less reimbursement
• How to handle weight loss/malnutrition in obese
patients?
• 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 2016
The 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 reduced
re-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