symposium 5 – the nutrition society symposium muscle ... · ndns data trimmed for under-reporting...
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Symposium 7 Muscle Wasting with Age – A New Challenge in Nutritional Care Part 2 - Management
Nutritional management of sarcopenia: is there anything known
to work?
D Joe Millward Nutritional Sciences,
Faculty of Health and Medical Sciences, University of Surrey, Guildford
Sarcopenia occurs in the physically active e.g. Korhonen et al J Appl Physiol 101:906-917, 2006
Sprint-trained athletes exhibit sarcopenia
• the physically active have higher food intakes
• sarcopenia is not a simple nutritional problem
can we slow its development?
Little & Phillips Appl. Physiol. Nutr. Metab. 34: 817–828 (2009)
physical activity
esp. strength training
is beneficial
food intake
Anabolic resistance of muscle in the healthy elderly
Cuthbertson et al 2005 FASEB J
19:422–4.
insulin
5 IU/mL
15 IU/mL
blunting of stimulation of protein
synthesis by amino acids blunting of inhibition of
proteolysis by insulin
Wilkes et al. Am J Clin Nutr
2009; 90:1343–50.
Little & Phillips Appl. Physiol. Nutr. Metab. 34: 817–828 (2009)
increased
protein?
physical activity
esp. strength training
is beneficial
food intake
Anabolic resistance of muscle and
dietary protein
Are the protein requirements for the elderly
increased because of anabolic resistance
Are protein intakes sufficient to meet these
requirements?
Does sarcopenia result from inadequate protein
intakes?
Is anabolic resistance overcome by higher protein
intakes?
No convincing evidence suggesting that protein
requirements (as g/kg) increase with age
Systematic review: no change with age
Millward & Roberts. Protein requirements of older individuals. Nutr Res Rev 1996;9:67–87.
Experimental studies (13C-1 leucine balance): slight fall with age Millward et al. Aging, protein requirements, and protein turnover. Am J Clin Nutr 1997; 66:
774–86.
Nitrogen balance meta analysis: no influence of age WHO/FAO/UNU 2007 Protein requirements report
Recent comprehensive N balance study: no influence of age. Campbell et al. Am J Clin Nutr 2008;88:1322–9.
but...................
protein requirements fall only
slightly with age and not at all in
adult life
energy requirements fall in
childhood and in adult life.
average energy and protein requirements
0
50
100
150
200
250
300
350
400
0.5 2.5 5 10 15 18-29 30-59 >60 Age (y)
kJ
/kg
/d
0.00
0.20
0.40
0.60
0.80
1.00
1.20
g p
rote
in/k
g/d
energy: PAL =1.55
protein
average protein-energy ratio of requirements
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.10
0.11
0.5 2.5 5 10 15 18-29 30-59 >60 Age (y)
P:E
ra
tio
protein-energy ratios of requirements increase with age
the elderly need the most protein-dense food
the sedentary elderly are most at risk from protein deficient diets
The protein-energy ratio of requirements increases with age
Implications of anabolic resistance of
muscle
Are the protein requirements for the elderly NO
increased because of anabolic resistance
Do protein intakes meet these requirements?
Does sarcopenia result from inadequate protein
intakes?
Is anabolic resistance overcome by higher protein
intakes?
Protein intakes in the free living elderly
NDNS data trimmed for under-reporting EI<1.35xBMR
median protein intake: 1.24 g/kg/d, or 13.7pcals%
no change with age within the cohort
intake range (0.63–2.38g/kg/d)
i.e. zero prevalence of deficiency.
latest NDNS data shows higher protein intakes
(17pcals%)
Protein intakes in the free living elderly in the UK exceed the requirements
Implications of anabolic resistance of
muscle
Are the protein requirements for the elderly NO
increased because of anabolic resistance
Do protein intakes meet these requirements? YES
Does sarcopenia result from inadequate protein
intakes?
Is anabolic resistance overcome by higher protein
intakes?
Protein intakes and sarcopenia are
unrelated in most studies
Two widely quoted studies showing a
relationship are seriously confounded
One study shows a relationship of dietary
protein with frailty
New Mexico Elder Health Survey (n=883) Baumgartner et al Am J Epidemiol 1998147, 755–763.
