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

D.Millward@surrey.ac.uk

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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