Small cross sectional study of protein intake, and skeletal
muscle mass in older men (n=44):
Starling et al Am J Clin Nutr 1999;70:91–6.
Cardiovascular Health Study (n=1400) influence of
nutritional factors on body composition in the elderly: Mitchell et al J Nutr Health Aging. 2003;7(3):130-9
Health ABC study of protein intake and sarcopenia (n =
2066) Houston et al Am J Clin Nutr 2008;87:150 –5
cross sectional studies: no relationship between sarcopenia and protein intakes:
confounded studies
1. Dietary animal protein intake: association with
muscle mass index in older women
Lord et al J Nutr, Health & Aging VIl, (5) 2007 383-387
Cohort includes overweight women: BMI 30: mean 26.44
FFMas BMI so FFM/H2 is highly correlated with BMI (r=0.714)
Animal protein intake is correlated with BMI
relationship between animal protein intake and MMI probably means that
meat intake is driving an increase in BMI and associated FFM.
Dietary animal protein intake: association with muscle mass index in older
women Lord et al J Nutr, Health & Aging VIl, (5) 2007 383-387
n=38 sedentary women, 57-75 y, many overweight, consuming a protein rich diet: P:E=17%
muscle mass index =FFM/H2, a poor index of sarcopenia in this cohort
longitudinal studies
1. 1993 and 1997 China Health and Nutrition Surveys (n=608, 50–70y):
changes over 4 years Stookey et al J. Nutr. 131: 2433S–2440S,2001
muscle mass change not associated with protein
intakes in those who lost muscle
2.
Houston et al Am J Clin Nutr 2008;87:150 –5
Conclusion: Dietary protein may be a modifiable risk factor for
sarcopenia in older adults and should be studied further to
determine its effects on preserving LM in this population.
Health ABC study: baseline data: n=2066 mean age 74.5
Appendicular LM (kg) by quintiles of protein intakes
0
5
10
15
20
25
30
P:E ratio 10.9 12.7 14.2 15.9 18.6
Q2 Q3 Q4 Q5
aL
M (
kg
)
p=0.42: ns
no cross sectional relationship
at baseline
no comment by the authors
Q1
Health ABC study: 3y longitudinal data
muscle mass change over 3y varies with protein intake
10.9% protein intake (% energy) 18.6%
clear result???
FIGURE 3. Adjusted appendicular lean mass (aLM) loss by quintile of energy-
adjusted total protein intake and weight change status. n _ 2066.
P for trend: weight losers (28.8% total: >3%), 0.03;
weight stable (49.5% total: 3%), 0.60;
weight gainers (21.7%total: >3%), 0.02.
sarcopenia over 3 y
no influence of protein
Discussion: “dietary protein appears to be associated with the
partitioning of body mass in those who gain and lose weight” but not with sarcopenia per se
Anabolic resistance of muscle, dietary
protein and sarcopenia
conclusions
Are the protein requirements for the elderly
increased because of anabolic resistance
Do protein intakes meet these requirements?
Does sarcopenia result from inadequate
protein intakes?
Is anabolic resistance overcome by higher
protein intakes?
NO
YES
NO
NO
Protein Intake and Incident Frailty in the Women’s Health
Initiative Observational Study
Beasley JM. et al J Am Geriatr Soc 58:1063–1071, 2010.
Frailty
Protein Intake and Incident Frailty in the Women’s Health Initiative Observational Study
Beasley JM. et al J Am Geriatr Soc 58:1063–1071, 2010.
Frailty and protein: prospective cohort study. n=24,417 women aged 65 to 79: 3 yr follow up for frailty measurement
frailty: questionnaires on physical function, poor endurance/exhaustion,
low physical activity, unintentional weight loss.
sarcopenia will contribute together with several other causes
Risk of frailty (adjusted for multiple variables) compared
with lowest quintile (Q1) of protein intake (%kcal):
as measured adjusted for under-reporting
Protein Intake and Incident Frailty in the Women’s Health Initiative Observational
Study
Beasley JM. et al J Am Geriatr Soc 58:1063–1071, 2010.
Frailty
authors comments
“higher protein intake positively associated with measures of
socioeconomic status…..
long-term intervention trials are needed to be certain that protein intake
has causal effects rather than serving as a marker of better overall
quality of life or diet quality”
Little & Phillips Appl. Physiol. Nutr. Metab. 34: 817–828 (2009)
The healthy diet?
Oily fish Fruit and veg
anti
inflammatory?
increased
protein?
ineffective
physical activity
esp. strength training
is beneficial
food intake
Findings:-
fish oil supplementation augments the amino acid-insulin induced increase
in muscle protein synthesis: i.e. attenuates anabolic resistance.
mechanism not entirely clear, i.e.,
partially mediated via increased activation of the mTOR-p70s6k
signaling pathway
no effects on serum markers of inflammation
8 wk supplementation of older adults with 4g EPA+DHA or corn oil
FISH OIL AND ANABOLIC RESISTANCE
Little & Phillips Appl. Physiol. Nutr. Metab. 34: 817–828 (2009)
The healthy diet?
Oily fish Fruit and veg
anti
inflammatory?
anti
oxidants?
& phase 2
protein
inducers
acid
buffering?
physical activity
esp. strength training
is beneficial
food intake
increased
protein?
ineffective
Anti oxidants & sarcopenia
Ershler WB A gripping reality: oxidative stress, inflammation, and the pathway
to frailty J Appl Physiol 103: 3–5, 2007.
(phase 2 protein inducers)
Evidence for an effect
on function from
human observational
studies
animal experimental
studies
Potassium Bicarbonate Reduces Urinary Nitrogen
Excretion in Postmenopausal Women Frassato et al J Clin Endocrinol Metab 82: 254–259, 1997
“magnitude is potentially sufficient
to prevent continuing loss and
restore previously accrued
deficits of muscle mass”
Fruit and veg should do the
same thing.
Acid buffering with KHCO3improves nitrogen
balance
change in total urinary N
KHCO3 dose:
60–120 mmol/day = 6-12g/d
cumulative N gain
≈ 14 g 0.43 kg LBM.
Alkaline diets favour lean
tissue mass in older adults Bess Dawson-Hughes et al 2008
AJCN 87:662–5
Higher intake of foods rich in
potassium, such as fruit and
vegetables, may favour the
preservation of muscle mass
in older men and women.
Acid buffering with fruit and vegetables
preserves lean body mass:
Little & Phillips Appl. Physiol. Nutr. Metab. 34: 817–828 (2009)
The healthy diet?
Oily fish Fruit and veg
anti
inflammatory?
anti
oxidants?
& phase 2
protein
inducers
acid
buffering?
Vitamin D
strength
preservation
in muscle and
bone?
physical activity
esp. strength training
is beneficial
food intake
increased
protein?
ineffective
Sirola & Kroger 2011 J Osteo. doi:10.4061/2011/536735
postmenopausal sarco-osteopenia and frailty syndrome
“vitamin D essential for muscle strength, function, and bone strength” muscle weakness
accompanies rickets
and osteomalacia
Mechanism of vit D
effect unclear: no
VDR in muscle Wang and DeLuca
Endocrinology, February
2011, 152(2):354–363
hypophosphatemia
responsible for
muscle weakness of
vit D deficiency? Schubert & DeLuca Arch
Biochem Biophys
(2010,500,157-161)
Vitamin D and muscle mass & function
Cross sectional studies
plasma 25(OH)D predicts
muscle power and force in adolescent girls: Ward et al J Clin Endocrinol Metab
94: 559–563, 2009
physical performance and its decline in older persons: Wicherts et al J Clin
Endocrinol Metab 92: 2058–2065, 2007
sarcopenia. Szulc et al Am J Clin Nutr 2004;80:496 –503
lower-extremity function in both active and inactive persons aged 60 y: Bischoff-Ferrari, Am J Clin Nutr 2004;80:752–8
Vitamin D and muscle mass & function
Interventions (RCTs)
Vit D supplements reduced risk of falls by > 20% among ambulatory or institutionalized elders
(meta analysis) Bischoff-Ferrari, H.A., JAMA, April 28, 2004—Vol 291,
No. 16 1999-2006
association between vitamin D and physical performance remains
controversial. Annweiler et al systematic review J Nutr Health Aging V13,
(10), 893-898, 2009
Supplemental vitamin D reduced the risk of falling among older individuals
for interventions 700 IU a day but not at lower doses: (meta analysis)
Bischoff-Ferrari, BMJ 2009; 339: b3692 doi:10.1136/bmj.b3692
19% reduction in risk of falling
by high dose vitamin D
no reduction in fall risk with
low dose vitamin D
Bischoff-Ferrari et al, BMJ 2009;
339:b3692 doi:10.1136/bmj.b3692
Vitamin D and muscle mass & function
Undoubtedly an important influence on muscle and with
multiple other benefits
Optimizing Vit D status at plasma 25(OH)D 75nmol/l
should be a priority.
However its extent may be limited with
exercise including some resistance exercise
a healthy diet with adequate fruit & veg & oily fish
which will supply sufficient protein
sunlight and/or vitamin D supplements
Can sarcopenia be prevented with a healthy lifestyle?
No:
• it occurs in aerobically fit master athletes
• it is unlikely to have a simple nutritional aetiology Harridge et al. Aging (Milano) 1997;9:80-7
Starling et al Am J Clin Nutr 1999;70:91–6
Korhonen et al J Appl Physiol 101:906-917, 2006
maximising Vit D levels
Barbara Miles
Scottish Patient Safety Fellow
Consultant Intensive Care Unit, Glasgow Royal Infirmary
Exercise in Intensive Care
BAPEN Annual Conference November 2011
Outcomes after ICU
Mortality
Functional
Cognitive and Neuropsychological
Quality of life
Mortality
Mortality 16.5 - 32.5%1
5 year follow up: mortality worse than the general population for 2- 4 years2,3
15 year follow up: mortality worse than the general population at all time points4
1 Case mix, outcome and length of stay for admissions to adult, general critical care units in England, Wales and Northern Ireland: the Intensive Care National Audit &
Research Centre Case Mix Programme Database. Crit Care 2004, 9:S1-13.
2 Five-year survival after intensive care–comparison of 12,180 patients with the general population. Finnish ICU Study Group. Crit Care Med 1996; 24:1962–1967
3 Longterm survival following intensive care: Subgroup analysis and comparison with the general population. Anaesthesia 2003; 58:637–642
4 Determinants of long-term survival after intensive care Crit Care Med 2008; 36:1523–1530
Functional Outcome
54% of patients have restrictions in daily functioning at 12 months3
69% of patients ventilated 48 hrs have ADL impairment at 12 months1
Approximately 75% of these limitations are severe
57% patients need caregiver support at 1-yr follow-up4
6 minute walk test is 66% of predicted at 1 yr5, 76% at 5yrs2
40% -54% patients have returned to work at 1 yr1,2,3
Muscle wasting /weakness responsible for persistent disability6
1 Poor functional recovery after a critical illness: A longitudinal study. J Rehabil Med 2009; 41:1041–1048
2 Functional Disability 5 Years after Acute Respiratory Distress Syndrome NEJM 364(14) 1293–1304
3 Functional Status after Intensive Care: a Challenge for Health Professionals to Improve Outcome J Rehabil Med 2009;41:780-781
4 Long term mortality and quality of life after prolonged mechanical ventilation. Crit Care Med 2004; 32:61–69
5 One-year outcomes in survivors of the acute respiratory distress syndrome NEJM 348 (8); 683,
6 ICU-Acquired Weakness Chest 2007;131;1541-1549
Cognitive and Psychological Outcome
25% - 78% patients have cognitive impairment after critical illness1
25% ARDS survivors still impaired 6 years after ICU discharge2
ICU patients with severe sepsis (≥65 yrs) had 4x more moderate /severe impairment – lasting up to 8 yrs3
Deficits in memory, executive functioning, attention and mental processing abilities1
Depression more common than general population (28% vs. 8%)1
PTSD also more common (22% vs. 3.5%)1
1 Short- and Long-Term Cognitive Outcomes in Intensive Care Unit Survivors Clin Chest Med 30 (2009) 143–153
2 The relationship between cognitive performance and employment and health status in long-term survivors of the acute respiratory distress syndrome:
Results of an exploratory study. Gen Hosp Psychiatry 2001; 23:90–96
3 Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 2010; 304:1787–1794
Quality of Life
Quality of life in the five years after intensive care: a cohort study Critical Care 2010, 14:R6
What happens to patients in
ICU?
Delirium
Delirium in the intensive care unit Critical Care 2008, 12(Suppl 3):S3
The Importance of Diagnosing and Managing ICU Delirium Chest 2007;132;624-636
Common – occurs 20-80% ICU patients
Acute and fluctuating disturbance of consciousness and cognition
Clinically ranges from hypoactivity to acute agitation
Independently associated 3 x increase in 6 month mortality
Associated multiple complications Self extubation, removal of catheters, failed extubation, prolonged
hospital stay, increased health care costs, long term cognitive impairment
Risk factors Sedatives, sleep disturbance, metabolic disturbances, age, severity
of illness, hypertension, alcoholism Immobilisation
ICU Acquired Weakness
Common – 25% -58% 2
Reported 50 -100% of sepsis patients2
Ranges from mild tetraparesis to severe tetraplegia
Independently linked to a higher risk of hospital death 1
Patients with ICU-acquired weakness need more days of ventilation and have increased mortality , 48% vs. 19%, p <0.035
Risk factors are hyperglycaemia, corticosteroids, multiple organ failure, neuromuscular blockade
Immobility is a likely contributor In healthy adults, muscle strength declines by 1%/day of strict bed rest3
In ICU, longer ventilation times associated with ICU weakness3
Muscle wasting highest during the first 2-3 wks of ICU4
1 Weakness in the ICU: a call to action Critical Care 2009, 13:1002
2 Intensive care unit-acquired weakness Crit Care Med 2010; 38:779 –787
3 Intensive care unit-acquired weakness: Risk factors and prevention Crit Care Med 2009; 37[Suppl.]:S309 –S315
4 Muscle wasting in intensive care patients: Ultrasound observation of the M. quadriceps femoris muscle layer. J Rehabil Med 2008; 40:185–189
5 Reducing Iatrogenic Risks Chest 2010; 138(5):1224–1233
Is exercise the solution?
ICU acquired weakness
Delirium
Poor Quality of Life in Survivors
Feasibility
ICU patients are inactive Patients progressed beyond bed rest in only 11% of 2470 ICU days2
Most common activity in ICU is position change1
2005 study observed 20 ICU patients for 8 hour period
Patients were active 13 of possible 160 hours
196 activity episodes 113 turning,11 ROM,2 sitting,1 standing
Turns took 11 minutes, ROM 8 mins Sitting took up nearly 8 of the total 13 hours of activity
Critically ill patients are viewed as “too sick” to tolerate activity ?
1 Activity in the Chronically Critically Ill DIMENS CRIT CARE NURS. 2005;24(6):281/290
2 Mobilizing Patients in the Intensive Care Unit: Improving Neuromuscular Weakness and Physical Function JAMA. 2008;300(14):1685-1690
Is it safe?
Early activity is feasible and safe in respiratory failure patients Crit Care Med 2007; 35:139–145
All patients ventilated for > 4 days over a 7 month period 2003
Activity events were sitting on bed, in chair and ambulating Neurologic, respiratory and circulatory criteria were met before
activity initiated
Pre and post activity 30 min rest period on ventilator if required
Adverse events : fall to knees, hypertension, hypotension, tube removal, significant desaturation and extubation
1,449 activity events in 103 patients 16% sit on bed, 31% sit chair, 53% ambulation
The median ambulation by survivors was 200 ft 69% patients could ambulate > 100ft at discharge
There were 14 adverse events in 9 patients (<1%)
Is it worth the effort?
First prospective study enrolled 330 patients within 48h of intubation
Usual care vs. usual care plus mobilisation protocol in ICU
The mobilisation group had more physical therapy 80 % ≥ 1physical therapy session vs. 47% usual care group; p <
.001 No adverse events during any of the mobilisation sessions
The mobilisation group were out of bed faster 8.5 d vs. 13.7; p < .001
The mobilisation group left hospital faster 14.9 d vs. 17.2; p 0.04
Hospital mortality was unchanged 12.1% of Mobilisation vs. 18.2% Usual Care ; p 0.125
Early intensive care unit mobility therapy in the treatment of acute respiratory failure Crit Care Med 2008; 36:2238–2243
Is it worth the effort?
Receiving Early Mobility During an Intensive Care Unit Admission Is a Predictor of Improved Outcomes in Acute Respiratory Failure: Am J Med Sci 2011;
341(5):373–377
280 survivors of this study followed up at 12 months
132 (47%) had at least 1 readmission or died
44 (17%) died
126 (45%) were not readmitted 22 (8%) were lost to follow-up
Readmission or death in the first year predicted by
Tracheostomy [OR 4.02 (95%CI, 1.72–9.40)] Female gender [OR1.94 (95%CI, 1.13–3.32)] Charlson Comorbidity Index [OR 1.15 (95%CI, 1.01–1.31)]
Acute severity of illness scores were not predictive
Lack of early ICU mobility therapy [OR1.77 (95%CI, 1.04 –3.01)]
Is it worth it?
Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial Lancet 2009; 373:
1874–82
First RCT daily sedation breaks with physical and occupational therapy Enrolled 104 sedated patients within 72h of ventilation
Intervention had therapy median 1.5 days post intubation vs. 7.4 controls (p<0.0001) Average duration of intervention 20 minutes
Intervention had shorter duration of delirium, median 2 days vs. 4 days, p=0.02
Intervention had more ventilator-free days during 28-day follow-up (23.5 vs. 21.1)
Intervention 59% independent at hospital discharge vs. 35% control (p=0.02) Functional status assessed by blinded therapist
No difference in sedation
1 serious adverse event in 498 therapy sessions (desaturation <80%).
Discontinuation of therapy as a result of patient instability occurred in 19 (4%) of all sessions(perceived patient-ventilator asynchrony)
Is it worth it?
Early exercise in critically ill patients enhances short-term functional recovery Crit Care Med 2009 Vol. 37, No. 9 Crit Care Med 2009; 37:2499 –2505
RCT, 90 patients ventilated for 5 days or more Expected to have another 7 days in ICU
Intervention 20 mins daily on bedside bicycle ergometer Previously used in haemodialysis and COPD patients
Passive or active
Median 7 cycling sessions , 4 times a week
425 sessions of cycling with no severe adverse events Exercise was terminated early in 16 individual sessions
ICU discharge – most patients couldn’t walk
Hospital discharge 6 minute walk 196 m intervention vs.143 m control p <0.05
(29% vs. 25% predicted)
Isometric quadriceps force, feeling of functional well-being (SF36) were higher intervention than controls (p < .05)
Exercise in Intensive Care
1 Intensive care unit-acquired weakness Crit Care Med 2010; 38:779 –787
2 Physiotherapy for adult patients with critical illness: recommendations of the European Respiratory Society and European Society of Intensive Care Medicine
Task Force on Physiotherapy for Critically Ill Patients Intensive Care Med (2008) 34:1188–1199
Hypothesis that exercise is good in ICU seems reasonable Immobility is a risk factor for delirium and ICU AW
Exercise releases anti inflammatory cytokines1
Bed rest helpful? No evidence of benefit1, evidence of harm in healthy subjects1
Atelectasis in ICU patients after 48h bed rest1
Multiple studies have demonstrated safety of exercise
RCTs in USA and Europe demonstrating an effect on function and delirium
Early mobilisation was shown 30 years ago to reduce the time to wean from mechanical ventilation2
Published guidance
Guidance
1 Physiotherapy for adult patients with critical illness: recommendations of the European Respiratory Society and European Society of Intensive Care
Medicine Task Force on Physiotherapy for Critically Ill Patients Intensive Care Med (2008) 34:1188–1199
2 Safety Issues That Should Be Considered When Mobilizing Critically Ill Patients Crit Care Clin 23 (2007) 35–53
Active or passive
mobilisation and
muscle training
should be instituted
early with
appropriate
monitoring1
‘How to’ advice is
available2
Guidance
Reducing Iatrogenic Risks ICU-Acquired Delirium and Weakness—Crossing the Quality Chasm Chest 2010; 138(5):1224–1233
ABCDE approach
Why isn’t it happening?
Barriers
Barriers
1 Brent James Intermountain Healthcare
2 Reducing Iatrogenic Risks ICU-Acquired Delirium and Weakness—Crossing the Quality Chasm Chest 2010; 138(5):1224–1233
3 Rehabilitation therapy and outcomes in acute respiratory failure: An observational pilot project Journal of Critical Care (2010) 25, 254–262
4 Crossing the Quality Chasm: A New Health System for the 21st Century .Washington, DC : The Institute of Medicine ; 2001
5 A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial Lancet 2010; 375: 475–80
17 years to put evidence into practice “health care today harms too frequently and routinely fails to deliver potential benefits”4
Inevitable consequence of critical illness
We need to sedate our patients Sedation breaks are beneficial2
Unblinded RCT 140 ventilated patients assigned to no sedation (n=70) or sedation with daily interruption until awake (n=70) 4
Patients receiving no sedation had significantly more days without ventilation, shorter ICU stay and hospital stays, less delirium and no more accidental extubations
Multidisciplinary silos2
Patients able to mobilise not identified3
Intensive Care Culture
Culture
1 Patients with respiratory failure increase ambulation after transfer to an intensive care unit where early activity is a priority Crit Care Med 2008; 36:1119–1124
2 Transforming ICU Culture to Facilitate Early Mobility Crit Care Clin 23 (2007) 81-96
Can it be overcome?
104 respiratory failure patients ventilated for >4 days Transferred to the respiratory ICU Probability of ambulation increased (p < .0001)
2 days after transfer, 3 x number of patients were ambulating
How?
Changing your culture 2
Changing organisation
Urgency, powerful guiding coalition, creating and communicating
a vision, short and long term wins, consolidating change, spread
No increase in cost
Summary
Critical illness is long term diagnosis with long term effects
ICU acquired weakness and delirium are not an inevitable consequence of critical illness
Exercise is safe, feasible and effective in modifying effects of critical illness at hospital discharge
It is possible to exercise patients in any Intensive Care
Systematic review and
meta-analysis of the effects of
high protein oral nutritional
supplements on strength.
A.L. Cawood1, R.J. Stratton1,2, M.Elia2.
1Medical Affairs, Nutricia, Trowbridge.
2Instititue of Human Nutrition, University of Southampton
Background
• Systematically obtained evidence on the effects of high protein oral nutritional supplements (ONS) in clinical practice is needed.
• We have previously reported ONS high in protein, compared to control can significantly improve nutritional intake, weight and muscle tissue1
• However it is not known if this is associated with improved functional outcomes.
Aim
This systematic review and meta-analysis
aimed to synthesize the evidence for
high protein ONS
on the functional outcome
handgrip strength.
Methods
Searches of databases and bibliographies
Search terms included: Sip; adult; nutrition; nutrition
support; supplement; oral; enteral; liquid; formula; protein.
Identified 36 RCT (n 3790) of multi-nutrient high protein
ONS used in addition to diet and compared with control.
Range of patient groups including elderly, respiratory
disease, hip fracture, cancer, GI disease and other critical
and acute illnesses
Meta Analysis undertaken using Comprehensive Meta-
Analysis v2.
Methods
Formulate study question
Retrieve potentially relevant
citations
Evaluate citation title/ abstract.
Does it fulfil inclusion criteria?
(n=11137) Citations excluded on the basis of
title/abstract which did not conform to the
inclusion/exclusion criteria.
(n=11018) Evaluate full study text. Does it
fulfil inclusion criteria?
(n=119)
Studies included in review
(n= 36)
Data extraction, quality
assessment, synthesis of
evidence
Studies excluded (n=83)
Reasons for exclusions:
Not high protein (43)
Not RCT (8)
Mixed Reasons (32)
Methods
Selection
criterion
Inclusion criteria Exclusion criteria
Population - Adults > 18 years
- Any nutritional status
- Any setting (hospital, community)
- Any sample size
- Animal studies
- Pregnancy and lactation
- Developing world
- Sports studies
Intervention - All studies using ONS (including those
simultaneously used or comparing with
dietary counselling and/or std diet)
- Multi-nutrient ONS
- High protein ONS
- Randomised controlled trials
- Any duration of intervention
- Dietary counselling only.
- Parenteral nutrition only.
- Enteral tube feeding
- ONS with <2 macronutrients
- ONS with no micronutrients
- ONS < 20% energy from
protein
Results – search findings
Full Search Handgrip strength
No. RCT 36 (n=3790) 6 (n=357)
Intervention period 2wks - 1 yr 49d – 180d (mean 108d)
No. subjects
Mean age / % F
10-672
74y (42-86y), 64%F
14-101
71y (53-85y), 71%F
Prescribed intake 149-995kcal
10-60g P
200-900kcal
15-60g P
%En P 20-54% 20-40%
Populations Elderly, hip fracture, leg &
pressure ulcers, COPD,
Cancer, GI disease, Critical
and acute illness
Elderly (1), respiratory
(2), hip fracture (2), & GI
disease (1)
Setting H 6 RCT (n=1093)
H-C 11 RCT (n=1540)
C 19 RCT (n=1157)
H 0 RCT (n=0)
H-C 1 RCT (n=82)
C 5 RCT (n=275)
Results
• Six studies reported handgrip strength
• One did not report any data but stated no differences
• 4/5 studies (n174) handgrip decreased in control group
• Five studies (n275) reported mean changes greater in the
ONS group compared to control
-0.5
0.0
0.5
1.0
1.5
2.0
HP ONS CONTROL
+1.8kg
-0.08kg
Mean
Ch
an
ge H
GS
(kg
)
Results
Study Setting Statistics for each study Difference in means and 95% CI
Difference Lower Upper in means limit limit p-Value
Efthimiou et al 1988 Community 2.200 0.048 4.352 0.045
Norman et al 2008 Community 4.400 1.871 6.929 0.001
Steiner et al 2003 Community 0.690 -0.120 1.500 0.095
Tidermark et al 2004 Community 1.100 -0.584 2.784 0.200
1.762 0.355 3.170 0.014
-8.00 -4.00 0.00 4.00 8.00
Favours CON Favours HP ONS
Random effects model n=219
Significant improvement in handgrip strength in favour of HP ONS
Results
Significant relationship between handgrip strength and prescribed protein
Regression of Grams of Protein in prescribed ONS on Difference in means
Grams of Protein in prescribed ONS
Dif
fere
nce i
n m
ean
s
16.00 20.80 25.60 30.40 35.20 40.00 44.80 49.60 54.40 59.20 64.00
6.00
5.40
4.80
4.20
3.60
3.00
2.40
1.80
1.20
0.60
0.00
Effect size 0.1kg / g protein prescribed (p=0.01)
Oral nutritional supplements (high in protein) compared to control:
Significantly increase total energy intake
313.6kcal, 95% CI 145.7 to 481.6kcal, 12 RCT, p<0.001
Significantly increase total protein intake
22g, 95% CI 10 to 34g, 10 RCT, p<0.001
Other Results
Significant improvement in nutritional intake
Difference in means 1.8kg; 95% CI 0.8-2.8 (p<0.001) (n 1244) (12 RCT)
Study Setting Difference in
means and 95% CI
Bruce et al 2003 Hospital-Community
Efthimiou et al 1988 Community
Gariballa et al 2006 Hospital-Community
Lauque et al 2000 Community
McEvoy et al 1982 Hospital
Norman et al 2008 Community
Olofsson et al 2007 Hospital
Otte et al 1989 Community
Steiner et al 2003 Community
Teixido-Planas et al 2005Community
Tidermark et al 2004 Community
Volkert et al 1996 Hospital-Community
-10.00 -5.00 0.00 5.00 10.00
Favours CON Favours ONS
Other Results
Significant increase in weight
Conclusion
This systematic review and meta-analysis
suggests that
high protein ONS can
significantly improve
skeletal muscle strength (handgrip)
compared to control
References
1. Cawood AL, Elia M, Stratton RJ (2010).
Clinical Nutrition Supplements; 5(2): 123-124
2. Lochs H, Allison SP, Meier R et al (2006).
Clinical Nutrition; 25(2): 180-186
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